Association between triglyceride glucose index-related indices with gallstone disease among US adults.

BACKGROUND: Triglyceride glucose (TyG) index combined with obesity-related indicators [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC)], represents emerging methodologies for assessing insulin resistance. The objective of this investigation was to explore the correlation between TyG-related indices and gallstone disease. METHODS: The study included 3740 adults from the 2017-2020 period of the National Health and Nutrition Examination Survey. TyG-BMI, TyG-WC, and TyG-WHtR were integrated as both continuous and categorical variables within the multivariate logistic model, respectively to evaluate the connection between various TyG-related indices and gallstone disease. Additionally, restriction cubic splines and subgroup analysis were employed to deepen our understanding of this relationship. RESULTS: When analyzed as continuous variables, positive correlations were observed between TyG-BMI, TyG-WC, TyG-WHtR and gallstone disease. The OR(95%CI) were 1.063(1.045,1.082) for TyG-BMI (per 10-unit), 1.026(1.018,1.034) for TyG-WC (per 10-unit) and 1.483(1.314,1.676) for TyG-WHtR (per 1-unit), respectively. When categorized into quartiles, these three TyG-related indices still show statistically significant associations with gallstone disease. Descending in order, the diagnostic capability for gallstone disease is demonstrated as follows: TyG-WHtR (AUC = 0.667), TyG-BMI (AUC = 0.647), and TyG-WC (AUC = 0.640). CONCLUSION: There were significantly positive associations between TyG-related indices, including TyG-BMI, TyG-WC, and TyG-WHtR, and gallstone disease. Of these indices, TyG-WHtR demonstrated the most favorable performance in identifying the risk of gallstone disease.

The mechanism of nickel-induced autophagy and its role in nephrotoxicity.

Nickel (Ni), an environmental health hazard, is nephrotoxic to humans, but the exact mechanism is unknown. This study aims to identify whether nephrotoxicity is associated with autophagy. Here, nickel chloride (NiCl2) increased autophagy in TCMK-1 cells. NiCl2 induces autophagy through Akt and AMPK/mTOR pathways. Next, oxidative stress was investigated in NiCl2-induced autophagy. The findings demonstrated that the antioxidant (NAC) or mitochondrial targeted antioxidant (Mito-TEMPO) attenuated NiCl2-induced autophagy, reversed the influence on AMPK-mTOR and Akt pathways. Additionally, our study examined the role of autophagy in NiCl2-induced nephrotoxicity. Autophagy inhibition with 3-MA could inhibit cell viability and increase apoptosis in the TCMK-1 cells, however, autophagy promotion with rapamycin relieved cytotoxicity and decreased apoptosis. Additionally, co-treatment with Z-VAD-FMK reduced cytotoxicity, but did not affect autophagy. Besides, NiCl2 can increase the level of mitophagy in vivo and vitro. Mitophagy inhibition could inhibit cell viability and increase apoptosis in the TCMK-1 cells, whereas, promotion of mitophagy could increase cell viability and decrease apoptosis. In summary, above-mentioned results showed that NiCl2 induces autophagy in TCMK-1 cells through oxidative stress-dependent AMPK/AKT-mTOR pathway, autophagy plays a role in reducing NiCl2-induced renal toxicity, and a major mechanism in autophagy's inhibitory effect on NiCl2-induced apoptosis may be mitophagy.

Protective effects of Abrus cantoniensis Hance against liver injury through modulation of intestinal microbiota and liver metabolites.

Abrus cantoniensis Hance (ACH) is an ancient Chinese medicine herb known for its therapeutic effects. This study investigated the potential protective effect of ACH against carbon tetrachloride (CCl4)-induced liver damage in mice. Fifty (n= 50) ICR mice were grouped into five groups. CCl4 was intraperitoneally injected into different mice groups: AM (CCl4 induced), AD (ACH-treated with 25 mg/kg), AZ (ACH-treated with 50 mg/kg), and AG (ACH-treated with100mg/kg) after every three days for a total of 31 days. The control group was denoted as AC. Additionally, groups AD, AZ, and AG received daily doses of ACH via gavage throughout the study period. According to our findings, ACH administration prominently mitigated liver pathological lesions and the increased liver index induced by CCl4 in mice (p < 0.05). Treatment with ACH resulted in a dose-dependent recovery of GSH-px, SOD, and CAT activities (p < 0.001). Moreover, the levels of TNF-α, MDA, and ALT showed significanlty decreasing trends with various doses of ACH (p < 0.001). Furthermore, 16 S rRNA gene sequencing demonstrated that ACH increased the abundance of beneficial genera of Comoclathris, Aureobasidium, and Kazachstania while decreased the presence of pathogenic genera such as Sporobolomyces and Filobasidium. Additionally, ACH treatment ameliorated the changes in liver metabolism due to CCl4 and enhanced the beneficial liver metabolites. In conclusion, ACH shows potential in protecting the liver against oxidative stress and inflammation caused by CCl4 exposure, possibly through its effects on gut microbiota and liver metabolism. Therefore, the use of ACH may offer an effective approach for alleviating CCl4-induced liver injury.

Comprehensive analysis of clinical indications and viral strain variants among patients infected with SARS-CoV-2 in Inner Mongolia, China.

Since the first appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, the virus is still evolving and mutating until now. In this study, we collected 6 throat swabs from patients who diagnosed with COVID-19 in Inner Mongolia, China, to understand the entry of multiple SARS-CoV-2 variants into Inner Mongolia and analyze the relationships between variants and clinical features observed in infected patients. In addition, we performed a combined analysis of clinical parameters associated with SARS-CoV-2 variants of interest, pedigree analysis, and detection of single-nucleotide polymorphisms. Our results showed that the clinical symptoms were generally mild although some patients demonstrated some degree of liver function abnormalities, and the SARS-CoV-2 strain was related to the Delta variant (B.1.617.2), AY.122 lineage. The epidemiological investigations and clinical manifestations confirmed that the variant exhibits strong transmission, a high viral load, and moderate clinical symptoms. SARS-CoV-2 has undergone extensive mutations in various hosts and countries. Timely monitoring of virus mutation can help to monitor the spread of infection and characterize the diversity of genomic variants, thus limiting future waves of SARS-CoV-2 infection.

Associations of dietary copper intake with cardiovascular disease and mortality: findings from the Chinese Perspective Urban and Rural Epidemiology (PURE-China) Study.

BACKGROUND: Previous in vitro and animal experiments have shown that copper plays an important role in cardiovascular health. Dietary copper is the main source of copper in the human body and the association between dietary copper and cardiovascular disease remains unclear. Our study aimed to investigate the associations of dietary copper intake with the risk of major cardiovascular disease incidence, cardiovascular disease mortality, and all-cause mortality in Chinese adults. METHODS: Our study is based on Prospective Urban Rural Epidemiology China (PURE-China), a large prospective cohort study of 47 931 individuals aged 35-70 years from 12 provinces in China. Dietary intake was recorded using a validated semi-quantitative food frequency questionnaire designed specifically for the Chinese population. The daily intake of copper was obtained by multiplying the daily food intake with the nutrient content provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary copper intake with mortality, major cardiovascular disease events, and their composite. RESULTS: A total of 45 101 participants (mean age: 51.1 ± 9.7 years old) with complete information were included in the current study. The mean dietary copper intake was 2.6 ± 1.1 mg/d. During the 482 833 person-years of follow-up, 2 644(5.9%) participants died, 4 012(8.9%) developed new cardiovascular diseases, and 5 608(12.4%) participants experienced the composite endpoint. Compared with those in the first and second quartile of dietary copper intake, individuals in the third and fourth quantile had higher risk of composite outcomes, all-cause death, cardiovascular disease death, major cardiovascular disease and stroke occurrences. The associations remained similar in the subgroup and sensitivity analyses. CONCLUSIONS: Our findings demonstrated that excessive dietary copper intake was associated with higher risks of death and cardiovascular diseases in Chinese adults. Further studies in populations with different dietary characteristics are needed to obtain dose-response relationships and to refine global dietary recommendations.

Sustained expression of MCP-1 induced low wall shear stress loading in conjunction with turbulent flow on endothelial cells of intracranial aneurysm.

Shear stress was reported to regulate the expression of AC007362, but its underlying mechanisms remain to be explored. In this study, to isolate endothelial cells of blood vessels, unruptured and ruptured intracranial aneurysm (IA) tissues were collected from IA patients. Subsequently, quantitative real-time PCR (qRT-PCR), Western blot and luciferase assay were performed to investigate the relationships between AC007362, miRNAs-493 and monocyte chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) exposed to shear stress. Reduced representation bisulphite sequencing (RRBS) was performed to assess the level of DNA methylation in AC007362 promoter. Accordingly, AC007362 and MCP-1 were significantly up-regulated while miR-493 was significantly down-regulated in HUVECs exposed to shear stress. AC007362 could suppress the miR-493 expression and elevate the MCP-1 expression, and miR-493 was shown to respectively target AC007362 and MCP-1. Moreover, shear stress in HUVECs led to the down-regulated DNA methyltransferase 1 (DNMT1), as well as the decreased DNA methylation level of AC007362 promoter. Similar results were also observed in ruptured IA tissues when compared with unruptured IA tissues. In conclusion, this study presented a deep insight into the operation of the regulatory network of AC007362, miR-493 and MCP-1 upon shear stress. Under shear stress, the expression of AC007362 was enhanced by the inhibited promoter DNA methylation, while the expression of MCP-1 was enhanced by sponging the expression of miR-493.

Corrosion Resistance of ZnO Nanorod Superhydrophobic Coatings with Rose Petal Effect or Lotus Leaf Effect.

Superhydrophobic ZnO nanorods coatings with a strong adhesive force to the surface (rose petal effect) or a low sliding angle (lotus leaf effect) were fabricated on the zinc plate by the hydrothermal plus sol-gel method. The corrosion resistance and durability of the superhydrophobic coatings in 5 wt% NaCl solution were investigated. The coating with loose ZnO nanostructure on ZnO nanorods shows a high adhesive force to water with low corrosion resistance, while the coating with a layer of dense nanotubes on nanorods exhibits a low adhesive to water with a high corrosion resistance due to a layer of trapped air among micro/nanostructures, which can delay the penetration of corrosive media. It can be found that the nanorods coating with lotus leaf effect lost its superhydrophobicity after 5150 s immersion in salt solution and the water repellency model is transformed from Cassie state to Wenzel state.

[Analysis of DSPP gene mutation in a Chinese pedigree affected with hereditary dentinogenesis imperfecta].

OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with hereditary dentinogenesis imperfecta and mutation of dentin sialophosphoprotein (DSPP) gene. METHODS: Affected members underwent intraoral photography, dental film and panoramic radiography. Genomic DNA was extracted from peripheral venous blood samples. Coding regions of the DSPP gene were subjected to PCR amplification and Sanger sequencing. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. The tertiary structure of wild type and mutant proteins were predicted by Swiss-Port. RESULTS: A heterozygous c.50C to T (p.P17L) mutation was identified in exon 2 of the DSPP gene in the proband and her father. The same mutation was not found among 200 unrelated healthy controls. The Pro-17 residues and its surrounding positions in DSPP are highly conserved across various species. The mutation was predicted to be damaging to the structure of DSPP protein. CONCLUSION: The c.50C to T (p.P17L) mutation of the DSPP gene probably underlies the disease in this pedigree. Above finding has expanded the spectrum of DSPP gene mutations and provided a basis for genetic counseling and prenatal diagnosis for this family.

Exosomes derived from endothelial progenitor cells attenuate vascular repair and accelerate reendothelialization by enhancing endothelial function.

BACKGROUND AIMS: Exosomes, a key component of cell paracrine secretion, can exert protective effects in various disease models. However, application of exosomes in vascular repair and regeneration has rarely been reported. In this study, we tested whether endothelial progenitor cell (EPC)-derived exosomes possessed therapeutic effects in rat models of balloon-induced vascular injury by accelerating reendothelialization. METHODS: Exosomes were obtained from the conditioned media of EPCs isolated from human umbilical cord blood. Induction of the endothelial injury was performed in the rats' carotid artery, and the pro-re-endothelialization capacity of EPC-derived exosomes was measured. The in vitro effects of exosomes on the proliferation and migration of endothelial cells were investigated. RESULTS: We found that the EPC-derived exosomes accelerated the re-endothelialization in the early phase after endothelial damage in the rat carotid artery. We also demonstrated that these exosomes enhanced the proliferation and migration of endothelial cells in vitro. Moreover, endothelial cells stimulated with these exosomes showed increased expression of angiogenesis-related molecules. CONCLUSIONS: Taken together, our results indicate that exosomes are an active component of the paracrine secretion of human EPCs and can promote vascular repair in rat models of balloon injury by up-regulating endothelial cells function.

Infrainguinal Endovascular Recanalization: Risk Factors for Arterial Thromboembolic Occlusions and Efficacy of Percutaneous Aspiration Thrombectomy.

PURPOSE: To investigate factors predictive of thromboembolic occlusions and evaluate the efficacy of percutaneous aspiration thrombectomy (PAT) for infrainguinal thromboembolic occlusions in patients undergoing endovascular recanalization (EVR). MATERIALS AND METHODS: In this single-center retrospective study, 23 patients who underwent PAT for thromboembolism during EVR and 237 patients who underwent successful EVR without thromboembolic occlusions (control group) were enrolled. Immediate posttreatment and follow-up outcomes between groups were compared. Multivariate analysis was performed to identify factors predictive of thromboembolic occlusions. Technical success of PAT was defined as achievement of < 30% residual stenosis and restoration of modified thrombolysis in myocardial infarction grade 3 flow. RESULTS: The technical success rate was 95.7% in the PAT group. After intervention, ankle brachial index (ABI), restoration of blood flow, and improvement in dorsal/plantar arterial pulse score showed no significant differences between the PAT and control groups. During follow-up, no significant differences were observed between groups in improvement of sustained ABI and maximum walking distance, ulcer healing, restenosis/occlusion and limb salvage rates, and pain relief in patients with critical ischemia. Stenosis greater than 90% with lesion occlusion (odds ratio, 12.891; 95% confidence interval, 1.676-99.161; P = .014) and intraluminal angioplasty (odds ratio, 18.423; 95% confidence interval, 2.408-140.942; P = .005) were associated with a high incidence of thromboembolism. CONCLUSIONS: Stenosis greater than 90% with lesion occlusion and intraluminal angioplasty may be factors predictive of thromboembolic occlusions. PAT is a safe and effective treatment for thromboembolism during infrainguinal arterial EVR.

Effects of registered nurse staffing level on hospital-acquired conditions in cardiac surgery patients: A propensity score matching analysis.

BACKGROUND: The ramifications of inadequate nurse staffing may have serious consequences due to reimbursement policies. PURPOSE: To determine the effects of registered nurse staffing on hospital-acquired conditions in cardiac surgery patients. METHOD: Data from the 2009 to 2011 Nationwide Inpatient Sample were used to construct a propensity score-matched cohort. Multivariate regressions were performed to compare the probability, length of stay, mortality, and costs of three common hospital-acquired conditions between low- and high-staffing hospitals. RESULTS: A total of 439,365 patients in low-staffing hospitals were 1:1 matched to patients in high-staffing hospitals. High-staffing hospitals had 10% to 25% fewer cases (adjusted odds ratio [AOR] 0.75-0.90, p < .0001), 5% to 20% lower mortality (AOR 0.80-0.95, p < .0001), and 4% to 6% shorter length of stay (coefficient -0.06 to -0.04, p < .0001). The costs for patients with hospital-acquired conditions were 13% to 17% greater in high-staffing hospitals (coefficient 0.13-0.17, p < .0001). CONCLUSIONS: Alternatives to the current staffing and reimbursement policies should be considered to reduce hospital-acquired conditions.

Associations of serum carotenoids with asthma and mortality in the US adults.

Objective: This study was to investigate the association between serum carotenoid levels and the prevalence of asthma, as well as the relationship between serum carotenoid levels and the risk of mortality among individuals with asthma. Methods: Data on five serum carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein/zeaxanthin, and lycopene) were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001-2006. Mortality data was extracted from the pertinent mortality records within the NHANES database, up to December 31, 2019. Logistic regression analysis was employed to investigate the association between serum carotenoid concentrations and asthma prevalence. Cox proportional hazards models were used to investigate the connection between serum carotenoids and mortality rates in asthma individuals. Results: Among the study population, 1569 (12.63 %) individuals were diagnosed with asthma, while 25.01 % of asthma patients died within a median follow-up duration of 15.5 (13.8-17.3) years. After controlling for all other variables, greater serum levels of certain carotenoids, such asα-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin, were found to be substantially linked with a decreased prevalence of asthma. Furthermore, persons with asthma who had greater levels of serum carotenoids in the fourth quartile had a significantly lower risk of all-cause death compared to those in the first quartile. Specifically, the presence of α-carotene, ß-cryptoxanthin, and lutein/zeaxanthin was associated with reductions in all-cause mortality by 45 % (HR = 0.55 [0.36-0.84], Ptrend = 0.002), 38 % (HR = 0.62 [0.42-0.92], Ptrend = 0.004), and 45 % (HR = 0.55 [0.41-0.73], Ptrend<0.001), respectively. The above relationships are mostly linear and remain robust in sensitivity analyses. Conclusions: Our findings indicate that higher serum carotenoids are related with a reduced likelihood of mortality in asthmatic individuals.

Nickel induces mitochondrial damage in renal cells in vitro and in vivo through its effects on mitochondrial biogenesis, fusion, and fission.

Nickel (Ni) and its compounds are common, widely distributed components of hazardous waste in the chemical industry. Excessive exposure to Ni can cause kidney damage in humans and animals. We investigated the impact of Ni on renal mitochondria using in vivo and in vitro models of Ni nephrotoxicity, and explored the Ni nephrotoxic mechanism. We showed that nickel chloride (NiCl2) damaged the renal mitochondria, causing mitochondrial swelling, breakage of the mitochondrial cristae, increased levels of mitochondrial reactive oxygen species (mt-ROS), and depolarization of the mitochondrial membrane potential (MMP). The levels of the mitochondrial respiratory chain complexes I-IV were reduced in the kidneys of mice treated with NiCl2. In addition, NiCl2 treatment inhibited mitochondrial biogenesis in renal cells by down-regulating mRNA and the protein expression of TFAM, PGC-1α, and NRF1. Moreover, NiCl2 reduced the levels of the proteins involved in mitochondrial fusion, including Mfn1 and Mfn2, while significantly augmenting the levels of the proteins Fis1 and Drip1 involved in mitochondrial fission in renal cells. Taken together, these results suggested that NiCl2 inhibited mitochondrial biogenesis, suppressed mitochondrial fusion, and promoted mitochondrial fission, resulting in mitochondrial dysfunction in renal cells, ultimately causing renal injury. This study provided novel insights into the mechanisms of nephrotoxicity of Ni and new ideas for the development of targeted treatments for Ni-induced kidney injury.

Data-Driven Linear Quadratic Optimization for Controller Synthesis With Structural Constraints.

For various typical cases and situations where the formulation results in an optimal control problem, the linear quadratic regulator (LQR) approach and its variants continue to be highly attractive. In certain scenarios, it can happen that some prescribed structural constraints on the gain matrix would arise. Consequently then, the algebraic Riccati equation (ARE) is no longer applicable in a straightforward way to obtain the optimal solution. This work presents a rather effective alternative optimization approach based on gradient projection. The utilized gradient is obtained through a data-driven methodology, and then projected onto applicable constrained hyperplanes. Essentially, this projection gradient determines a direction of progression and computation for the gain matrix update with a decreasing functional cost; and then the gain matrix is further refined in an iterative framework. With this formulation, a data-driven optimization algorithm is summarized for controller synthesis with structural constraints. This data-driven approach has the key advantage that it avoids the necessity of precise modeling which is always required in the classical model-based counterpart; and thus the approach can additionally accommodate various model uncertainties. Illustrative examples are also provided in the work to validate the theoretical results.

Clinical application of blood purification in polymyositis/dermatomyositis.

INTRODUCTION: We investigated the clinical efficacy and safety of blood purification technology in patients with polymyositis/dermatomyositis. METHODS: In a study of 22 patients, 10 cases received blood purification treatment (5 cases received plasma exchange, 5 cases received plasma HA280 immunoadsorption), and 12 cases served as the control group. A 3-month follow-up was conducted to compare the clinical manifestations and laboratory examination. RESULTS: Symptoms and signs of patients in treatment group were significantly improved, and the hormone usage was lower than the control group. For patients with normal creatine kinase level and ferritin level below three times the upper limit of normal, there was a positive correlation between their N/L values and MDAAT scores. CONCLUSION: The results of this study suggest that blood purification therapy, including plasma HA280 immunoadsorption and plasma exchange, is an effective and safe treatment for patients with polymyositis/dermatomyositis, offering assistance in reducing hormone usage in the long-term.

Association of preserved ratio impaired spirometry with mortality and cardiovascular diseases: a systematic review and meta-analysis.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is a type of abnormal lung function. PRISm and mortality have been explored in several studies, but a comprehensive evaluation of the associations is limited. The current study aims to conduct a systematic review and meta-analysis in order to investigate the mortality and cardiovascular diseases in patients with PRISm. METHODS: PubMed, Embase, and Web of Science databases, as well as gray literature sources, were searched for relevant studies published up to 7 September 2023 without language restrictions. This review included all published observational cohort studies that investigated the association of PRISm with mortality in the general population, as well as subgroup analyses in smokers and pre-bronchodilation spirometry studies. The outcomes of interest were all-cause mortality, cardiovascular mortality, and respiratory-related mortality. The Newcastle-Ottawa scale assessed study quality. Sensitivity and subgroup analyses explored heterogeneity and robustness. Publication bias was assessed with Egger's and Begg's tests. RESULTS: Overall, eight studies were included in this meta-analysis. The pooled HR was 1.60 (95% CI, 1.48-1.74) for all-cause mortality, 1.68 (95% CI, 1.46-1.94) for CVD mortality, and 3.09 (95% CI, 1.42-6.71) for respiratory-related mortality in PRISm group compared to normal group. In the subgroup analysis, participants with PRISm had a higher effect (HR, 2.11; 95% CI, 1.74-2.54) on all-cause mortality among smokers relative to participants with normal spirometry. Furthermore, the association between PRISm and mortality risk was consistent across several sensitivity analyses. CONCLUSIONS: People with PRISm were associated with an increased risk of all-cause mortality, CVD mortality, and respiratory-related mortality as compared to those with normal lung function in the general population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023426872.

Solid pseudopapillary neoplasm of the pancreas: a retrospective study of 195 cases.

Objective: Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare exocrine tumor of the pancreas. The aim of our study is to summarize the clinical features of SPN and to analyze the risk factors for malignant SPN. Methods: From May 2013 to September 2022, patients who were pathologically confirmed to have SPN were retrospectively reviewed. Demographic data, clinical and pathological features, follow-up data were collected and analyzed. To investigate the factors influencing the benign or malignant nature of SPN, we employed logistic regression. Additionally, we utilized Kaplan-Meier curves to depict and analyze the overall prognosis. Results: A total of 195 patients were included, 163 of whom were female and the average age of all patients was 31.7 years old. Among 195 patients, 101 patients (51.8%) had no obvious clinical symptoms and their pancreatic lesions were detected during routine examination. The primary symptom was abdominal pain and distension in 64 cases (32.8%). The maximum diameter of SPN tumors ranged from 1-17 cm (mean 6.19 cm). Forty-eight postoperative complications developed in 43 (22.1%) patients. After a median follow-up duration of 44.5 months, the overall 5-year survival rate was 98.8% and the recurrence rate was 1.5%. Furthermore, we observed a statistically significant difference in the completeness of the tumor capsule between benign and malignant SPN. Conclusion: SPN is associated with a favorable long-term survival after surgery in our large sample size cohort. For malignant SPN, tumor capsule incompleteness is an independent risk factor.

S-Adenosylmethionine (SAM) diet promotes innate immunity via histone H3K4me3 complex.

S-adenosylmethionine (SAM) was a methyl donor for modifying histones, which had crucial roles in lipid accumulation, tissue injury, and immune responses. SAM fluctuation might be linked to variations in histone methylation. However, the underlying molecular mechanisms of whether the SAM diet influenced the immune response via histone modification remained obscure. In this study, we utilized the Caenorhabditis elegans as a model to investigate the role of SAM diet in innate immunity. We found that 50 µM SAM increased resistance to Gram-negative pathogen Pseudomonas aeruginosa PA14 by reducing the bacterial burden in the intestine. Furthermore, through the genetic screening in C. elegans, we found that SAM functioned in germline to enhance innate immunity via an H3K4 methyltransferase complex to upregulate the immune response genes, including irg-1 and T24B8.5. Intriguingly, SAM also protected mice from P. aeruginosa PA14 infection by reducing the bacterial burden in lung. These findings provided insight into the mechanisms of molecular connections among SAM diet, histone modifications and innate immunity.

Polysaccharide from Panax japonicus C.A. Mey prevents non-alcoholic fatty liver disease development based on regulating liver metabolism and gut microbiota in mice.

In this study, a new polysaccharide (PSPJ) with specific molecular weight and monosaccharide compositions was isolated and purified from the water extract of Panacis Japonici Rhizoma (PJR). 16S rRNA analysis and untargeted metabolomic analysis were used to assess PSPJ's efficacy in averting non-alcoholic fatty liver disease (NAFLD). This study indicated that PSPJ significantly reduced liver fat accumulation, the increase in blood lipids and ALT caused by HFD, indicating that PSPJ can prevent NAFLD. We demonstrated through cell experiments that PSPJ does not directly affect liver cells. The gut microbiota disorder and alterations in short-chain fatty acids (SCFAs) induced by the high-fat diet (HFD) were ameliorated by PSPJ, as evidenced by the analysis of 16S rRNA. In particular, supplementing PSPJ reduced the abundance of Turicibacter, Dubosiella, and Staphylococcus, and increased the abundance of Bacteroides, Blautia, and Lactobacillus. Untargeted metabolomic analysis shows that PSPJ improves liver metabolic disorders by regulating arachidonic acid metabolism, carbohydrate digestion and absorption, fatty acid biosynthesis, fatty acid metabolism and retinol metabolism. The findings of our investigation indicate that PSPJ has the potential to modulate liver metabolism through alterations in the composition of intestinal bacteria, hence preventing NAFLD.

Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127 594 people from 20 countries (PURE): a prospective cohort study.

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.