Structure-anti-inflammatory activity relationship of garlic fructans in mice with dextran sulfate sodium-induced colitis: Impact of chain length.

The present study identified the protective effects of garlic oligo/poly-saccharides of different chain lengths against dextran sulfate sodium (DSS)-induced colitis in mice and elucidated the structure-function relationships. The results showed that oral intake of garlic oligo/poly-saccharides decreased disease activity index, reduced colon shortening and spleen enlargement, and ameliorated pathological damage in the mouse colon. The dysregulation of colonic pro/anti-inflammatory cytokines was significantly alleviated, accompanied by up-regulated antioxidant enzymes, blocked TLR4-MyD88-NF-κB signaling pathway, enhanced intestinal barrier integrity, and restored SCFA production. Garlic oligo/poly-saccharides also reversed gut microbiota dysbiosis in colitic mice by expanding beneficial bacteria and suppressing the growth of harmful bacteria. High-molecular-weight polysaccharides exhibited stronger alleviating effects on DSS-induced colitic symptoms in mice than low-molecular-weight oligo/poly-saccharides did, probably due to their greater ability to be fermented in the colon. Taken together, this study demonstrated the anti-inflammatory effects of garlic oligo/poly-saccharides and revealed that high-molecular-weight polysaccharide fractions were more effective in alleviating DSS-induced colitis.

Quercetin Attenuates KLF4-Mediated Phenotypic Switch of VSMCs to Macrophage-like Cells in Atherosclerosis: A Critical Role for the JAK2/STAT3 Pathway.

The objective of this study was to elucidate the protective role of quercetin in atherosclerosis by examining its effect on the phenotypic switch of vascular smooth muscle cells (VSMCs) to macrophage-like cells and the underlying regulatory pathways. Aorta tissues from apolipoprotein E-deficient (ApoE KO) mice fed a high-fat diet (HFD), treated with or without 100 mg/kg/day quercetin, were analyzed for histopathological changes and molecular mechanisms. Quercetin was found to decrease the size of atherosclerotic lesions and mitigate lipid accumulation induced by HFD. Fluorescence co-localization analysis revealed a higher presence of macrophage-like vascular smooth muscle cells (VSMCs) co-localizing with phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 3 (p-STAT3), and Krüppel-like factor 4 (KLF4) in regions of foam cell aggregation within aortic plaques. However, this co-localization was reduced following treatment with quercetin. Quercetin treatment effectively inhibited the KLF4-mediated phenotypic switch in oxidized low-density lipoprotein (ox-LDL)-loaded mouse aortic vascular smooth muscle cells (MOVAS), as indicated by decreased expressions of KLF4, LGALS3, CD68, and F4/80, increased expression of alpha smooth muscle actin (α-SMA), reduced intracellular fluorescence Dil-ox-LDL uptake, and decreased lipid accumulation. In contrast, APTO-253, a KLF4 activator, was found to reverse the effects of quercetin. Furthermore, AG490, a JAK2 inhibitor, effectively counteracted the ox-LDL-induced JAK2/STAT3 pathway-dependent switch to a macrophage-like phenotype and lipid accumulation in MOVAS cells. These effects were significantly mitigated by quercetin but exacerbated by coumermycin A1, a JAK2 activator. Our research illustrates that quercetin inhibits the KLF4-mediated phenotypic switch of VSMCs to macrophage-like cells and reduces atherosclerosis by suppressing the JAK2/STAT3 pathway.

Association of Dietary Retinol Intake and Serum Neurofilament Light Chain Levels: Results from NHANES 2013-2014.

BACKGROUND: There is increasing evidence suggesting that serum neurofilament light chain (sNfL) levels can be used as biomarkers for axonal injury. Retinol is recognized for its significant involvement in nervous system function, but the precise connection between dietary retinol and sNfL levels remains uncertain. OBJECTIVE: Our objective was to investigate the relationship between dietary retinol intake and sNfL, and to find an optimal retinol intake level for neurological health. METHODS: In the National Health and Nutrition Examination Survey (NHANES), conducted from 2013 to 2014, a cohort of 1684 participants who met the criteria were selected for the study. sNfL levels were measured from stored serum samples using a novel high-throughput immunoassay platform from Siemens Healthineers. Assessment of dietary retinol intake was performed by a uniformly trained interviewer through a 24 h dietary recall method. A generalized linear model was evaluated to assess the correlation between dietary retinol intake and sNfL concentrations. Furthermore, the nonlinear association between the two is further explored using restricted cubic spline (RCS) analysis. RESULTS: Upon adjusting for potential confounders, a 10% increase in dietary retinol intake was associated with a 3.47% increase in sNfL levels (95% CI: 0.54%, 6.49%) across all participants. This relationship was more pronounced in specific subgroups, including those under 60 years of age, non-obese, impaired estimated glomerular filtration rate (eGFR), and non-diabetic. In subgroup analysis, among those younger than 60 years of age (percent change: 3.80%; 95% CI: 0.43%, 7.28%), changes were found in non-obese participants (percent change: 6.28%; 95% CI: 2.66%, 10.02%), those with impaired eGFR (percent change: 6.90%; 95% CI: 1.44%, 12.65%), and non-diabetic patients (percentage change: 4.17%; 95% CI: 1.08%, 7.36%). RCS analysis showed a linear relationship between dietary retinol intake and sNfL levels. Furthermore, the positive correlation between the two was more significant after the inflection point, according to piecewise linear analysis. CONCLUSION: This current investigation uncovered a J-shaped relationship between dietary retinol and sNfL levels, suggesting that axonal damage can occur when dietary retinol intake increases more than a specific threshold. These findings need to be further confirmed in future prospective studies to determine the precise intake level that may trigger axonal injury.

Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

The blockade of the TGF-ß pathway alleviates abnormal glucose and lipid metabolism of lipodystrophy not obesity.

TGF-ß is thought to be involved in the physiological functions of early organ development and pathological changes in substantial organ fibrosis, while studies around adipose tissue function and systemic disorders of glucolipid metabolism are still scarce. In this investigation, two animal models, aP2-SREBP-1c mice and ob/ob mice, were used. TGF-ß pathway showed up-regulated in the inguinal white adipose tissue (iWAT) of the two models. SB431542, a TGF-ß inhibitor, successfully increased inguinal white adipocyte size by more than 1.5 times and decreased the weight of Peripheral organs including liver, Spleen and Kidney to 73.05%/62.18%/73.23% of pre-administration weights. The iWAT showed elevated expression of GLUTs and lipases, followed by a recovery of circulation GLU, TG, NEFA, and GLYCEROL to the wild-type levels in aP2-SREBP-1c mice. In contrast, TGF-ß inhibition did not have similar effects on that of ob/ob mice. In vitro, TGF-ß blocker treated mature adipocytes had considerably higher levels of glycerol and triglycerides than the control group, whereas GLUTs and lipases expression levels were unchanged. These findings show that inhibiting the abnormally upregulated TGF-ß pathway will only restore iWAT expansion and ameliorate the global metabolic malfunction of glucose and lipids in lipodystrophy, not obesity.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway / 中华创伤杂志(英文版)

PURPOSE@#The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.@*METHODS@#We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant.@*RESULTS@#Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression.@*CONCLUSIONS@#CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Research progress on iron metabolism in aging-related diseases / 中华老年医学杂志

With the acceleration of population aging in China, the issue of population aging is becoming increasingly severe.The investigation of the pathogenesis of aging-related diseases has become a focal point in the field of modern geriatrics.Iron is an essential trace element in the human body and plays a crucial role in maintaining normal physiological functions.Numerous studies have demonstrated the association between the disruption of iron metabolism and the occurrence and progression of various aging-related diseases.This review aims to briefly summarize the potential mechanisms of iron metabolism disorders in common aging-related diseases, and provide a theoretical basis for the diagnosis and treatment of such diseases.

Research progress of targeted pulmonary vascular endothelial dysfunction in treatment of pulmonary hypertension / 中国药理学通报

Pulmonary hypertension (PH) is a progressive and fatal disease. The dysfunction of pulmonary artery endothelial cells (PAECs) is one of its important pathogenic factors. PAECs are monolayer flat epithelial cells, which play an important role in maintaining pulmonary vascular homeostasis. Studies have found that PAECs show damage and apoptosis at the early stage of PH development, while PAECs show anti-apoptotic characteristics at the late stage of PH development. The transition of PAECs into mesenchymal cells induced by hypoxic and inflammatory factors is also involved in the pathogenesis of PH. Carcinoid metabolism and mitochondrial dysfunction, bone mor- phogenic type 2 receptor mutation, epigenetic changes and inflammation of PAECs are the main pathogenesis of pulmonary vascular endothelial dysfunction in PH patients. New therapeutic measures targeting PAECs dysfunction are expected to play an important role in the treatment of PH in the future.

Inverse J-Shaped Relationship of Dietary Carbohydrate Intake with Serum Klotho in NHANES 2007-2016.

BACKGROUND: The relationship between dietary carbohydrate intake and serum Klotho levels, an aging biomarker, remains uncertain. OBJECTIVE: This study aimed to investigate the association between dietary carbohydrate intake and serum Klotho levels among American adults aged 40-79. METHODS: We analyzed data from 10,669 adults aged 40-79 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Trained interviewers assessed dietary carbohydrate intake using a 24 h dietary recall. Serum Klotho concentrations were measured using commercially available ELISA kits provided by IBL International, Japan, which served as the study outcome. Generalized linear models were used to assess the relationship between the carbohydrate energy percentage and serum Klotho concentration, and restricted cubic spline (RCS) analysis was employed to explore any nonlinear associations. RESULTS: After adjusting for multiple variables, we observed a nonlinear inverse J-shaped relationship (p for non-linearity < 0.001) between the carbohydrate energy percentage and serum Klotho levels. Specifically, the highest serum Klotho levels were associated with a total carbohydrate energy percentage ranging from 48.92% to 56.20% (third quartile). When the carbohydrate energy percentage was evaluated in quartiles, serum Klotho levels decreased by 5.37% (95% CI: -7.43%, -3.26%), 2.70% (95% CI: -4.51%, -0.86%), and 2.76% (95% CI: -4.86%, -0.62%) in the first quartile (<41.46%), second quartile (41.46% to 48.92%), and fourth quartile (≥56.20%), respectively, compared to the third quartile. This relationship was more pronounced in male, non-obese and non-diabetic participants under 60 years of age. CONCLUSION: A non-linear inverse J-shaped relationship exists among the general U.S. middle-aged and older population between the carbohydrate energy percentage and serum Klotho levels, with the highest levels observed at 48.92% to 56.20% carbohydrate intake.

Potential Correlation between Microbial Diversity and Volatile Flavor Substances in a Novel Chinese-Style Sausage during Storage.

A novel Chinese-style sausage with Chinese traditional fermented condiments used as additional ingredients is produced in this study. The aim of this study was to investigate the microbial community's structure, the volatile flavor substances and their potential correlation in the novel Chinese sausage. High-throughput sequencing (HTS) and solid-phase microextraction-gas chromatography-mass spectrometry (GC-MS) were, respectively, used to analyze the microbial diversity and volatile flavor substances of the novel Chinese-style sausage during storage. The results showed that Firmicutes, Proteobacteria and Actinobacteria were the predominant bacterial genera, and Hyphopichia and Candida were the predominant fungal genera. A total of 88 volatile flavor substances were identified through GC-MS, among which 18 differential flavor compounds were screened (VIP > 1), which could be used as potential biomarkers to distinguish the novel sausages stored for different periods. Lactobacillus exhibited a significant negative correlation with 2,3-epoxy-4,4-dimethylpentane and acetoin and a significant positive correlation with 2-phenyl-2-butenal. Hyphopichia significantly positively correlated with ester. Leuconostoc significantly positively correlated with ethyl caprate, ethyl palmate, ethyl tetradecanoate and ethyl oleate while it negatively correlated with hexanal. This study provides a theoretical basis for revealing the flavor formation mechanisms and the screening of functional strains for improving the flavor quality of the novel Chinese-style sausage.

CUL4B functions as a tumor suppressor in KRAS-driven lung tumors by inhibiting the recruitment of myeloid-derived suppressor cells.

Lung cancer is the leading cause of cancer-related death worldwide. KRAS mutations are the most common oncogenic alterations found in lung cancer. Unfortunately, treating KRAS-mutant lung adenocarcinoma (ADC) remains a major oncotherapeutic challenge. Here, we used both autochthonous and transplantable KRAS-mutant tumor models to investigate the role of tumor-derived CUL4B in KRAS-driven lung cancers. We showed that knockout or knockdown of CUL4B promotes lung ADC growth and progression in both models. Mechanistically, CUL4B directly binds to the promoter of Cxcl2 and epigenetically represses its transcription. CUL4B deletion increases the expression of CXCL2, which binds to CXCR2 on myeloid-derived suppressor cells (MDSCs) and promotes their migration to the tumor microenvironment. Targeting of MDSCs significantly delayed the growth of CUL4B knockdown KRAS-mutant tumors. Collectively, our study provides mechanistic insights into the novel tumor suppressor-like functions of CUL4B in regulating KRAS-driven lung tumor development.

The Association between Dietary Fiber Intake and Serum Klotho Levels in Americans: A Cross-Sectional Study from the National Health and Nutrition Examination Survey.

BACKGROUND: Klotho is an aging-related marker closely associated with a number of diseases. A growing body of evidence suggests that dietary factors and lifestyle habits can impact serum Klotho levels. The effect of dietary fiber, a key component of a healthy diet, on the body's serum Klotho levels has not been fully elucidated. OBJECTIVE: The aim of this study was to explore the relationship between dietary fiber intake and serum Klotho levels in people aged 40-79 years in the United States. METHODS: A total of 11,282 participants were included in this study, all from the National Health and Nutrition Examination Survey from 2007 to 2016. Dietary fiber intake was assessed by uniformly trained interviewers using the 24 h dietary recall method. Serum Klotho was quantified using commercially available ELISA kits manufactured by IBL International, Japan. The relationship between dietary fiber intake and serum Klotho levels was analyzed using a multiple linear regression model. Subsequently, the non-linear dose-response relationship between the two was further explored using a restricted cubic spline (RCS) model. RESULTS: After adjusting for potential confounders, serum Klotho levels increased by 1.9% (95% confidence interval [CI]: 0.8%, 3.0%) for each interquartile range increase in dietary fiber intake in all participants. Considering dietary fiber intake as a categorical variable, serum Klotho levels were found to be 4.7% higher in participants in the highest quartile of dietary fiber intake than in those in the lowest quartile (95% CI: 1.8%, 7.6%). RCS plots depicted a non-linear positive correlation between dietary fiber intake and serum Klotho levels. Subgroup analysis revealed that the relationship between dietary fiber intake and serum Klotho levels was more pronounced in older (percentage change: 7.0%; 95% CI: 2.5%, 11.7%) and overweight and obese participants (percentage change: 4.9%; 95% CI: 1.5%, 8.4%). CONCLUSIONS: The results of this study showed that dietary fiber intake was significantly associated with serum Klotho levels in participants. This finding is yet to be further confirmed by prospective studies.

Corrigendum: Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome.

[This corrects the article DOI: 10.3389/fendo.2023.1122709.].

Quercetin alleviates atherosclerosis by suppressing oxidized LDL-induced senescence in plaque macrophage via inhibiting the p38MAPK/p16 pathway.

Quercetin is a widely known and biologically active phytochemical and exerts therapeutic effects against atherosclerosis. The removal of senescent plaque macrophages effectively slows the progression of atherosclerosis and decreases the plaque burden. Still, whether quercetin alleviates atherosclerosis by inhibiting the senescence of plaque macrophages, including the potential mechanisms, remains unclear. ApoE-/- mice were fed with a normal chow diet or high-fat diet (HFD) supplemented or not with quercetin (100 mg/kg of body weight) for 16 weeks. An accumulation of senescent macrophages was observed in the plaque-rich aortic tissues from the mice with HFD, but quercetin supplementation effectively reduced the amount of senescent plaque macrophage, inhibited the secretion of key senescence-associated secretory phenotype factors, and alleviated atherosclerosis by inhibiting p38MAPK phosphorylation and p16 expression. In vitro, SB203580 (a specific inhibitor of p38 MAPK) significantly inhibited oxidized low-density lipoprotein (ox-LDL)-induced senescence in mouse RAW264.7 macrophages, as evidenced by decreased senescence-associated markers (SA-ß-gal staining positive cells and p16 expression). Furthermore, quercetin not only effectively reversed ox-LDL-induced senescence in RAW264.7 cells but also decreased the mRNA levels of several key senescence-associated secretory phenotype factors by suppressing p38 MAPK phosphorylation and p16 expression. The p38 MAPK agonist Asiatic acid reversed the effects of quercetin. In conclusion, these findings indicate that quercetin suppresses ox-LDL-induced senescence in plaque macrophage and attenuates atherosclerosis by inhibiting the p38 MAPK/p16 pathway. This study elucidates the mechanisms of quercetin against atherosclerosis and supports quercetin as a nutraceutical for the management of atherosclerosis.

Garlic polysaccharide-Cr (III) complexes with enhanced in vitro and in vivo hypoglycemic activities.

This study aimed to prepare a complex of Cr (III) and garlic polysaccharides (GPs) and evaluate the in vitro and in vivo hypoglycemic activities of GPs and GP-Cr (III) complexes. The chelation of GPs with Cr (III) increased molecular weight, modified crystallinity, and altered morphological characteristics, through targeting the OH of hydroxyl groups and involving the C-O/O-C-O structure. The GP-Cr (III) complex had a higher thermal stability over 170-260 °C and higher stability throughout the gastrointestinal digestion. In vitro, the GP-Cr (III) complex exhibited a significantly stronger inhibitory effect against α-glucosidase compared with the GP. In vivo, the GP-Cr (III) complex at a high dose (4.0 mg Cr/kg body weight) generally had a higher hypoglycemic activity than the GP in (pre)-diabetic mice induced by a high-fat and high-fructose diet, based on indices like body weight, blood glucose levels, glucose tolerance, insulin resistance, insulin sensitivity, blood lipid levels, and hepatic morphology and function. Therefore, GP-Cr (III) complexes could be a potential Cr (III) supplement with an enhanced hypoglycemic activity.

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome.

Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated. Methods: A pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice. Results: Our results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis. Conclusion: These results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.

The characteristics of dome-shaped macula in Chinese children aged 4-6 years using optical coherence tomography angiography.

PURPOSE: To evaluate the characteristics of dome-shaped macula (DSM) in children aged 4-6 years with normal visual acuity using optical coherence tomography angiography. METHOD: This is a cross-sectional study. A total of 19 children aged 4-6 years were included. The results of optical coherence tomography angiography images were analysed to identify and quantify retinal structural and vascular parameters in DSM children. The dome height, dome base, and sub-dome choroidal thickness were manually measured. Participants with DSM and those without DSM from our previous study were compared on these parameters. RESULTS: Nineteen eyes of the preschool subjects with normal visual acuity showed horizontal DSM on optical coherence tomography (OCT). The DSM was significantly smooth and low in the children, and we did not observe differences between sex and age. Compared to the children without DSM, the average axial length was longer, and the average macular vessel density was lower in the DSM group, especially in the deep retinal vascular density. Additionally, the dome height was positively correlated with the sub-dome choroidal thickness. When the dome base/height was increased, the fovea avascular zone (FAZ) area was larger. CONCLUSION: Dome-shaped macula was detected in the preschool children in the process of the emmetropization with normal visual acuity. The changes in macular structure and vasculature provide new ideas for further investigation into the characteristics of DSM formation.

Advancement and prospects of production, transport, functional activity and structure-activity relationship of food-derived angiotensin converting enzyme (ACE) inhibitory peptides.

Food-derived antihypertensive peptides have attracted increasing attention in functional foods for health promotion, due to their high biological activity, low toxicity and easy metabolism in the human body. Angiotensin converting enzyme (ACE) is a key enzyme that causes the increase in blood pressure in mammals. However, few reviews have summarized the current understanding of ACE inhibitory peptides and their knowledge gaps. This paper focuses on the food origins and production methods of ACE inhibitory peptides. Compared with conventional methods, the advanced technologies and emerging bioinformatics approaches have recently been applied for efficient and targeted release of ACE inhibitory peptides from food proteins. Furthermore, the transport and underlying mechanisms of ACE inhibitory peptides are emphatically described. Molecular modeling and the Michaelis-Menten equation can provide information on how ACE inhibitors function. Finally, we discuss the structure-activity relationships and other bio-functional properties of ACE inhibitory peptides. Molecular weight, hydrophobic amino acid residues, charge, amino acid composition and sequence (especially at the C-terminal and N-terminal) have a significant influence on ACE inhibitory activity. Some studies are required to increase productivity, improve bioavailability of peptides, evaluate their bio-accessibility and efficiency on reducing blood pressure to provide a reference for the development and application of health products and auxiliary treatment drugs.

Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi / 中国医学科学院学报

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

Association between peripheral blood growth differentiation factor 15 deoxyribonucleic acid methylation and sarcopenia among the elderly / 中华老年医学杂志

Objective:To examine the relationship between sarcopenia and DNA methylation in the promoter of the growth differentiation factor 15(GDF15)gene in elderly individuals.Methods:This cross-sectional study collected data from 865 elderly individuals aged 65 years and above who underwent physical examination at the Yuetang Town Community Medical Center in Yangzhou City between May and September 2020.The verification set included 431 males and 434 females with an age range of 65-100 years and a mean age of(76.0±5.9)years.The diagnosis of sarcopenia was based on the consensus diagnostic criteria of the Asian Sarcopenia Working Group in 2019.The study included 295 cases in the non-sarcopenia group and 470 cases in the sarcopenia group.The study selected 50 non-sarcopenia patients and 50 age-gender matched sarcopenia patients as the explore set for DNA methylation sequencing of the GDF15 gene.The sequencing results were then verified using the methylation-specific polymerase chain(PCR)method in the verification center.Additionally, serum GDF15 levels were detected using the enzyme-linked immunosoradsorption method.The study analyzed the correlation between GDF15 methylation levels, serum GDF15 levels, and sarcopenia.Results:The study found that individuals with sarcopenia had lower levels of body mass index(BMI), appendicular skeletal muscle mass(ASMI), grip strength, and gait speed in both the discovery and validation sets compared to those without sarcopenia( P<0.05). Additionally, the DNA methylation of GDF15 was found to be lower in the sarcopenic group compared to the non-sarcopenic group[93.7%(79.6%, 98.0%) vs.97.7%(95.3%, 99.0%), Z=-9.294, P<0.01]. The results of the correlation analysis indicate a positive relationship between the methylation level and appendicular skeletal muscle mass( r=0.206, P<0.01), grip strength( r=0.297, P<0.01), and gait speed( r=0.383, P<0.01). Conversely, there was a negative correlation between the methylation level and serum GDF15 level( r=-0.249, P<0.05). The study conducted ROC analysis to determine the predictive ability of GDF15 methylation for sarcopenia found that the area under the curve was 0.700 with a cut-off score of 92.7%.Furthermore, binary regression analysis revealed that low GDF15 methylation( OR=1.136, 95% CI: 1.098~1.175, P<0.01)was linked to a higher risk of sarcopenia, even after adjusting for age, sex, and BMI.The serum GDF15 level was higher in the sarcopenic group compared to the non-sarcopenic group[(0.665±0.432)pg/L vs.(0.465±0.211)pg/L( t=-2.452, P<0.05)]. Additionally, it was observed that the methylation of GDF15 was negatively correlated with the serum GDF15 level( r=-0.249, P<0.05). Conclusions:A low level of GDF15 methylation has been found to be linked with a higher risk of sarcopenia, suggesting that measuring GDF15 methylation could potentially serve as a biomarker for diagnosing sarcopenia.