Global research trends in non-alcoholic fatty liver disease.

OBJECTIVES: This study aimed to analyze the global profile of the literature in non-alcoholic fatty liver disease (NAFLD) research. BACKGROUND: Non-alcoholic fatty liver disease is a clinically heterogeneous condition characterized by fat accumulation in the liver and the absence of significant alcohol consumption or underlying genetic disorders. These manifestations are associated with inflammation, steatosis, and fibrosis that can develop into cirrhosis and even hepatocellular carcinoma. However, a study about the research trend in NAFLD has never been reported before. METHODS: The NAFLD bibliometric analysis was performed on articles indexed in the Scopus database from 1973 to 2022. RESULTS: The total number of articles published worldwide is 28,673 documents, with an annual average of 561 documents. The United States generated the most articles (n = 6548), followed by China (n = 6180), Italy (n = 2434), and Japan (n = 2032). Since 2013, the number of publications on NAFLD has increased dramatically worldwide. The popular topics in the field include medicine, biochemistry, genetics and molecular biology, pharmacology, toxicology and pharmaceutics, and nursing. CONCLUSIONS: This study provides a unique composite picture of NAFLD research worldwide and evaluates research productivity from 1973 to 2022. This finding suggests that the prospects for interventions in NAFLD remain promising (Tab. 5, Fig. 4, Ref. 57). Text in PDF www.elis.sk Keywords: bibliometric analysis, NAFLD, Scopus.

Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain.

In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain.

Bibliometric analysis of organoids in regenerative medicine-related research worldwide over two decades (2002-2022).

Aim: This study aimed to evaluate the trends in organoid culture research within the field of regenerative medicine from 2002 to 2022. Methods: The worldwide distribution of organoid research in regenerative medicine articles indexed in the Scopus database was analyzed. Result: A total of 840 documents were analyzed, averaging 42 publications annually. The USA (n = 296) led in publications, followed by China (n = 127), Japan (n = 91) and the UK (n = 75). Since 2011, research has surged, particularly in China, which emerged as a prominent center. Conclusion: The findings highlight significant growth in organoid research, promising future organ transplantation. Research trends integrate tissue engineering, gene modification and induced pluripotent stem cell technologies, reflecting a move toward personalized medicine.

The Effect of Yoga on Health-Related Fitness among Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

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.

Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.

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.

Regulation of colonic epithelial cell homeostasis by mTORC1.

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 3ß 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.

Regulation of Small Intestinal Epithelial Homeostasis by Tsc2-mTORC1 Signaling.

Mammalian target of rapamycin complex 1 (mTORC1), a protein complex containing the serine/threonine kinase mTOR, integrates various growth stimulating signals. mTORC1 is expressed in intestinal epithelial cells (IECs), whereas the physiological roles of this protein complex in homeostasis of IECs remain virtually unknown. We here generated mice, in which tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, was specifically ablated in IECs (Tsc2 CKO mice). Ablation of Tsc2 enhanced the phosphorylation of mTORC1 downstream molecules such as ribosomal S6 protein and 4E-BP1 in IECs. Tsc2 CKO mice manifested the enhanced proliferative activity of IECs in intestinal crypts as well as the promoted migration of these cells along the crypt-villus axis. The mutant mice also manifested the increased apoptotic rate of IECs as well as the increased ectopic Paneth cells, which are one of the major differentiated IECs. In addition, in vitro study showed that ablation of Tsc2 promoted the development of intestinal organoids without epidermal growth factor, while mTORC1 inhibitor, rapamycin, diminished this phenotype. Our results thus suggest that Tsc2-mTORC1 signaling regulates the proliferation, migration, and positioning of IECs, and thereby contributes to the proper regulation of intestinal homeostasis.

Role of lysophosphatidic acid in proliferation and differentiation of intestinal epithelial cells.

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.

Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.

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.