Articoli di riviste: "Myosin 1g"

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Estrada-Abreo, Laura A., Leonor Rodríguez-Cruz, Yanelly Garfias-Gómez, Janeth E. Araujo-Cardenas, Gabriela Antonio-Andrés, Alfonso R. Salgado-Aguayo, Darío Orozco-Ruiz et al. "High expression of Myosin 1g in pediatric acute lymphoblastic leukemia". Oncotarget 12, n. 19 (14 settembre 2021): 1937–45. http://dx.doi.org/10.18632/oncotarget.28055.

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Dart, A. E., S. Tollis, M. D. Bright, G. Frankel e R. G. Endres. "The motor protein myosin 1G functions in Fc R-mediated phagocytosis". Journal of Cell Science 125, n. 24 (4 ottobre 2012): 6020–29. http://dx.doi.org/10.1242/jcs.109561.

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Méndez, Irene, Ana Isabel Fernández, Maria Ángeles Espinosa, Sofía Cuenca, Rebeca Lorca, José Fernando Rodríguez, Maria Tamargo et al. "Founder mutation in myosin-binding protein C with an early onset and a high penetrance in males". Open Heart 8, n. 2 (settembre 2021): e001789. http://dx.doi.org/10.1136/openhrt-2021-001789.

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ObjectiveOne of the challenges in hypertrophic cardiomyopathy (HCM) is to determine the pathogenicity of genetic variants and to establish genotype/phenotype correlations. This study aimed to: (1) demonstrate that MYBPC3 c.2149–1G>A is a founder pathogenic variant, (2) describe the phenotype and clinical characteristics of mutation carriers and (3) compare these patients with those with the most frequent pathogenic HCM variants: MYBPC3 p.Arg502Trp/Gln.MethodsWe reviewed genetic tests performed in HCM probands at our institution. We carried out transcript analyses to demonstrate the splicing effect, and haplotype analyses to support the founder effect of MYBPC3 c.2149–1G>A. Carriers with this mutation were compared with those from MYBPC3 p.Arg502Trp/Gln in terms of presentation features, imaging and outcomes.ResultsMYBPC3 c.2149–1G>A was identified in 8 of 570 probands and 25 relatives. Penetrance was age and sex dependent, 50.0% of the carriers over age 36 years and 75.0% of the carriers over 40 years showing HCM. Penetrance was significantly higher in males: in carriers older than 30 years old, 100.0% of males vs 50.0% of females had a HCM phenotype (p=0.01). Males were also younger at diagnosis (32±13 vs 53±10 years old, p<0.001). MYBPC3 c.2149–1G>A resulted in an abnormal transcript that led to haploinsufficiency and was segregated in two haplotypes. However, both came from one founder haplotype. Affected carriers showed a better functional class and higher left ventricular ejection fraction (LVEF) than patients with MYBPC3 p.Arg502Trp/Gln (p<0.05 for both). Nevertheless, the rate of major adverse outcomes was similar between the two groups.ConclusionsMYBPC3 c.2149–1G>A splicing variant is a founder mutation. Affected males show an early onset of HCM and with higher penetrance than women. Carriers show better functional class and higher LVEF than MYBPC3 p.Arg502Trp/Gln carriers, but a similar rate of major adverse outcomes.

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Konno, Tetsuo, Masami Shimizu, Hidekazu Ino, Noboru Fujino, Katsuharu Uchiyama, Tomohito Mabuchi, Kenji Sakata et al. "A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe ventricular hypertrophy and sudden death". Clinical Science 110, n. 1 (12 dicembre 2005): 125–31. http://dx.doi.org/10.1042/cs20050189.

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It has been demonstrated previously that clinical phenotypes of HCM (hypertrophic cardiomyopathy) caused by mutations in the cardiac MyBP-C (myosin-binding protein C) gene show late onset, low penetrance and favourable clinical course. However, we have encountered severe phenotypes in several carriers of the MyBP-C gene mutations. The aim of the present study was to screen novel MyBP-C gene mutations in patients with HCM and to investigate the genetic differences in affected subjects with severe phenotypes. The MyBP-C gene was screened in 292 Japanese probands with HCM, and a novel c.2067+1G→A mutation was present in 15 subjects in five families. Clinical phenotypes of carriers of the c.2067+1G→A mutation were compared with those of a previously identified Arg820Gln (Arg820→Gln) mutation in the MyBP-C gene. The disease penetrance in subjects aged ≥30 years was 90% in carriers of the c.2067+1G→A mutation and 61% in carriers of the Arg820Gln mutation. Sudden death occurred in four subjects from three families with the c.2067+1G→A mutation and in two subjects from one family with the Arg820Gln mutation. Two carriers of the c.2067+1G→A mutation had substantial hypertrophy (maximal wall thickness ≥30 mm). In contrast, two carriers of the Arg820Gln mutation had end-stage HCM. In conclusion, the c.2067+1G→A mutation is associated with HCM with substantial hypertrophy and moderate incidence of sudden death, whereas the Arg820Gln mutation is associated with end-stage HCM. These observations may provide important prognostic information regarding the clinical practice of HCM.

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Rodríguez-Téllez, Rosa Isela, Rosa María Ribas-Aparicio e Genaro Patiño-López. "Detection of Myosin 1g Overexpression in Pediatric Leukemia by Novel Monoclonal Antibodies". International Journal of Molecular Sciences 23, n. 7 (1 aprile 2022): 3912. http://dx.doi.org/10.3390/ijms23073912.

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Myosin 1g (Myo1g) is a mechanoenzyme associated with actin filaments, expressed exclusively in hematopoietic cells, and involved in various cellular functions, including cell migration, adhesion, and membrane trafficking. Despite the importance of Myo1g in distinct functions, there is currently no monoclonal antibody (mAb) against Myo1g. mAbs are helpful tools for the detection of specific antigens in tumor cells and other tissues. The development of mAbs against targeted dysregulated molecules in cancer cells remains a crucial tool for aiding in the diagnosis and the treatment of patients. Using hybridoma technology, we generated a panel of hybridomas specific for Myo1g. ELISA, immunofluorescence, and Western blot assay results revealed the recognition of Myo1g by these novel monoclonal antibodies in normal and transformed T and B cells. Here, we report the development and application of new monoclonal antibodies against Myo1g for their potential use to detect its overexpression in acute lymphoblastic leukemia (ALL) patients.

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Olety, Balaji, Mike Wälte, Ulrike Honnert, Hermann Schillers e Martin Bähler. "Myosin 1G (Myo1G) is a haematopoietic specific myosin that localises to the plasma membrane and regulates cell elasticity". FEBS Letters 584, n. 3 (4 dicembre 2009): 493–99. http://dx.doi.org/10.1016/j.febslet.2009.11.096.

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Maravillas-Montero, José L., Orestes López-Ortega, Genaro Patiño-López e Leopoldo Santos-Argumedo. "Myosin 1g regulates cytoskeleton plasticity, cell migration, exocytosis, and endocytosis in B lymphocytes". European Journal of Immunology 44, n. 3 (16 gennaio 2014): 877–86. http://dx.doi.org/10.1002/eji.201343873.

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Patino Lopez, Genaro, E. Michael Ostap e Stephen Shaw. "Myosin 1G is a hematopoietic-restricted protein highly enriched in lymphocyte plasma membrane/microvilli whose deficiency impairs lymphocyte activation (35.40)". Journal of Immunology 182, n. 1_Supplement (1 aprile 2009): 35.40. http://dx.doi.org/10.4049/jimmunol.182.supp.35.40.

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Abstract Class I myosins regulate diverse aspects of locomotion, vesicular traffic, and peripheral process architecture in amoeba and in mammalian cells. Mass spectrometric analysis of lymphocyte fractions enriched for plasma membrane/microvilli identified myosin 1G (Myo1G) as abundant and enriched from human peripheral blood T-cells and Myo1G plus Myo1C as abundant and enriched from a mouse pre-B-cell line. To understand its structure and function, we have investigated Myo1G by immunofluorescence, by immunoblot, by transfection of wt and mutant constructs and by creation of a knockout mouse. Myo1G is abundant in multiple hematopoietic lineages, but absent in most other cell types. Endogenous Myo1G is highly enriched at the plasma membrane and in microvilli/ruffles of lymphocytes (as is transfected Myo1G in Jurkat T-cells). Structure-function analysis with truncation and point mutants show that Myo1G localization at the membrane, like Myo1C, requires a conserved "PH-like" domain present in the tail. But unlike Myo1C, it also depends on presence of its actin-binding motor domain. Knockout mice have no obvious defect in hematopoietic cell development. However preliminary studies shown that there are defects in activation of splenic T cells after stimulation with anti TCR. Studies are in progress to elucidate the underlying mechanism by which Myo1G contributes to T-cell activation.

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Picquet, F., V. Bouet, L. Cochon, M. Lacour e M. Falempin. "Changes in rat soleus muscle phenotype consecutive to a growth in hypergravity followed by normogravity". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 289, n. 1 (luglio 2005): R217—R224. http://dx.doi.org/10.1152/ajpregu.00596.2004.

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It has been demonstrated that a long-term stay in hypergravity (HG: 2G) modified the phenotype and the contractile properties of rat soleus muscle. The ability of this muscle to contract was drastically reduced, which is a sign of anticipated aging. Consequently, our aim was to determine whether rats conceived, born, and reared in hypergravity showed adaptative capacities in normogravity (NG: 1G). This study was performed on rats divided into two series: the first was reared in HG until 100 days and was submitted to normogravity until 115 to 220 postnatal days (HG-NG rats); the second was made up of age paired groups reared in normogravity (NG rats). The contractile, morphological, and phenotypical properties of soleus muscle were studied. Our results showed that the NG rats were characterized by coexpressions of slow and fast myosin, respectively, 76.5 and 23.5% at 115 days. During their postnatal maturation, the fast isoform was gradually replaced by slow myosin. At 220 days, the relative proportions were respectively 91.05% and 8.95%. From 115 to 220 days, the HG-NG rats expressed 100% of slow myosin isoform and they presented a slower contractile behavior compared with their age-matched groups; at 115 days, the whole muscle contraction time was increased by 35%, and by 15%, at 220 days. Our study underlined the importance of gravity in the muscular development and suggested the existence of critical periods in muscle phenotype installation.

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Patino-Lopez, Genaro, L. Aravind, Xiaoyun Dong, Michael J. Kruhlak, E. Michael Ostap e Stephen Shaw. "Myosin 1G Is an Abundant Class I Myosin in Lymphocytes Whose Localization at the Plasma Membrane Depends on Its Ancient Divergent Pleckstrin Homology (PH) Domain (Myo1PH)". Journal of Biological Chemistry 285, n. 12 (12 gennaio 2010): 8675–86. http://dx.doi.org/10.1074/jbc.m109.086959.

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Majumder, Sananda, Partha Pratim Chakraborty, Prakash Chandra Ghosh e Mitali Bera. "Cushing’s syndrome in early infancy due to isolated sporadic bilateral micronodular adrenocortical disease associated with myosin heavy chain 8 mutation: diagnostic challenges, too many!" BMJ Case Reports 13, n. 10 (ottobre 2020): e236850. http://dx.doi.org/10.1136/bcr-2020-236850.

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Endogenous Cushing’s syndrome (CS) is rare in infancy. Bilateral micronodular adrenocortical disease (BMAD), either primary pigmented nodular adrenocortical disease or the non-pigmented isolated micronodular adrenocortical disease is an important aetiology of CS in this age group, which requires bilateral adrenalectomy for cure. BMAD may be isolated, or a component of Carney complex. Isolated sporadic BMAD without other systemic manifestations poses a diagnostic challenge. Paradoxical cortisol response to dexamethasone suggests, while adrenal histopathology and mutational analysis of the culprit genes confirm BMAD. BMAD was suspected in 6-year-old infant with midnormal adrenocorticotrophic hormone, inconclusive adrenal and pituitary imaging and paradoxical increase in cortisol following high dose of dexamethasone. Exome sequencing revealed heterozygous c.354+1G>C (5′ splice site) variant in the myosin heavy chain gene (MYH8), located in chromosome 17. This particular variant has not been reported in the literature. In view of suspected phenotype and its absence in the population databases, the variant was classified as pathogenic.

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Xu, Fei, Lulu Zhang, Yuxia Xu, Di Song, Wenting He, Xiaomeng Ji e Jianyong Shao. "Hypermethylation of SCAND3 and Myo1g Gene Are Potential Diagnostic Biomarkers for Hepatocellular Carcinoma". Cancers 12, n. 8 (18 agosto 2020): 2332. http://dx.doi.org/10.3390/cancers12082332.

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Presently, there is a lack of effective blood-based biomarkers facilitating the diagnosis of hepatocellular carcinoma (HCC). Thus, we aimed to investigate novel methylation markers for HCC diagnosis, and explore relationships between biomarker methylation and clinicopathology of HCC. The methylation status of the SCAN domain containing three (SCAND3) and myosin 1g (Myo1g) genes in HCC cell lines and tissues were detected by digital droplet PCR. The serum SCAND3 and Myo1g methylation levels were analyzed in HCC-afflicted patients and unafflicted controls. The results indicated SCAND3 and Myo1g methylation were abnormally high in the HCC cell lines and tissues. The values of serum SCAND3, Myo1g, and SCAND3 + Myo1g methylation with respect to facilitating the detection, and early detection of HCC were better than for alpha-fetoprotein (AFP) alone. Furthermore, when we combined SCAND3 + Myo1g with AFP, a high sensitivity and specificity resulted. Notably, in the AFP-negative HCC group, the methylation of SCAND3 and Myo1g also showed an excellent diagnostic performance. Besides this, a high serum SCAND3 methylation level was an independent risk factor for predicting portal vein tumor thrombus (PVTT) in HCC patients (OR = 4.746, p = 0.013). Finally, SCAND3 and Myo1g enhanced the HCC diagnostics as noninvasive serum methylation biomarkers, and the SCAND3 methylation status effectively indicated HCC accompanied by PVTT.

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Fitts, Robert H., Danny R. Riley e Jeffrey J. Widrick. "Functional and structural adaptations of skeletal muscle to microgravity". Journal of Experimental Biology 204, n. 18 (15 settembre 2001): 3201–8. http://dx.doi.org/10.1242/jeb.204.18.3201.

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SUMMARY Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20–48% following 6 months in space, while a 21% decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm−2), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V0) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V0, peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiology has not been established.

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Moravikova, J., Z. Kozmik, L. Hlavata, M. Putzova, P. Skalicka, M. Michaelides, F. Malinka, Lubica Dudakova e P. Liskova. "Phenotype Variability in Czech Patients Carrying PAX6 Disease-Causing Variants". Folia Biologica 66, n. 4 (2020): 123–32. http://dx.doi.org/10.14712/fb2020066040123.

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The aim of this study was to report PAX6 disease-causing variants in six Czech families, to describe the associated phenotypes, and to perform functional assessment of the splice site variants. Detailed ophthalmic examination was performed. The PAX6 coding region was directly sequenced in three probands. Two probands were analysed by exome sequencing and one by genome sequencing. The effect of two variants on pre-mRNA splicing was evaluated using an exon trapping assay. Six different heterozygous PAX6 variants were identified, with c.111_120del and c.1183+1G>T being novel. Both c.1183+1G>T and c.1032+1G>A were proved to cause aberrant splicing with exon skipping and subsequent frameshift. The phenotypic features were variable between and within families. One individual, aged 31 years, presented with mild unilateral ptosis accompanied by aniridia in the right eye, partial aniridia in the left eye, and bilateral congenital cataracts, without marked foveal hypoplasia. Bilateral microcornea, partial aniridia, congenital cataracts, and a large posterior segment coloboma were found in another proband, aged 32 years. One child, aged 8 years, had bilateral high myopia, optic nerve colobomas, anterior polar cataracts, but no iris defects. Another individual, aged 46 years, had bilateral congenital ptosis, iris hypoplasia, keratopathy with marked fibrovascular pannus, anterior polar cataract, and foveal hypoplasia combined with impaired glucose tolerance. However, his daughter, aged 11 years, showed classical features of aniridia. Our study extends the genetic spectrum of PAX6 disease-causing variants and confirms that the associated phenotypic features may be very broad and different to the ‘classical’ aniridia.

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Chong, Fenny, Pauline Dizon, Genghis H. Lopez, Glenda M. Millard, Tanya Powley, Catherine A. Hyland, Daniel Kolarich e Rebecca E. Griffiths. "Urea Transporter B Is Produced in the Jk Null Blood Group Yet Fails to Integrate into the Red Cell Membrane Impacting Erythropoiesis and Erythrocytes". Blood 142, Supplement 1 (28 novembre 2023): 141. http://dx.doi.org/10.1182/blood-2023-181467.

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The Kidd (Jk) blood group is carried by an integral membrane glycoprotein, urea transporter B (UT-B), which transports urea through the red blood cell (RBC) membrane. The absence of both Jk a and Jk b antigens, designated phenotypically as Jk(a-b-) (Jk null), is very rare with a significantly increased prevalence in certain ethnicities, most abundantly within the Polynesian population where it is found at 0.9% prevalence. Provision of blood for patients requiring this phenotype is challenging. In Australia, there are only 15 active Jk null blood donors. Individuals of the Jk null phenotype have been shown to have suboptimal urine concentrating ability but erythrocytes appear phenotypically normal with shape, size and lifespan within normal reference indices (Lawicki et al., Transfus Med Rev, 2017). Where UT-B integrates in the RBC membrane is unknown although protein 4.1R deficiency is reported to lead to the absence of UT-B (Azouzi et al., Br J Haematol, 2015). Our aim was to identify and characterise the molecular basis for the Jk null phenotype in Australian blood donors and decipher the biological impact of the Jk null phenotype using our ex vivo model of erythropoiesis to help inform clinical transfusion practice. Massively parallel sequencing showed that all blood donors (n=9) were homozygous for JK c.342-1G>A (splice site variant) and c.838G>A polymorphisms resulting in the JK*02N.01/*02N.01 genotype. This genotype predicts a Jk null phenotype, and a truncated UT-B protein caused by the formation of a premature stop codon. The assumption from the genomics data is that the putative truncated UT-B protein would not be translated. To test this hypothesis we examined the RBCs of Jk null individuals and confirmed the lack of UT-B expression on the RBC surface by live flow cytometry and confocal imaging. In control RBCs UT-B is seen in discrete microdomains on the RBC surface by live confocal microscopy. To establish the expression of UT-B during erythropoiesis we cultured CD34+ cells from control and Jk null buffy coats after whole blood donation. Flow cytometry and confocal microscopy of control cells identified that UT-B is expressed intracellularly and at the cell surface in the developing erythroid cells. Notably we identified that the UT-B protein can also be found intracellularly in developing Jk null erythroid cells but is not detectable in the plasma membrane. In Jk null reticulocytes, UT-B colocalises with markers of protein degradation and destruction implying that the truncated UT-B protein is quickly removed by controlled protein degradation pathways. Quantitative proteomics was used to assess the global effect of the Jk null phenotype on the mature RBC membrane proteome. These data confirmed the absence of UT-B but also uncovered that in mature Jk null RBCs, RBC proteins involved in solute transport (aquaporin-1, stomatin) and membrane-cytoskeleton stabilisation (alpha and beta adducins, and dematin) are significantly downregulated. In contrast, actin binding proteins including tropomyosin and myosin IIA were upregulated in Jk null RBCs. The proteomics data also revealed that numerous major plasma proteins including alpha-2-macroglobulin, hemopexin and immunoglobulins are associated exclusively with Jk null RBCs. These findings imply that the lack of functional, membrane embedded UT-B induces various compensatory mechanisms in the Jk null RBCs membrane. In conclusion, we show that a truncated UT-B protein is produced in Jk null erythroid cells but fails to mature into a RBC membrane integrated, functional glycoprotein. Our data also suggest that the absence of a functional UT-B glycoprotein on the RBC surface affects the RBC membrane and cytoskeletal proteome and its interaction with major plasma glycoproteins.

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Nikolaeva, E. A., A. N. Semyachkina, G. V. Dzhivanshiryan, N. V. Shcherbakova e A. V. Smirnova. "A rare combination of monogenic connective tissue diseases — Marfan and Stickler syndromes — in one patient". Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) 67, n. 4 (21 settembre 2022): 93–98. http://dx.doi.org/10.21508/1027-4065-2022-67-4-93-98.

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As DNA sequencing techniques have been used more widely in clinical practice, there have been reports of a combination of hereditary diseases in a single patient. Cases of combining diseases with similar clinical symptoms present a particular difficulty for diagnosis. We observe a child who has been identified to have a combination of autosomal dominant diseases associated with connective tissue involvement — Marfan and Stickler type 1 syndromes. Common symptoms of both diseases were as follows: marfanoid habitus, arachnodactyly, kyphoscoliosis, chest deformity, involvement in the process of joints (hypermobile syndrome) and eyes. Marfan syndrome was evidenced by dissociation of mass-growth parameters at birth, tallstature, “Gothic” palate, crowded teeth, aortic dilation at the level of Valsalva sinuses and its ascending part. Type 1 Stickler syndrome was indicated by high-grade myopia, degenerative vitreous changes requiring vitrectomy, flat face, mandibular micrognathia, latent cleft of the soft and hard palate, grade 1 bilateral conductive hearing loss, mild cognitive failure. The diagnosis of both diseases was confirmed by the detection of de novo heterozygous mutations in the FBN1 gene (c.5060_5061 delGCinvAA, p. Cys1687) and COL2A1 gene (c.4074+1G>A). Establishing a final diagnosis is of great importance for predicting the course of the disease and genetic counseling of the proband and their relatives.

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Garcia-Martinez, V., C. Lopez Sanchez, W. Hamed, W. Hamed, JH Hsu, R. Ferrer-Lorente, Maryam Alshamrani et al. "Poster session 2Morphogenetic mechanisms290MiR-133 regulates retinoic acid pathway during early cardiac chamber specification291Bmp2 regulates atrial differentiation through miR-130 during early heart looping formationDevelopmental genetics294Association of deletion allele of insertion/deletion polymorphism in alpha 2B adrenoceptor gene and hypertension with or without type 2 diabetes mellitus295Association of G1359A polymorphism of the endocannabinoid type 1 receptor (CNR1) with coronary artery disease (CAD) with type 2 diabetes mellitusCell growth, differentiation and stem cells - Vascular298Gamma-secretase inhibitor prevents proliferation and migration of ductus arteriosus smooth muscle cells: a role of Notch signaling in postnatal closure of ductus arteriosus299Mesenchymal stromal-like cells (MLCs) derived from induced pluripotent stem (iPS) cells: a promising therapeutic option to promote neovascularization300Sonic Hedgehog promotes mesenchymal stem cell differentiation to vascular smooth muscle cells in cardiovacsular disease301Proinflammatory cytokine secretion and epigenetic modification in endothelial cells treated LPS-GinfivalisCell death and apoptosis - Vascular304Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipidsTranscriptional control and RNA species - Vascular307MicroRNA-34a role in vascular calcification308Local delivery of a miR-146a inhibitor utilizing a clinically applicable approach attenuates neointima formation after vascular injury309Long noncoding RNA landscape of hypoxic endothelial cells310Specific circulating microRNAs levels associate with hypertension, hyperglycemia and dysfunctional HDL in acute coronary syndrome patientsCytokines and cellular inflammation - Vascular313Phosphodiesterase5A up-regulation in vascular endothelium under pro-inflammatory conditions: a newly disclosed anti-inflammatory activity for the omega-3polyunsaturated aatty acid docosahexaenoic acid314Cardiovascular risk modifying with extra-low dose anticytokine drugs in rhematoid arthritis315Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation316Lymphocytic myocarditis coincides with increased plaque inflammation and plaque hemorrhage in coronary arteries, facilitating myocardial infarction317Serum osteoprotegerin level predictsdeclined numerous of circulating endothelial- derived and mononuclear-derived progenitor cells in patients with metabolic syndromeGrowth factors and neurohormones - Vascular320Effect of gastrin-releasing peptide (GRP) on vascular inflammationSignal transduction - Heart323A new synthetic peptide regulates hypertrophy in vitro through means of the inhibition of nfkb324Inducible fibroblast-specific knockout of p38 alpha map kinase is cardioprotective in a mouse model of isoproterenol-induced cardiac hypertrophy325Regulation of beta-adrenoceptor-evoked inotropic responses by inhibitory G protein, adenylyl cyclase isoforms 5 and 6 and phosphodiesterases326Binding to RGS3 and stimulation of M2 muscarinic acetylcholine receptors modulates the substrate specificity of p190RhoGAP in cardiac myocytes327Cardiac regulation of post-translational modifications, parylation and deacetylation in LMNA dilated cardiomyopathy mouse model328Beta-adrenergic regulation of the b56delta/pp2a holoenzyme in cardiac myocytes through b56delta phosphorylation at serine 573Nitric oxide and reactive oxygen species - Vascular331Oxidative stress-induced miR-200c disrupts the regulatory loop among SIRT1, FOXO1 and eNOS332Antioxidant therapy prevents oxidative stress-induced endothelial dysfunction and Enhances Wound Healing333Morphological and biochemical characterization of red blood cell in coronary artery diseaseCytoskeleton and mechanotransduction - Heart336Novel myosin activator, JSH compounds, increased myocardial contractility without chronotropic effect in ratsExtracellular matrix and fibrosis - Vascular339Ablation of Toll-like receptor 9 causes cardiac rupture after myocardial infarction by attenuating proliferation and differentiation of cardiac fibroblasts340Altered vascular remodeling in the mouse hind limb ischemia model in Factor VII activating protease (FSAP) deficiencyVasculogenesis, angiogenesis and arteriogenesis343Pro-angiogenic effects of proly-hydroxylase inhibitors and their potential for use in a novel strategy of therapeutic angiogenesis for coronary total occlusion344Nrf2 drives angiogenesis in transcription-independent manner: new function of the master regulator of oxidative stress response345Angiogenic gene therapy, despite efficient vascular growth, is not able to improve muscle function in normoxic or chronically ischemic rabbit hindlimbs -role of capillary arterialization and shunting346Effect of PAR-1 inhibition on collateral vessel growth in the murine hind limb model347Quaking is a key regulator of endothelial cell differentiation, neovascularization and angiogenesis348"Emerging angiogenesis" in the chick chorioallantoic membrane (CAM). An in vivo study349Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis in vitro and in vivo via EMMPRINEndothelium352Reciprocal regulation of GRK2 and bradykinin receptor stimulation modulate Ca2+ intracellular level in endothelial cells353The roles of bone morphogenetic proteins 9 and 10 in endothelial inflammation and atherosclerosis354The contribution of GPR55 to the L-alpha-lysophosphatidylinositol-induced vasorelaxation in isolated human pulmonary arteries355The endothelial protective ACE inhibitor Zofenoprilat exerts anti-inflammatory activities through H2S production356A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction357Endothelial progenitor cells to apoptotic endothelial cell-derived microparticles ration differentiatesas preserved from reduced ejection fractionheart failure358Proosteogenic genes are activated in endothelial cells of patients with thoracic aortic aneurysm359Endothelin ETB receptors mediate relaxing responses to insulin in pericardial resistance arteries from patients with cardiovascular disease (CVD)Smooth muscle and pericytes362CX3CR1 positive myeloid cells regulate vascular smooth muscle tone by inducing calcium oscillations via activation of IP3 receptors363A novel function of PI3Kg on cAMP regulation, role in arterial wall hyperplasia through modulation of smooth muscle cells proliferation364NRP1 and NRP2 play important roles in the development of neointimal hyperplasia in vivo365Azithromycin induces autophagy in aortic smooth muscle cellsCoagulation, thrombosis and platelets368The real time in vivo evaluation of platelet-dependent aldosterone prothrombotic action in mice369Development of a method for in vivo detection of active thrombi in mice370The antiplatelet effects of structural analogs of the taurine chloramine371The influence of heparin anticoagulant drugs on functional state of human platelets372Regulation of platelet aggregation and adenosine diphosphate release by d dimer in acute coronary syndrome (in vitro study)Oxygen sensing, ischaemia and reperfusion375Sirtuin 5 mediates brain injury in a mouse model of cerebral ischemia-reperfusion376Abscisic acid: a new player in cardiomyocyte protection from ischaemia?377Protective effects of ultramicronized palmitoylethanolamide (PEA-um) in myocardial ischaemia and reperfusion injury in vivo378Identification of stem cell-derived cardiomyocytes using cardiac specific markers and additional testing of these cells in simulated ischemia/reperfusion system379Single-dose intravenous metformin treatment could afford significant protection of the injured rat kidney in an experimental model of ischemia-reperfusion380Cardiotoxicity of long acting muscarinic receptor antagonists used for chronic obstructive pulmonary disease381Dependence antioxidant potential on the concentration of amino acids382The impact of ischemia-reperfusion on physiological parameters,apoptosis and ultrastructure of rabbit myocardium with experimental aterosclerosisMitochondria and energetics385MicroRNA-1 dependent regulation of mitochondrial calcium uniporter (MCU) in normal and hypertrophied hearts386Mitochondrial homeostasis and cardioprotection: common targets for desmin and aB-crystallin387Overexpression of mitofusin-2 (Mfn2) and associated mitochondrial dysfunction in the diabetic heart388NO-dependent prevention of permeability transition pore (MPTP) opening by H2S and its regulation of Ca2+ accumulation in rat heart mitochondria389G protein coupled receptor kinase 2 (GRK2) is fundamental in recovering mitochondrial morphology and function after exposure to ionizing radiation (IR)Gender issues392Sex differences in pulmonary vascular control; focus on the nitric oxide pathwayAging395Heart failure with preserved ejection fraction develops when feeding western diet to senescence-accelerated mice396Cardiovascular markers as predictors of cognitive decline in elderly hypertensive patients397Changes in connexin43 in old rats with volume overload chronic heart failureGenetics and epigenetics400Calcium content in the aortic valve is associated with 1G>2G matrix metalloproteinase 1 polymorphism401Neuropeptide receptor gene s (NPSR1) polymorphism and sleep disturbances402Endothelin-1 gene Lys198Asn polymorphism in men with essential hypertension complicated and uncomplicated with chronic heart failure403Association of common polymorphisms of the lipoprotein lipase and pon1 genes with the metabolic syndrome in a sample of community participantsGenomics, proteomics, metabolomics, lipidomics and glycomics405Gene expression quantification using multiplexed color-coded probe pairs to determine RNA content in sporadic cardiac myxoma406Large-scale phosphorylation study of the type 2 diabetic heart subjected to ischemia / reperfusion injury407Transcriptome-based identification of new anti-inflammatory properties of the olive oil hydroxytyrosol in vascular endothelial cell under basal and proinflammatory conditions408Gene polymorphisms combinations and risk of myocardial infarctionComputer modelling, bioinformatics and big data411Comparison of the repolarization reserve in three state-of-the-art models of the human ventricular action potentialMetabolism, diabetes mellitus and obesity414Endothelial monocyte-activating polypeptide-II improves heart function in type -I Diabetes mellitus415Admission glucose level is independent predictor of impaired left ventricular function in patients with acute myocardial infarction: a two dimensional speckle-tracking echocardiography study416Association between biochemical markers of lipid profile and inflammatory reaction and stiffness of the vascular wall in hypertensive patients with abdominal obesity417Multiple common co-morbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress and myocardial stiffening418Investigating the cardiovascular effects of antiretroviral drugs in a lean and high fat/sucrose diet rat model of obesity419Statins in the treatment of non-alcoholic steatohepatitis (NASH). Our experience from a 2-year prospective study in Constanta County, Romania420Epicardial adipose tissue as a predictor of cardiovascular outcome in patients with ACS undergoing PCI?Arterial and pulmonary hypertension423Dependence between heart rhythm disorers and ID polymorphism of ACE gene in hypertensive patients424Molecular mechanisms underlying the beneficial effects of Urocortin 2 in pulmonary arterial hypertension425Inhibition of TGf-b axis and action of renin-angiotensin system in human ascending aorta aneurysms426Early signs of microcirculation and macrocirculation abnormalities in prehypertension427Vascular smooth muscle cell-expressed Tie-2 controls vascular tone428Cardiac and vascular remodelling in the development of chronic thrombo-embolic pulmonary hypertension in a novel swine modelBiomarkers431Arrhythmogenic cardiomyopathy: a new, non invasive biomarker432Can circulating microRNAs distinguish type 1 and type 2 myocardial infarction?433Design of a high-throughput multiplex proteomics assay to identify left ventricular diastolic dysfunction in diabetes434Monocyte-derived and P-selectin-carrying microparticles are differently modified by a low fat diet in patients with cardiovascular risk factors who will and who will not develop a cardiovascular event435Red blood cell distribution width assessment by polychromatic interference microscopy of thin films in chronic heart failure436Invasive and noninvasive evaluation of quality of radiofrequency-induced cardiac denervation in patients with atrial fibrillation437The effect of therapeutic hypothermia on the level of brain derived neurotrophic factor (BDNF) in sera following cardiopulmonary resustitation438Novel biomarkers to predict outcome in patients with heart failure and severe aortic stenosis439Biological factors linking depression and anxiety to cardiovascular disease440Troponins and myoglobin dynamic at coronary arteries graftingInvasive, non-invasive and molecular imaging443Diet composition effects on the genetic typing of the mouse ob mutation: a micro-ultrasound characterization of cardiac function, macro and micro circulation and liver steatosis444Characterization of pig coronary and rabbit aortic lesions using IV-OCT quantitative analysis: correlations with histologyGene therapy and cell therapy447Enhancing the survival and angiogenic potential of mouse atrial mesenchymal cells448VCAM-1 expression in experimental myocardial infarction and its relation to bone marrow-derived mononuclear cell retentionTissue engineering451Advanced multi layered scaffold that increases the maturity of stem cell-derived human cardiomyocytes452Response of engineered heart tissue to simulated ischemia/reperfusion in the presence of acute hyperglycemic conditions453Serum albumin hydrogels prevent de-differentiation of neonatal cardiomyocytes454A novel paintbrush technique for transfer of low viscosity ultraviolet light curable cyan methacrylate on saline immersed in-vitro sheep heart". Cardiovascular Research 111, suppl 1 (1 luglio 2016): S56—S81. http://dx.doi.org/10.1093/cvr/cvw149.

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Cruz-Zárate, David, Carlos Emilio Miguel-Rodríguez, Irving Ulises Martínez-Vargas e Leopoldo Santos-Argumedo. "Myosin 1g and 1f: A Prospective Analysis in NK Cell Functions". Frontiers in Immunology 12 (14 dicembre 2021). http://dx.doi.org/10.3389/fimmu.2021.760290.

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NK cells are contained in the ILC1 group; they are recognized for their antiviral and antitumor cytotoxic capacity; NK cells also participate in other immune response processes through cytokines secretion. However, the mechanisms that regulate these functions are poorly understood since NK cells are not as abundant as other lymphocytes, which has made them difficult to study. Using public databases, we identified that NK cells express mRNA encoding class I myosins, among which Myosin 1g and Myosin 1f are prominent. Therefore, this mini-review aims to generate a model of the probable participation of Myosin 1g and 1f in NK cells, based on information reported about the function of these myosins in other leukocytes.

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Aboouf, Mostafa A., Cora S. Thiel, Sergey M. Borisov, Svantje Tauber, Eva Bönzli, Nelli Schetle, Oliver Ullrich, Max Gassmann e Johannes Vogel. "Expression of hypoxia-inducible genes is suppressed in altered gravity due to impaired nuclear HIF1α accumulation". Scientific Reports 13, n. 1 (4 settembre 2023). http://dx.doi.org/10.1038/s41598-023-41686-1.

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AbstractExtravehicular activities, the backbone of manned space exploration programs, set astronauts into mild hypoxia. Unfortunately, microgravity aggravates threatening symptoms of hypoxia such as vision impairment and brain edema. Hypoxia-inducible factors (HIFs) sense cellular hypoxia and, subsequently, change the cells’ expression profile instantaneously by rapidly translocating—most likely cytoskeleton-dependently—into the nucleus and subsequently forming transcription complexes with other proteins. We tested the hypothesis that this fundamental process could be altered by sudden changes in gravitational forces in parabolic flights using a newly developed pocket-size cell culture lab that deoxygenizes cells within 15 min. Sudden gravity changes (SGCs 1g–1.8g–0g–1.8g–1g) during hypoxic exposure suppressed expression of the HIF1α-dependent genes investigated as compared with hypoxia at constant 1g. Normoxic cells subjected to SGCs showed reduced nuclear but not cytoplasmatic HIF1α signal and appeared to have disturbed cytoskeleton architecture. Inhibition of the actin-dependent intracellular transport using a combination of myosin V and VI inhibitors during hypoxia mimicked the suppression of the HIF1α-dependent genes observed during hypoxic exposure during SGCs. Thus, SGCs seem to disrupt the cellular response to hypoxia by impairing the actin-dependent translocation of HIF1α into the nucleus.

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Hitsumoto, Tatsuro, Osamu Tsukamoto, Ken Matsuoka, Junjun Li, Li Liu, Yuki Kuramoto, Shuichiro Higo et al. "Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin". Circulation, 2 maggio 2023. http://dx.doi.org/10.1161/circulationaha.122.062885.

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Background: Cardiac-specific myosin light chain kinase (cMLCK), encoded by MYLK3 , regulates cardiac contractility through phosphorylation of ventricular myosin regulatory light chain. However, the pathophysiological and therapeutic implications of cMLCK in human heart failure remain unclear. We aimed to investigate whether cMLCK dysregulation causes cardiac dysfunction and whether the restoration of cMLCK could be a novel myotropic therapy for systolic heart failure. Methods: We generated the knock-in mice ( Mylk3 +/fs and Mylk 3 fs/fs ) with a familial dilated cardiomyopathy–associated MYLK3 frameshift mutation ( MYLK3 +/fs ) that had been identified previously by us (c.1951-1G>T; p.P639Vfs*15) and the human induced pluripotent stem cell–derived cardiomyocytes from the carrier of the mutation. We also developed a new small-molecule activator of cMLCK (LEUO-1154). Results: Both mice ( Mylk3 +/fs and Mylk 3 fs/fs ) showed reduced cMLCK expression due to nonsense-mediated messenger RNA decay, reduced MLC2v (ventricular myosin regulatory light chain) phosphorylation in the myocardium, and systolic dysfunction in a cMLCK dose–dependent manner. Consistent with this result, myocardium from the mutant mice showed an increased ratio of cardiac superrelaxation/disordered relaxation states that may contribute to impaired cardiac contractility. The phenotypes observed in the knock-in mice were rescued by cMLCK replenishment through the AAV9_ MYLK3 vector. MYLK3 +/fs induced pluripotent stem cell–derived cardiomyocytes reduced cMLCK expression by 50% and contractile dysfunction, accompanied by an increased superrelaxation/disordered relaxation ratio. CRISPR-mediated gene correction, or cMLCK replenishment by AAV9_ MYLK3 vector, successfully recovered cMLCK expression, the superrelaxation/disordered relaxation ratio, and contractile dysfunction. LEUO-1154 increased human cMLCK activity ≈2-fold in the V max for ventricular myosin regulatory light chain phosphorylation without affecting the K m . LEUO-1154 treatment of human MYLK3 +/fs induced pluripotent stem cell–derived cardiomyocytes restored the ventricular myosin regulatory light chain phosphorylation level and superrelaxation/disordered relaxation ratio and improved cardiac contractility without affecting calcium transients, indicating that the cMLCK activator acts as a myotrope. Finally, human myocardium from advanced heart failure with a wide variety of causes had a significantly lower MYLK3 / PPP1R12B messenger RNA expression ratio than control hearts, suggesting an altered balance between myosin regulatory light chain kinase and phosphatase in the failing myocardium, irrespective of the causes. Conclusions: cMLCK dysregulation contributes to the development of cardiac systolic dysfunction in humans. Our strategy to restore cMLCK activity could form the basis of a novel myotropic therapy for advanced systolic heart failure.

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Yamamoto, Yuta, Victoria N. Parikh e Euan A. Ashley. "Abstract 14660: Truncating Variants in MYBPC3 Cause Ubiquitin Proteasome System Dysfunction Related to Hypertrophic Cardiomyopathy in Human Induced Pluripotent Stem Cell Model". Circulation 146, Suppl_1 (8 novembre 2022). http://dx.doi.org/10.1161/circ.146.suppl_1.14660.

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Introduction: Hypertrophic cardiomyopathy (HCM) is the most common inherited monogenic cardiomyopathy. Cardiac myosin binding protein C ( MYBPC3 ) is the most frequently mutated gene in this disease, and most pathogenic variants in MYBPC3 are truncating variants including splice site variants. The ubiquitin proteasome system (UPS), a major intracellular protein degradation system, plays an important role in the heart. Although impairment of UPS is reportedly caused by truncated cMyBP-C, the underlying molecular mechanism causing HCM is largely unknown. Hypothesis: Truncating variants in MYBPC3 lead to impaired UPS activity in human iPS cell-derived cardiomyocytes (hiPSC-CMs) and are associated with HCM phenotypes. Methods: Patient derived iPSC clones were generated from HCM patients with MYBPC3 variants (IVS11-9G>A and IVS27+1G>A). Corrected isogenic control of IVS27+1G>A was generated by base editing. To evaluate UPS activity, we employed ubiquitin fusion degradation reporter, Ub-G76V-GFP, which provides fluorescence readout of UPS activity. BNP expression of hiPSC-CMs were evaluated by antibody labeling and fluorescence-activated cell sorting (FACS). Contractility and Ca 2+ transient were measured from single biopatterned hiPSC-CMs. Results: Both MYBPC3 variant lines exhibited UPS impairment as reflected by increased GFP fluorescence compared to isogenic and healthy controls (Fig. A). IVS27+1G>A showed higher expression of BNP (Fig. B and C). Enhanced contractility and Ca 2+ handling abnormalities were observed in MYBPC3 variant iPSC-CM lines as compared to control (Fig. D and E). Conclusions: Impairment of UPS activity may be associated with a marker of cellular hypertrophy, and contractility and Ca 2+ handling abnormalities in hiPSC-CMs with MYBPC3 truncating variants. These findings support prior reports suggesting that decreased UPS activity contribute to the pathophysiological mechanism of HCM caused by truncating MYBPC3 variants.

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López-Ortega, Orestes, e Leopoldo Santos-Argumedo. "Myosin 1g Contributes to CD44 Adhesion Protein and Lipid Rafts Recycling and Controls CD44 Capping and Cell Migration in B Lymphocytes". Frontiers in Immunology 8 (11 dicembre 2017). http://dx.doi.org/10.3389/fimmu.2017.01731.

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Araujo-Cárdenas, Janeth E., Miguel A. Rodríguez-Ruiz, Jaime A. López-Valdez, Rosa I. Rodríguez-Téllez, Yanelly Garfias-Gómez, Israel Parra-Ortega e Genaro Patiño-López. "Myosin 1g as a high-risk biomarker in a pediatric patient with lineage switch from acute lymphoblastic leukemia to myeloid phenotype". Boletín Médico del Hospital Infantil de México 80, n. 2 (2 maggio 2023). http://dx.doi.org/10.24875/bmhim.22000041.

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Hedberg-Oldfors, Carola, Ólöf Elíasdóttir, Mats Geijer, Christopher Lindberg e Anders Oldfors. "Dominantly inherited myosin IIa myopathy caused by aberrant splicing of MYH2". BMC Neurology 22, n. 1 (15 novembre 2022). http://dx.doi.org/10.1186/s12883-022-02935-4.

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Abstract Background Myosin heavy chain (MyHC) isoforms define the three major muscle fiber types in human extremity muscles. Slow beta/cardiac MyHC (MYH7) is expressed in type 1 muscle fibers. MyHC IIa (MYH2) and MyHC IIx (MYH1) are expressed in type 2A and 2B fibers, respectively. Whereas recessive MyHC IIa myopathy has been described in many cases, myopathy caused by dominant MYH2 variants is rare and has been described with clinical manifestations and muscle pathology in only one family and two sporadic cases. Methods We investigated three patients from one family with a dominantly inherited myopathy by clinical investigation, whole-genome sequencing, muscle biopsy, and magnetic resonance imaging (MRI). Results Three siblings, one woman and two men now 54, 56 and 66 years old, had experienced muscle weakness initially affecting the lower limbs from young adulthood. They have now generalized proximal muscle weakness affecting ambulation, but no ophthalmoplegia. Whole-genome sequencing identified a heterozygous MYH2 variant, segregating with the disease in the three affected individuals: c.5673 + 1G > C. Analysis of cDNA confirmed the predicted splicing defect with skipping of exon 39 and loss of residues 1860–1891 in the distal tail of the MyHC IIa, largely overlapping with the filament assembly region (aa1877–1905). Muscle biopsy in two of the affected individuals showed prominent type 1 muscle fiber predominance with only a few very small, scattered type 2A fibers and no type 2B fibers. The small type 2A fibers were frequently hybrid fibers with either slow MyHC or embryonic MyHC expression. The type 1 fibers showed variation in fiber size, internal nuclei and some structural alterations. There was fatty infiltration, which was also demonstrated by MRI. Conclusion Dominantly inherited MyHC IIa myopathy due to a splice defect causing loss of amino acids 1860–1891 in the distal tail of the MyHC IIa protein including part of the assembly competence domain. The myopathy is manifesting with slowly progressive muscle weakness without overt ophthalmoplegia and markedly reduced number and size of type 2 fibers.

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Reza, Nosheen, Alejandro De Feria, Teresa Wang, Jessica Chowns, Lily Hoffman-Andrews, Jessica Kim, Nicole Hornsby et al. "Abstract 11644: Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy in Adult Solid Organ Transplant Recipients". Circulation 144, Suppl_1 (16 novembre 2021). http://dx.doi.org/10.1161/circ.144.suppl_1.11644.

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Introduction: Data on the incidence and prevalence of HCM in adult post-transplant patients are limited. We describe the characteristics of adult solid organ transplant recipients diagnosed with HCM at a single center. Methods: Solid organ transplant recipients with LV wall thickness > 13 mm on TTE were included in this retrospective analysis. Clinical characteristics and outcomes were abstracted. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges (IQR) and compared using the Wilcoxon Rank Sum test. A 2-sided p value < 0.05 was considered statistically significant. Results: Twelve transplant recipients — 3 (25%) lung, 5 (42%) kidney, 4 (33%) liver — were identified. Half (50%) were women, and 42% were non-White. One kidney transplant patient had a pathogenic variant in Myosin Binding Protein C (MYBPC3 c.3190+1G>A), and one kidney transplant patient had a likely pathogenic variant in Myosin Heavy Chain 7 (MYH7 c.5561C>T). Most (75%) had NYHA II-III symptoms. Five (42%) had hypertension. 10 (83%) were treated with tacrolimus and 2 (17%) with cyclosporine for a median 11.5 years (IQR 5.0,17.5). All had normal to hyperdynamic LVEF on first TTE (median LVEF 72.5% [IQR 60,75]). Median septal thickness at diagnosis was significantly greater than LV posterior wall thickness (17 vs. 13 mm, p <0.001). Seven had resting LVOT gradients >50 mm Hg. Nine (75%) were on beta-blocker, and 3 (25%) were concomitantly on calcium channel blocker. Four patients underwent successful septal reduction therapy: 2 (kidney) with septal myectomy and 2 (lung, kidney) with alcohol septal ablation. Conclusions: We report the largest series of adult solid organ transplant recipients with HCM. Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients. Medical management and septal reduction therapy are options for severe symptomatic disease. Prospective study of LVH in these patients is needed.

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Watanabe, T., Y. Matsumoto, H. Amamizu, S. Morosawa, K. Ohyama, K. Nishimiya, T. Shindo et al. "2381Low-intensity pulsed ultrasound ameliorates DES-induced coronary adventitial inflammation and hyperconstricting responses in pigs in vivo - A novel non-invasive therapy for coronary inflammation". European Heart Journal 40, Supplement_1 (1 ottobre 2019). http://dx.doi.org/10.1093/eurheartj/ehz748.0144.

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Abstract Background We previously demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of coronary artery spasm, including drug-eluting stent (DES)-induced coronary hyperconstricting responses, in pigs and humans. Indeed, the coronary adventitia has recently attracted much attention as the important site for vascular inflammation. However, a direct therapeutic approach to the coronary adventitia remains to be developed. We have developed a non-invasive low-intensity pulsed ultrasound (LIPUS) therapy for angina, which exerts anti-inflammatory effects through improved coronary microcirculation. Purpose In this study, we aimed to examine whether our LIPUS therapy ameliorates DES-induced coronary hyperconstricting responses in pigs in vivo, and if so, what mechanisms are involved. Methods An everolimus-eluting stent (EES) was implanted into the left anterior descending (LAD) coronary artery in normal male pigs. They were randomly assigned to the LIPUS or the sham therapy groups. After EES implantation, in the LIPUS group, LIPUS (32 cycles, 193 mW/cm2) was applied to the heart at 3 different levels (proximal and distal stent edges and middle portion of the stent) through X-ray for 20 min at each level for every other day for 2 weeks (6 days in total) (Figs. 1A, 1B). The sham therapy group was treated in the same manner but without LIPUS. At 4 weeks after the procedure, we performed coronary angiography to examine coronary vasoconstricting responses to intracoronary serotonin in vivo. Finally, stented coronary vessels were harvested for immunohistochemistry of vasa vasorum, lymphatic vessels (LYVE-1), sympathetic nerve fibers (SNF), vascular inflammation (macrophages and IL-1β expression), Rho-kinase expression and activity as evaluated by phosphorylated myosin phosphatase target subunit-1 (pMYPT-1). Results Coronary vasoconstricting responses to intracoronary serotonin were significantly enhanced in the sham therapy group but were significantly suppressed in the LIPUS group at the DES edges in the LAD, whereas those responses were comparable at the non-DES implanted segments in the left circumflex (LCx) coronary arteries between the 2 groups. (Figs. 1C, 1D). Furthermore, in vivo lymph transport speed was significantly faster in the LIPUS group than in sham group (Figs. 1E–1G). Histological analysis showed that except vasa vasorum formation, the number of lymphatic vessels, adventitial inflammatory cells infiltration, Rho-kinase expression and activity were all significantly enhanced in the sham therapy group and were significantly suppressed in the LIPUS group (Figs. 1G–1K). Figure 1 Conclusion We were able to develop a non-invasive LIPUS therapy for coronary functional abnormalities caused by chronic adventitial inflammation in pigs in vivo, for which multiple beneficial effects appear to be involved (Fig. 1L).

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Manoharan, Manoj K., Swapnil Thakur, Rohit Dhakal, Satish K. Gupta, Jacinth J. Priscilla, Shashank K. Bhandary, Alok Srivastava, Srinivas Marmamula, Nitish Poigal e Pavan K. Verkicharla. "Myopia progression risk assessment score (MPRAS): a promising new tool for risk stratification". Scientific Reports 13, n. 1 (31 maggio 2023). http://dx.doi.org/10.1038/s41598-023-35696-2.

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AbstractTimely identification of individuals “at-risk” for myopia progression is the leading requisite for myopia practice as it aids in the decision of appropriate management. This study aimed to develop ‘myopia progression risk assessment score’ (MPRAS) based on multiple risk factors (10) to determine whether a myope is “at-risk” or “low-risk” for myopia progression. Two risk-score models (model-1: non-weightage, model-2: weightage) were developed. Ability of MPRAS to diagnose individual “at-risk” for myopia progression was compared against decision of five clinicians in 149 myopes, aged 6–29 years. Using model-1 (no-weightage), further 7 sub-models were created with varying number of risk factors in decreasing step-wise manner (1a: 10 factors to 1g: 4 factors). In random eye analysis for model-1, the highest Youden’s J-index (0.63–0.65) led to the MPRAS cut-off score of 41.50–43.50 for 5 clinicians with a sensitivity ranging from 78 to 85% and specificity ranging from 79 to 87%. For this cut-off score, the mean area under the curve (AUC) between clinicians and the MPRAS model ranged from 0.89 to 0.90. Model-2 (weighted for few risk-factors) provided similar sensitivity, specificity, and AUC. Sub-model analysis revealed greater AUC with high sensitivity (89%) and specificity (94%) in model-1g that has 4 risk factors compared to other sub-models (1a–1f). All the MPRAS models showed good agreement with the clinician’s decision in identifying individuals “at-risk” for myopia progression.

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Tian, Runyi, Ping Tong, Yuhong He, Liyu Zang, Shimin Zhou e Qi Tian. "Exome sequencing‐aided precise diagnosis of four families with type I Stickler syndrome". Molecular Genetics & Genomic Medicine, 11 dicembre 2023. http://dx.doi.org/10.1002/mgg3.2331.

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AbstractBackgroundStickler syndrome is a multisystemic disorder characterized by ophthalmological and non‐ophthalmological abnormalities, frequently misdiagnosed due to high clinical heterogeneity. Stickler syndrome type I (STL1) is predominantly caused by mutations in the COL2A1 gene.MethodsExome sequencing and co‐segregation analysis were utilized to scrutinize 35 families with high myopia, and pathogenic mutations were identified. Mutant COL2A1 was overexpressed in cells for mechanistic study. A retrospective genotype–phenotype correlation analysis was further conducted.ResultsTwo novel pathogenic mutations (c.2895+1G>C and c.3505G>A (p.Val1169Ile)) and two reported mutations (c.1597C>T (p.Arg533*) and c.1693C>T (p.Arg565Cys)) in COL2A1 were identified causing STL1. These mutations are all in the G‐X‐Y triplet, and c.2895+1G>C contributed to aberrant RNA splicing. COL2A1 mutants tended to form large aggregates in the endoplasmic reticulum (ER) and elevated ER stress. Additionally, mutations c.550G>A (p.Ala184Thr) and c.2806G>A (p.Gly936Ser) in COL2A1 were found in high myopia families, but were likely benign, although c.2806G>A (p.Gly936Ser) is on G‐X‐Y triplet. Moreover, genotype–phenotype correlation analysis revealed that mutations in exon 2 mainly contribute to retinal detachment, whereas mutations in the collagen alpha‐1 chain region of COL2A1 tend to cause non‐ophthalmologic symptoms.ConclusionThis study broadens the COL2A1 gene mutation spectrum, provides evidence for ER stress caused by pathogenic COL2A1 mutations and highlights the importance of non‐ophthalmological examination in clinical diagnosis of high myopia.

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Chong, Shuk Ching, Yuet-Ping Yuen, Ye Cao, Sze-Shing Fan, Tak Yeung Leung, Emily K. Y. Chan e Xian Lun Zhu. "Case Report: Novel Biallelic Variants in the COL18A1 Gene in a Chinese Family With Knobloch Syndrome". Frontiers in Neurology 13 (26 maggio 2022). http://dx.doi.org/10.3389/fneur.2022.853918.

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Knobloch syndrome is a rare collagenopathy characterized by severe early onset myopia, retinal detachment, and occipital encephalocele with various additional manifestations due to biallelic changes in the COL18A1 gene. Here we reported a Chinese family with two affected siblings presented with antenatal occipital encephalocele, infantile onset retinal detachment, and pronounced high myopia at early childhood. Quartet whole exome sequencing was performed in this family and identified that both siblings carried novel compound heterozygous variants in the COL18A1 gene (NM_001379500.1): the maternally inherited variant c.1222-1G>A at the consensus acceptor splice site of intron 8, and the paternally inherited frameshift variant c.3931_3932delinsT p.(Gly1311Serfs*25) in the last exon. Both patients had successful surgical treatment for the occipital encephalocele soon after birth. They had normal neurocognitive outcome and good general conditions examined at the age of 7 years old for the elder sister and 4 years old for the younger brother. The younger brother developed infantile onset retinal detachment at 7 months of age while the sister had high myopia without signs of retinal detachment until 7 years old. This report expands the phenotype and genotype spectrum of Knobloch syndrome with antenatal and postnatal findings.

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Durmaz, Durmus, Ayca Dilruba Aslanger, Zehra Yavas Abali, Yasin Yilmaz, Volkan Karaman, Gozde Yesil Sayin, Guven Toksoy, Aysegul Unuvar e Zehra Oya Uyguner. "A Rare Inherited Bone Marrow Failure Syndrome Disclosed by Reanalysis of the Exome Data of a Patient Evaluated for Cytopenia and Dysmorphic Features". Journal of Pediatric Hematology/Oncology, 27 febbraio 2024. http://dx.doi.org/10.1097/mph.0000000000002839.

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Background: Multisystemic findings of inherited bone marrow failure syndromes may cause difficulty in diagnosis. Exome sequencing (ES) helps to define the etiology of rare diseases and reanalysis offers a valuable new diagnostic approach. Herein, we present the clinical and molecular characteristics of a girl who was referred for cytopenia and frequent infections. Case report: A 5-year-old girl with cytopenia, dysmorphism, short stature, developmental delay, and myopia was referred for genetic counseling. Reanalysis of the ES data revealed a homozygous splice-site variant in the DNAJC21 (NM_001012339.3:c.983+1G>A), causing Shwachman-Diamond Syndrome (SDS). It was shown by the RNA sequencing that exon 7 was skipped, causing an 88-nucleotide deletion. Conclusions: Precise genetic diagnosis enables genetic counseling and improves patient management by avoiding inappropriate treatment and unnecessary testing. This report would contribute to the clinical and molecular understanding of this rare type of SDS caused by DNAJC21 variants and expand the phenotypic features of this condition.

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Zhao, Sha, Zhenqing Luo, Zhenghui Xiao, Liping Li, Rui Zhao, Yongjia Yang e Yan Zhong. "Case report: two novel VPS13B mutations in a Chinese family with Cohen syndrome and hyperlinear palms". BMC Medical Genetics 20, n. 1 (21 novembre 2019). http://dx.doi.org/10.1186/s12881-019-0920-x.

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Abstract Background Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. Case presentation A Chinese family with two offspring–patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. Conclusions This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.

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"Short Term Effects of the Vaginal Administration of Gestrinone and Miodesin™ on Endometriosis Pain". Journal of Clinical Review & Case Reports 4, n. 8 (9 agosto 2019). http://dx.doi.org/10.33140/jcrc.04.08.01.

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Introduction: Gestrinone a 19 nor testosterone derivative with androgenic, anti-estrogenic and anti-progesterone properties was used either alone or associated with plant derived anti-inflammatory drugs to treat pain in deep endometriosis patients. Patient and Methods: In the present study Gestrinone was used alone or in combination with either a higher (500 mg) or a lower (170 mg) doses of Myodesin™ in order to treat pelvic pain in patients with deep endometriosis . In the higher dose group Miodesin™ was dispensed without Astaxanthin. Miodesin is the trade name for a herbal complex prepared by Fagron Brazil whose composition contains a mixture of plant extracts from an amazon tree Uncaria tomentosa together other plants. In the lower dose group (170 mg), on the other hand, a novel composition of Miodesin™ was tested that also contained H. pluviallis extract containing Astaxanthin. Forty patients with deep endometriosis and severe pain were enrolled for this study. Patients were divided into 3 groups according to treatment scheme. In Group A (n=11) they were treated with vaginal Gestrinone alone (2,5mg/g twice a week). In Group B (n=17) the patients received Gestrinone (2.5 mg/g twice a week) together with Miodesin™ (500 mg/3g daily)(Fagron Brazil). In Group C (n=12) the patients were treated with a daily dose of 1 mg/g of Gestrinone together with a lower dose of Miodesin™ 170 mg/g containing H pluvialis extract as described above . All medications were dispensed vaginally dissolved in Pentravan® (Fagron, Netherland). In group C only 1g of Pentravan® was necessary to dissolve 170 mg of the new composition of Miodesin™ containing H. pluvialis extract while in group B it was necessary to use 3g to solubilize the 500 mg of traditional Miodesin™. Results: In all 3 groups total pain scores reduced significantly after one month of treatment. However the post treatment scores were always significantly lower in patients who had used either the higher dose of Miodesin™ (Group B) or the new composition of Miodesin™ (Groups C) when compared to Gestrinone alone (Group A )(p<0.02). Conclusion: Although Miodesin™ was administered in a lower dose in group C the addiction of H.pluviallis extract standardized to contain Astaxanthin increased its efficacy to treat endometriosis pain when used together with Gestrinone. Miodesin™ is an inhibitor of NF-kappa-b activation while Astaxanthin is a carotenoid with potent antioxidant effects and their combined administration had a synergetic effect that allowed the reduction of the doses of Miodesin™ without compromising its efficacy.

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