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1.
Birth Defects Res ; 116(4): e2310, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563145

RESUMO

INTRODUCTION: In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA. METHODS: Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress. RESULTS: An increase of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals. CONCLUSION: The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.


Assuntos
Transtorno Autístico , Ácido Valproico , Gravidez , Ratos , Masculino , Feminino , Animais , Ácido Valproico/toxicidade , Transtorno Autístico/induzido quimicamente , Antioxidantes/metabolismo , Ratos Wistar , Eixo Encéfalo-Intestino , Estresse Oxidativo , Interleucina-6
2.
Vet World ; 17(2): 470-479, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595672

RESUMO

Background and Aim: Over the last decades, the poultry industry has experienced steady growth. Although the industry is gradually expanding in Indonesia, poultry feed production has always been expensive. There is a need to study alternative ingredients to obtain affordable feed from natural resources. Chaetomorpha linum (CL) is an abundant macroalgae available throughout the year in Indonesia. This study aimed to determine the effect of CL on the histological structure of the small intestine, pectoralis muscle, growth performance, and meat quality of broilers. Materials and Methods: This study used 300-day-old chick (DOC) male broilers that were reared until they were 21 days old. This study used a completely randomized design with four treatment groups and five replications, and each replication group contained 15 DOC individuals. The treatment groups consisted of Control (CON), CON basal feed (BF), CL1 (0.75%/kg BF), CL2 (1.5%/kg BF), and CL3 (3%/kg BF) groups. The histological structure of the small intestine, pectoralis muscle, growth performance, and meat quality of the broiler was examined. Results: Small intestine and pectoral muscle histomorphology, growth performance, and meat quality were significantly improved in the CL2 (1.5%) and CL3 (3%) groups compared with the CL1 (0.75%) and CON groups. Conclusion: Dietary CL supplementation ameliorates small intestine and pectoral muscle histomorphology, growth performance, and meat quality of broilers.

3.
Front Microbiol ; 15: 1352586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596375

RESUMO

Introduction: Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported. Methods: By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography-tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome. Results: PINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi. Conclusion: We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.

4.
Semin Cardiothorac Vasc Anesth ; : 10892532241247122, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598365

RESUMO

This review highlights noteworthy literature published in 2023 and pertinent to anesthesiologists and critical care physicians caring for patients undergoing abdominal organ transplantation. We feature 9 studies from 593 peer-reviewed papers on pancreatic transplantation, 3 from 194 on intestinal transplantation, and 28 from over 4513 on kidney transplantation. The liver transplantation section includes a special focus on 20 studies from 5666 clinical trial publications. We explore a broad range of topics, including donor management, perioperative recipient management, and innovative pharmacologic and mechanical interventions tested for the improvement of patient and graft outcomes and survival.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38593468

RESUMO

Lysophosphatidic acid (LPA) is a bioactive lipid molecule that regulates a wide array of cellular functions, including proliferation, differentiation, and survival, via activation of cognate receptors. The LPA5 receptor is highly expressed in the intestinal epithelium, but its function in restoring intestinal epithelial integrity following injury has not been examined. Here, we use a radiation-induced injury model to study the role of LPA5 in regulating intestinal epithelial regeneration. Control mice (Lpar5f/f) and mice with an inducible, epithelial cell-specific deletion of Lpar5 in the small intestine (Lpar5IECKO) were subjected to 10 Gy total body X-ray irradiation and analyzed during recovery. Repair of the intestinal mucosa was delayed in Lpar5IECKO mice, with reduced epithelial proliferation and increased crypt cell apoptosis. These effects were accompanied by reduced numbers of OLFM4+ intestinal stem cells (ISCs). The effects of LPA5 on ISCs were corroborated by studies using organoids derived from Lgr5-lineage tracking reporter mice with deletion of Lpar5 in Lgr5+-stem cells (Lgr5Cont or Lgr5ΔLpar5). Irradiation of organoids resulted in fewer numbers of Lgr5ΔLpar5 organoids retaining Lgr5+-derived progenitor cells compared to Lgr5Cont organoids. Finally, we observed that impaired regeneration in Lpar5IECKO mice was associated with reduced numbers of Paneth cells and decreased expression of YAP, a critical factor for intestinal epithelial repair. Our study highlights a novel role for LPA5 in regeneration of the intestinal epithelium following irradiation and its effect on the maintenance of Paneth cells that support the stem cell niche.

6.
Front Vet Sci ; 11: 1374803, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585300

RESUMO

In the present study, we propose the use of swabs in non-lethal sampling procedures to collect the mucosa-adhered gut microbiota from the posterior intestine of fish, and therefore, we compare the bacterial communities collected by conventional scraping and by swabbing methods. For this purpose, samples of the posterior intestine of rainbow trout (Oncorhynchus mykiss) were collected first using the swabbing approach, and after fish euthanasia, by mucosa scraping. Finally, bacterial communities were compared by 16S rRNA gene Illumina sequencing. Results from the current study revealed that similar values of bacterial richness and diversity were found for both sampling procedures. Similarly, there were no differences between procedures when using qualitative metrics (Jaccard and unweighted UniFrac) for estimating inter-individual diversity, but the quantitative metrics (Bray-Curtis and weighted UniFrac) showed a higher dispersion when samples were obtained by swabbing compared to scraping. In terms of bacterial composition, there were differences in abundance for the phyla Firmicutes and Proteobacteria. The cause of these differential abundances may be the inability of the swab to access to certain areas, such as the basal region of the intestinal villi. Moreover, swabbing allowed a higher representation of low abundant taxa, which may also have an important role in host microbiome regardless of their low abundance. Overall, our results demonstrate that the sampling method is a factor to be considered in experimental design when studying gut bacterial communities to avoid potential biases in the interpretation or comparison of results from different studies. In addition, the advantages and disadvantages of each procedure (swabbing vs scraping) are discussed in detail, concluding that swabbing can be implemented as a reliable and non-lethal procedure for posterior gut microbiota studies, which is of particular interest for animal welfare and the 3Rs principle, and may offer a wide range of novel applications.

7.
Food Sci Biotechnol ; 33(6): 1413-1423, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38585556

RESUMO

Animal intestines is considered as a source of lactic acid bacteria (LAB) that have potential to decrease the nitrite level during fermentation of food such as pickles. It was hypothesized that optimized level of LAB has a high capacity to degrade nitrite during Chinese pickle fermentation and benefit a higher acceptability of the Chinese pickle product. This study aims to investigate the performance of a goose intestine-isolated LAB strain G6 under the species Lactiplantibacillus plantarum as a starter culture of Chinese pickles. The results showed that Lactiplantibacillus sp. G6 had a nitrite degradation rate close to 100% under the MRS broth condition of 25 °C, 2% inoculum volume and pH at 5. As a starter culture for Chinese pickle, this strain was able to achieve a higher LABs amount, lower nitrite residue after fermentation, compared with the group without the starter, which implicates its feasibility of applying on fermented food for reducing nitrite level. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01433-8.

8.
Biochim Biophys Acta Mol Cell Res ; 1871(5): 119711, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38574824

RESUMO

Enterotoxigenic Escherichia coli (ETEC) is recognized globally as a major gastrointestinal pathogen that impairs intestinal function. ETEC infection can lead to oxidative stress and disruption of intestinal integrity. The present study investigated the mechanism of increased oxidative stress and whether restoration of antioxidant defense could improve intestinal integrity in a piglet model with ETEC infection. Weaned piglets were divided into three groups: control, ETEC-infection and ETEC-infection with antibiotic supplementation. The infection caused a significant elevation of serum diamine oxidase activity and D-lactate levels coupled with a reduced intestinal (mid-jejunum) tight-junction protein expression, suggesting increased intestinal permeability and impaired gut function. The infection also inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) activation, decreased the expression of glutathione synthesizing enzymes, superoxide dismutase-1 (SOD1), and heme oxygenase-1 (HO-1) in the intestine. This led to a decreased antioxidant glutathione level and an increased lipid peroxidation in the intestine and serum, indicating oxidative stress. The infection stimulated the expression of pro-inflammatory cytokines (IL-6, TNF-α). Antibiotic supplementation attenuated oxidative stress, in part, through restoration of glutathione levels and antioxidant enzyme expression in the intestine. Such a treatment enhanced tight-junction protein expression and improved intestinal function. Furthermore, induction of oxidative stress in Caco2 cells by hydrogen peroxide inhibited tight-junction protein expression and stimulated inflammatory cytokine expression. Glutathione supplementation effectively attenuated oxidative stress and restored tight-junction protein expression. These results suggest that downregulation of Nrf2 activation may weaken antioxidant defense and increase oxidative stress in the intestine. Mitigation of oxidative stress can improve intestinal function after infection.

9.
Clin Immunol ; 263: 110202, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38575045

RESUMO

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

10.
Fish Physiol Biochem ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625479

RESUMO

Supplementing a fishmeal-free diet with yeast extract improves rainbow trout (Oncorhynchus mykiss) growth performance and modulates the hepatic and intestinal transcriptomic response. These effects are often observed in the long term but are not well documented after short periods of fasting. Fasting for a few days is a common practice in fish farming, especially before handling the fish, such as for short sorting, tank transfers, and vaccinations. In the present study, rainbow trout were subjected to a 4-day fast and then refed, for 8 days, a conventional diet containing fishmeal (control diet) or alternative diets composed of terrestrial animal by-products supplemented or not with a yeast extract. During the refeeding period alone, most of the parameters considered did not differ significantly in response to the different feeds. Only the expression of claudin-15 was upregulated in fish fed the yeast-supplemented diet compared to the control diet. Conversely, fasting followed by refeeding significantly influenced most of the parameters analyzed. In the proximal intestine, the surface area of villi significantly increased, and the density of goblet cell tended to decrease during refeeding. Although no distinct plasma immune response or major signs of gut inflammation were observed, some genes involved in the structure, complement pathway, antiviral functions, coagulation, and endoplasmic reticulum stress response of the liver and intestine were significantly regulated by refeeding after fasting. These results indicate that short-term fasting, as commonly practiced in fish farming, significantly alters the physiology of the liver and intestine regardless of the composition of the diet.

11.
Pediatr Transplant ; 28(3): e14744, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38566341

RESUMO

BACKGROUND: There is limited data in the literature about pediatric kidney transplant (KT) following gut transplant (GT). The purpose of this study is to highlight the technical challenges and outcomes of KT in pediatric gut recipients who developed kidney failure (KF). METHODS: A retrospective single-center study of pediatric GT recipients from January 2000 to December 2019 was performed. In total, 14 (7%) out of 206 pediatric GT recipients developed KF and were listed for KT. Ten patients underwent kidney after gut transplant (KAGT), three patients underwent simultaneous kidney and re-do gut transplant (SKAGT), and one patient died on the KT waitlist. RESULTS: 1-, 5-, and 10-year kidney graft survival was 100%, 91%, and 78%, respectively. 1-, 5-, and 10-year GT graft survival was 100%, 77%, and 77%, respectively. 1-, 5-, and 10-year patient survival was 100%, 91%, and 91%, respectively. CONCLUSION: Despite the technical complexity, KAGT and SKAGT for pediatric GT recipients that develop KF can be performed with favorable outcomes.


Assuntos
Transplante de Rim , Humanos , Criança , Estudos Retrospectivos , Transplantados , Sobrevivência de Enxerto
12.
World J Methodol ; 14(1): 89723, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38577199

RESUMO

BACKGROUND: Excessive saturated fat intake compromises the integrity of the intestinal mucosa, leading to low-grade inflammation, impaired mucosal integrity, and increased intestinal permeability, resulting in the migration of lipopolysaccharide (LPS) to other tissues. AIM: To evaluate the chronic effects (at 10 and 16 wk) of a high-fat diet (HFD) (with 50% energy as fat) on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice. METHODS: Forty adult male mice were divided into four nutritional groups, where the letters refer to the type of diet (control and HFD or HF) and the numbers refer to the period (in weeks) of diet administration: Control diet for 10 wk, HFD for 10 wk, control diet for 16 wk, and HFD for 16 wk. After sacrifice, biochemical, molecular, and stereological analyses were performed. RESULTS: The HF groups were overweight, had gut dysbiosis, had a progressive decrease in occludin immunostaining, and had increased LPS concentrations. Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group, consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake. CONCLUSION: Chronic HFD intake causes overweight, gut dysbiosis, and morphological and functional alterations of the intestinal barrier after 10 or 16 wk. Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.

13.
BMC Genomics ; 25(1): 341, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575858

RESUMO

BACKGROUND: Parasitic nematodes, significant pathogens for humans, animals, and plants, depend on diverse organ systems for intra-host survival. Understanding the cellular diversity and molecular variations underlying these functions holds promise for developing novel therapeutics, with specific emphasis on the neuromuscular system's functional diversity. The nematode intestine, crucial for anthelmintic therapies, exhibits diverse cellular phenotypes, and unraveling this diversity at the single-cell level is essential for advancing knowledge in anthelmintic research across various organ systems. RESULTS: Here, using novel single-cell transcriptomics datasets, we delineate cellular diversity within the intestine of adult female Ascaris suum, a parasitic nematode species that infects animals and people. Gene transcripts expressed in individual nuclei of untreated intestinal cells resolved three phenotypic clusters, while lower stringency resolved additional subclusters and more potential diversity. Clusters 1 and 3 phenotypes displayed variable congruence with scRNA phenotypes of C. elegans intestinal cells, whereas the A. suum cluster 2 phenotype was markedly unique. Distinct functional pathway enrichment characterized each A. suum intestinal cell cluster. Cluster 2 was distinctly enriched for Clade III-associated genes, suggesting it evolved within clade III nematodes. Clusters also demonstrated differential transcriptional responsiveness to nematode intestinal toxic treatments, with Cluster 2 displaying the least responses to short-term intra-pseudocoelomic nematode intestinal toxin treatments. CONCLUSIONS: This investigation presents advances in knowledge related to biological differences among major cell populations of adult A. suum intestinal cells. For the first time, diverse nematode intestinal cell populations were characterized, and associated biological markers of these cells were identified to support tracking of constituent cells under experimental conditions. These advances will promote better understanding of this and other parasitic nematodes of global importance, and will help to guide future anthelmintic treatments.


Assuntos
Anti-Helmínticos , Nematoides , Humanos , Animais , Caenorhabditis elegans , Intestinos , Nematoides/genética , Perfilação da Expressão Gênica , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico
14.
BMC Biol ; 22(1): 76, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581018

RESUMO

BACKGROUND: The gut microbiota, vital for host health, influences metabolism, immune function, and development. Understanding the dynamic processes of bacterial accumulation within the gut is crucial, as it is closely related to immune responses, antibiotic resistance, and colorectal cancer. We investigated Escherichia coli behavior and distribution in zebrafish larval intestines, focusing on the gut microenvironment. RESULTS: We discovered that E. coli spread was considerably suppressed within the intestinal folds, leading to a strong physical accumulation in the folds. Moreover, a higher concentration of E. coli on the dorsal side than on the ventral side was observed. Our in vitro microfluidic experiments and theoretical analysis revealed that the overall distribution of E. coli in the intestines was established by a combination of physical factor and bacterial taxis. CONCLUSIONS: Our findings provide valuable insight into how the intestinal microenvironment affects bacterial motility and accumulation, enhancing our understanding of the behavioral and ecological dynamics of the intestinal microbiota.


Assuntos
Microbioma Gastrointestinal , Intestinos , Animais , Intestinos/microbiologia , Escherichia coli/fisiologia , Fatores Biológicos , Peixe-Zebra/fisiologia , Microbioma Gastrointestinal/fisiologia , Bactérias
15.
Nutrients ; 16(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38613116

RESUMO

Small intestinal bacterial overgrowth (SIBO) arises from dysbiosis in the small intestine, manifesting with abdominal symptoms. This study aims to assess the efficacy of combined antibiotic therapy, herbal supplements, probiotics, and dietary modifications in SIBO management. A total of 179 SIBO-diagnosed patients underwent clinical evaluation and breath testing. Patients were categorized into hydrogen (H2-SIBO) and methane (CH4-SIBO) groups. The control group received standard antibiotic therapy and a low-FODMAP diet, while the intervention group received additional herbal antibiotics, probiotics, and prebiotics. After treatment, both groups exhibited reduced gas levels, particularly in CH4-SIBO. Clinical remission rates were higher in the intervention group, especially in CH4-SIBO cases. Logistic regression analysis showed gas concentrations at diagnosis as significant predictors of treatment success. In conclusion, adjunctive herbal supplements and probiotics did not significantly impact gas levels, but showed potential for clinical improvement, especially in CH4-SIBO.


Assuntos
Dieta , Probióticos , Humanos , Probióticos/uso terapêutico , Prebióticos , Proteínas do Sistema Complemento , Antibacterianos/uso terapêutico
16.
Pathol Oncol Res ; 30: 1611705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605931

RESUMO

Background: Langerhans cell histiocytosis is a rare disease characterized by the abnormal proliferation of Langerhans cells within a single organ or multiple organs. This case report aims to improve the knowledge of the presentation of gastrointestinal Langerhans cell histiocytosis to facilitate the diagnosis and management of this rare disorder. Case presentation: A 19-month-old female presented with repeatedly mucinous bloody stools. The abdominal ultrasound revealed a slightly enlarged spleen. The initial colonoscopy revealed chronic enteritis with a very early onset inflammatory bowel disease. After anti-inflammatory treatment without improvement, an intestinal biopsy was performed at The Forth Affiliated Hospital of Zhejiang University. The final intestinal biopsy and histopathology examination confirmed the presence of Langerhans cell histiocytosis. After diagnosis, additional lung and head imaging examinations revealed no abnormalities. Her condition improved gradually after being treated with chemotherapy (vincristine and prednisone) and molecular-targeted drug(dalafinil) treatment. Conclusion: The clinical symptoms of Langerhans cell histiocytosis involving the gastrointestinal tract are not specific and may resemble symptoms observed in inflammatory bowel disease and other primary gastrointestinal tumors. Therefore, in cases of infants presenting with inflammatory gastrointestinal symptoms that do not resolve after treatment, a biopsy is essential to obtain a differential diagnosis.


Assuntos
Histiocitose de Células de Langerhans , Doenças Inflamatórias Intestinais , Humanos , Lactente , Feminino , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/patologia , Prednisona/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pulmão/patologia , Doenças Raras
17.
Mol Microbiol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623070

RESUMO

Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. Understanding the ability of each distinct community member to promote or impair host health, alone or in the context of the community, is imperative for understanding how differences in community structure affect host health and vice versa. Recently, a reference 12-member microbiota for the model organism Caenorhabditis elegans, known as CeMbio, was defined. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh-WNT, and HLH-30/TFEB pathways. Although distinct CeMbio members differed in their ability to activate the PMK-1/p38 pathway, the ability to do so did not correlate with bacterial-induced lifespan reduction in wild-type or immunodeficient animals. In contrast, most species activated HLH-30/TFEB and showed virulence toward hlh-30-deficient animals. These results suggest that the microbiota of C. elegans is rife with bacteria that can shorten the host's lifespan if host defense is compromised and that HLH-30/TFEB is a fundamental and key host protective factor.

18.
Biomed Pharmacother ; 175: 116590, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38653109

RESUMO

Alcohol-associated liver disease (ALD) is a leading factor of liver-related death worldwide. ALD has various manifestations that include steatosis, hepatitis, and cirrhosis and is currently without approved pharmacotherapies. The Src homology phosphatase 2 (Shp2) is a drug target in some cancers due to its positive regulation of Ras-mitogen-activated protein kinase signaling and cell proliferation. Shp2 pharmacological inhibition yields beneficial outcomes in animal disease models, but its impact on ALD remains unexplored. This study aims to investigate the effects of Shp2 inhibition and its validity using a preclinical mouse model of ALD. We report that the administration of SHP099, a potent and selective allosteric inhibitor of Shp2, partially ameliorated ethanol-induced hepatic injury, inflammation, and steatosis in mice. Additionally, Shp2 inhibition was associated with reduced ethanol-evoked activation of extracellular signal-regulated kinase (ERK), oxidative, and endoplasmic reticulum (ER) stress in the liver. Besides the liver, excessive alcohol consumption induces multi-organ injury and dysfunction, including the intestine. Notably, Shp2 inhibition diminished ethanol-induced intestinal inflammation and permeability, abrogated the reduction in tight junction protein expression, and the activation of ERK and stress signaling in the ileum. Collectively, Shp2 pharmacological inhibition mitigates the deleterious effects of ethanol in the liver and intestine in a mouse model of ALD. Given the multifactorial aspects underlying ALD pathogenesis, additional studies are needed to decipher the utility of Shp2 inhibition alone or as a component in a multitherapeutic regimen to combat this deadly malady.

19.
BMJ Case Rep ; 17(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589238

RESUMO

Few cases of spontaneous bowel evisceration (SBE) through umbilical hernias (UHs) in adult patients have been reported in the literature. Interestingly, the spontaneous rupture of the hernia sac is a rare complication usually seen in adult cirrhotic patients with persistent ascites or in patients with congenital wall defects. A man in his early 50s was admitted to our emergency department with SBE through a long-standing acquired UH. He was not clinically cirrhotic, although being HCV positive. Surgeons performed an urgent laparotomy with ileal resection, latero-lateral ileal anastomosis and direct hernioplasty without mesh. Given the rarity of this presentation, we reported it and reviewed the available literature on this subject. Elective hernioplasty is currently suggested to lower the risk of complications. Mesh placement should be preferred, but only if comorbidities and infectious risks do not contraindicate its use. In emergency situations, a direct hernia repair is preferred.


Assuntos
Hérnia Inguinal , Hérnia Umbilical , Humanos , Masculino , Ascite/complicações , Hérnia Inguinal/cirurgia , Hérnia Umbilical/complicações , Hérnia Umbilical/cirurgia , Intestino Delgado , Cirrose Hepática/complicações , Pessoa de Meia-Idade
20.
Ecotoxicol Environ Saf ; 277: 116326, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38640800

RESUMO

The available information regarding the impact of antimony (Sb), a novel environmental pollutant, on the intestinal microbiota and host health is limited. In this study, we conducted physiological characterizations to investigate the response of adult zebrafish to different environmental concentrations (0, 30, 300, and 3000 µg/L) of Sb over a period of 14 days. Biochemical and pathological changes demonstrated that Sb effectively compromised the integrity of the intestinal physical barrier and induced inflammatory responses as well as oxidative stress. Analysis of both intestinal microbial community and metabolome revealed that exposure to 0 and 30 µg/L of Sb resulted in similar microbiota structures; however, exposure to 300 µg/L altered microbial communities' composition (e.g., a decline in genus Cetobacterium and an increase in Vibrio). Furthermore, exposure to 300 µg/L significantly decreased levels of bile acids and glycerophospholipids while triggering intestinal inflammation but activating self-protective mechanisms such as antibiotic presence. Notably, even exposure to 30 µg/L of Sb can trigger dysbiosis of intestinal microbiota and metabolites, potentially impacting fish health through the "microbiota-intestine-brain axis" and contributing to disease initiation. This study provides valuable insights into toxicity-related information concerning environmental impacts of Sb on aquatic organisms with significant implications for developing management strategies.

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