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1
Soyano, Takashi, Masaki Ishikawa, Ryuichi Nishihama, Satoshi Araki, Mayumi Ito, Masaki Ito, and Yasunori Machida. "Control of plant cytokinesis by an NPK1–mediated mitogen–activated protein kinase cascade." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 357, no. 1422 (June 29, 2002): 767–75. http://dx.doi.org/10.1098/rstb.2002.1094.
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Cytokinesis is the last essential step in the distribution of genetic information to daughter cells and partition of the cytoplasm. In plant cells, various proteins have been found in the phragmoplast, which corresponds to the cytokinetic apparatus, and in the cell plate, which corresponds to a new cross wall, but our understanding of the functions of these proteins in cytokinesis remains incomplete. Reverse genetic analysis of NPK1 MAPKKK (nucleus– and phragmoplast–localized protein kinase 1 mitogen–activated protein kinase kinase kinase) and investigations of factors that might be functionally related to NPK1 have helped to clarify new aspects of the mechanisms of cytokinesis in plant cells. In this review, we summarize the evidence for the involvement of NPK1 in cytokinesis. We also describe the characteristics of a kinesin–like protein and the homologue of a mitogen–activated protein kinase that we identified recently, and we discuss possible relationships among these proteins in cytokinesis.
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Guertin, David A., Susanne Trautmann, and Dannel McCollum. "Cytokinesis in Eukaryotes." Microbiology and Molecular Biology Reviews 66, no. 2 (June 2002): 155–78. http://dx.doi.org/10.1128/mmbr.66.2.155-178.2002.
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SUMMARY Cytokinesis is the final event of the cell division cycle, and its completion results in irreversible partition of a mother cell into two daughter cells. Cytokinesis was one of the first cell cycle events observed by simple cell biological techniques; however, molecular characterization of cytokinesis has been slowed by its particular resistance to in vitro biochemical approaches. In recent years, the use of genetic model organisms has greatly advanced our molecular understanding of cytokinesis. While the outcome of cytokinesis is conserved in all dividing organisms, the mechanism of division varies across the major eukaryotic kingdoms. Yeasts and animals, for instance, use a contractile ring that ingresses to the cell middle in order to divide, while plant cells build new cell wall outward to the cortex. As would be expected, there is considerable conservation of molecules involved in cytokinesis between yeast and animal cells, while at first glance, plant cells seem quite different. However, in recent years, it has become clear that some aspects of division are conserved between plant, yeast, and animal cells. In this review we discuss the major recent advances in defining cytokinesis, focusing on deciding where to divide, building the division apparatus, and dividing. In addition, we discuss the complex problem of coordinating the division cycle with the nuclear cycle, which has recently become an area of intense research. In conclusion, we discuss how certain cells have utilized cytokinesis to direct development.
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Neto, Hélia, Louise L. Collins, and Gwyn W. Gould. "Vesicle trafficking and membrane remodelling in cytokinesis." Biochemical Journal 437, no. 1 (June 14, 2011): 13–24. http://dx.doi.org/10.1042/bj20110153.
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All cells complete cell division by the process of cytokinesis. At the end of mitosis, eukaryotic cells accurately mark the site of division between the replicated genetic material and assemble a contractile ring comprised of myosin II, actin filaments and other proteins, which is attached to the plasma membrane. The myosin–actin interaction drives constriction of the contractile ring, forming a cleavage furrow (the so-called ‘purse-string’ model of cytokinesis). After furrowing is completed, the cells remain attached by a thin cytoplasmic bridge, filled with two anti-parallel arrays of microtubules with their plus-ends interdigitating in the midbody region. The cell then assembles the abscission machinery required for cleavage of the intercellular bridge, and so forms two genetically identical daughter cells. We now know much of the molecular detail of cytokinesis, including a list of potential genes/proteins involved, analysis of the function of some of these proteins, and the temporal order of their arrival at the cleavage site. Such studies reveal that membrane trafficking and/or remodelling appears to play crucial roles in both furrowing and abscission. In the present review, we assess studies of vesicular trafficking during cytokinesis, discuss the role of the lipid components of the plasma membrane and endosomes and their role in cytokinesis, and describe some novel molecules implicated in cytokinesis. The present review covers experiments performed mainly on tissue culture cells. We will end by considering how this mechanistic insight may be related to cytokinesis in other systems, and how other forms of cytokinesis may utilize similar aspects of the same machinery.
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O'Connell, Kevin F., Charles M. Leys, and John G. White. "A Genetic Screen for Temperature-Sensitive Cell-Division Mutants of Caenorhabditis elegans." Genetics 149, no. 3 (July 1, 1998): 1303–21. http://dx.doi.org/10.1093/genetics/149.3.1303.
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Abstract A novel screen to isolate conditional cell-division mutants in Caenorhabditis elegans has been developed. The screen is based on the phenotypes associated with existing cell-division mutations: some disrupt postembryonic divisions and affect formation of the gonad and ventral nerve cord—resulting in sterile, uncoordinated animals—while others affect embryonic divisions and result in lethality. We obtained 19 conditional mutants that displayed these phenotypes when shifted to the restrictive temperature at the appropriate developmental stage. Eighteen of these mutations have been mapped; 17 proved to be single alleles of newly identified genes, while 1 proved to be an allele of a previously identified gene. Genetic tests on the embryonic lethal phenotypes indicated that for 13 genes, embryogenesis required maternal expression, while for 6, zygotic expression could suffice. In all cases, maternal expression of wild-type activity was found to be largely sufficient for embryogenesis. Cytological analysis revealed that 10 mutants possessed embryonic cell-division defects, including failure to properly segregate DNA, failure to assemble a mitotic spindle, late cytokinesis defects, prolonged cell cycles, and improperly oriented mitotic spindles. We conclude that this approach can be used to identify mutations that affect various aspects of the cell-division cycle.
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Ralston, Katherine S., Alana G. Lerner, Dennis R. Diener, and Kent L. Hill. "Flagellar Motility Contributes to Cytokinesis in Trypanosoma brucei and Is Modulated by an Evolutionarily Conserved Dynein Regulatory System." Eukaryotic Cell 5, no. 4 (April 2006): 696–711. http://dx.doi.org/10.1128/ec.5.4.696-711.2006.
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ABSTRACT The flagellum of Trypanosoma brucei is a multifunctional organelle with critical roles in motility and other aspects of the trypanosome life cycle. Trypanin is a flagellar protein required for directional cell motility, but its molecular function is unknown. Recently, a trypanin homologue in Chlamydomonas reinhardtii was reported to be part of a dynein regulatory complex (DRC) that transmits regulatory signals from central pair microtubules and radial spokes to axonemal dynein. DRC genes were identified as extragenic suppressors of central pair and/or radial spoke mutations. We used RNA interference to ablate expression of radial spoke (RSP3) and central pair (PF16) components individually or in combination with trypanin. Both rsp3 and pf16 single knockdown mutants are immotile, with severely defective flagellar beat. In the case of rsp3, this loss of motility is correlated with the loss of radial spokes, while in the case of pf16 the loss of motility correlates with an aberrant orientation of the central pair microtubules within the axoneme. Genetic interaction between trypanin and PF16 is demonstrated by the finding that loss of trypanin suppresses the pf16 beat defect, indicating that the DRC represents an evolutionarily conserved strategy for dynein regulation. Surprisingly, we discovered that four independent mutants with an impaired flagellar beat all fail in the final stage of cytokinesis, indicating that flagellar motility is necessary for normal cell division in T. brucei. These findings present the first evidence that flagellar beating is important for cell division and open the opportunity to exploit enzymatic activities that drive flagellar beat as drug targets for the treatment of African sleeping sickness.
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Smith, Gregory R., Scott A. Givan, Paul Cullen, and George F. Sprague. "GTPase-Activating Proteins for Cdc42." Eukaryotic Cell 1, no. 3 (June 2002): 469–80. http://dx.doi.org/10.1128/ec.1.3.469-480.2002.
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ABSTRACT The Rho-type GTPase, Cdc42, has been implicated in a variety of functions in the yeast life cycle, including septin organization for cytokinesis, pheromone response, and haploid invasive growth. A group of proteins called GTPase-activating proteins (GAPs) catalyze the hydrolysis of GTP to GDP, thereby inactivating Cdc42. At the time this study began, there was one known GAP, Bem3, and one putative GAP, Rga1, for Cdc42. We identified another putative GAP for Cdc42 and named it Rga2 (Rho GTPase-activating protein 2). We confirmed by genetic and biochemical criteria that Rga1, Rga2, and Bem3 act as GAPs for Cdc42. A detailed characterization of Rga1, Rga2, and Bem3 suggested that they regulate different subsets of Cdc42 function. In particular, deletion of the individual GAPs conferred different phenotypes. For example, deletion of RGA1, but not RGA2 or BEM3, caused hyperinvasive growth. Furthermore, overproduction or loss of Rga1 and Rga2, but not Bem3, affected the two-hybrid interaction of Cdc42 with Ste20, a p21-activated kinase (PAK) kinase required for haploid invasive growth. These results suggest Rga1, and possibly Rga2, facilitate the interaction of Cdc42 with Ste20 to mediate signaling in the haploid invasive growth pathway. Deletion of BEM3 resulted in cells with severe morphological defects not observed in rga1Δ or rga2Δ strains. These data suggest that Bem3 and, to a lesser extent, Rga1 and Rga2 facilitate the role of Cdc42 in septin organization. Thus, it appears that the GAPs play a role in modulating specific aspects of Cdc42 function. Alternatively, the different phenotypes could reflect quantitative rather than qualitative differences in GAP activity in the mutant strains.
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Hanaei, Sara, Sina Abdollahzade, Alireza Khoshnevisan, Christopher K. Kepler, and Nima Rezaei. "Genetic aspects of intervertebral disc degeneration." Reviews in the Neurosciences 26, no. 5 (October 1, 2015): 581–606. http://dx.doi.org/10.1515/revneuro-2014-0077.
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AbstractIntervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.
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Hold, Georgina L., and M. Emad El-Omar. "Genetic aspects of inflammation and cancer." Biochemical Journal 410, no. 2 (February 12, 2008): 225–35. http://dx.doi.org/10.1042/bj20071341.
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Chronic inflammation is involved in the pathogenesis of most common cancers. The aetiology of the inflammation is varied and includes microbial, chemical and physical agents. The chronically inflamed milieu is awash with pro-inflammatory cytokines and is characterized by the activation of signalling pathways that cross-talk between inflammation and carcinogenesis. Many of the factors involved in chronic inflammation play a dual role in the process, promoting neoplastic progression but also facilitating cancer prevention. A comprehensive understanding of the molecular and cellular inflammatory mechanisms involved is vital for developing preventive and therapeutic strategies against cancer. The purpose of the present review is to evaluate the mechanistic pathways that underlie chronic inflammation and cancer with particular emphasis on the role of host genetic factors that increase the risk of carcinogenesis.
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Bellini, Marilanda Ferreira, Rosana Silistino-Souza, Marileila Varella-Garcia, Maria Tercília Vilela de Azeredo-Oliveira, and Ana Elizabete Silva. "Biologic and Genetics Aspects of Chagas Disease at Endemic Areas." Journal of Tropical Medicine 2012 (2012): 1–11. http://dx.doi.org/10.1155/2012/357948.
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The etiologic agent of Chagas Disease is theTrypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of theT. cruziand the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease.
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Drutskaya, M. S., E. O. Gubernatorova, E. A. Gorshkova, K. S. N. Athertkhany, M. A. Nosenko, V. S. Gogoleva, O. A. Namakanova, R. V. Zvartsev, A. A. Kruglov, and S. A. Nedospasov. "Cytokines, reverse genetics and anti-cytokine therapy." Bulletin of Siberian Medicine 18, no. 1 (May 16, 2019): 38–48. http://dx.doi.org/10.20538/1682-0363-2019-1-38-48.
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Cytokines comprise the molecular language of communication between the cells, which is needed to maintain the homeostatic functions of the body (including the immune system) and mediate various diseases. Many aspects of inflammation, autoimmune diseases and neoplasia are associated with cytokine signaling through specific receptors. The establishment of new physiological functions of “old” cytokines and understanding the molecular and cellular mechanisms of their involvement in disease pathogenesis, as well as the search for new therapeutic targets and development of innovative approaches to anti-cytokine therapy, present a fundamental problem. When assessing the tremendous success of anti-cytokine therapy in treatment of certain autoimmune diseases, we should not forget that (a) this treatment does not eliminate the causes of the disease:autoreactive T-cell clones; and that (b) less than half of the patients respond to this therapy; and that (c) anti-cytokine therapy has serious side effects.
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Cerabona, Donna, Zahi Abdul Sater, Elizabeth Sierra Potchanant, Ying He, Zejin Sun, and Grzegorz Nalepa. "Impaired Spindle Assembly Checkpoint In Vivo Promotes MDS/AML in a Novel Mouse Model of Fanconi Anemia." Blood 126, no. 23 (December 3, 2015): 1211. http://dx.doi.org/10.1182/blood.v126.23.1211.1211.
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Abstract The Fanconi anemia (FA/BRCA) signaling network prevents bone marrow failure and cancer by protecting genomic integrity. Biallelic germline mutations within this gene network result in Fanconi anemia, an inherited bone marrow failure syndrome characterized by genomic instability and a predisposition to bone marrow failure, myelodysplasia and cancer, particularly acute myelogenous leukemia (AML). Heterozygous inborn mutations in the BRCA branch of FA network increase risk of breast and ovarian cancers as well as other tumors, and somatic mutations of FA/BRCA genes occur in malignancies in non-Fanconi patients. Thus, disruption of FA/BRCA signaling promotes malignancies in the inherited genetic syndromes and in the general population. The FA/BRCA network functions as a genome gatekeeper throughout the cell cycle. In interphase, the FA/BRCA network provides a crucial line of defense against mutagenesis by coordinating DNA damage response to a variety of genotoxic insults, from endogenous aldehydes to replication errors and mutagen exposure. Less is known about the role of the FA/BRCA pathway during mitosis. However, FA signaling has recently been implicated in multiple aspects of cell division, including the spindle assembly checkpoint (SAC) that ensures high-fidelity chromosome segregation at metaphase to anaphase transition; cytokinesis; centrosome maintenance and repair of ultrafine anaphase bridges. Although chromosomal instability due to mitotic errors is a hallmark of cancer, the in vivo contribution of abnormal mitosis to malignant transformation of FA-deficient hematopoietic cells remains unknown. To determine whether error-prone chromosome segregation upon loss of FA signaling contributes to abnormal hematopoiesis and cancer, we generated a novel murine FA model by genetically weakening the SAC in the FA-deficient background. The resulting mice were viable and born at expected Mendelian ratios, but exhibited increased baseline in vivo chromosomal instability evidenced by elevated red blood cell micronucleation, increased frequency of chromosome missegregation and DNA breakage in microscopy-based cytome assays, and augmented bone marrow karyotype instability. Importantly, unlike FA or SAC control animals, the FA-SAC mice were prone to premature death due to the development of myelodysplasia and AML at young age, recapitulating disease manifestations of human Fanconi anemia. This study provides the in vivo evidence supporting the essential role of compromised chromosome segregation in the development of myelodysplasia and acute leukemia due to impaired FA signaling. Our observations provide novel insights into complex mechanisms of genomic instability and carcinogenesis due to FA deficiency. Impaired mitosis is a well-established therapeutic target, and our independent ex vivo experiments using FA patient-derived primary cells show that exposure to antimitotic chemotherapeutics is synthetic lethal with loss of the FA network. Thus, our findings may have implications for future precision strategies against FA-deficient, chromosomally unstable hematopoietic cancers. The FA-SAC mouse model offers a preclinical platform to systematically test this hypothesis in vivo. Disclosures No relevant conflicts of interest to declare.
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Wesserlking, Martyna. "Role of genetic aspect in pathogenesis of atopic dermatitis." Folia Biologica et Oecologica 9 (December 31, 2013): 1–8. http://dx.doi.org/10.2478/fobio-2013-0005.
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The pathogenesis of atopic dermatitis (AD) is a very complicated process that involves an intricate array of molecules. Nowadays it is generally accepted that cytokines play an important role in the progression of the clinical presentation of atopic dermatitis. However, emerging data point to the possible involvement of cornified envelope proteins in the development of skin barrier dysfunction and illness. Unfortunately, our knowledge on relation of particular genotype to progression of AD is very limited. Therefore, intensive studies are needed to increase our understanding of genetic background of atopic dermatitis. Hopefully the future research will identify new factors that help us to determine the additional risk for certain patients with atopic dermatitis.
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Hartwell, Leland H., and David Smith. "ALTERED FIDELITY OF MITOTIC CHROMOSOME TRANSMISSION IN CELL CYCLE MUTANTS OF S. CEREVISIAE." Genetics 110, no. 3 (July 1, 1985): 381–95. http://dx.doi.org/10.1093/genetics/110.3.381.
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ABSTRACT Thirteen of 14 temperature-sensitive mutants deficient in successive steps of mitotic chromosome transmission (cdc2, 4, 5, 6, 7, 8, 9, 13, 14, 15, 16, 17 and 20) from spindle pole body separation to a late stage of nuclear division exhibited a dramatic increase in the frequency of chromosome loss and/or mitotic recombination when they were grown at their maximum permissive temperatures. The increase in chromosome loss and/or recombination is likely to be due to the deficiency of functional gene product rather than to an aberrant function of the mutant gene product since the mutant alleles are, with one exception, recessive to the wild-type allele for this phenotype. The generality of this result suggests that a delay in almost any stage of chromosome replication or segregation leads to a decrease in the fidelity of mitotic chromosome transmission. In contrast, temperature-sensitive mutants defective in the control step of the cell cycle (cdc28), in cytokinesis (cdc3) or in protein synthesis (ils1) did not exhibit increased recombination or chromosome loss.—Based upon previous results with mutants and DNA-damaging agents in a variety of organisms, we suggest that the induction of mitotic recombination in certain mutants is due to the action of a repair pathway upon nicks or gaps left in the DNA. This interpretation is supported by the fact that the induced recombination is dependent upon the RAD52 gene product, an essential component in the recombinogenic DNA repair pathway. Gene products whose deficiency leads to induced recombination are, therefore, strong candidates for proteins that function in DNA metabolism. Among the mutants that induce recombination are those known to be defective in some aspect of DNA replication (cdc2, 6, 8, 9) as well as some mutants defective in the G2 (cdc13 and 17) and M (cdc5 and 14) phases of the mitotic cycle. We suggest that special aspects of DNA metabolism may be occurring in G2 and M in order to prepare the chromosomes for proper segregation.
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Bocheva, Georgeta St, Radomir M. Slominski, and Andrzej T. Slominski. "Immunological Aspects of Skin Aging in Atopic Dermatitis." International Journal of Molecular Sciences 22, no. 11 (May 27, 2021): 5729. http://dx.doi.org/10.3390/ijms22115729.
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The cutaneous immune response is important for the regulation of skin aging well as for the development of immune-mediated skin diseases. Aging of the human skin undergoes immunosenescence with immunological alterations and can be affected by environmental stressors and internal factors, thus leading to various epidermal barrier abnormalities. The dysfunctional epidermal barrier, immune dysregulation, and skin dysbiosis in the advanced age, together with the genetic factors, facilitate the late onset of atopic dermatitis (AD) in the elderly, whose cases have recently been on the rise. Controversial to the healthy aged skin, where overproduction of many cytokines is found, the levels of Th2/Th22 related cytokines inversely correlated with age in the skin of older AD patients. As opposed to an endogenously aged skin, the expression of the terminal differentiation markers significantly increases with age in AD. Despite the atenuated barrier disturbances in older AD patients, the aged skin carries an impairment associated with the aging process, which reflects the persistence of AD. The chronicity of AD in older patients might not directly affect skin aging but does not allow spontaneous remission. Thus, adult- and elderly subtypes of AD are considered as a lifelong disease.
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Zulkarneev, Shamil R., Rustem H. Zulkarneev, Gulnaz Faritovna Korytina, Irshat A. Gibadullin, Arthur M. Avzaletdinov, Zhihui Niu, Jiayu Guo, Yulia Genadievna Aznabaeva, Guzel M. Nurtdinova, and Naufal Shamilevich Zagidullin. "Genetic and non-genetic risk factors of idiopathic pulmonary fibrosis: A review." Global Translational Medicine 1, no. 2 (September 26, 2022): 107. http://dx.doi.org/10.36922/gtm.v1i2.107.
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Idiopathic pulmonary fibrosis (IPF) is the most common form of fibrosis of internal organs. The etiology and pathogenesis of IPF are still not well understood. However, a growing line of evidence shows that both genetic and non-genetic factors contribute to IPF development. The release of pro-inflammatory cytokines activates the immune cells. The enhanced synthesis of interleukins and cytokines, especially transforming growth factor β1 leads to the proliferation of fibroblasts, increased extracellular matrix formation, and epithelial-mesenchymal transformation of the lung tissue. These pathological changes could lead to fibrosis. Polymorphisms of genes responsible for the function of mucociliary clearance (MUC5B), telomerases (TERT, TERC), as well as signaling pathway related-genes such as Sonic hedgehog, Wnt, and some other genes are also risk factors for IPF development. Epigenetic regulatory mechanisms, such as methylation and acetylation of DNA and histones, may also influence the development and progression of this disease. At present, the role of non-coding RNAs, in particular long non-coding RNAs (lncRNA) in the development of fibrotic processes, is actively studied. LncRNA is an RNA that is longer than 200 base pairs and does not code for any proteins. LncRNAs perform various functions in the cell, from nuclear compartmentation to epigenetic regulation of gene expression and post-translational modification of proteins. In this review, we present the important aspects in the pathogenesis of IPF.
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Baseri, Milad, Faraz Radmand, Reyhaneh Hamedi, Mehdi Yousefi, and Hossein Samadi Kafil. "Immunological Aspects of Dental Implant Rejection." BioMed Research International 2020 (December 9, 2020): 1–12. http://dx.doi.org/10.1155/2020/7279509.
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Nowadays, dental implants are a prominent therapeutic approach among dentists for replacing missing teeth. Failure in dental implants is a severe challenge recently. The factors which lead to dental implant failure are known. These factors can be categorized into different groups. In this article, we discussed the immunological aspects of implant failure as one of these groups. Cytokines and immune cells have extensive and various functions in peri-implantitis. The equilibrium between pro and anti-inflammatory cytokines and cells, which involve in this orchestra, has a crucial role in implant prognosis. In conclusion, immune cells, especially macrophages and dendritic cells, almost increased in the patients with implant failure. Also, proinflammatory cytokines were proposed as diagnostic factors according to their higher levels in dental implant rejection.
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Al Hadra, Bushra N. "Some of the Immunogenetics Aspects of Aging." Journal of Biomedical and Clinical Research 14, no. 1 (June 1, 2021): 16–30. http://dx.doi.org/10.2478/jbcr-2021-0003.
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Summary The human life span could be influenced by the combined effect of environment, lifestyle, and genetic factors. Twin and family studies suggest that our genes control up to 25% of the lifespan. The aging immune system undergoes age-associated changes at multiple levels, resulting in a gradual loss of its ability to protect the organism against infections, low vaccine responses, and an increased probability of developing autoimmune diseases and malignancies. The highly polymorphic HLA complex is one of the major gene candidates associated with aging due to its crucial role in developing adaptive immunity and protecting the organism. Most of the data available have so far demonstrated a positive association with healthy aging for HLA alleles/haplotypes as protective against malignancies, autoimmune diseases, and conferring better control and response to infections. One of aging’s main manifestations is the chronic, low-grade inflammatory state observed in older people, caused by an imbalance between pro- and anti-inflammatory cytokines. In general, it is has been agreed that longevity is related to anti-inflammatory genotype profiles. With advanced age, changes also occur in the B cell repertoire, which significantly affects the humoral immunity and leads to inadequate responses to infections and vaccines in the elderly. New genetic biomarkers associated with aging are being explored and discovered, contributing to a better understanding of the molecular processes underlying the immune dysfunction related to aging and developing strategies for rejuvenating the immune system based on immune-risk phenotypes.
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Liu, J., H. Wang, and M. K. Balasubramanian. "A checkpoint that monitors cytokinesis in Schizosaccharomyces pombe." Journal of Cell Science 113, no. 7 (April 1, 2000): 1223–30. http://dx.doi.org/10.1242/jcs.113.7.1223.
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Cell division in Schizosaccharomyces pombe is achieved through the use of a medially positioned actomyosin ring. A division septum is formed centripetally, concomitant with actomyosin ring constriction. Genetic screens have identified mutations in a number of genes that affect actomyosin ring or septum assembly. These cytokinesis-defective mutants, however, undergo multiple S and M phases and die as elongated cells with multiple nuclei. Recently, we have shown that a mutant allele of the S. pombe drc1(+)/cps1(+) gene, which encodes a 1,3-(beta)-glucan synthase subunit, is defective in cytokinesis but displays a novel phenotype. drc1-191/cps1-191 cells are capable of assembling actomyosin rings and completing mitosis, but are incapable of assembling the division septum, causing them to arrest as binucleate cells with a stable actomyosin ring. Each nucleus in arrested cps1-191 cells is able to undergo S phase but these G(2) nuclei are significantly delayed for entry into the M phase. In this study we have investigated the mechanism that causes cps1-191 to block with two G(2) nuclei. We show that the inability of cps1-191 mutants to proceed through multiple mitotic cycles is not related to a defect in cell growth. Rather, the failure to complete some aspect of cytokinesis may prevent the G(2)/M transition of the two interphase-G(2) nuclei. The G(2)/M transition defect of cps1-191 mutants is suppressed by a mutation in the wee1 gene and also by the dominant cdc2 allele cdc2-1w, but not the cdc2-3w allele. Transient depolymerization of all F-actin structures also allowed a significant proportion of the cps1-191 cells to undergo a second round of mitosis. We conclude that an F-actin and Wee1p dependent checkpoint blocks G(2)/M transition until previous cytokinesis is completed.
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Vozianova, S. V., L. A. Bolotna, and O. I. Sarian. "Women’s hair loss: pathophysiological, diagnostic and therapeutic aspects." Reproductive health of woman, no. 5 (October 7, 2022): 26–33. http://dx.doi.org/10.30841/2708-8731.5.2022.265471.
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The article presents a review of modern ukrainian and foreign publications on the pathogenesis, clinical manifestations and diagnostics of female pattern hair loss (FPHL), which is a common type of hair loss and its frequency increases with age. The questions of terminology, disease prevalence, and risk factors of hair loss are considered. It is emphasized that FPHL is a clinical problem and that it is advisable to clarify the comorbid profile of female patients and to screen for metabolic disorders. There is still no complete understanding of the pathophysiology of FPHL. There is evidence that hormonal, genetic, and environmental factors are involved in the process of hair loss in women. Current data concerning systemic hormonal disturbances in ovarian and adrenal gland diseases in women as well as the importance of disorders of androgen-dependent mechanisms of regulation of the hair follicle growth cycle are presented.The attention is drawn to genetic abnormalities in the case of FPHL. The role of growth factors, cytokines, microinflammation, iron deficiency, perifollicular fibrosis, oxidative stress in regression of the hair follicle is considered. FPHL is characterized as non-scarring alopecia, which develops due to progressive miniaturization of hair follicles and further hair reduction, especially in the central (frontal and parietal) scalp, gradual replacement of long terminal hair by short pubic (vellus) hair. Three models of female hair loss, modern classification according to the stages of progression used in practice, possible causes of clinical differences in alopecia in men and women are presented. The main directions of diagnostics (history, clinical and laboratory examination, special dermatological tests) are outlined, the possibilities of modern noninvasive diagnostic method of dermoscopy are emphasized. Pharmacotherapy, recommended on the basis of evidence-based medicine, is limited to two drugs – topical minoxidil and systemic finasteride. The necessity of interdisciplinary approach to the management of patients with FPHL has been proved.
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Baronio, Manuela, Hajra Sadia, Stefano Paolacci, Domenico Prestamburgo, Danilo Miotti, Vittorio A. Guardamagna, Giuseppe Natalini, Stephanie G. B. Sullivan, and Matteo Bertelli. "Molecular Aspects of Regional Pain Syndrome." Pain Research and Management 2020 (April 11, 2020): 1–10. http://dx.doi.org/10.1155/2020/7697214.
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The purpose of this review is to summarize the pathophysiology of complex regional pain syndrome (CRPS), the underlying molecular mechanisms, and potential treatment options for its management. CRPS is a multifactorial pain condition. CRPS is characterized by prolonged or excessive pain and changes in skin color and temperature, and/or swelling in the affected area, and is generally caused by stimuli that lead to tissue damage. An inflammatory response involving various cytokines and autoantibodies is generated in response to acute trauma/stress. Chronic phase pathophysiology is more complex, involving the central and peripheral nervous systems. Various genetic factors involved in the chronicity of pain have been identified in CRPS patients. As with other diseases of complex pathology, CRPS is difficult to treat and no single treatment regimen is the same for two patients. Stimulation of the vagus nerve is a promising technique being tested for different gastrointestinal and inflammatory diseases. CRPS is more frequent in individuals of 61–70 years of age with a female to male ratio of 3 : 1. Menopause, migraine, osteoporosis, and asthma all represent risk factors for CRPS and in smokers the prognosis appears to be more severe. The pathophysiological mechanisms underlying CRPS involve both inflammatory and neurological pathways. Understanding the molecular basis of CRPS is important for its diagnosis, management, and treatment. For instance, vagal nerve stimulation might have the potential for treating CRPS through the cholinergic anti-inflammatory pathway.
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Manickan, E., R. J. Rouse, Z. Yu, W. S. Wire, and B. T. Rouse. "Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes." Journal of Immunology 155, no. 1 (July 1, 1995): 259–65. http://dx.doi.org/10.4049/jimmunol.155.1.259.
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Abstract Plasmid DNA encoding proteins represent a convenient novel approach to vaccination. We have investigated this "genetic immunization" approach as a means to protect against herpes simplex virus (HSV) infection using a mouse zosteriform model that mimics several aspects of reactivated HSV infection of humans. After i.m. immunization with plasmid DNA-encoding glycoprotein B (gB), (pc-gB), 80% of BALB/c mice were completely protected and lesions were delayed in the remaining animals. Upon pc-gB vaccination, the animals developed both gB- and HSV-specific IgG Ab response and the isotype examination revealed a predominance of IgG2a. These mice also have low levels (1/16) of HSV-neutralizing Abs. Immune splenocytes obtained from pc-gB-immunized mice, when restimulated in vitro with HSV resulted in production of type 1 cytokines. Evidence for CD(8+)-mediated cytotoxic T lymphocyte response was equivocal. Protection could be adoptively transferred to nude mice recipients by CD4+ T cells from pc-gB-immunized mice but not by CD8+ T cells. Our results demonstrate that genetic immunization is a potent means of inducing protection against HSV and that the mechanism of immunity responsible for clearing virus from cutaneous sites is principally by CD4+ T cells. It is likely that these cells are Th1 cells because type 1 cytokines were the major cytokines detected upon in vitro Ag stimulation.
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Genovesi, Simonetta, and Gianfranco Parati. "Cardiovascular Risk in Children: Focus on Pathophysiological Aspects." International Journal of Molecular Sciences 21, no. 18 (September 10, 2020): 6612. http://dx.doi.org/10.3390/ijms21186612.
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Cardiovascular diseases are the leading cause of death, disability, and health care costs in industrialized countries. In general, cardiovascular diseases occur in adulthood, but cardiovascular damage, including stiffening of the arteries, begins very early. Already in the first decade of life, alterations that will favor the formation of atherosclerotic plaques may be present. Cardiovascular risk factors, associated with genetic predisposition, may trigger a sequence of pathophysiological changes which are associated with the progression of the atherosclerosis process. In this frame, the role of obesity has been increasingly emphasized. Different mechanisms linking obesity to cardiovascular disease have been postulated. Endothelial dysfunction and subclinical inflammation seem to be related to the worsening of cardiovascular risk factors in obese subjects and might have an essential role in the development of insulin resistance and the initiation and progression of atherosclerotic lesions. Excess weight, and in particular visceral adiposity, are associated with hypertrophy and hyperplasia of the adipocytes, increased secretion of adipokines and inflammatory cytokines and increase in serum uric acid levels. The list of obesity-related biomarkers associated with cardiovascular damage is rapidly expanding and their importance has already been described in children as well. Pathophysiological changes involved in determining early cardiovascular damage starting from childhood are discussed in this Special Issue.
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Nagy, György, Peter C. Huszthy, Even Fossum, Yrjö Konttinen, Britt Nakken, and Peter Szodoray. "Selected Aspects in the Pathogenesis of Autoimmune Diseases." Mediators of Inflammation 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/351732.
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Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.
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Garlepp, MJ, and CC Leong. "Biological and immunological aspects of malignant mesothelioma." European Respiratory Journal 8, no. 4 (April 1, 1995): 643–50. http://dx.doi.org/10.1183/09031936.95.08040643.
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Malignant mesothelioma (MM) is an aggressive tumour, which is strongly associated with previous asbestos exposure and is resistant to all conventional anticancer therapies. An understanding of the biological properties of MM may provide insights into useful therapeutic strategies, and MM cell lines and animal models have been major contributors to our current knowledge of this tumour. Although karyotypic abnormalities are frequent, there is no clear evidence of a mesothelioma-specific chromosomal aberration. Similarly, there is no evidence of activation or over-expression of a known oncogene, or of the inactivation of currently identified tumour suppressor genes. A number of growth factors, including platelet derived growth factors A and B (PDGF-A and -B), insulin-like growth factor I and transforming growth factor-beta (TGF-beta), and some of their receptors, have been reported to be expressed by MM cells, and each has the potential to play a role as a growth stimulant for MM or to modify immune responses to the tumour. Some data support an autocrine role for PDGF-A. MM cell lines are susceptible to lysis by a variety of immune effector cells, and their growth can often be inhibited by cytokines. The possibility of stimulating an immune response to MM by genetic manipulation of the tumour cells has been investigated using a murine model. The data so far suggest that transfection of allogeneic class I major histocompatibility complex genes or syngeneic class II genes alone is unlikely to induce protective immunity.(ABSTRACT TRUNCATED AT 250 WORDS)
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Arganova, О. N., and N. G. Kosheleva. "Etiо pathogenesis of spontaneous abortion." Journal of obstetrics and women's diseases 53, no. 1 (January 14, 2004): 37–41. http://dx.doi.org/10.17816/jowd87126.
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One studied immunologic and genetic aspects of spontaneous abortion and the placenta insufficiency role in this pathology. It was determined, that increasing the production of cytokines by placenta's macrophages through something leads to increasing the reduced myometrium activity. Under cariotyping husbands and wives had spontaneous abortions on early terms it was found various genic and endocrine disturbtions. Modern topic diagnostics and algorithm of pregnancy observation with consideration of spontaneous abortion etiopathogenesis, treatment and placenta insufficiency prophylactics have permitted in most cases (more 93%) to give normal term of birth, to decrease perinatal losses.
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Cho, Chul-Hyun, Kwang-Soon Song, Beom-Soo Kim, Du Hwan Kim, and Yun-Mee Lho. "Biological Aspect of Pathophysiology for Frozen Shoulder." BioMed Research International 2018 (2018): 1–8. http://dx.doi.org/10.1155/2018/7274517.
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It is fairly well understood that frozen shoulder involves several stages, which reflect the series of process from capsular inflammation and fibrosis to spontaneous resolution of this fibrosis. However, the underlying pathophysiologic process remains poorly determined. For this reason, management of frozen shoulder remains controversial. Determining the pathophysiological processes of frozen shoulder is a pivotal milestone in the development of novel treatment for patients with frozen shoulder. This article reviews what is known to date about the biological pathophysiology of frozen shoulder. Although articles for the pathophysiology of frozen shoulder provide inconsistent and inconclusive results, they have suggested both inflammation and fibrosis mediated by cytokines, growth factors, matrix metalloproteinases, and immune cells. Proinflammatory cytokines and growth factors released from immune cells control the action of fibroblast and matrix remodeling is regulated by the matrix metalloproteinases and their inhibitors. To improve our understanding of the disease continuum, better characterizing the biology of these processes at clearly defined stages will be needed. Further basic studies that use standardized protocols are required to more narrowly identify the role of cytokines, growth factors, matrix metalloproteinases, and immune cells. The results of these studies will provide needed clarity into the control mechanism of the pathogenesis of frozen shoulder and help identify new therapeutic targets for its treatment.
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Giacomini, Elisa, Sabrina Minetto, Letizia Li Piani, Luca Pagliardini, Edgardo Somigliana, and Paola Viganò. "Genetics and Inflammation in Endometriosis: Improving Knowledge for Development of New Pharmacological Strategies." International Journal of Molecular Sciences 22, no. 16 (August 21, 2021): 9033. http://dx.doi.org/10.3390/ijms22169033.
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According to a rich body of literature, immune cell dysfunctions, both locally and systemically, and an inflammatory environment characterize all forms of endometriosis. Alterations in transcripts and proteins involved in the recruitment of immune cells, in the interaction between cytokines and their receptors, cellular adhesion and apoptosis have been demonstrated in endometriotic lesions. The objective of this narrative review is to provide an overview of the components and mechanisms at the intersection between inflammation and genetics that may constitute vanguard therapeutic approaches in endometriosis. The GWAS technology and pathway-based analysis highlighted the role of the MAPK and the WNT/β-catenin cascades in the pathogenesis of endometriosis. These signaling pathways have been suggested to interfere with the disease establishment via several mechanisms, including apoptosis, migration and angiogenesis. Extracellular vesicle-associated molecules may be not only interesting to explain some aspects of endometriosis progression, but they may also serve as therapeutic regimens per se. Immune/inflammatory dysfunctions have always represented attractive therapeutic targets in endometriosis. These would be even more interesting if genetic evidence supported the involvement of functional pathways at the basis of these alterations. Targeting these dysfunctions through next-generation inhibitors can constitute a therapeutic alternative for endometriosis.
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Skroza, Nevena, Ilaria Proietti, Riccardo Pampena, Giorgio La Viola, Nicoletta Bernardini, Francesca Nicolucci, Ersilia Tolino, Sara Zuber, Valentina Soccodato, and Concetta Potenza. "Correlations between Psoriasis and Inflammatory Bowel Diseases." BioMed Research International 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/983902.
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For a long time the relationship between inflammatory bowel diseases (IBDs) and psoriasis has been investigated by epidemiological studies. It is only starting from the 1990s that genetic and immunological aspects have been focused on. Psoriasis and IBD are strictly related inflammatory diseases. Skin and bowel represent, at the same time, barrier and connection between the inner and the outer sides of the body. The most important genetic correlations involve the chromosomal loci 6p22, 16q, 1p31, and 5q33 which map several genes involved in innate and adaptive immunity. The genetic background represents the substrate to the common immune processes involved in psoriasis and IBD. In the past, psoriasis and IBD were considered Th1-related disorders. Nowadays the role of new T cells populations has been highlighted. A key role is played by Th17 and T-regs cells as by the balance between these two cells types. New cytokines and T cells populations, as IL-17A, IL-22, and Th22 cells, could play an important pathogenetic role in psoriasis and IBD. The therapeutic overlaps further support the hypothesis of a common pathogenesis.
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Kondo, Yasuteru, Yoshiyuki Ueno, and Tooru Shimosegawa. "Dysfunction of Immune Systems and Host Genetic Factors in Hepatitis C Virus Infection with Persistent Normal ALT." Hepatitis Research and Treatment 2011 (June 14, 2011): 1–7. http://dx.doi.org/10.1155/2011/713216.
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Patients with chronic hepatitis C (CHC) virus infection who have persistently normal alanine aminotransferase levels (PNALT) have mild inflammation and fibrosis in comparison to those with elevated ALT levels. The cellular immune responses to HCV are mainly responsible for viral clearance and the disease pathogenesis during infection. However, since the innate and adaptive immune systems are suppressed by various kinds of mechanisms in CHC patients, the immunopathogenesis of CHC patients with PNALT is still unclear. In this review, we summarize the representative reports about the immune suppression in CHC to better understand the immunopathogenesis of PNALT. Then, we summarize and speculate on the immunological aspects of PNALT including innate and adaptive immune systems and genetic polymorphisms of HLA and cytokines.
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Darmadi, Darmadi, and Riska Habriel Ruslie. "Immunological Aspect in Inflammatory Bowel Disease." Open Access Macedonian Journal of Medical Sciences 9, F (December 6, 2021): 708–11. http://dx.doi.org/10.3889/oamjms.2021.7733.
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Inflammatory bowel disease (IBD) is a chronic inflammation in the alimentary tract due to improper immune response toward external and internal antigens. The disease consists of 2 entities: ulcerative colitis (UC) and Crohn’s disease (CD). The disease’s prevalence is increasing worldwide due to westernization and industrialization. Europe still holds the highest prevalence of IBD in the world. There are 2 peaks of disease incidence. The first is in the third decade of life and the second is in the fourth decade. Slight male predominance is observed in IBD. Internal and external risk factors play important role in the occurrence of IBD including genetic, smoking, reduced fibre intake, less or absent breastfeeding, sedentary occupation, pollution exposure, and medications. The disease carries heavy economic burden and hampers patient’s quality of life. The immune concept of IBD was hypothesized in 1950s since the symptoms resolved with the administration of steroid. Innate and adaptive immune systems are involved in the pathogenesis of IBD. Antigen presenting cells are found hyperactive, intestinal barrier is disrupted, and autophagy activity is increased. Molecular mimicry occurs between foreign and self antigen. The activity of T helper (Th)1, Th2, and Th17 is amplified while regulatory T cell’s activity is suppressed. Pro-inflammatory cytokine production is elevated but anti-inflammatory cytokines is lowered. Finally, there is increased immunoglobulin G level in intestinal mucosa and imbalance of gut microorganism. All the above immune disturbances lead to chronic inflammation in IBD.
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Tripathy, Manas K., Renu Deswal, and Sudhir K. Sopory. "Plant RABs: Role in Development and in Abiotic and Biotic Stress Responses." Current Genomics 22, no. 1 (April 12, 2021): 26–40. http://dx.doi.org/10.2174/1389202922666210114102743.
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Endosomal trafficking plays an integral role in various eukaryotic cellular activities and is vital for higher-order functions in multicellular organisms. RAB GTPases are important proteins that influence various aspects of membrane traffic, which consequently influence many cellular functions and responses. Compared to yeast and mammals, plants have evolved a unique set of plant-specific RABs that play a significant role in their development. RABs form the largest family of small guanosine triphosphate (GTP)-binding proteins, and are divided into eight sub-families named RAB1, RAB2, RAB5, RAB6, RAB7, RAB8, RAB11 and RAB18. Recent studies on different species suggest that RAB proteins play crucial roles in intracellular trafficking and cytokinesis, in autophagy, plant microbe interactions and in biotic and abiotic stress responses. This review recaptures and summarizes the roles of RABs in plant cell functions and in enhancing plant survival under stress conditions.
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Stanciu, Silviu, Florentina Ionita-Radu, Constantin Stefani, Daniela Miricescu, Iulia-Ioana Stanescu-Spinu, Maria Greabu, Alexandra Ripszky Totan, and Mariana Jinga. "Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects." International Journal of Molecular Sciences 23, no. 17 (September 4, 2022): 10132. http://dx.doi.org/10.3390/ijms231710132.
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Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.
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Buquicchio, Rosalba, Caterina Foti, and Maria Teresa Ventura. "The Psoriasis Pathogenesis and the Metabolic Risk." Open Dermatology Journal 12, no. 1 (July 31, 2018): 70–79. http://dx.doi.org/10.2174/1874372201812010070.
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Summary Psoriasis is a multifactorial disease that can be related to genetic, environmental and immunological causes. Therefore, not only a single factor but different aspects contribute to the onset of the disease, varying from individual to individual. It would be characterized by an abnormal proliferation and differentiation of keratinocytes, mediated by a dysregulation in the auto-immune T cell response in which several cytokines participate, including Interleukin (IL)-17, IL-17A, IL-12, IL-22, IL-23. These cells and cytokines are responsible for the aggression on skin cells, inflammation and accelerated reproduction of the cells of the epidermis. Due to the chronic inflammation, psoriasis is frequently associated with other concomitant non-dermatological morbid conditions such as arthropathy which can be complicated by a disabling evolution. Psoriasis is also frequently associated with comorbidities such as Cardiovascular Diseases (CVD), hyperlipidemia, diabetes and obesity. The knowledge of common inflammatory pathways and of the potential links between psoriasis and other diseases should encourage dermatologists to a multidisciplinary approach to psoriasis and to an optimal management also in the light of new therapeutic possibilities.
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El-Abaseri, Taghrid Bahig, Brianna Hammiller, Susan K. Repertinger, and Laura A. Hansen. "The Epidermal Growth Factor Receptor Increases Cytokine Production and Cutaneous Inflammation in Response to Ultraviolet Irradiation." ISRN Dermatology 2013 (June 25, 2013): 1–11. http://dx.doi.org/10.1155/2013/848705.
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The epidermal growth factor receptor (EGFR) is activated in cutaneous keratinocytes upon ultraviolet (UV) exposure and has been implicated in ultraviolet-(UV-)induced inflammation and skin tumorigenesis. Egfr mutant mice and EGFR inhibitors were used to investigate the hypothesis that EGFR activation augments inflammation following UV irradiation. Topical treatment of mouse skin with the EGFR inhibitor AG1478 before UV exposure suppressed UV-induced erythema, edema, mast cell infiltration, and neutrophil infiltration. Genetic ablation of Egfr and EGFR inhibition by AG1478 also suppressed the increase in the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin-1α, KC (murine IL-8), and cyclooxygenase-2 (COX-2) after UV exposure of cultured keratinocytes. Finally, genetic ablation of inhibition of EGFR in cultured keratinocytes decreased p38 activation after UV, while inhibition of p38 kinase reduced COX-2 expression after UV. These data demonstrate that EGFR regulates multiple aspects of UV-induced inflammation and suggest activation of p38 kinase leading to increased COX-2 and cytokine expression as one mechanism through which it acts.
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Tu-Rapp, Hoang, Liying Pu, Andreia Marques, Christoph Kulisch, Xinhua Yu, Philip Gierer, Saleh M. Ibrahim, and Brigitte Vollmar. "Genetic control of leucocyte—endothelial cell interaction in collagen-induced arthritis." Annals of the Rheumatic Diseases 69, no. 3 (March 2010): 606–10. http://dx.doi.org/10.1136/ard.2009.100636.
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ObjectiveDespite considerable work on defining disease pathways, several aspects of collagen-induced arthritis (CIA) remain poorly defined, in particular those contributing to the initiation phase of the disease. It is thought that in CIA the activation of circulating leucocytes, their interaction with the endothelial lining followed by subsequent transendothelial migration and infiltration into tissue represents the first and determining step in a complex sequence of processes mediating tissue injury. In this study we attempted to define the genetic basis of this stage of disease using genetic linkage studies, in-vivo imaging and expression profiling.MethodsA genome scan with 132 informative markers was performed on 155 (DBA/1J×FVB/N) F2 mice. Linkage analysis was performed by combining genotyping data from the genome scan and the phenotypic data of leucocyte adherence, leucocyte rolling fraction, functional capillary density, centre line red blood cell velocity and capillary width as well as the expression level of the selected genes Cd44, Il13rα1, Ccr3, Defb3, Sele, Sell, Selp, Xcl1, Il1β, Tnfα and Ifnγ as traits.ResultsMultiple classic quantitative trail loci (QTL) controlling leucocyte–endothelial cell interactions were identified on chromosomes 8 and 17 as well as expression QTL controlling the expression of several differentially expressed adhesion molecules and cytokines on chromosomes 1, 2, 5, 6, 7, 8, 12, 15, 16 and 17.ConclusionThe study describes for the first time QTL controlling the CIA initiating leucocyte–endothelial cell interaction.
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Takahara, Miki, Takumi Kumai, Kan Kishibe, Toshihiro Nagato, and Yasuaki Harabuchi. "Extranodal NK/T-Cell Lymphoma, Nasal Type: Genetic, Biologic, and Clinical Aspects with a Central Focus on Epstein–Barr Virus Relation." Microorganisms 9, no. 7 (June 25, 2021): 1381. http://dx.doi.org/10.3390/microorganisms9071381.
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Extranodal NK/T-Cell Lymphoma, nasal type (ENKTL-NT) has some salient aspects. The lymphoma is commonly seen in Eastern Asia, has progressive necrotic lesions in the nasal cavity, makes midfacial destructive lesions, and shows poor prognosis. The lymphoma cell is originated from either NK- or γδ T-cells, which express CD56. Since the authors first demonstrated the existence of Epstein–Barr virus (EBV) DNA and EBV oncogenic proteins in lymphoma cells, ENKTL-NT has been recognized as an EBV-associated malignancy. Because the angiocentric and polymorphous lymphoma cells are mixed with inflammatory cells on a necrotic background, the diagnosis of ENKTL-NT requires CD56 immunostaining and EBER in situ hybridization. In addition, serum the EBV DNA level is useful for the diagnosis and monitoring of ENKTL-NT. Although ENKTL-NT is refractory lymphoma, the prognosis is improved by the development of therapies such as concomitant chemoradiotherapy. The basic research reveals that a wide variety of intracellular/cell surface molecules, cytokines, chemokines, and micro RNAs are involved in lymphomagenesis, and some of them are related to EBV. Understanding lymphoma behavior introduces new therapeutic strategies, such as the usage of immune checkpoint inhibitors, peptide vaccines, and molecular targeting therapy. This review addresses recent advances in basic and clinical aspects of ENKTL-NT, especially its relation to EBV features.
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Kim, Jae-Hong, Md Habibur Rahman, Donghwi Park, Myungjin Jo, Hyung-Jun Kim, and Kyoungho Suk. "Identification of Genetic Modifiers of TDP-43: Inflammatory Activation of Astrocytes for Neuroinflammation." Cells 10, no. 3 (March 18, 2021): 676. http://dx.doi.org/10.3390/cells10030676.
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Transactive response DNA-binding protein 43 (TDP-43) is a ubiquitously expressed DNA/RNA-binding protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 has been implicated in numerous aspects of the mRNA life cycle, as well as in cell toxicity and neuroinflammation. In this study, we used the toxicity of the TDP-43 expression in Saccharomyces cerevisiae as an assay to identify TDP-43 genetic interactions. Specifically, we transformed human TDP-43 cDNAs of wild-type or disease-associated mutants (M337V and Q331K) en masse into 4653 homozygous diploid yeast deletion mutants and then used next-generation sequencing readouts of growth to identify yeast toxicity modifiers. Genetic interaction analysis provided a global view of TDP-43 pathways, some of which are known to be involved in cellular metabolic processes. Selected putative loci with the potential of genetic interactions with TDP-43 were assessed for associations with neurotoxicity and inflammatory activation of astrocytes. The pharmacological inhibition of succinate dehydrogenase flavoprotein subunit A (SDHA) and voltage-dependent anion-selective channel 3 (VDAC3) suppressed TDP-43-induced expression of proinflammatory cytokines in astrocytes, indicating the critical roles played by SDHA and VDAC3 in TDP-43 pathways during inflammatory activation of astrocytes and neuroinflammation. Thus, the findings of our TDP-43 genetic interaction screen provide a global landscape of TDP-43 pathways and may help improve our understanding of the roles of glia and neuroinflammation in ALS and FTD pathogenesis.
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Jahan, Shah, Romeeza Tahir, Faheem Shahzad, Khursheed Javed, Muhammad Kashif, and Nadeem Afzal. "Immunological Basis of COVID-19." BioMedica 36, no. 2S (June 24, 2020): 125–29. http://dx.doi.org/10.51441/biomedica//biomedica/5-449.
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<p>Currently major challenge for scientists is to cope with Coronavirus infection that alters host immune response in different ways. There is variability in immune response in diverse populations against this infection and particularly immunity of a certain population against SARS-CoV-2is not clear. Many factors such as viral and host genetics that play crucial in this infection but immunological aspects are more important in infection and disease progression. Its different patterns of spread and severity needs timely focus to design strategies against this disease. This review sums up the concepts related to host immune response to SARS-CoV-2, cellular and humoral immunity, cytokines storm and immunization against COVID-19.</p>
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Durmaz, Ceyda, and Berrin Erdag. "Overview of current approaches in cancer immunotherapy and personalized opportunities for future aspect." Genetics & Applications 6, no. 2 (November 30, 2022): 1–17. http://dx.doi.org/10.31383/ga.vol6iss2ga01.
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Cancer refers to a group of diseases characterized by a rapid and uncontrolled proliferation of cells in the body after undergoing a series of structural variations. Non-specific methods such as surgery, radiotherapy, and chemotherapy are used widely in cancer treatment. Recently, there is a special focus on specific methods such as immunotherapy that targets certain parts of the patient’s immune system. New treatment options are needed in this respect because nonspecific methods are insufficient in curing the disease, do not increase patient's survival, and healthy cells are damaged as well as cancer cells. Immunotherapy has less toxicity, fewer side effects during treatment, and is a patient-specific individualized treatment modality. Due to the fact that human tumors occur with a combination of genetic and epigenetic changes, cancer cells manage to recognize immunity and escape subsequent destruction. The main goal of cancer immunotherapy is to reactivate the immune system to neutralize tumor cells. Immunotherapy has many advantages such as preventing the side effects of chemotherapy/radiotherapy, avoiding metastases, and targeting cancer stem cells. The main treatment methods used in cancer immunotherapy, are cancer vaccines, adoptive cell therapy, cytokines, and monoclonal antibodies. In this review, we outline some of the main strategies in cancer immunotherapy and discuss the progress in personalized cancer therapy.
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Rabiah, N. A. Al, A. C. O. Evans, J. McCormack, J. A. Browne, P. Lonergan, and T. Fair. "6 Immunological aspects of ovarian follicle ovulation and corpus luteum formation in cattle." Reproduction, Fertility and Development 33, no. 2 (2021): 110. http://dx.doi.org/10.1071/rdv33n2ab6.
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Ovarian follicle ovulation and subsequent luteinization have been described as a controlled inflammatory event, comprising tissue damage and repair. To elaborate this further in cattle, the contribution of immune cells to dominant follicle luteinization, ovulation, and corpus luteum formation was investigated. Ovulation in beef heifers was synchronized using an 8-day progesterone-based synchronization program. Heifers were slaughtered at a local abattoir at 5 timepoints (T): (T1) 24h before ovulation (n=10); (T2) 2h before ovulation (n=9); (T3) 6h after ovulation (n=10); (T4) 24h after ovulation (n=10); (T5) 72h after ovulation (n=10), and ovarian tissue was collected and returned to the laboratory on ice. Follicular fluid, theca, granulosa, and corpus luteum (CL) tissues were recovered by dissection and processed for analysis. The concentrations of a panel of cytokines were measured using an antibody-conjugated magnetic bead immunoassay. The abundance of T-lymphocytes, mast cells, neutrophils, eosinophils, monocytes, macrophages, and dendritic cells was determined by immunohistochemistry. The mRNA relative abundance of candidate genes, including angiogenic growth factors, adhesion factors, chemokines and cytokines, was determined by quantitative real-time PCR analysis. The resulting datasets were analysed using the linear mixed model procedure of SAS and data are presented as least squares means; reported differences were deemed significant at P≤0.05. The cytokines IFNy, IP-10, IL-10, IL-36RA, MCP-1, MIP-1a, MIP-1b, and VEGF-A were detected in follicular fluid. The concentrations (pg mL−1) of IL-10 and VEGF-A were significantly higher in T1 follicular fluid samples compared with T2 (7.70 vs. 0.86 and 2193.33 vs. 293.93, respectively). Although dendritic cells were the most abundant cells in bovine ovulatory follicular and early corpus luteum tissue at all time points (P<0.05), their numbers peaked in ovulatory (T2) thecal tissue (261.5 cells/mm2). The greatest number of neutrophils was identified in thecal tissue at T1 (45/mm2); thereafter, their numbers declined to 1.1/mm2 in CL tissue by T5. Similarly, the numbers of T-lymphocytes, mast cells, monocytes, and macrophages declined in CL tissue at T4 and T5. Candidate gene mRNA expression profiles appeared to be time- and tissue-specific; for example, IFNA was highest in the preovulatory granulosa tissue (T1), IL8 was highest in peri-ovulatory thecal tissue (T2), VEGFA and MMP9 were highest in the early CL tissue (T4 and T5), MMP1, TIMP1, and VCAM1 expression was highest in theca, granulosa, and CL tissue collected on or after ovulation (T2, T4, T5), expression of the prostaglandin-related genes PTGES and PTGS2 was lowest in CL tissue, and that of PTGIS was highest. The current findings support the hypothesis that ovulation in heifers is characterised by an initial proinflammatory cascade followed by a dramatic switch to tissue repair, growth, and remodelling, all occurring within a 72-h period and commencing with the LH surge. Our results highlight the roles of neutrophils, dendritic cells, and macrophages as the key actors in this process.
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Rabiah, N. A. Al, A. C. O. Evans, J. McCormack, J. A. Browne, P. Lonergan, and T. Fair. "6 Immunological aspects of ovarian follicle ovulation and corpus luteum formation in cattle." Reproduction, Fertility and Development 33, no. 2 (2021): 110. http://dx.doi.org/10.1071/rdv33n2ab6.
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Ovarian follicle ovulation and subsequent luteinization have been described as a controlled inflammatory event, comprising tissue damage and repair. To elaborate this further in cattle, the contribution of immune cells to dominant follicle luteinization, ovulation, and corpus luteum formation was investigated. Ovulation in beef heifers was synchronized using an 8-day progesterone-based synchronization program. Heifers were slaughtered at a local abattoir at 5 timepoints (T): (T1) 24h before ovulation (n=10); (T2) 2h before ovulation (n=9); (T3) 6h after ovulation (n=10); (T4) 24h after ovulation (n=10); (T5) 72h after ovulation (n=10), and ovarian tissue was collected and returned to the laboratory on ice. Follicular fluid, theca, granulosa, and corpus luteum (CL) tissues were recovered by dissection and processed for analysis. The concentrations of a panel of cytokines were measured using an antibody-conjugated magnetic bead immunoassay. The abundance of T-lymphocytes, mast cells, neutrophils, eosinophils, monocytes, macrophages, and dendritic cells was determined by immunohistochemistry. The mRNA relative abundance of candidate genes, including angiogenic growth factors, adhesion factors, chemokines and cytokines, was determined by quantitative real-time PCR analysis. The resulting datasets were analysed using the linear mixed model procedure of SAS and data are presented as least squares means; reported differences were deemed significant at P≤0.05. The cytokines IFNy, IP-10, IL-10, IL-36RA, MCP-1, MIP-1a, MIP-1b, and VEGF-A were detected in follicular fluid. The concentrations (pg mL−1) of IL-10 and VEGF-A were significantly higher in T1 follicular fluid samples compared with T2 (7.70 vs. 0.86 and 2193.33 vs. 293.93, respectively). Although dendritic cells were the most abundant cells in bovine ovulatory follicular and early corpus luteum tissue at all time points (P<0.05), their numbers peaked in ovulatory (T2) thecal tissue (261.5 cells/mm2). The greatest number of neutrophils was identified in thecal tissue at T1 (45/mm2); thereafter, their numbers declined to 1.1/mm2 in CL tissue by T5. Similarly, the numbers of T-lymphocytes, mast cells, monocytes, and macrophages declined in CL tissue at T4 and T5. Candidate gene mRNA expression profiles appeared to be time- and tissue-specific; for example, IFNA was highest in the preovulatory granulosa tissue (T1), IL8 was highest in peri-ovulatory thecal tissue (T2), VEGFA and MMP9 were highest in the early CL tissue (T4 and T5), MMP1, TIMP1, and VCAM1 expression was highest in theca, granulosa, and CL tissue collected on or after ovulation (T2, T4, T5), expression of the prostaglandin-related genes PTGES and PTGS2 was lowest in CL tissue, and that of PTGIS was highest. The current findings support the hypothesis that ovulation in heifers is characterised by an initial proinflammatory cascade followed by a dramatic switch to tissue repair, growth, and remodelling, all occurring within a 72-h period and commencing with the LH surge. Our results highlight the roles of neutrophils, dendritic cells, and macrophages as the key actors in this process.
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Vaughan, Sue, and Keith Gull. "The structural mechanics of cell division in Trypanosoma brucei." Biochemical Society Transactions 36, no. 3 (May 21, 2008): 421–24. http://dx.doi.org/10.1042/bst0360421.
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Undoubtedly, there are fundamental processes driving the structural mechanics of cell division in eukaryotic organisms that have been conserved throughout evolution and are being revealed by studies on organisms such as yeast and mammalian cells. Precision of structural mechanics of cytokinesis is however probably no better illustrated than in the protozoa. A dramatic example of this is the protozoan parasite Trypanosoma brucei, a unicellular flagellated parasite that causes a devastating disease (African sleeping sickness) across Sub-Saharan Africa in both man and animals. As trypanosomes migrate between and within a mammalian host and the tsetse vector, there are periods of cell proliferation and cell differentiation involving at least five morphologically distinct cell types. Much of the existing cytoskeleton remains intact during these processes, necessitating a very precise temporal and spatial duplication and segregation of the many single-copy organelles. This structural precision is aiding progress in understanding these processes as we apply the excellent reverse genetics and post-genomic technologies available in this system. Here we outline our current understanding of some of the structural aspects of cell division in this fascinating organism.
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Egresi, Anna, Gabriella Lengyel, Anikó Somogyi, Anna Blázovics, and Krisztina Hagymási. "Az idült májbetegségek progressziójához vezető folyamatok." Orvosi Hetilap 157, no. 8 (February 2016): 290–97. http://dx.doi.org/10.1556/650.2015.30377.
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As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression. Orv. Hetil., 2016, 157(8), 290–297.
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Avdeeva, A. S. "Inflammatory markers in rheumatic diseases." Rheumatology Science and Practice 60, no. 6 (December 25, 2022): 561–69. http://dx.doi.org/10.47360/1995-4484-2022-561-569.
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Immune-mediated rheumatic diseases (IMRDs) are a broad group of pathological conditions based on impaired immunological tolerance to one’s own tissues leading to inflammation and irreversible organ damage. Laboratory diagnosis of IMRDs includes a wide range of biomarkers (autoantibodies, acute phase proteins, cytokines, markers of endothelial damage, components of the complement system, immunoglobulins, cryoglobulins, lymphocyte subpopulations, indicators of bone metabolism, apoptosis markers, genetic markers, etc). One of the leading aspects of laboratory diagnosis of IMRDs is the study of the level of inflammation markers in the blood (erythrocyte sedimentation rate, C-reactive protein (CRP), serum amyloid protein (CAA), ferritin, procalcitonin, apolipoprotein AI, calprotectin, etc). The analysis of inflammation markers makes it possible to assess the disease activity, the nature of the progression and the prognosis of the outcomes of a chronic inflammatory process, as well as the effectiveness of the therapy. The review presents the latest data on the role of the most frequently studied inflammatory markers such as CRP, CAA and ferritin.
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Sanap, Jayshree B., Anil V. Chandewar, Nitin Kochar, and Shatrughna Uttam Nagrik. "The Potentials of Herbal Plant against the Psoriasis." Journal of Drug Delivery and Therapeutics 13, no. 1 (January 15, 2023): 179–82. http://dx.doi.org/10.22270/jddt.v13i1.5903.
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Chronic autoimmune skin disease termed psoriasis is characterised by excessive keratinocyte multiplication, scaly plaques, severe inflammation, and erythema. T lymphocytes, leukocytes, vascular endothelium, and epidermal keratinocytes also contribute in the pathogenesis of psoriasis. Increased leukocyte recruitment and increased levels of cytokines, growth factors, and genetic factors like interleukin (IL)-1, IL-6, IL-17, IL-22, IL-23, tumour necrosis factor (TNF), interferon (IFN), transforming growth factor (TGF), toll-like receptor (TLR)-2, signal transducer and activator of transcription (STAT-3), 15-lipoxygenase (LOX)-2. The most important aspects impacting the treatment of psoriasis are coiled-coil alpha-helical rod protein 1 (CCHCR1), steroidogenic acute regulatory protein (StAR), and vitamin D receptor (VDR). Various synthetic medicinal drugs have also been known to have the side effect of psoriasis. Due to their safety and accessibility, herbal medications may indicate the potential as effective anti-psoriatic agents.
Keywords: Psoriasis, Herbal Drug, Silybum marianum, Thespesia populnea, Mahonia aquifolium
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Di Donato, Giulia, Debora Mariarita d’Angelo, Luciana Breda, and Francesco Chiarelli. "Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives." International Journal of Molecular Sciences 22, no. 12 (June 14, 2021): 6360. http://dx.doi.org/10.3390/ijms22126360.
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Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.
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Wright, Eric G. "Commentary on radiation-induced bystander effects." Human & Experimental Toxicology 23, no. 2 (February 2004): 91–94. http://dx.doi.org/10.1191/0960327104ht424oa.
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The paradigm of genetic alterations being restricted to direct DNA damage after exposure to ionizing radiation has been challenged by observations in which effects of ionizing radiation arise in cells that in themselves receive no radiation exposure. These effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that are in contact with irradiated cells or receive certain signals from irradiated cells (radiation-induced bystander effects). Bystander signals may be transmitted either by direct intercellular communication through gap junctions, or by diffusible factors, such as cytokines released from irradiated cells. In both phenomena, the untargeted effects of ionizing radiation appear to be associated with free radical-mediated processes. There is evidence that radiation-induced genomic instability may be a consequence of, and in some cell systems may also produce, bystander interactions involving intercellular signalling, production of cytokines and free radical generation. These processes are also features of inflammatory responses that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. Thus, radiation-induced genomic instability and untargeted bystander effects may reflect interrelated aspects of inflammatory type responses to radiation-induced stress and injury and contribute to the variety of the pathological consequences of radiation exposures.
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Novikova, A. V., N. G. Pravdyuk, and N. A. Shostak. "Cellular and molecular aspects of degenerative disc disease and potential strategies of biological therapy." Clinician 14, no. 1-2 (May 8, 2020): 42–54. http://dx.doi.org/10.17650/1818-8338-2020-14-1-2-42-54.
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Back pain is one of the main global health problems with a high level of prevalence and patients’ disability. In most cases, it is associated with degenerative spine damage (degenerative disc disease), dorsopathy, discopathy (M51 and M53 according to the International Classification of Diseases, 10th revision), affecting all levels of the intervertebral disc (IVD) (cytological, chemical and biochemical) as a whole as well as biological molecules that regulate homeostasis of the disc intercellular substance (growth factors, pro-inflammatory cytokines, enzymes). A key point in IVD dehydration is that catabolic processes predominate over anabolic ones due to changed gene expression in the corresponding biologically active molecules, disc angiogenesis and neoinnervation of the structures of the fibrous ring and pulpous nucleus. The latter is responsible for chronic pain in patients.Cells supporting homeostasis in nucleus pulpous, chondrocytes, continuously synthesize and restore proteoglycans and hyaluronic acid in nucleus pulpous, restoring shock-absorbing functions of the vertebral-motor segment. Decreased activity and death of chondrocytes in the avascular disc structure is a serious problem for reparative medicine. In accordance with IVD molecular-cellular mechanisms, numerous approaches to treat degenerative disc disease are being developed, each of which, influencing one of the links in the pathogenesis, has a direct or indirect effect on IVD repair.The article describes morphology, pathogenesis and genetics of degenerative disc disease, as well as main modern strategies of biological therapy: tissue engineering, biologically active substances locally used in IVD matrix, including PRP therapy (Platelet Rich Plasma therapy), methods of gene (using the viral vector) and cell therapy, as well as experience in the local use of genetically engineered biological products. Most successful studies are a combination of cell and gene therapy with the use of synthesized matrices.
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Budnevsky, Andrey V., Evgeniy S. Ovsyannikov, Victoria V. Shishkina, Dmitry I. Esaulenko, Bogdan R. Shumilovich, Inessa A. Savushkina, and Nadezhda G. Alekseeva. "Possible Unexplored Aspects of Covid-19 Pathogenesis: The Role of Carboxypeptidase A3." International Journal of Biomedicine 12, no. 2 (June 5, 2022): 179–82. http://dx.doi.org/10.21103/article12(2)_ra1.
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Background: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First reported in 2019, it has already caused more than 500 million cases worldwide. The problem of COVID-19 treatment is still relevant, and it is necessary to study in detail the pathogenesis of COVID-19, including the involvement of different immune cells and their mediators. There is increasing evidence of the important role of mast cells (MCs) and their specific protease carboxypeptidase A3 (CPA3) in the pathogenesis of COVID-19. MCs chymase and tryptase are already well studied, while CPA3 is of growing interest. The aim of this review is to study the CPA3 features and mechanisms of its participation in the pathogenesis of COVID-19 and some other infectious and non-infectious diseases. Methods and Results: A literature search was carried out using Scopus, Web of Science, PubMed, Medline, and E-Library databases. Of the158 articles analyzed, 33 were included in the review. CPA3, expressed by MCs in various organs, including human lungs, plays a role in the pathogenesis of COVID-19 by indirectly causing pulmonary fibrosis, associating with levels of inflammatory cytokines and chemokines, and severity of COVID-19.
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Dudek, Michal, Nan Yang, Jayalath PD Ruckshanthi, Jack Williams, Elzbieta Borysiewicz, Ping Wang, Antony Adamson, et al. "The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration." Annals of the Rheumatic Diseases 76, no. 3 (August 3, 2016): 576–84. http://dx.doi.org/10.1136/annrheumdis-2016-209428.
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ObjectivesThe circadian clocks are internal timing mechanisms that drive ∼24-hour rhythms in a tissue-specific manner. Many aspects of the physiology of the intervertebral disc (IVD) show clear diurnal rhythms. However, it is unknown whether IVD tissue contains functional circadian clocks and if so, how their dysregulation is implicated in IVD degeneration.MethodsClock gene dynamics in ex vivo IVD explants (from PER2:: luciferase (LUC) reporter mice) and human disc cells (transduced with lentivirus containing Per2::luc reporters) were monitored in real time by bioluminescence photon counting and imaging. Temporal gene expression changes were studied by RNAseq and quantitative reverse transcription (qRT)-PCR. IVD pathology was evaluated by histology in a mouse model with tissue-specific deletion of the core clock gene Bmal1.ResultsHere we show the existence of the circadian rhythm in mouse IVD tissue and human disc cells. This rhythm is dampened with ageing in mice and can be abolished by treatment with interleukin-1β but not tumour necrosis factor α. Time-series RNAseq revealed 607 genes with 24-hour patterns of expression representing several essential pathways in IVD physiology. Mice with conditional knockout of Bmal1 in their disc cells demonstrated age-related degeneration of IVDs.ConclusionsWe have established autonomous circadian clocks in mouse and human IVD cells which respond to age and cytokines, and control key pathways involved in the homeostasis of IVDs. Genetic disruption to the mouse IVD molecular clock predisposes to IVD degeneration. These results support the concept that disruptions to circadian rhythms may be a risk factor for degenerative IVD disease and low back pain.