To see the other types of publications on this topic, follow the link: Control of the porcine proliferative enteropathies.
Journal articles on the topic 'Control of the porcine proliferative enteropathies'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 44 journal articles for your research on the topic 'Control of the porcine proliferative enteropathies.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
McOrist, S., N. MacIntyre, C. R. Stokes, and G. H. Lawson. "Immunocytological responses in porcine proliferative enteropathies." Infection and Immunity 60, no. 10 (1992): 4184–91. http://dx.doi.org/10.1128/iai.60.10.4184-4191.1992.
Full text
2
McOrist, S., R. Boid, G. Lawson, and I. McConnell. "Monoclonal antibodies to intracellular campylobacter-like organisms of the porcine proliferative enteropathies." Veterinary Record 121, no. 18 (October 31, 1987): 421–22. http://dx.doi.org/10.1136/vr.121.18.421.
Full text
3
Lawson, G., S. McOrist, A. Rowland, E. McCartney, and L. Roberts. "Serological diagnosis of the porcine proliferative enteropathies: implications for aetiology and epidemiology." Veterinary Record 122, no. 23 (June 4, 1988): 554–57. http://dx.doi.org/10.1136/vr.122.23.554.
Full text
4
McOrist, Steven, Gordon H. K. Lawson, Douglas J. Roy, and Richard Boid. "DNA analysis of intracellular campylobacter-like organisms associated with the porcine proliferative enteropathies: novel organism proposed." FEMS Microbiology Letters 69, no. 3 (June 1990): 189–93. http://dx.doi.org/10.1111/j.1574-6968.1990.tb04227.x.
Full text
5
McOrist, S., R. Boid, and G. H. Lawson. "Antigenic analysis of Campylobacter species and an intracellular Campylobacter-like organism associated with porcine proliferative enteropathies." Infection and Immunity 57, no. 3 (1989): 957–62. http://dx.doi.org/10.1128/iai.57.3.957-962.1989.
Full text
6
McOrist, S., M. F. H. Shearn, and J. Morgan. "Control of porcine proliferative enteropathy by oral administration of chlortetracycline." Veterinary Record 144, no. 2 (January 9, 1999): 48–49. http://dx.doi.org/10.1136/vr.144.2.48.
Full text
7
Guedes, R. M. C., S. A. Franca, G. S. Machado, M. A. Blumer, and E. C. da Costa Cruz. "Use of tylvalosin-medicated feed to control porcine proliferative enteropathy." Veterinary Record 165, no. 12 (September 19, 2009): 342–45. http://dx.doi.org/10.1136/vr.165.12.342.
Full text
8
Lee, Sang Won, Tae Jong Kim, Seung Yong Park, Chang Sun Song, Hyung Kwan Chang, Jae Kil Yeh, Hye In Park, and Joong Bok Lee. "Prevalence of porcine proliferative enteropathy and its control with tylosin in Korea." Journal of Veterinary Science 2, no. 3 (2001): 209. http://dx.doi.org/10.4142/jvs.2001.2.3.209.
Full text
9
Holyoake, PK, A. Collins, M. Donahoo, R. Lising, and D. Emery. "Identifying obstacles to reducing the use of antibiotics to control porcine proliferative enteropathy." Australian Veterinary Journal 87, no. 1-2 (January 2009): 33–34. http://dx.doi.org/10.1111/j.1751-0813.2008.00372.x.
Full text
10
Otoni, Luisa V. A., Michelle P. Gabardo, Núbia R. Macêdo, Mariane M. Wagatsuma, Marina M. Pereira, and Roberto Maurício C. Guedes. "Tylosin injectable for the treatment of porcine proliferative enteropathy in experimentally inoculated pigs." Pesquisa Veterinária Brasileira 39, no. 3 (March 2019): 168–74. http://dx.doi.org/10.1590/1678-5150-pvb-6066.
Full textAbstract:
ABSTRACT: Porcine proliferative enteropathy (PPE) is one of the most common enteric diseases in growing and finishing pigs. PPE is characterized by reduced growth performance, accompanied or not by diarrhea. PPE is highly prevalent in several countries of the Americas, Europe and Asia, causing high economic losses in swine herds. The most common form of PPE control in pigs is antibiotic therapy. The objective of this study was to evaluate a new product based on tylosin injectable (Eurofarma Laboratórios S.A.) to control PPE in experimentally inoculated animals. Sixty 5-week-old pigs with mean weight of 9.5kg were divided into two experimental groups of 30 animals: medication and control. All pigs were challenged with Lawsonia intracellularis, the etiologic agent of PPE, on day zero. Fecal score, body condition score, and behavior were daily evaluated. Pigs were weighted on days -2, 13 and 21 of the experiment. Pigs in the Medication Group received tylosin injectable 13 days after inoculation, in three doses with a 12-hour interval between them. Pigs in the Control Group received injectable saline solution following the same protocol. In the Control Group, 23pigs presented with diarrhea before day 13. After day 13, the number of diarrheic animals in this group was reduced to 17. In the Medication Group, 26 pigs presented with diarrhea in the initial period, and in the period after medication, only 11 animals had diarrhea. The score of gross intestinal PPE lesions in the Medication Group was lower than that in the Control Group (p=0.031). The Medication Group also showed lower score for Lawsonia intracellularis antigen-labeling by immunohistochemistry compared with that of the Control Group (p=0.032), showing lower level of infection. These results demonstrate that tylosin injectable (Eurofarma Laboratórios S.A.), administrated in three doses (1mL/20kg) every 12 hours, was effective for the control of PPE in experimentally inoculated pigs.
11
Segalés, J., and M. Domingo. "Clinical presentation, epidemiological findings, diagnosis, immunity, prevention and control of postweaning multisystemic wasting syndrome (PMWS)." Proceedings of the British Society of Animal Science 2003 (2003): 223. http://dx.doi.org/10.1017/s1752756200013806.
Full textAbstract:
Postweaning multisystemic wasting syndrome (PMWS) was initially described in 1991 in Saskatchewan (Canada) and has now been described in all continents rearing pigs but Oceania. Porcine circovirus type 2 (PCV2) is the aetiology of this disease, which has also been called porcine circovirosis in some countries. Although the full spectrum of clinical signs and lesions observed in natural cases of PMWS is very difficult to reproduce under experimental infections using PCV2 alone, little doubt exists on the causal relationship between the virus and the wasting syndrome. Furthermore, the clinical and pathological scope of PCV2 infection has been expanded since 1991, and it has been implicated in other conditions: reproductive disorders, porcine dermatitis and nephropathy syndrome (PDNS), the so-called porcine respiratory disease complex (PRDC), proliferative and necrotising pneumonia (PNP), and congenital tremors. The role of PCV2 in these conditions has not been fully clarified and, in some of these cases, it remains as a controversial issue. The objective of this presentation is to review some practical aspects of PMWS.
12
Krüger, Leandi, Liara M. Gonzalez, Tiffany A. Pridgen, Shannon J. McCall, Richard J. von Furstenberg, Ivan Harnden, Gwendolyn E. Carnighan, Abigail M. Cox, Anthony T. Blikslager, and Katherine S. Garman. "Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair." American Journal of Physiology-Gastrointestinal and Liver Physiology 313, no. 3 (September 1, 2017): G180—G191. http://dx.doi.org/10.1152/ajpgi.00036.2017.
Full textAbstract:
Esophageal injury is a risk factor for diseases such as Barrett’s esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs. To test our hypothesis that ESMGs activate after esophageal injury with an increase in proliferation, generation of a ductal phenotype, and expression of SOX9, we developed a porcine model of esophageal injury and repair using radiofrequency ablation (RFA). The porcine esophagus contains ESMGs, and RFA produces a consistent and reproducible mucosal injury in the esophagus. Here we present a temporal assessment of this model of esophageal repair. Porcine esophagus was evaluated at 0, 6, 18, 24, 48, and 72 h and 5 and 7 days following RFA and compared with control uninjured esophagus. Following RFA, ESMGs demonstrated an increase in ductal phenotype, echoing our prior studies in humans. Proliferation increased in both squamous epithelium and ESMGs postinjury with a prominent population of SOX9-positive cells in ESMGs postinjury. This model promises to be useful in future experiments evaluating mechanisms of esophageal repair. NEW & NOTEWORTHY A novel porcine model of injury and repair using radiofrequency ablation has been developed, allowing for reproducible injury to the esophagus to study repair in an animal model with esophageal submucosal glands, a key anatomical feature and missing in rodent models but possibly harboring progenitor cells. There is a strong translational component to this porcine model given the anatomical and physiological similarities between pigs and humans.
13
Nygård, Ingvild Engdal, Kim Erlend Mortensen, Jakob Hedegaard, Lene Nagstrup Conley, Christian Bendixen, Baldur Sveinbjørnsson, and Arthur Revhaug. "Tissue Remodelling following Resection of Porcine Liver." BioMed Research International 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/248920.
Full textAbstract:
Aim.To study genes regulating the extracellular matrix (ECM) and investigate the tissue remodelling following liver resection in porcine.Methods.Four pigs with 60% partial hepatectomy- (PHx-) induced liver regeneration were studied over six weeks. Four pigs underwent sham surgery and another four pigs were used as controls of the normal liver growth. Liver biopsies were taken upon laparotomy, after three and six weeks. Gene expression profiles were obtained using porcine-specific oligonucleotide microarrays. Immunohistochemical staining was performed and a proliferative index was assessed.Results.More differentially expressed genes were associated with the regulation of ECM in the resection group compared to the sham and control groups. Secreted protein acidic and rich in cysteine (SPARC) and collagen 1, alpha 2 (COL1A2) were both upregulated in the early phase of liver regeneration, validated by immunopositive cells during the remodelling phase of liver regeneration. A broadened connective tissue was demonstrated by Masson’s Trichrome staining, and an immunohistochemical staining against pan-Cytokeratin (pan-CK) demonstrated a distinct pattern of migrating cells, followed by proliferating cell nuclear antigen (PCNA) positive nuclei.Conclusions.The present study demonstrates both a distinct pattern of PCNA positive nuclei and a deposition of ECM proteins in the remodelling phase of liver regeneration.
14
Bagby, S. P., E. A. Kirk, L. H. Mitchell, M. M. O'Reilly, W. E. Holden, P. E. Stenberg, and A. C. Bakke. "Proliferative synergy of ANG II and EGF in porcine aortic vascular smooth muscle cells." American Journal of Physiology-Renal Physiology 265, no. 2 (August 1, 1993): F239—F249. http://dx.doi.org/10.1152/ajprenal.1993.265.2.f239.
Full textAbstract:
To test growth effects of angiotensin II (ANG II) in porcine vascular smooth muscle cells (VSMC) and potential ANG II synergy with epidermal growth factor (EGF), we exposed subconfluent, near-quiescent porcine aortic VSMC to ANG II, EGF, or ANG II + EGF (each 10(-9) M) in Dulbecco's modified Eagle's-Ham's F-12 medium with insulin + 0.4% fetal calf serum (FCS) selected for minimal ANG II-degrading capacity. Cell number and DNA and protein synthesis (by [3H]-thymidine and [35S]methionine incorporation, respectively) were determined serially over 1-6 days. ANG II alone induced an early 20% increase and then a plateau in cell number over the 0.4% FCS control (P < 0.01; n = 8), thus without sustained increase in proliferation rate. Yet ANG II alone did not increase fractional DNA or protein synthesis (each as cpm/10(3) cells) and, by flow cytometry, reduced S phase fraction without increase in cell size. EGF alone induced brisk DNA synthesis yet minimal cell division over days 0-4, thus late-cycle arrest. ANG II + EGF, despite no increase in fractional DNA or protein synthesis rates over EGF alone, induced significant indomethacin-resistant dose-dependent (P < 0.001) increase in cell proliferation rate over EGF alone with a median effective dose of 5 x 10(-10) M ANG II, thus proliferative synergy. We propose that 1) ANG II induces a subpopulation of cells arrested in or beyond S phase to proceed through mitosis but does not influence G1 traversal or S phase entry and 2) ANG II + EGF achieve proliferative synergy by complementary actions at sequential cell cycle loci, with EGF supporting progression from G0/G1 to S phase and ANG II inducing completion of mitosis by cells already in or beyond S phase ("late-cycle completion").
15
Safley, Susan A., Judith A. Kapp, and Collin J. Weber. "Proliferative and Cytokine Responses in CTLA4-Ig-Treated Diabetic NOD Mice Transplanted with Microencapsulated Neonatal Porcine ICCs." Cell Transplantation 11, no. 7 (October 2002): 695–705. http://dx.doi.org/10.3727/000000002783985413.
Full textAbstract:
Our goal is to develop effective islet xenografts for treating human diabetes. We have studied microencapsulated neonatal porcine islet cell clusters (ICCs) transplanted intraperitoneally in spontaneously diabetic NOD mice, where they function to maintain normoglycemia in the autoimmune host. Nonencapsulated neonatal porcine ICCs functioned for 4.5 ± 0.5 days before being rejected; encapsulation prolonged graft function to 17 ± 2 days. CTLA4-Ig treatment did not enhance the survival of nonencapsulated ICCs. However, CTLA4-Ig treatment significantly extended the function of encapsulated ICCs to 73 ± 5 days. Histological analyses demonstrated a profuse pericapsular cellular reaction associated with rejection of encapsulated islet xenografts in untreated mice, while this reaction was significantly reduced in CTLA4-Ig-treated mice. To study mechanisms of xenograft rejection in this model, we analyzed proliferative responses to neonatal porcine ICCs and cytokines present in the peritoneal cavities of transplanted mice. Spleen cells from both CTLA4-Ig-treated and untreated rejecting NODs exhibited vigorous proliferation in the absence of antigenic stimulation, suggesting prior activation in vivo, while splenocytes from CTLA4-Ig-treated NODs with functioning grafts had low proliferative levels, equal to controls. Islet-specific proliferation was not detected in islet-rejecting mice, perhaps due to their high background levels. With the exception of elevated IL-6 levels, empty capsules did not provoke a significant peritoneal cytokine response compared with sham surgery or untransplanted control mice. However, IL-5, IL-12, TGF-β, and IL-1β were significantly elevated in NODs receiving encapsulated neonatal porcine ICCs compared with untransplanted controls. There were no significant differences between peritoneal cytokine concentrations in CTLA4-Ig-treated mice with long-term functioning grafts compared to mice that rejected grafts at earlier time points. We conclude that the combination of donor islet microencapsulation and brief treatment of the recipient with co-stimulatory blockade delays sensitization of the host, possibly by altering mechanism(s) for recruitment and/or activation of host effector cells.
16
Halbur, Patrick G., Prem S. Paul, Eric M. Vaughn, and John J. Andrews. "Experimental Reproduction of Pneumonia in Gnotobiotic Pigs with Porcine Respiratory Coronavirus Isolate AR310." Journal of Veterinary Diagnostic Investigation 5, no. 2 (April 1993): 184–88. http://dx.doi.org/10.1177/104063879300500207.
Full textAbstract:
The pathogenicity of porcine respiratory coronavirus (PRCV) isolate AR310 was determined for gnotobiotic pigs. PRCV-AR310 was isolated from the intestines of a nursery pig from a herd with endemic transmissible gastroenteritis. The AR310 isolate was plaque purified and cell culture propagated, passed once in a gnotobiotic pig, then used as inoculum for a gnotobiotic pig pathogenicity study. Eight pigs were inoculated oronasally with 2 × 106 plaque-forming units of PRCV-AR310. Eight pigs served as controls and received cell culture medium. Two pigs from each group were necropsied at 3, 5, 10, and 15 days postinoculation (DPI). There was moderate multifocal to coalescing reddish tan consolidation of 60% of the lung by 10 DPI. Microscopic examination revealed a necrotizing and proliferative bronchointerstitial pneumonia characterized by necrosis, squamous metaplasia, dysplasia, proliferation of airway epithelium, mononuclear cell infiltration of alveolar septa, mild type II pneumocyte proliferation, and lymphohistiocytic alveolar exudation. The microscopic lesions were mild by 3 DPI, moderate by 5 DPI, severe by 10 DPI, and mostly resolved by 15 DPI. No lesions were observed in the intestines of these pigs. There was no clinical respiratory disease. Control pigs remained normal and had no lesions. PRCV was isolated from the lungs but not from the intestines of inoculated pigs. PRCV was not isolated from the lungs or intestines of control pigs. PRCV was also isolated from the nasal and rectal swabs of inoculated but not of control pigs.
17
Levine, Richard, Magnus S. Agren, and Patricia M. Mertz. "Effect of Occlusion on Cell Proliferation during Epidermal Healing." Journal of Cutaneous Medicine and Surgery 2, no. 4 (April 1998): 193–98. http://dx.doi.org/10.1177/120347549800200403.
Full textAbstract:
Background: Occlusive dressings influence epithelization of superficial wounds by some unknown mechanism(s). Objective: The effects of occlusion on epidermal cell proliferation in two types of wounds were examined. Methods: Partial-thickness wounds and tape-stripped skin wounds were compared. An immunohistochemical technique, employing PC10 — a monoclonal antibody against proliferating cell nuclear antigen (PCNA) — was applied to formalin-fixed, paraffin-embedded porcine tissue sections. Results: The number of PC10-positive cells was low during the migratory phase, then increased to a peak of proliferation 2 to 3 days after resurfacing. An overall increased proliferative response (mean = 21%) was seen in occluded compared to control partial-thickness wounds (day 10 postoperatively); an opposite effect of occlusion on epidermal proliferation was seen in tape-stripped skin. Occlusion decreased the proliferative response (mean = 42%) compared to air-exposure. Conclusion: Occlusion increased epidermal cell proliferation in wounds (where the entire surface epithelium and papillary dermis was removed), whereas an opposite effect was seen in tape-stripped skin from which only the stratum corneum had been removed.
18
Guedes, Roberto M. C., Connie J. Gebhart, Nathan L. Winkelman, and Rebecca A. Mackie-Nuss. "A Comparative Study of an Indirect Fluorescent Antibody Test and an Immunoperoxidase Monolayer Assay for the Diagnosis of Porcine Proliferative Enteropathy." Journal of Veterinary Diagnostic Investigation 14, no. 5 (September 2002): 420–23. http://dx.doi.org/10.1177/104063870201400512.
Full textAbstract:
The currently used indirect fluorescent antibody test (IFAT) for the detection of antibodies against porcine proliferative enteropathy (PPE) was compared to an immunoperoxidase monolayer assay (IPMA). Serum samples used in this comparison were collected from 5-week-old pigs on day 0 (pre-experimental challenge) and on days 7, 14, 21, and 28 after oral inoculation with intestinal homogenate from pigs affected by PPE (28 challenged pigs) and sucrose phosphate glutamate solution (2 control pigs). All animals were euthanized 4 weeks after inoculation. Immunohistochemistry staining was applied to formalin-fixed, paraffin-embedded sections of ileum for the detection of Lawsonia intracellularis antigen. The serology results with each method agreed in all samples, except on days 0 and 7 in 1 control animal, which was positive by IPMA, but negative by IFAT. The percentage of agreement between IFAT and IPMA was 98.6%.
19
Gonkowski, Sławomir, Piotr Burliński, Piotr Szwajca, and Jarosław Całka. "Changes in Cocaine- and Amphetamine-Regulated Transcript-Like Immunoreactive (CART-LI) Nerve Structures of the Porcine Descending Colon During Proliferative Enteropathy." Bulletin of the Veterinary Institute in Pulawy 56, no. 2 (June 1, 2012): 199–203. http://dx.doi.org/10.2478/v10213-012-0036-y.
Full textAbstract:
Abstract The distribution pattern of CART- like immunoreactive (CART-LI) nerve structures was studied by a double immunofluorescence technique in the circular muscle layer, myenteric (MP), outer submucous (OSP), and inner submucous plexuses (ISP), as well as in the mucosal layer of porcine descending colon under physiological conditions and during proliferative enteropathy (PE). In control animals, CART-LI perikarya have been shown to constitute 3.18 ±0.51%, 3.44 ±0.6%, and 3.33 ±0.72% in MP, OSP, and ISP, respectively. PE caused a decrease in the number of CART - LI neurons in MP and ISP. In OSP, the observed changes were not statistically significant. During PE, the number of CART-LI perikarya amounted to 2.18 ±0.27%, 3.07 ±0.06%, and 0.07 ±0.02% within MP, OSP, and ISP, respectively. Moreover, PE caused an increase in the number of CART-LI nerve fibers in the colonic circular muscle and mucosal layers as well as in MP. This study describes for the first time changes in CART-LI nerve structures of the porcine descending colon during Lawsonia intracellularis infection, and suggests the participation of this neuropeptide in the regulation of gut functions, not only under physiological conditions, but also during pathological processes.
20
Bowles, D. K., K. K. Maddali, V. C. Dhulipala, and D. H. Korzick. "PKCδ mediates anti-proliferative, pro-apoptic effects of testosterone on coronary smooth muscle." American Journal of Physiology-Cell Physiology 293, no. 2 (August 2007): C805—C813. http://dx.doi.org/10.1152/ajpcell.00127.2007.
Full textAbstract:
Sex hormone status has emerged as an important modulator of coronary physiology and cardiovascular disease risk in both males and females. Our previous studies have demonstrated that testosterone increases protein kinase C (PKC) δ expression and activity in coronary smooth muscle (CSMC). Because PKCδ has been implicated in regulation of proliferation and apoptosis in other cell types, we sought to determine if testosterone modulates CSMC proliferation and/or apoptosis through PKCδ. Porcine CSMC cultures (passages 2–6) from castrated males were treated with testosterone for 24 h. Testosterone (20 and 100 nM) decreased [3H]thymidine incorporation in proliferating CSMC to 59 ± 5.3 and 33.1 ± 4.5% of control. Flow cytometric analysis demonstrated that testosterone induced G1arrest in CSMC with a concomitant reduction in the S phase cells. Testosterone reduced protein levels of cyclins D1and E and phosphorylation of retinoblastoma protein while elevating levels of p21cip1and p27kip1. There were no significant differences in the levels of cyclins D3, CDK2, CDK4, or CDK6. Testosterone significantly reduced kinase activity of CDK2 and -6, but not CDK4, -7, or -1. PKCδ small interfering RNA (siRNA) prevented testosterone-mediated G1arrest, p21cip1upregulation, and cyclin D1and E downregulation. Furthermore, testosterone increased CSMC apoptosis in a dose-dependent manner, which was blocked by either PKCδ siRNA or caspase 3 inhibition. These findings demonstrate that the anti-proliferative, pro-apoptotic effects of testosterone on CSMCs are substantially mediated by PKCδ.
21
Pidsudko, Z., K. Wasowicz, J. Kaleczyc, M. Majewski, and M. Lakomy. "Proliferative enteropathy (PPE)-induced changes in the expression of DBH, VAChT and NOS in the neurons of intramural ganglia of the porcine ileum." Veterinární Medicína 53, No. 10 (November 4, 2008): 533–42. http://dx.doi.org/10.17221/1964-vetmed.
Full textAbstract:
As enteric neurons are regarded to be highly adaptive in their response to various pathological states, including inflammation, it appears to be of interest to study the chemical coding of neurons in the intramural ganglia of the ileum wall in the course of porcine proliferative enteropathy (PPE) evoked by <I>Lawsonia intracellularis.</I> The study was performed on 12 juvenile pigs of the Large White Polish breed. The pigs were divided into the control (C, <I>n</I> = 6) group and the group consisting of pigs with clinically diagnosed <I>Lawsonia intracellularis</I> infection (E, <I>n</I> = 6). In E group animals the infection was confirmed with a PCR-based test. All the animals were sacrificed and segments of the ileum being pathologically changed were processed for double-labelling immunofluorescence using antibody against protein gene-product 9.5 (PGP 9.5) combined with antibody for dopamine β-hydroxylase (DβH), vesicular acetylcholine transporter (VAChT) or nitric oxide synthase (NOS). Immunohistochemistry revealed in the inner submucous plexus (ISP) and outer submucous plexus (OSP) an increase of the number of neurons containing DβH and VAChT in the E group. Interestingly, a decrease in the number of DβH- and VAChT-positive neurons in meynteric plexus (MP) ganglia of the E group animals was observed. The most remarkable difference in the chemical coding of enteric neurons between the control and PPE-suffering pigs was a significant increase of the number of NOS-positive nerve cells in the MP and OSP of the infected animals. The present results show that acetylcholine, catecholamines and NO may be involved in the regulation of functions of the porcine enteric nerve pathways not only under physiological, but also pathological conditions.
22
Zhang, Huawei, Wei Wen, Genxi Hao, Huanchun Chen, Ping Qian, and Xiangmin Li. "A Subunit Vaccine Based on E2 Protein of Atypical Porcine Pestivirus Induces Th2-type Immune Response in Mice." Viruses 10, no. 12 (November 28, 2018): 673. http://dx.doi.org/10.3390/v10120673.
Full textAbstract:
An atypical porcine pestivirus (APPV) causing congenital tremor type A-II in piglets was identified in China in 2016. An increased number of cases of APPV have been reported in various countries all over the world since 2015. This study aimed to develop an effective subunit vaccine against APPV based on the E2 protein, which is the main immunogenicity protein of APPV. In this study, E2 protein was successfully expressed by the baculovirus expression system. E2 protein was confirmed by Western blot assay, which showed that E2 protein possesses N-linked glycosylation sites. The immunogenicity of E2 subunit vaccine was evaluated in mice. The E2 protein emulsified with ISA 201VG adjuvant induced significantly higher levels of APPV-specific antibodies and elicited stronger lymphocyte proliferative responses and higher interleukin-10 secretion than those of the E2 protein emulsified with IMS 1313VG adjuvant. This observation indicates that the E2 subunit vaccine induces a Th2-type immune response. Our results showed that E2 protein can be developed as a safe and effective subunit vaccine for the control of APPV infection.
23
Marcinčáková, D., M. Kolesárová, M. Falis, Ch Horn, M. Miłek, and J. Legáth. "Potential Role of Agrimonia eupatoria L. Extract in Cell Protection Against Toxicity Induced by Bisphenol A." Folia Veterinaria 66, no. 1 (March 1, 2022): 33–41. http://dx.doi.org/10.2478/fv-2022-0004.
Full textAbstract:
Abstract The aim of this study is to reveal the potentially protective role of ethanolic extract of agrimony (Agrimonia eupatoria L.) against the cytotoxic effect of bisphenol A (BPA) in vitro, using an intestinal porcine epithelial cell line (IPEC-1). The cells were exposed to different concentrations of BPA: 12.5, 25, 50, 100, and 200 µg.ml–1 alone and in combination with agrimony extract (250 µg.ml–1). The proliferative cell response was monitored for 72 h by a xCELLigence system or real-time cell analyser (RTCA), recorded as the cell index (CI) and expressed as a proliferative activity (% PA) compared to the control cells without treatment. The metabolic activity was measured by a MTS colorimetric test, performed after 48 h of treatment with the tested substances. The cytotoxic effect on cells exposed to BPA alone, in comparison to the control cells without treatment, was observed in both assays (P < 0.0001). It was confirmed that BPA reduces both the metabolic activity and the proliferation of cells. After the cell treatment with agrimony, the metabolic activity had increased to reach over the control (101.52 %), while reducing the proliferation of the cells. The protective role of agrimony against cytotoxicity caused by BPA was observed after cell treatment with agrimony in combination with lower concentrations of BPA (12.5; 25 and 50 µg.ml–1). The slight improvement in the adherence was observed in cells treated with these combinations, in comparison to the cells treated with BPA alone. On the other hand, the metabolic activity was slightly improved in cells treated with a combination of agrimony and BPA at higher concentrations (50 a 100 µg.ml–1). This supported our assumption that agrimony can protect a model organism against cytotoxicity caused by BPA.
24
Huang, Chi-Ping, Chi-Cheng Chen, Yi-Tung Tsai, Chun-Chie Wu, and Chih-Rong Shyr. "Intravesical Administration of Xenogeneic Porcine Urothelial Cells Attenuates Cyclophosphamide-Induced Cystitis in Mice." Cell Transplantation 28, no. 3 (January 24, 2019): 296–305. http://dx.doi.org/10.1177/0963689718822773.
Full textAbstract:
The urothelium of the bladder, renal pelvis, ureter and urethra is maintained through the regulated proliferation and differentiation of urothelial stem and progenitor cells. These cells provide a rich source of a novel urothelial cell therapy approach that could be used to protect, regenerate, repair and restore a damaged urothelium. Urothelial injury caused by physical, chemical and microbial stress is the pathological basis of cystitis (bladder inflammation). The loss of urothelial integrity triggers a series of inflammatory events, resulting in pain and hematuria such as hemorrhage cystitis and interstitial cystitis. Here we investigate a novel cell therapy strategy to treat cystitis by protecting the urothelium from detrimental stresses through intravesically instilling porcine urothelial cells (PUCs) into the bladder. Using a chemical-induced urothelial injury mouse model of cyclophosphamide (CPP)-induced hemorrhagic cystitis, we determined how the intravesical instillation of PUCs could protect the urothelium from toxic attack from CPP metabolites. We show that intravesical PUC instillation protected the bladder from toxic chemical attack in mice receiving CPP with reduced inflammation and edema. Compared with the vehicle control mice, the proliferative response to chemical injury and apoptotic cells within the bladder tissues were reduced by intravesical PUC treatment. Furthermore, the urothelium integrity was maintained in the intravesical PUC-treated group. After xenogeneic PUCs were introduced and adhered to the mouse urothelium, immunological rejection responses were observed with increased neutrophil infiltration in the lamina propria and higher immune-related gene expression. Our findings provide an innovative and promising intravesical PUC cell therapy for cystitis with urothelial injury by protecting the urothelium from noxious agents.
25
Szczotka-Bochniarz, Anna, Jacek Karamon, Agnieszka Nowak, Marian Porowski, Paweł Karbowiak, Andrzej Holeniewski, and Zygmunt Pejsak. "Balantidium coli in pig farms suspected of porcine circovirus type 2 (PCV2) associated enteritis." Journal of Veterinary Research 65, no. 4 (October 26, 2021): 425–30. http://dx.doi.org/10.2478/jvetres-2021-0057.
Full textAbstract:
Abstract Introduction Diarrhoea in growing-finishing pigs is a common problem of commercial pig farms. Among many causative factors, porcine circovirus type 2 (PCV2) is one considered an important pathogen in modern pig production. The aim of the study was to verify if PCV2 was responsible for antibiotic non-responsive diarrhoea and wasting in pigs. Material and Methods A total of 13 dead pigs aged between 12 and 15 weeks from three Polish farms with persistent herd symptoms suggestive of PCV2 infection were provided for evaluation. Sections of lymph nodes and intestines were analysed by in situ hybridization (ISH) for PCV2 and histopathological examination. Faeces and intestinal scrapings were tested for Lawsonia intracellularis and Brachyspira hyodysenteriae by real-time PCR and for parasitic infection by flotation and decantation. Results ISH and histopathological examination showed that all pigs were PCV2 systemic disease negative. Swine dysentery was confirmed by real-time PCR on two farms, and proliferative enteropathy on one farm. In histological examinations, erosions of the caecal and colonic mucosa were found, together with cysts and trophozoites of Balantidium coli. The protozoa were present in the intestinal lumen and mucosa. B. coli cysts were identified in faeces from all examined pigs. Conclusion These results suggest that monitoring of B. coli infections should be an additional measure of control and prevention of gastrointestinal tract disorders in modern swine husbandry.
26
Taylor, W. R., and R. W. Alexander. "Autocrine control of wound repair by insulin-like growth factor I in cultured endothelial cells." American Journal of Physiology-Cell Physiology 265, no. 3 (September 1, 1993): C801—C805. http://dx.doi.org/10.1152/ajpcell.1993.265.3.c801.
Full textAbstract:
The repair process of the vascular endothelium is modulated by growth factors from both endogenous (within the vessel wall) and exogenous (blood borne) sources. We utilized a tissue culture model of endothelial wounding to gain further insight into the potential autocrine control of proliferation during wound repair. Cultured porcine aortic endothelial monolayers were mechanically wounded by passing a 7-mm sterile glass rod over the surface of the culture. Proliferation at the wound edge was quantified using [3H]thymidine autoradiography. In wounded cultures incubated in media supplemented with 10% fetal calf serum, 81 +/- 2% of the nuclei at the wound edge were labeled. When the cultures were incubated in serum-free media, proliferation at the wound edge was only slightly diminished with 65 +/- 3% (P < 0.05) of the cells labeled. These findings raise the possibility that there is a significant contribution from autocrine growth factors to endothelial wound repair. To evaluate the potential role of insulin-like growth factor I (IGF-I) in the wound repair process, we used a radioimmunoassay to measure IGF-I secretion. Wounded cultures exhibited a 187 +/- 58% increase in IGF-I production when compared with nonwounded cultures (P < 0.05). To determine the extent to which endogenous IGF-I mediates the proliferative response of endothelial cell monolayers to wounding, wounded cultures were incubated with inactivating concentrations of IGF-I antibody. When IGF-I antibody was present in the culture media, only 26 +/- 3% of the nuclei at the wound edge were labeled with [3H]thymidine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
27
Bagby, S. P., M. M. O'Reilly, E. A. Kirk, L. H. Mitchell, P. E. Stenberg, M. T. Makler, and A. C. Bakke. "EGF is incomplete mitogen in porcine aortic smooth muscle cells: DNA synthesis without cell division." American Journal of Physiology-Cell Physiology 262, no. 3 (March 1, 1992): C578—C588. http://dx.doi.org/10.1152/ajpcell.1992.262.3.c578.
Full textAbstract:
To characterize growth effects of epidermal growth factor (EGF) in subconfluent quiescent porcine aortic vascular smooth muscle cells (VSMC), we measured DNA and protein synthesis by [3H]thymidine (Thd) and [35S]methionine (Met) incorporation, respectively, and cell proliferation rates over 0-6 days in Dulbecco's modified Eagle's-Ham's F-12 media containing 0.4% fetal calf serum (FCS) and insulin. EGF induced dose-dependent [3H]Thd uptake (P less than 0.001); after 10(-9) M EGF, DNA synthesis rate peaked at 24 h, averaging 77% of the response to 10% FCS, and then declined steeply with nadir at 48-60 h. Unexpectedly, EGF failed to induce cell proliferation in the first 4 days, leaving this initial burst of DNA synthesis (12-60 h) uncoupled from cell division. A second lesser but sustained phase of increased DNA synthesis, apparent by day 3-4, was associated with a small increase in cell number on day 6 (P less than 0.05). The early unsustained burst of DNA synthesis reflects EGF's potent mitogenic efficacy for DNA synthesis (G1- to S-phase traversal), probably acting on a subset of cells partially synchronized initially at an EGF-responsive G0/G1 locus; the minimal cell division despite brisk DNA synthesis documents EGF's limited efficacy for (or inhibition of) late cell-cycle events required for completion of mitosis. Late cell-cycle processes are thus rate limiting. EGF also increased protein synthetic rate over control (P less than 0.03) but to a lesser degree (P less than 0.01) than 10% FCS. Indomethacin (10(-6) M) did not alter DNA or proliferative responses to 10(-9) M EGF but transiently augmented EGF-induced protein synthesis (P less than 0.025) at 24 h only.(ABSTRACT TRUNCATED AT 250 WORDS)
28
Cowin, A. J., E. L. Heaton, S. H. Cheshire, and S. P. Bidey. "The proliferative responses of porcine thyroid follicular cells to epidermal growth factor and thyrotrophin reflect the autocrine production of transforming growth factor-β1." Journal of Endocrinology 148, no. 1 (January 1996): 87–94. http://dx.doi.org/10.1677/joe.0.1480087.
Full textAbstract:
Abstract The present study has investigated an involvement of autocrine transforming growth factor-β1 (TGF-β1) in regulating the proliferative response of porcine thyroid follicular cells (TFCs) to epidermal growth factor (EGF) and TSH. Primary monolayer TFC cultures exposed to EGF over the range 0–0·4 nmol/l showed a dose-dependent increase in [methyl-3H]thymidine incorporation, whereas higher EGF doses were associated with a reduction in the level of [methyl-3 H]thymidine incorporation. TGF-β immunoneutralisation had little effect on the stimulatory action of low EGF doses, but led to an increase in [methyl-3H]thymidine incorporation at higher EGF levels. In TFC cultures exposed to TSH, the level of [methyl-3H]thymidine incorporation attained at a dose of 1 U TSH/1 was enhanced in the presence of TGF-β1 antiserum, although the similar stimulatory effect of 8-bromo cAMP was unaffected. Treatment of TFCs with phorbol 12-myristate 13-acetate (8 nmol/l) to activate protein kinase C (PKC) led to an enhanced incorporation of [methyl-3H]thymidine which was increased further after neutralisation of endogenous TGF-β1. While confirming, therefore, a role for autocrine TGF-β1 in maintaining control of TFC DNA synthesis in vitro, these findings provide evidence that an increase in the availability of autocrine TGF-β1 effected by EGF and TSH may play an instrumental role in limiting the cellular hyperplasia induced by these factors within the thyroid follicular microenvironment. Moreover, the present data also suggest that the availability of active autocrine TGF-β1 to TFCs under such conditions may be dependent upon a PKC-mediated mechanism. Journal of Endocrinology (1996) 148, 87–94
29
Brandt, John E., Amelia M. Bartholomew, Jeffrey D. Fortman, Mary C. Nelson, Edward Bruno, Luci M. Chen, Julius V. Turian, Thomas A. Davis, John P. Chute, and Ronald Hoffman. "Ex Vivo Expansion of Autologous Bone Marrow CD34+ Cells With Porcine Microvascular Endothelial Cells Results in a Graft Capable of Rescuing Lethally Irradiated Baboons." Blood 94, no. 1 (July 1, 1999): 106–13. http://dx.doi.org/10.1182/blood.v94.1.106.413k01_106_113.
Full textAbstract:
Hematopoietic stem cell (HSC) self-renewal in vitro has been reported to result in a diminished proliferative capacity or acquisition of a homing defect that might compromise marrow repopulation. Our group has demonstrated that human HSC expanded ex vivo in the presence of porcine microvascular endothelial cells (PMVEC) retain the capacity to competitively repopulate human bone fragments implanted in severe combined immunodeficiency (SCID) mice. To further test the marrow repopulating capacity of expanded stem cells, our laboratory has established a myeloablative, fractionated total body irradiation conditioning protocol for autologous marrow transplantation in baboons. A control animal, which received no transplant, as well as two animals, which received a suboptimal number of marrow mononuclear cells, died 37, 43, and 59 days postirradiation, respectively. Immunomagnetically selected CD34+ marrow cells from two baboons were placed in PMVEC coculture with exogenous human cytokines. After 10 days of expansion, the grafts represented a 14-fold to 22-fold increase in cell number, a 4-fold to 5-fold expansion of CD34+ cells, a 3-fold to 4-fold increase of colony-forming unit–granulocyte-macrophage (CFU-GM), and a 12-fold to 17-fold increase of cobblestone area-forming cells (CAFC) over input. Both baboons became transfusion independent by day 23 posttransplant and achieved absolute neutrophil count (ANC) >500/μL by day 25 ± 1 and platelets >20,000/μL by day 29 ± 2. This hematopoietic recovery was delayed in comparison to two animals that received either a graft consisting of freshly isolated, unexpanded CD34+ cells or 175 × 106/kg unfractionated marrow mononuclear cells. Analysis of the proliferative status of cells in PMVEC expansion cultures demonstrated that by 10 days, 99.8% of CD34+ cells present in the cultures had undergone cycling, and that the population of cells expressing a CD34+ CD38− phenotype in the cultures was also the result of active cell division. These data indicate that isolated bone marrow CD34+ cells may undergo cell division during ex vivo expansion in the presence of endothelial cells to provide a graft capable of rescuing a myeloablated autologous host.
30
Tora, Muhibullah S., Kecheng Lei, Purva P. Nagarajan, David P. Bray, Rima S. Rindler, Stewart G. Neill, Michelle Zhang, et al. "MODL-28. DEVELOPING A STRATEGY FOR MODELING HIGH-GRADE GLIOMA IN GӦTTINGEN MINIPIGS." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii297. http://dx.doi.org/10.1093/neuonc/noac209.1155.
Full textAbstract:
Abstract BACKGROUND The current literature does not describe a reproducible large animal model of intracranial high-grade glioma (HGG). Prior work has demonstrated the feasibility of inducing HGG de-novo in rodents by targeting specific oncogenic pathways. Here we report our approach to the production of supratentorial HGG in a series of minipigs through lentiviral gene transfer and subsequent initial characterization of a porcine glioma cell line. METHODS Four minipigs received injections into the subcortical white matter using a combination of lentiviral vectors expressing platelet-derived growth factor beta (PDGF-B), HRAS, and shRNA-p53. Animals underwent behavioral monitoring through porcine neurobehavioral scoring (PNS) and veterinary monitoring. Magnetic resonance imaging (MRI) was conducted at endpoint prior to necropsy. Post-mortem tissue biopsies underwent tissue culture and neuropathologic evaluation with hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescent staining. Data are presented using appropriate statistical tests where relevant and descriptive statistics. RESULTS Two pigs received 50ul injections and reached endpoint by the end of post-operative week 1 and 2. Two pigs received 25 ul injections and were asymptomatic until a pre-determined endpoint of 4 weeks. MRI scans at endpoint demonstrated contrast enhancing, mass forming lesions at the site of injection with evidence of hemorrhage and perilesional edema, consistent with high-grade glioma. On H&E staining high-grade glioma growth was identified in 100% of animals. We observed immunopositivity for tumor markers GFAP, OLIG2, NG2, SOX2, and PDGFRA, as well as redox markers, and microenvironmental features consistent with high-grade glioma. Porcine glioma cell cultures were found to have significantly greater proliferative rate compared to control, and demonstrated GFAP, OLIG2, PDGFRA, and CD68 immunopositivity. CONCLUSIONS Lentiviral gene transfer represents a feasible strategy for glioma modeling in the Gӧttingen minipig. With our described methodology, we present a realistic strategy for reproducible modeling of intracranial glioma as a platform for preclinical neurosurgical development programs.
31
Dommisch, H., KN Stolte, J. Jager, K. Vogel, R. Müller, S. Hedtrich, M. Unbehauen, R. Haag, and K. Danker. "Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa." Clinical Oral Investigations 25, no. 10 (April 5, 2021): 5795–805. http://dx.doi.org/10.1007/s00784-021-03884-x.
Full textAbstract:
Abstract Objectives Topical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal tissues, and thereby, increase the bioavailability of topically applied drugs. Material and methods To evaluate adhesion and penetration, the fluorescence-labeled CMS 10-E-15-350 nanocarrier was applied to ex vivo porcine masticatory and lining mucosa in a Franz cell diffusion assay and to an in vitro 3D model. In gingival epithelial cells, potential cytotoxicity and proliferative effects of the nanocarrier were determined by MTT and sulphorhodamine B assays, respectively. Transepithelial electrical resistance (TEER) was measured in presence and absence of CMS 10-E-15-350 using an Endohm-12 chamber and a volt-ohm-meter. Cellular nanocarrier uptake was analyzed by laser scanning microscopy. Inflammatory responses were determined by monitoring pro-inflammatory cytokines using real-time PCR and ELISA. Results CMS nanocarrier adhered to mucosal tissues within 5 min in an in vitro model and in ex vivo porcine tissues. The CMS nanocarrier exhibited no cytotoxic effects and induced no inflammatory responses. Furthermore, the physical barrier expressed by the TEER remained unaffected by the nanocarrier. Conclusions CMS 10-E-15-350 adhered to the oral mucosa and adhesion increased over time which is a prerequisite for an efficient drug release. Since TEER is unaffected, CMS nanocarrier may enter the oral mucosa transcellularly. Clinical relevance Nanocarrier technology is a novel and innovative approach for efficient topical drug delivery at the oral mucosa.
32
Hilker, Renée Emily, Bo Pan, Xiaoshu Zhan, and Julang Li. "MicroRNA-21 enhances estradiol production by inhibiting WT1 expression in granulosa cells." Journal of Molecular Endocrinology 68, no. 1 (January 1, 2022): 11–22. http://dx.doi.org/10.1530/jme-21-0162.
Full textAbstract:
In antral follicles, the transition of proliferative granulosa cells to estradiol-producing is critical for proper oocyte maturation. MicroRNAs are noncoding RNAs that play important roles in ovarian follicular development; however, this has yet to be fully characterized. MicroRNA-21 is significantly higher in granulosa cells isolated from large antral follicles compared to those from small antral follicles. To investigate the function of miR-21, porcine granulosa cells were transfected with miR-21 mimic or miR-21 targeted siRNA. Cells with the miR-21 mimic had higher aromatase expression and estradiol production but decreased WT1 expression. Conversely, cells with the miR-21 siRNA secreted less estradiol and had higher WT1 expression. We hypothesized that miR-21 promotes estradiol production by inhibiting WT1 protein synthesis. We found a potential miR-21 binding site in the 3’UTR of the WT1 transcript and performed a dual-luciferase reporter assay using the WT and mutated 3’UTR. Compared to the negative control, the miR-21 mimic induced a significant decrease in luciferase activity in the WT 3’UTR. This decrease was reversed when the 3’UTR was mutated, suggesting miR-21 targets this site to inhibit WT1 expression. We next transfected porcine granulosa cells with WT1 targeted siRNA and observed a significant increase in aromatase expression and estradiol secretion. We propose that miR-21 represses WT1 expression in granulosa cells to potentially promote aromatase expression and estradiol production. This study offers the first report of a microRNA regulating WT1 expression in granulosa cells and reveals the role of miR-21 in WT1’s regulation of estradiol production.
33
Guevarra, Robin B., Jae Hyoung Cho, Jin Ho Cho, Jun Hyung Lee, Hyeri Kim, Sheena Kim, Eun Sol Kim, et al. "Oral Vaccination against Lawsoniaintracellularis Changes the Intestinal Microbiome in Weaned Piglets." Animals 11, no. 7 (July 13, 2021): 2082. http://dx.doi.org/10.3390/ani11072082.
Full textAbstract:
Lawsoniaintracellularis, which causes porcine proliferative enteropathy (PPE), is a common swine intestinal pathogen that is prevalent in pig production sites worldwide. In this study, the alteration in the microbiome composition of weaned pigs was investigated in response to vaccination against L. intracellularis, using 16S rRNA gene sequencing. A total of 64 crossbred (Duroc × [Landrace × Yorkshire]) healthy weanling pigs weaned at 4 weeks of age were randomly assigned to four treatment groups (four pigs/pen; four pens/treatment), using a randomized complete block design for the 42-day trial. Pigs in the treatment groups were orally administered with three different doses (1 dose = 2 mL) of vaccine against L. intracellularis (Enterisol® Ileitis, Boehringer Ingelheim Vetmedica GmbH), namely the following: LAW1 (0.5 dose), LAW2 (1 dose), LAW3 (2 dose). A non-vaccinated group served as a negative control (CONT). Alpha diversity analysis revealed that vaccination led to significant changes in species evenness but not species richness of the gut microbiota. Beta diversity analysis revealed that vaccination against L. intracellularis caused a significant shift in the microbial community structure. At the genus level, there was a significant increase in Streptococcus and a significant decrease in Clostridium in the fecal microbiota of vaccinated pigs, regardless of dose.
34
Cooper, V. L., A. R. Doster, R. A. Hesse, and N. B. Harris. "Porcine Reproductive and Respiratory Syndrome: NEB-1 PRRSV Infection did not Potentiate Bacterial Pathogens." Journal of Veterinary Diagnostic Investigation 7, no. 3 (July 1995): 313–20. http://dx.doi.org/10.1177/104063879500700303.
Full textAbstract:
A 2-phase study was conducted to evaluate the ability of the NEB-1 strain of porcine reproductive and respiratory syndrome virus (PRRSV) to potentiate common bacterial pathogens of swine. In phase I, 25 of 50 4-5-week-old specific-pathogen-free (SPF) pigs were exposed to NEB-1 PRRSV (day 0). Seven days after virus inoculation, 8 groups received 1 of 4 bacterial pathogens: Haemophihs parasuis, Streptococcus suis, Salmonella cholerasuis, and Pasteurella multocida. The ability of NEB-1 PRRSV to produce clinical disease, viremia, neutralizing antibody, gross and microscopic lesions and to potentiate bacterial pathogens was assessed. Response to NEB-1 PRRSV was similar among inoculated pigs; prolonged hyperthermia, lethargy, mild to moderate dyspnea, and cutaneous erythema were consistent clinical signs. No clinical differences were observed in groups after bacterial challenge. Virus was isolated from serum at weekly intervals through the end of the study, and all PRRSV-inoculated pigs had seroconverted by study termination. Two of 5 pigs died in non-PRRSV-inoculated groups challenged with H. parasuis and Streptococcus suis. Mortality in PRRSV-infected pigs was limited to 1 of 5 pigs from the Salmonella cholerasuis-challenged group. Gross lesions were seen in pigs dying after inoculation in H. parasuis- and Streptococcus suis-inoculated groups, in Salmonella cholerasuis-and P. multocida-challenged pigs, and in 1 non-PRRSV-inoculated control pig. Microscopic lesions consisted of mild to moderate proliferative interstitial pneumonia, nonsuppurative myocarditis, lymphoid hyperplasia, and nonsuppurative encephalitis in PRRSV-inoculated pigs. Findings in phase I indicated that NEB-1 PRRSV does not potentiate bacterial disease while inducing consistent clinical signs, viremia, seroconversion, and microscopic lesions. Based upon initial findings in phase I, in phase II, 18 of 36 4-6-week-old SPF pigs were exposed to NEB-1 PRRSV (day 0). Two days after virus inoculation, 2 of 4 groups were exposed to either Streptococcus suis or P. multocida. Clinical findings were similar to those of phase I. One of 6 pigs died in each of the Streptococcus suis-challenged groups. Animals succumbed 3 and 5 days after bacterial challenge in the non-PRRSV-inoculated and PRRSV-inoculated groups, respectively. Mild gross and microscopic pulmonary lesions were observed. Phase II findings support the conclusions of phase I that NEB-1 PRRSV does not potentiate certain bacterial infections of swine.
35
Marks, Hannah, Łukasz Grześkowiak, Beatriz Martinez-Vallespin, Heiko Dietz, and Jürgen Zentek. "Porcine and Chicken Intestinal Epithelial Cell Models for Screening Phytogenic Feed Additives—Chances and Limitations in Use as Alternatives to Feeding Trials." Microorganisms 10, no. 3 (March 16, 2022): 629. http://dx.doi.org/10.3390/microorganisms10030629.
Full textAbstract:
Numerous bioactive plant additives have shown various positive effects in pigs and chickens. The demand for feed additives of natural origin has increased rapidly in recent years to support the health of farm animals and thus minimize the need for antibiotics and other drugs. Although only in vivo experiments can fully represent their effect on the organism, the establishment of reliable in vitro methods is becoming increasingly important in the goal of reducing the use of animals in experiments. The use of cell models requires strict control of the experimental conditions so that reliability and reproducibility can be achieved. In particular, the intestinal porcine epithelial cell line IPEC-J2 represents a promising model for the development of new additives. It offers the possibility to investigate antioxidative, antimicrobial, anti- or pro-proliferative and antiviral effects. However, the use of IPEC-J2 is limited due to its purely epithelial origin and some differences in its morphology and functionality compared to the in vivo situation. With regard to chickens, the development of a reliable intestinal epithelial cell model has attracted the attention of researchers in recent years. Although a promising model was presented lately, further studies are needed to enable the standardized use of a chicken cell line for testing phytogenic feed additives. Finally, co-cultivation of the currently available cell lines with other cell lines and the development of organoids will open up further application possibilities. Special emphasis was given to the IPEC-J2 cell model. Therefore, all publications that investigated plant derived compounds in this cell line were considered. The section on chicken cell lines is based on publications describing the development of chicken intestinal epithelial cell models.
36
Li, D., V. J. Hall, K. Freude, M. Rasmussen, and P. Hyttel. "203 IDENTIFICATION OF A POTENTIAL MULTILINEAGE-DIFFERENTIATING STRESS ENDURING CELL POPULATION IN PORCINE FETAL FIBROBLASTS." Reproduction, Fertility and Development 25, no. 1 (2013): 250. http://dx.doi.org/10.1071/rdv25n1ab203.
Full textAbstract:
Physiologically, humans and pigs are very similar, which makes cell model systems such as porcine-induced pluripotent stem (iPS) cells an attractive model for studying human diseases. Recently, it has been shown that a finite population of cells, termed multilineage-differentiating stress enduring (MUSE) cells, which are particularly prone for reprogramming, exists in human fibroblasts. Human MUSE cells co-express the cell surface markers, SSEA-3 and CD105; however, it is unknown if a similar subpopulation of cells exists in porcine fibroblasts. Therefore, we examined the expression level of varying cell surface markers, including SSEA-1, SSEA-3, CD105, and Vimentin (positive control), in 9 porcine fetal fibroblast lines from 3 different breed backgrounds (Danish Landrace lines 2, 4, 5; Gottingen minipig lines A1, B2, B3; Yucatan minipig lines 1, 3, 4) by performing chromogen immunocytochemistry. The results revealed that all the 9 cell lines were 100% positive for Vimentin and negative for SSEA-3. However, a small positive population of SSEA-1 cells could be detected in Danish Landrace lines 2, 4, 5 (0.267%, 0.441%, 0.292%, respectively) and in Gottingen minipig lines A1, B2, B3 (0.207%, 0.214%, 0.325%, respectively). Furthermore, CD105 could only be detected in the Yucatan minipig lines (0.170, 0.177, and 0.233%, in lines 1, 3, and 4, respectively). To identify if any of these lines were more receptive to reprogramming, we performed non-integrating vector-based reprogramming. A total of 1 × 105 cells from each cell line was electroporated with 3 episomal plasmids (pCXLE-hOCT3/4-shp53; pCXLE-hSK; pCXLE-hUL), which were diluted to 1 µg µL–1, and then plated in DMEM-AQ + 10% FBS without antibiotics. The medium was replaced with the addition of penicillin/streptomycin on Day 2, and on Day 7 cells were trypsinized and passaged onto mitomycin C-treated mouse embryonic fibroblasts in iPS culture medium (DMEM-F12 + 20%KSR + NEAA + Pen/strep + 2 µL mL–1 β-Me + 10 ng mL–1 bFGF). Only a select number of Danish Landrace lines 2 and 4 formed ES-like colonies after 14 days, and few colonies with neural-like morphology emerged in Yucatan minipig line 3, but all these colonies lost their proliferative potential after a few passages. The reprogramming efficiency observed on Day 21 was 0.0787, 0.0170, and 0.0033% for Danish Landrace 2, Danish Landrace 4, and Yucatan 3 lines, respectively. The NANOG immunostaining was also performed at passage 1, and a minor proportion of the colonies in Danish Landrace line 2 was found to contain small populations of cells with nuclear staining for NANOG. Interestingly, Danish Landrace lines 2 and 4, which formed ES-like colonies, also expressed SSEA1, which may suggest that SSEA1 could potentially be a marker of a MUSE cell population. Further studies are ongoing to investigate this hypothesis. This research may further support the elite hypothesis for how reprogramming may occur.
37
Lebedeva, I., O. Mityashova, A. Smekalova, E. Montvila, G. Singina, and A. Lopukhov. "172 Expression of proliferation and apoptosis markers in cumulus cells surrounding matured and aged oocytes exposed to luteotropic factors during the second phase of in vitro maturation." Reproduction, Fertility and Development 31, no. 1 (2019): 210. http://dx.doi.org/10.1071/rdv31n1ab172.
Full textAbstract:
The quality and developmental capacity of mammalian oocytes depends on cooperation with surrounding cumulus cells. The functional state and activity of cumulus cells changes with oocyte maturation, especially during the oocyte transition from metaphase I (MI) to metaphase II (MII) stage. In the present work, effects of 3 luteotropic factors, progesterone (P4), prolactin (PRL), and LH, during the second phase of in vitro maturation (IVM) on the subsequent expression of proliferation and apoptosis markers in bovine cumulus cells surrounding matured and aged oocytes were studied. A total of 1532 cumulus-oocyte complexes (COC) were cultured for 12h in TCM-199 containing 10% fetal calf serum (FCS), 10μg mL−1 porcine FSH, and 10μg mL−1 ovine LH at 38.5°C and 5% CO2. Thereafter, COC were transferred to the following IVM systems: (1) TCM-199 containing 10% FCS (Control 1) and (2) a monolayer of granulosa cells (GC) precultured for 12h in TCM-199 containing 10% FCS (Control 2). In both systems, the medium of experimental groups was supplemented with either P4 (50 ng mL−1) or bovine PRL (50ng mL−1) or ovine LH (5μg mL−1); then, the COC were matured for next 12h. Half of the COC matured for 12h in both systems were cultured for an additional 24h in fresh TCM-199 containing 10% FCS to test long-term hormonal effects during oocyte aging. After culture, the cumulus expression of the proliferation marker proliferating cell nuclear antigen (PCNA) and the pro-apoptotic markers caspase-3 and Bax was assessed by the immunocytochemical method. The data from 4 to 5 replicates using 84 to 106 COC per treatment were analysed by ANOVA. After IVM in System 1, the rate of PCNA-positive cumulus cells was higher (P<0.05) in the PRL-treated group (41.3±1.6%) than in the control (34.6±2.3%) or LH-treated group (29.9±2.9%), but did not differ from that in the P4-treated group (38.2±4.8%). In the presence of GC (System 2), the respective rates did not change but were more variable. Aging of COC matured in both systems led to a 1.4- to 1.9-fold reduction in the proportion of the cells containing the proliferation marker PCNA (P<0.05). Meanwhile, none of the hormones tested had any long-term effect on the proliferative activity of senescent cumulus cells. The rate of cumulus cells expressing caspase-3 in different groups varied from 48.5±4.9 to 53.8±5.8% and did not depend on the hormones, IVM system, or oocyte aging. The proportion of the Bax-positive cells was also unaffected by luteotropic factors but increased 1.4 to 1.6 times (P<0.01) following 24h of COC aging. Our findings indicate that PRL can exert a short-term stimulatory action on the proliferative activity of bovine cumulus cells in the course of the second phase of IVM. Meanwhile, the cumulus expression of pro-apoptotic markers caspase-3 and Bax is not responsive to P4, PRL, or LH during the second step of IVM. The study was supported by the Russian Science Foundation (project 16-16-10069).
38
Antonson, Adrienne M., Bindu Balakrishnan, Emily C. Radlowski, Geraldine Petr, and Rodney W. Johnson. "Altered Hippocampal Gene Expression and Morphology in Fetal Piglets following Maternal Respiratory Viral Infection." Developmental Neuroscience 40, no. 2 (2018): 104–19. http://dx.doi.org/10.1159/000486850.
Full textAbstract:
Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) at gestational day (GD) 76 and the fetuses were removed by cesarean section at GD 111 (3 days before anticipated parturition). The gilts infected with PRRSV had elevated plasma interleukin-6 levels and developed transient febrile and anorectic responses lasting approximately 21 days. Despite having a similar overall body weight, fetuses from the PRRSV-infected gilts had a decreased brain weight and altered hippocampal gene expression compared to fetuses from control gilts. Notably, maternal infection caused a reduction in estimated neuronal numbers in the fetal dentate gyrus and subiculum. The number of proliferative Ki-67+ cells was not altered, but the relative integrated density of GFAP+ staining was increased, in addition to an increase in GFAP gene expression, indicating astrocyte-specific gliosis. Maternal viral infection caused an increase in fetal hippocampal gene expression of the inflammatory cytokines TNF-α and IFN-γ and the myelination marker myelin basic protein. MHCII protein, a classic monocyte activation marker, was reduced in microglia, while expression of the MHCII gene was decreased in hippocampal tissue of the fetuses from PRRSV-infected gilts. Together, these data suggest that maternal viral infection at the beginning of the last trimester results in a reduction in fetal hippocampal neurons that is evident 5 weeks after infection, when fetal piglets are near full term. The neuronal reduction was not accompanied by pronounced neuroinflammation at GD 111, indicating that any activation of classic neuroinflammatory pathways by maternal viral infection, if present, is mostly resolved by parturition.
39
Copeland, Katherine M., Bryn L. Brazile, J. Ryan Butler, Jim Cooley, Erin Brinkman-Ferguson, Andrew Claude, Sallie Lin, et al. "Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model." Bioengineering 9, no. 8 (August 18, 2022): 401. http://dx.doi.org/10.3390/bioengineering9080401.
Full textAbstract:
Researchers have shown that adult zebrafish have the potential to regenerate 20% of the ventricular muscle within two months of apex resection, and neonatal mice have the capacity to regenerate their heart after apex resection up until day 7 after birth. The goal of this study was to determine if large mammals (porcine heart model) have the capability to fully regenerate a resected portion of the left ventricular apex during the neonatal stage, and if so, how long the regenerative potential persists. A total of 36 piglets were divided into the following groups: 0-day control and surgical groups and seven-day control and surgical groups. For the apex removal groups, each piglet was subjected to a partial wall thickness resection (~30% of the ventricular wall thickness). Heart muscle function was assessed via transthoracic echocardiograms; the seven-day surgery group experienced a decrease in ejection fraction and fractional shortening. Upon gross necropsy, for piglets euthanized four weeks post-surgery, all 0-day-old hearts showed no signs of scarring or any indication of the induced injury. Histological analysis confirmed that piglets in the 0-day surgery group exhibited various degrees of regeneration, with half of the piglets showing full regeneration and the other half showing partial regeneration. However, each piglet in the seven-day surgery group demonstrated epicardial fibrosis along with moderate to severe dissecting interstitial fibrosis, which was accompanied by an abundant collagenous extracellular matrix as the result of a scar formation in the resection site. Histology of one 0-day apex resection piglet (briefly lain on and accidentally killed by the mother sow three days post-surgery) revealed dense, proliferative mesenchymal cells bordering the fibrin and hemorrhage zone and differentiating toward immature cardiomyocytes. We further examined the heart explants at 5-days post-surgery (5D PO) and 1-week post-surgery (1W PO) to assess the repair progression. For the 0-day surgery piglets euthanized at 5D PO and 1W PO, half had abundant proliferating mesenchymal cells, suggesting active regeneration, while the other half showed increased extracellular collagen. The seven-day surgery piglets euthanized at 5D PO, and 1W PO showed evidence of greatly increased extracellular collagen, while some piglets had proliferating mesenchymal cells, suggesting a regenerative effort is ongoing while scar formation seems to predominate. In short, our qualitative findings suggest that the piglets lose the full myocardial regenerative potential by 7 days after birth, but greatly preserve the regenerative potential within 1 day post-partum.
40
Gerst, Felicia, Elisabeth Kemter, Estela Lorza-Gil, Gabriele Kaiser, Ann-Kathrin Fritz, Rita Nano, Lorenzo Piemonti, et al. "The hepatokine fetuin-A disrupts functional maturation of pancreatic beta cells." Diabetologia 64, no. 6 (March 25, 2021): 1358–74. http://dx.doi.org/10.1007/s00125-021-05435-1.
Full textAbstract:
Abstract Aims/hypothesis Neonatal beta cells carry out a programme of postnatal functional maturation to achieve full glucose responsiveness. A partial loss of the mature phenotype of adult beta cells may contribute to a reduction of functional beta cell mass and accelerate the onset of type 2 diabetes. We previously found that fetuin-A, a hepatokine increasingly secreted by the fatty liver and a determinant of type 2 diabetes, inhibits glucose-stimulated insulin secretion (GSIS) of human islets. Since fetuin-A is a ubiquitous fetal glycoprotein that declines peripartum, we examined here whether fetuin-A interferes with the functional maturity of beta cells. Methods The effects of fetuin-A were assessed during in vitro maturation of porcine neonatal islet cell clusters (NICCs) and in adult human islets. Expression alterations were examined via microarray, RNA sequencing and reverse transcription quantitative real-time PCR (qRT-PCR), proteins were analysed by western blotting and immunostaining, and insulin secretion was quantified in static incubations. Results NICC maturation was accompanied by the gain of glucose-responsive insulin secretion (twofold stimulation), backed up by mRNA upregulation of genes governing beta cell identity and function, such as NEUROD1, UCN3, ABCC8 and CASR (Log2 fold change [Log2FC] > 1.6). An active TGFβ receptor (TGFBR)–SMAD2/3 pathway facilitates NICC maturation, since the TGFBR inhibitor SB431542 counteracted the upregulation of aforementioned genes and de-repressed ALDOB, a gene disallowed in mature beta cells. In fetuin-A-treated NICCs, upregulation of beta cell markers and the onset of glucose responsiveness were suppressed. Concomitantly, SMAD2/3 phosphorylation was inhibited. Transcriptome analysis confirmed inhibitory effects of fetuin-A and SB431542 on TGFβ-1- and SMAD2/3-regulated transcription. However, contrary to SB431542 and regardless of cMYC upregulation, fetuin-A inhibited beta cell proliferation (0.27 ± 0.08% vs 1.0 ± 0.1% Ki67-positive cells in control NICCs). This effect was sustained by reduced expression (Log2FC ≤ −2.4) of FOXM1, CENPA, CDK1 or TOP2A. In agreement, the number of insulin-positive cells was lower in fetuin-A-treated NICCs than in control NICCs (14.4 ± 1.2% and 22.3 ± 1.1%, respectively). In adult human islets fetuin-A abolished glucose responsiveness, i.e. 1.7- and 1.1-fold change over 2.8 mmol/l glucose in control- and fetuin-A-cultured islets, respectively. In addition, fetuin-A reduced SMAD2/3 phosphorylation and suppressed expression of proliferative genes. Of note, in non-diabetic humans, plasma fetuin-A was negatively correlated (p = 0.013) with islet beta cell area. Conclusions/interpretation Our results suggest that the perinatal decline of fetuin-A relieves TGFBR signalling in islets, a process that facilitates functional maturation of neonatal beta cells. Functional maturity remains revocable in later life, and the occurrence of a metabolically unhealthy milieu, such as liver steatosis and elevated plasma fetuin-A, can impair both function and adaptive proliferation of beta cells. Data availability The RNAseq datasets and computer code produced in this study are available in the Gene Expression Omnibus (GEO): GSE144950; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144950 Graphical abstract
41
Lima, A. S., S. A. Malusky, M. R. B. Mello, S. J. Lane, J. R. Rivera, and M. B. Wheeler. "200 TRANSPLANTATION AND IN VIVO DIFFERENTIATION OF ADIPOSE-DERIVED STEM CELLS IN SWINE." Reproduction, Fertility and Development 18, no. 2 (2006): 208. http://dx.doi.org/10.1071/rdv18n2ab200.
Full textAbstract:
A primary concern in stem cell biology is that observations made in vitro may be an artifact of the in vitro culture environment. In vitro derived stem cells can be implanted into the environment from which they are derived so that their response to physiological conditions may be observed. Several important cellular characteristics need to be examined following the cell's reintroduction to the in vivo environment, including the potential for differentiation, proliferative ability, and life span. Studying implanted stem cells will assist in determining the potential for stem cell use in clinical therapies and provide further understanding of the role adult stem cells have in the adult body. Currently, the scientific literature is lacking a detailed description of the cellular response of adipose-derived stem cells (ADSCs) reintroduced to their exact tissue of origin. Thus, the aim of this study was to evaluate porcine ADSC growth in vivo and to analyze cell differentiation in vivo following injection of undifferentiated ADSCs into subcutaneous fat. Subcutaneous adipose tissue was isolated from the back fat of male pigs (11 months of age) and digested with 0.075% collagenase at 37�C for 90 min. The digested tissue was centrifuged at 200g for 10 min to obtain a cell pellet. The pellet was re-suspended with DMEM and the ADSCs were plated onto 75 cm2 flasks (5000-10 000 cells per cm2) and cultured in DMEM supplemented with 10% fetal bovine serum (FBS) and 1% gentamicin. Passage 3 ADSCs were labeled with fluorescent dye (PKH26; Sigma, St. Louis, MO, USA) and sorted by flow cytometry. After sorting, positive cells were washed and re-suspended in culture medium. For transplantation, 100 �L of cell suspension in DMEM containing one of four cell concentrations (0 (control); 30 000; 300 000; and 900 000 cells) were placed in a 1-mL syringe and injected into the subcutaneous back fat of recipient pigs (n = 2). Each pig had previously been tattooed with 12 13 � 13 squares to mark injection sites. The treatments were replicated three times within each animal. Two and three weeks after transplantation, animals were euthanized, the back fat containing the transplantation site was harvested, and the cells were disaggregated as described above. The buoyant adipocytes and pelleted ADSCs cells were then analyzed by flow cytometry. The results indicated that there were dose- and time-dependent increases in labeled ADSCs and labeled adipocytes in the fat samples with increasing cell number (from 0 to 300 000 cells). There was, however, a decrease in labeled ADSCs at the 900 000-cell dose, which is likely due to excess cells being transplanted or an immune reaction. Both of these aspects are currently being evaluated. In conclusion, undifferentiated ADSCs from swine can be isolated from and returned to the subcutaneous adipose layer and differentiate into mature adipocytes. This work was supported by the Council for Food and Agricultural Research (C-FAR) Sentinel Program, University of Illinois.
42
Tao, Yu, Rui Yang, Jianhong Shu, Wenqian Zheng, Jian Chen, Yuehong Wu, and Yulong He. "Immune responses induced by a combined vaccination with a recombinant chimera of Mycoplasma hyopneumoniae antigens and capsid virus-like particles of porcine circovirus type 2." BMC Veterinary Research 16, no. 1 (September 16, 2020). http://dx.doi.org/10.1186/s12917-020-02560-8.
Full textAbstract:
Abstract Background Mycoplasma hyopneumoniae (Mhp) and porcine circovirus type 2 (PCV2) are two important pathogens causing Mycoplasma pneumonia of swine (MPS) and porcine circovirus diseases and porcine circovirus-associated diseases (PCVDs/PCVADs), respectively, and resulted in considerable economic loss to the swine industry worldwide. Currently, vaccination is one of the main measures to control these two diseases; however, there are few combination vaccines that can prevent these two diseases. To determine the effect of combination immunization, we developed capsid-derived (Cap) virus-like particles (VLPs) of PCV2 and a new recombinant chimera composed of the P97R1, P46, and P42 antigens of Mhp. Then we investigated the immune responses induced by the immunization with this combination vaccine in mice and piglets. Results The high level antibodies against three protein antigens (P97R1, P46, and P42 of Mhp) were produced after immunization, up to or higher than 1:400,000; the antibody levels in Pro group continuously increased throughout the 42 days for all the antigens tested. The lymphocyte proliferative response in PCV2 group was stronger than that in PBS, VP, Mhp CV in mice. The antibody levels for Cap remained stable and reached the peak at 35 DAI. The IFN-γ and IL-4 in sera were significantly enhanced in the Pro group than that in the negative control-VP group on Day 14 and 28 post-the first immunization in piglets. Conclusions Above all, the combination immunization could induce humoral and cellular immune responses against all four antigens in mice and piglets. Therefore, our approach is a simple and effective vaccination strategy to protect pigs against MPS and PCVD/PCVAD.
43
Maegdefessel, Lars, Junya Azuma, Ryuji Toh, Alicia Deng, Denis Merk, Azad Raiesdana, Nicholas J. Leeper, et al. "Abstract 255: Induction of microRNA-21 Inhibits Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion." Arteriosclerosis, Thrombosis, and Vascular Biology 32, suppl_1 (May 2012). http://dx.doi.org/10.1161/atvb.32.suppl_1.a255.
Full textAbstract:
Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRs) are crucial regulators of cardiovascular pathology, and represent possible targets for the inhibition of AAA expansion. We identified miR-21 as a key modulator of proliferation and apoptosis in developing AAA in two established murine models: porcine-pancreatic-elastase, and angiotensin II-infusion. In both models, miR-21 increased with AAA development. Lentiviral overexpression of miR-21 (pre-21) induced cell proliferation and decreased apoptosis in the aortic wall, with protective effects on aneurysm expansion (as shown in Picrosirius Red stained images in the attached Figure below). miR-21 overexpression substantially decreased phosphatase and tensin homolog (PTEN), leading to increased levels of p-AKT, a known pro-proliferative and anti-apoptotic pathway. Systemic injection of a locked-nucleic-acid-modified antagomiR targeting miR-21 (anti-21) diminished the pro-proliferative impact of down-regulated PTEN, leading to significantly increased AAA size as compared to scrambled-control-miR (scr-miR). Importantly, similar results were seen in nicotine-augmented murine AAAs, while parallel findings were observed in human aortic tissue samples from patients undergoing surgical AAA repair (with more pronounced effects in smokers). In vitro studies using human aortic smooth muscle cells, fibroblasts as well as endothelial cells identified NFκB signaling pathways as the key regulator of miR-21 induction. Modulation of miR-21 expression shows great potential as a novel and powerful therapeutic option to limit AAA disease progression.
44
Stewart, Amy Stieler, Cecilia Renee Schaaf, Jennifer A. Luff, John M. Freund, Thomas C. Becker, Sara R. Tufts, James B. Robertson, and Liara M. Gonzalez. "HOPX+ injury-resistant intestinal stem cells drive epithelial recovery after severe intestinal ischemia." American Journal of Physiology-Gastrointestinal and Liver Physiology, September 22, 2021. http://dx.doi.org/10.1152/ajpgi.00165.2021.
Full textAbstract:
Intestinal ischemia is a life-threatening emergency with mortality rates of 50-80% due to epithelial cell death and resultant barrier loss.Loss of the epithelial barrier occurs in conditions including intestinal volvulus and neonatal necrotizing enterocolitis.Survival depends on effective epithelial repair; crypt-based intestinal epithelial stem cells (ISCs) are the source of epithelial renewal in homeostasis and after injury. Two ISC populations have been described: 1) active ISC [aISC; highly proliferative; leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5+) positive or sex-determining region Y-box 9 -antigen Ki67 positive (SOX9+Ki67+)] and 2) reserve ISC [rISC; less proliferative; homeodomain-only protein X positive (HOPX+)].The contributions of these ISCs have been evaluated both in vivo andin vitrousing a porcine model of mesenteric vascular occlusion to understand mechanisms that modulate ISC recovery responses following ischemic injury. In our previously published work, we observed that rISC conversion to an activated state was associated with decreased HOPXexpression during in vitrorecovery. In the present study, we wished to evaluate the direct role of HOPXon cellular proliferation during recovery after injury. Our data demonstrated that during early in vivo recovery, injury-resistant HOPX+cells maintain quiescence. Subsequent early regeneration within the intestinal crypt occurs around 2 days post injury, a period in which HOPX expression decreased. When HOPX was silenced in vitro,cellular proliferation of injured cells was promoted during recovery. This suggests that HOPXmay serve a functional role in ISC mediated regeneration after injury and could be a target to control ISC proliferation.