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The life span of intestinal epithelial cells (IECs) is short (3-5 days), and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen-free (SPF) mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs) as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs.

Cell signaling important for homeostatic regulation of colonic epithelial cells (CECs) remains poorly understood. Mammalian target of rapamycin complex 1 (mTORC1), a protein complex that contains the serine-threonine kinase mTOR, mediates signaling that underlies the control of cellular functions such as proliferation and autophagy by various external stimuli. We here show that ablation of tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, specifically in intestinal epithelial cells of mice resulted in increased activity of mTORC1 of, as well as increased proliferative activity of, CECs. Such Tsc2 ablation also reduced the population of Lgr5-positive colonic stem cells and the expression of Wnt target genes in CECs. The stimulatory phosphorylation of the kinase Akt and inhibitory phosphorylation of glycogen synthase kinase 3β were both markedly decreased in the colon of the Tsc2 conditional knockout (CKO) mice. Development of colonic organoids with cryptlike structures was enhanced for Tsc2 CKO mice compared with control mice. Finally, Tsc2 CKO mice manifested increased susceptibility to dextran sulfate sodium–induced colitis. Our results thus suggest that mTORC1 activity promotes the proliferation of, as well as the expression of Wnt target genes in, CECs and thereby contributes to colonic organogenesis and homeostasis.

Intestinal epithelial cells (IECs) are regenerated continuously from intestinal stem cells (ISCs) near the base of intestinal crypts in order to maintain homeostasis and structural integrity of intestinal epithelium. Epidermal growth factor (EGF) is thought to be important to drive the proliferation and differentiation of IECs from ISCs, it remains unknown whether other growth factors or lipid mediators are also important for such regulation, however. Here we show that lysophosphatidic acid (LPA), instead of EGF, robustly promoted the development of intestinal organoids prepared from the mouse small intestine. Indeed, LPA exhibited the proliferative activity of IECs as well as induction of differentiation of IECs into goblet cells, Paneth cells, and enteroendocrine cells in intestinal organoids. Inhibitors for LPA receptor 1 markedly suppressed the LPA-promoted development of intestinal organoids. LPA also promoted the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in intestinal organoids, whereas inhibition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 significantly suppressed the development of, as well as the proliferative activity and differentiation of, intestinal organoids in response to LPA. Our results thus suggest that LPA is a key factor that drives the proliferation and differentiation of IECs.

Cross talk between different signaling pathways is thought to be important for regulation of homeostasis of, as well as oncogenesis of, the intestinal epithelium. Expression of an active form of K-Ras specifically in intestinal epithelial cells (IECs) of mice (IEC-RasDA mice) resulted in the development of hyperplasia in the small intestine and colon of mice. IEC-RasDA mice also manifested the increased proliferation of IECs. In addition, the number of goblet cells markedly increased, while that of Paneth cells decreased in IEC-RasDA mice. Development of intestinal organoids was markedly enhanced for IEC-RasDA mice compared with control mice. Whereas, the expression of Wnt target genes was significantly reduced in the in intestinal crypts from IEC-RasDA mice compared with that apparent for the control. Our results thus suggest that K-Ras promotes the proliferation of IECs as well as generation of goblet cells. By contrast, Ras counter-regulates the Wnt signaling and thereby contribute to the proper regulation of intestinal epithelial cell homeostasis.

Obesity is a global health problem with an ever-increasing prevalence in society. This condition can be a risk factor for developing other health issues, including infertility. This study aims to examine the relationship between body composition and total motile sperm count (TMSC) in infertile male patients with varicocele. A cross-sectional study was conducted on 37 infertile male patients diagnosed with varicocele based on physical examination. The study examined the effect of body composition parameters (Body Mass Index, body fat percentage, visceral fat level, and waist circumference) on sperm parameters. The results were tabulated and analyzed using the Statistical Package for the Social Sciences (SPSS) software. It was identified that body fat percentage and visceral fat level significantly affect sperm concentration and TMSC ( p <0.05). However, BMI and waist circumference did not show a statistically significant effect on sperm parameters. This study suggests that BMI alone cannot always be used as an indicator of sperm quality and quantity in infertile men. Therefore, examination of other body composition parameters should be considered when conducting sperm assessments in infertile men.

Antiviral peptides (AVPs) are small molecules that inhibit the replication of viruses in living cells. AVPs are being investigated as potential alternatives to traditional antiviral drugs. The development of novel antiviral agents is of the highest concern because some traditional antiviral medications can be ineffective and lead to resistant viruses emergence. We conducted a bibliometric study on the global distribution of AVP research to comprehend the trends and patterns in the field. For this analysis, we retrieved data from the Scopus database on AVP-related publications from 1951 to 2022, including the number of publications, citations, and authors. Overall, 10,279 papers were published, with an annual average of 146 publications. The United States released the most documents, followed by China, Germany, and the United Kingdom. Since 2001, there has been a substantial increase in global publications on AVPs, with prominent themes including virology, genetics, protease inhibitors, polypeptide antimicrobial agents, and viral entry. This bibliometric analysis can be used to guide future research in this field.

Background: There is a need for a type of physical activity that could address the challenging cycle of physical inactivity, impaired health-related fitness, and type 2 diabetes mellitus (T2DM) conditions. Yoga could be one type of exercise to overcome the barriers to adhere to regular physical activity. The current study aimed to systematically review the effect of yoga on health-related fitness, including cardiorespiratory fitness, muscle strength, body composition, balance, and flexibility, among patients with T2DM. Methods: We systematically searched four databases and two registries (Pubmed, Scopus, Cochrane, Embase, WHO-ITCRP, and Clinicaltrials.gov) in September 2021, following a registered protocol on PROSPERO (CRD42022276225). Study inclusion criteria were T2DM patients with or without complication, yoga intervention as a single component or as a complement compared to other kinds of exercise or an inactive control, health-related fitness, and a randomized, controlled trial or quasi-experimental with control group design. The ROBINS-I tool and ROB 2.0 tool were used to assess the risk of bias in the included studies. A vote-counting analysis and meta-analysis computed using random effects’ models were conducted. Results: A total of 10 records from 3 quasi-experimental and 7 randomized, controlled trials with 815 participants in total were included. The meta-analysis favored yoga groups compared to inactive controls in improving muscle strength by 3.42 (95% confidence interval 2.42 to 4.43), repetitions of chair stand test, and improving cardiorespiratory fitness by 6.6% (95% confidence interval 0.4 to 12.8) improvement of baseline forced vital capacity. The quality of evidence for both outcomes was low. Conclusion: Low-quality evidence favored yoga in improving health-related fitness, particularly muscle strength and cardiorespiratory fitness, among patients with T2DM. Funding: All authors in this systematic review received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Objectives: This  study  aimed  to  analyze  the  global  profile  of  the nucleotide/nucleoside  analogs  (NAs)  for  chronic  hepatitis virus therapy-related research. Background: NAs, which closely resemble the structure of naturally occurring  nucleotides/nucleosides,  function  by  disrupting the elongation of the nascent DNA strand. These compounds are  considered  safe  and  well-tolerated,  as  they  specifically target  viral,  but  not  human,  polymerases  involved  in  DNA replication.  NAs  are  crucial  in  treating  viral  infections, including hepatitis, and are widely used due to their efficacy and safety. However, a study about trends in NAs for chronic hepatitis therapy-related research was never reported before. Methods: The  NAs  for  chronic  hepatitis  therapy-related  research bibliometric  analysis  was  performed  on  articles  indexed  in the Scopus database from 1986 to 2022. Results: The  total  number  of  articles  published  worldwide  is  2,341 documents,  with  an  annual  average  of  65  documents.  The United States generated the most articles (n = 486), followed by China (n = 454), France (n = 191), and Italy (n = 179). Since 1992, the number of publications has increased dramatically worldwide. Globally, liver cell carcinoma, antiviral therapy, hepatitis  B  (e)  antigen,  and  alanine  aminotransferase  are becoming hot research topics in the field. Conclusions: This  study  provides  a  unique  composite  picture  of  NAs for  chronic  hepatitis  therapy-related  research  worldwide and  evaluates  research  productivity  from  1986  to  2022. This finding suggests that the prospects for interventions in chronic hepatitis remain promising. Bangladesh Journal of Medical Science Vol. 23 No. 03 July’24 Page : 747-756

Los péptidos antivirales (AVPs) son pequeñas moléculas que inhiben la replicación de virus en células vivas. Los AVPs están siendo investigados como posibles alternativas a los medicamentos antivirales tradicionales. El desarrollo de nuevos agentes antivirales es de gran relevancia, ya que algunos medicamentos antivirales tradicionales pueden tener baja eficacia y llevar a la aparición de virus resistentes. Llevamos a cabo un estudio bibliométrico sobre la distribución global de la investigación en AVPs para comprender las tendencias y patrones en el campo. Para este análisis, obtuvimos datos de la base de datos Scopus sobre publicaciones relacionadas con AVPs entre 1951 y 2022, incluyendo el número de publicaciones, citas y autores. En total, se publicaron 10.279 artículos, con un promedio anual de 146 publicaciones. Estados Unidos publicó el mayor número de documentos, seguido de China, Alemania y el Reino Unido. Desde 2001, ha habido un aumento sustancial en las publicaciones globales sobre AVPs, con temas prominentes que incluyen virología, genética, inhibidores de proteasas, agentes antimicrobianos polipeptídicos y entrada viral. Este análisis bibliométrico puede ser utilizado para guiar futuras investigaciones en este campo.