Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Rutin enhances mitochondrial function and improves the developmental potential of vitrified ovine GV-stage oocyte.

Vitrification of oocyte has become an important component of assisted reproductive technology and has important implications for animal reproduction and the preservation of biodiversity. However, vitrification adversely affects mitochondrial function and oocyte developmental potential, mainly because of oxidative damage. Rutin is a highly effective antioxidant, but no information is available to the effect of rutin on the mitochondrial function and development in vitrified oocytes. Therefore, we studied the effects of rutin supplementation of vitrification solution on mitochondrial function and developmental competence of ovine germinal vesicle (GV) stage oocytes post vitrification. The results showed that supplementation of vitrification solution with 0.6 mM rutin significantly increased the cleavage rate (71.6 % vs. 59.3 %) and blastocyst rate (18.9 % vs. 6.8 %) compared to GV-stage oocytes in the vitrified group. Then, we analyzed the reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and membrane potential (ΔΨm), endoplasmic reticulum (ER) Ca2+, and annexin V (AV) of vitrified sheep GV-stage oocytes. Vitrified sheep oocytes exhibited increased levels of ROS and Ca2+, higher rate of AV-positive oocytes, and decreased mitochondrial activity, GSH and ΔΨm levels. However, rutin supplementation in vitrification solution decreased the levels of ROS, Ca2+ and AV-positive oocytes rate, and increased the GSH and ΔΨm levels in vitrified oocytes. Results revealed that rutin restored mitochondrial function, regulated Ca2+ homeostasis and decreased apoptosis potentially caused by mitophagy in oocytes. To understand the mechanism of rutin functions in vitrified GV-stage oocytes in sheep, we analyzed the transcriptome and found that rutin mediated oocytes development and mitochondrial function, mainly by affecting oxidative phosphorylation and the mitophagy pathways. In conclusion, supplementing with 0.6 mM rutin in vitrification solution significantly enhanced developmental potential through improving mitochondrial function and decreased apoptosis potentially caused by mitophagy after vitrification of ovine GV-stage oocytes.

Cichoric acid ameliorates sepsis-induced acute kidney injury by inhibiting M1 macrophage polarization.

Cichoric acid (CA), a widely utilized polyphenolic compound in medicine, has garnered significant attention due to its potential health benefits. Sepsis-induced acute kidney disease (AKI) is related with an elevated risk of end-stage kidney disease (ESKD). However, it remains unclear whether CA provides protection against septic AKI. The aim of this study is to investigated the protective effect and possible mechanisms of CA against LPS-induced septic AKI. Sepsis-induced AKI was induced in mice through intraperitoneal injection of lipopolysaccharide (LPS), and RAW264.7 macrophages were incubated with LPS. LPS exposure significantly increased the levels of M1 macrophage biomarkers while reducing the levels of M2 macrophage indicators. This was accompanied by the release of inflammatory factors, superoxide anion production, mitochondrial dysfunction, activation of succinate dehydrogenase (SDH), and subsequent succinate formation. Conversely, pretreatment with CA mitigated these abnormalities. CA attenuated hypoxia-inducible factor-1α (HIF-1α)-induced glycolysis by lifting the NAD+/NADH ratio in macrophages. Additionally, CA disrupted the K (lysine) acetyltransferase 2A (KAT2A)/α-tubulin complex, thereby reducing α-tubulin acetylation and subsequently inactivating the NLRP3 inflammasome. Importantly, administration of CA ameliorated LPS-induced renal pathological damage, apoptosis, inflammation, oxidative stress, and disturbances in mitochondrial function in mice. Overall, CA restrained HIF-1α-mediated glycolysis via inactivation of SDH, leading to NLRP3 inflammasome inactivation and the amelioration of sepsis-induced AKI.

Genome-Wide Identification and Expression Profiling of the ABF Transcription Factor Family in Wheat (Triticum aestivum L.).

Members of the abscisic acid (ABA)-responsive element (ABRE) binding factor (ABF) and ABA-responsive element binding protein (AREB) families play essential roles in the regulation of ABA signaling pathway activity and shape the ability of plants to adapt to a range of stressful environmental conditions. To date, however, systematic genome-wide analyses focused on the ABF/AREB gene family in wheat are lacking. Here, we identified 35 ABF/AREB genes in the wheat genome, designated TaABF1-TaABF35 according to their chromosomal distribution. These genes were further classified, based on their phylogenetic relationships, into three groups (A-C), with the TaABF genes in a given group exhibiting similar motifs and similar numbers of introns/exons. Cis-element analyses of the promoter regions upstream of these TaABFs revealed large numbers of ABREs, with the other predominant elements that were identified differing across these three groups. Patterns of TaABF gene expansion were primarily characterized by allopolyploidization and fragment duplication, with purifying selection having played a significant role in the evolution of this gene family. Further expression profiling indicated that the majority of the TaABF genes from groups A and B were highly expressed in various tissues and upregulated following abiotic stress exposure such as drought, low temperature, low nitrogen, etc., while some of the TaABF genes in group C were specifically expressed in grain tissues. Regulatory network analyses revealed that four of the group A TaABFs (TaABF2, TaABF7, TaABF13, and TaABF19) were centrally located in protein-protein interaction networks, with 13 of these TaABF genes being regulated by 11 known miRNAs, which play important roles in abiotic stress resistance such as drought and salt stress. The two primary upstream transcription factor types found to regulate TaABF gene expression were BBR/BPC and ERF, which have previously been reported to be important in the context of plant abiotic stress responses. Together, these results offer insight into the role that the ABF/AREB genes play in the responses of wheat to abiotic stressors, providing a robust foundation for future functional studies of these genes.

Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice.

BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.

SIRT2 regulates apoptosis by inducing mitophagy in sheep cumulus cells.

Cumulus cells surrounding oocytes furnish nutritional support crucial for oocyte maturation in vitro, and thereby enhance oocyte quality significantly. Our previous studies affirmed the role of SIRT2 in regulation of mitochondrial function in sheep granulosa cells. However, the effect of SIRT2 action on mitophagy in these cells remain unclear. Here, RNA-seq was used to scrutinize pathways where differentially expressed genes (DEGs) are enriched following SIRT2 knockdown in cumulus cells. Prior to SIRT2 knock down, cumulus cells were treated with the mitophagy inhibitor Mdivi-1. Potential mechanisms by which SIRT2 affects apoptosis via mitophagy were explored. Results indicated that DEGs after SIRT2 knockdown were enriched in various pathways including mitochondria, mitophagy, and apoptosis. The expression levels of CASP3/CASP9 were significantly increased after mitophagy activation (P < 0.01), whereas inhibition of mitophagy had no effect on apoptosis (P > 0.05). Pretreatment of cumulus cells with Mdivi-1 prior to SIRT2 knockdown significantly reduced the expression of mitophagy-related genes, the number of autolysosomes, the expression of CASP3/CASP9, and the levels of Ca2+ and cytochrome C (P < 0.05). In addition, an improvement in mitochondrial morphology and increases in ATP levels and mitochondrial DNA (mtDNA) copy numbers were observed. Interestingly, double knockdown of SIRT2 and MAPK15 was found to reverse increased mitophagy and apoptosis activity caused by SIRT2 knockdown. Our findings indicate that SIRT2 modulate apoptosis in cumulus cells by regulating mitophagy, with MAPK15 likely playing a pivotal role in this process.

Comparative Transcriptome Analysis Reveals the Genes and Pathways Related to Wheat Root Hair Length.

Tube-like outgrowths from root epidermal cells, known as root hairs, enhance water and nutrient absorption, facilitate microbial interactions, and contribute to plant anchorage by expanding the root surface area. Genetically regulated and strongly influenced by environmental conditions, longer root hairs generally enhance water and nutrient absorption, correlating with increased stress resistance. Wheat, a globally predominant crop pivotal for human nutrition, necessitates the identification of long root hair genotypes and their regulatory genes to enhance nutrient capture and yield potential. This study focused on 261 wheat samples of diverse genotypes during germination, revealing noticeable disparities in the length of the root hair among the genotypes. Notably, two long root hair genotypes (W106 and W136) and two short root hair genotypes (W90 and W100) were identified. Transcriptome sequencing resulted in the development of 12 root cDNA libraries, unveiling 1180 shared differentially expressed genes (DEGs). Further analyses, including GO function annotation, KEGG enrichment, MapMan metabolic pathway analysis, and protein-protein interaction (PPI) network prediction, underscored the upregulation of root hair length regulatory genes in the long root hair genotypes. These included genes are associated with GA and BA hormone signaling pathways, FRS/FRF and bHLH transcription factors, phenylpropanoid, lignin, lignan secondary metabolic pathways, the peroxidase gene for maintaining ROS steady state, and the ankyrin gene with diverse biological functions. This study contributes valuable insights into modulating the length of wheat root hair and identifies candidate genes for the genetic improvement of wheat root traits.

The clinical effectiveness and safety of traditional Chinese medicine uremic clearance granule combined with high-flux hemodialysis in the treatment of uremic pruritus: A protocol for systematic review and meta analysis.

BACKGROUND: Skin pruritus is a common complication in patients with uremia. When the hemodialysis time of patients is extended, and the probability of skin pruritus is greater. Patients often have the symptoms of skin pruritus intolerable, affecting the normal sleep and normal life of patients. The patients with uremic pruritus often constant scratching and pruritus skin, resulting in broken skin, and further symptoms such as infection, and subsequent skin shedding, prurigo nodularis, and other adverse complications, aggravating the patient's condition. Some patients will experience symptoms such as depression and insomnia due to skin pruritus, and simply scratching the skin lead to infection. Severely affected patients may even show suicidal tendency, endangering the physical and mental health of patients, and it is needed to give the effective treatment to patients. Hemodialysis is a common treatment for uremic pruritus, which can effectively relieve the pruritus symptoms of patients. The drugs can also relieve the symptoms and improve the degree of pruritus in patients. And some studies show that traditional Chinese medicine UCG combined with HFH in the treatment of uremic pruritus has a very good effect, Therefore, this study will systematically evaluate the clinical efficacy and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. METHODS: Use computer to search English and Chinese databases, English databases include: PubMed, Web of Science, EMbase, The Cochrane Library. Chinese databases include: CNKI, CBM, WanFang Data and VIP databases, collecting the RCT on the clinical effectiveness and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. The retrieval time is from the beginning of each database to May 1, 2021. In order to improve the retrieval rate of the literature, the references cited in the included research are also collected and screened. Set Chinese and English as the search language. Two members of the research group independently collected, included and excluded the literatures. In case of disagreement, consulting the third party to assist in the judgment. For the literature with missing data, the original author should be contacted as far as possible to obtain complete data. Two evaluators evaluate the bias risk of included studies according to the Cochrane Handbook bias risk assessment tool for RCT. RevMan 5.3 software is used for statistical analysis and the forest plot is drawn to show the outcome indicators and funnel plot is drawn to show the publication bias. RESULTS: This study evaluates the advantages and disadvantages of traditional Chinese medicine UCG combined with HFH and HFH alone in the treatment of uremic pruritus through the clinical effectiveness and safety-related indicators. CONCLUSION: This study will give a positive conclusion on the efficacy and safety of uremic clearance granule in the treatment of uremic pruritus, and the research results will be published in professional journals in the form of academic papers, thus benefiting more patients. ETHICS AND DISSEMINATION: This study belongs to meta-analysis and all data comes from academic papers published publicly in formal academic journals, so there are no ethical issues involved in this study and no ethical review or approval is required. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/W8P5G.

Serum Glycated Albumin Levels Are Affected by Alcohol in Men of the Jinuo Ethnic Group in China.

AIM: To investigate the effects of alcohol on serum glycated albumin (GA) levels in Chinese men. METHODS: A total of 2314 male subjects from the Jinuo ethnic group in China were enrolled. Of these, 986 subjects drank alcohol frequently and 404 subjects did not. Lifestyle information was gathered by using a questionnaire, and measurements of blood pressure, body mass index, blood glucose level, liver function, and kidney function were collected. GA was measured by using an enzymatic method. Frequent drinking was defined as a history of drinking ethanol > 80 g/d within the past two weeks. Nondrinking was defined as no alcohol consumption in the past three months. Subjects with an alcohol intake between 0 and 80 g/d in the past two weeks were included in the drinking-occasionally group. Analysis of variance (ANOVA), correlation analysis, and linear regression were used to evaluate the effects of drinking on serum GA levels. Decision tree regression (DTR) algorithm was used to evaluate the effect of features (variables) on GA levels. RESULTS: We found that male subjects who drank frequently had significantly lower serum GA levels than subjects who did not drink (13.0 ± 1.7 vs. 14.1 ± 3.7, p < 0.05). Spearman's correlation analysis calculated a coefficient of -0.152 between drinking and GA (p < 0.005). Linear regression established that drinking was an independent predictor for GA levels with a standardized regression coefficient of -0.144 (p < 0.05). Decision tree regression showed that the effect of drinking on GA levels (0.0283) is five times higher than that of smoking (0.0057). CONCLUSIONS: Frequent alcohol consumption could result in decreased GA levels in men of the Jinuo ethnic group in China.

Serum Cytokines Th1, Th2, and Th17 Expression Profiling in Active Lupus Nephritis-IV: From a Southern Chinese Han Population.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV.

[Chemical fractionation and pollution characteristics of heavy metals in the sediment of Nansihu Lake and its main inflow rivers, China].

Chemical forms of Cr, Cu, Mn, Ni, Pb and Zn in the surface sediments of Nansihu Lake and its main inflow rivers are determined by the BCR sequential extraction method. The chemical fractionation composition characteristics, pollution state and potential ecological effects of the heavy metals are discussed. Cr, Cu, Ni and Zn in the sediments of Sihe River, Jinghang Canal, Zhuzhaoxin River, Guangfu River, south area of the Upper Lakes, and Down Lakes mainly exist in residual fraction, which account for 80% - 90% of their content, mainly reflecting the natural characteristics of the heavy metals; but for the sediment of Old Canal, Guangfu River estuary, Baima River, nearly 80% of Cr, Cu, Ni and Zn exist in extractable fractions due to human pollution, especially with high oxidizable and acid extractable fractions content. Pb and Mn mainly exist in residual fraction and oxidizable fraction in the sediment of Nansihu Lake and its main inflow rivers, which account for 95% and 70% of the content of Pb and Mn, similar to other unpolluted sediments. With the mineralization and decomposition of organic matter and change of environment condition of the surface sediment, the extractable fractions of Cr, Cu, Ni, Zn in the polluted sediment can be reactivated, bringing on ecological harm to the water ecological system.

Association of HLA genes with diffuse panbronchiolitis in Chinese patients.

Diffuse panbronchiolitis (DPB) is a pulmonary disease of unknown etiology that predominantly affects East Asians, particularly Japanese with a prevalence of 0.00028. Research has shown that HLA-B54 and HLA-A11 are positively associated with this disease. HLA-A, -B, and -DR loci were analyzed using an oligonucleotide microarray in both Chinese patients with DPB and normal control subjects. The most marked difference between the patients and the controls was the decreased frequency of HLA-A2 (p=0.001, OR=0.12), which showed a negative association with the disease; however, there was no significant contribution of HLA-B loci. Interestingly, the frequency of HLA-A11 was increased (p=0.007, OR=3.9), in accordance with previous reports on Japanese and Koreans. In addition, the frequency of HLA-DRB5*010/020 slightly increased (p=0.049). The HLA-associated genes for DPB are located between the HLA-A and HLA-B loci. Differences in HLA-associated genes may partially explain differences in the incidence of DPB among different populations.