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Context: Qi‐dan‐dihuang decoction (QDD) has been used to treat diabetic kidney disease (DKD), but the underlying mechanisms are poorly understood. Objective: This study reveals the mechanism by which QDD ameliorates DKD. Materials and Methods: The compounds in QDD were identified by high‐performance liquid chromatography and quadrupole‐time‐of‐flight tandem mass spectrometry (HPLC‐Q‐TOF‐MS). Key targets and signaling pathways were screened through bioinformatics. Nondiabetic Lepr db/m mice were used as control group, while Lepr db/db mice were divided into model group, dapagliflozin group, 1% QDD‐low (QDD‐L), and 2% QDD‐high (QDD‐H) group. After 12 weeks of administration, 24 h urinary protein, serum creatinine, and blood urea nitrogen levels were detected. Kidney tissues damage and fibrosis were evaluated by pathological staining. In addition, 30 mmol/L glucose‐treated HK‐2 and NRK‐52E cells to induce DKD model. Cell activity and migration capacity as well as protein expression levels were evaluated. Results: A total of 46 key target genes were identified. Functional enrichment analyses showed that key target genes were significantly enriched in the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) and mitogen‐activated protein kinase (MAPK) signaling pathways. In addition, in vivo and in vitro experiments confirmed that QDD ameliorated renal fibrosis in diabetic mice by resolving inflammation and inhibiting the epithelial‐mesenchymal transition (EMT) via the p38MAPK and AKT‐mammalian target of rapamycin (mTOR) pathways. Discussion and Conclusion: QDD inhibits EMT and the inflammatory response through the p38MAPK and AKT/mTOR signaling pathways, thereby playing a protective role in renal fibrosis in DKD. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process. Purpose: The study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated. Methods and Results: Three-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects. Conclusion: Taken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome. [ABSTRACT FROM AUTHOR]

Inflammation and apoptosis of vascular endothelial cells play a key role in the occurrence and development of atherosclerosis (AS), and the AMPK/mTOR/Nrf2 signaling pathway plays an important role in alleviating the symptoms of AS. Geniposide combined with notoginsenoside R1 (GN combination) is a patented supplement for the prevention and treatment of AS. It has been proven to improve blood lipid levels and inhibit the formation of AS plaques; however, it is still unclear whether GN combination can inhibit inflammation and apoptosis in AS by regulating the AMPK/mTOR/Nrf2 signaling pathway and its downstream signals. Our results confirmed that the GN combination could improve blood lipid levels and plaque formation in ApoE −/− mice fed with a high-fat diet (HFD), inhibit the secretion of serum inflammatory factors and oxidative stress factors. It also decreased the expression of pyrin domain containing protein 3 (NLRP3) inflammasome-related protein and Bax/Bcl2/caspase-3 pathway-related proteins. At the same time, the GN combination could also inhibit the H2O2-induced inflammatory response and apoptosis of human umbilical vein endothelial cells (HUVECs), which is mainly related to the activation of the AMPK/mTOR pathway by GN combination, which in turn induces the activation of Nrf2/HO-1 signal. In addition, the above phenomenon could be significantly reversed by dorsomorphin. Therefore, our experiments proved for the first time that the GN combination can effectively inhibit AS inflammation and apoptosis by activating the AMPK/mTOR/Nrf2 signaling pathway to inhibit the NLRP3 inflammasome and Bax/Bcl2/caspase-3 pathway. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth leading cancer type and the second most common gynecological malignancy among women worldwide. Silibinin (SB), a chief bioactive natural polyphenolic flavonoid of Silybum marianum L., has been used clinically for its hepatocyte protective effects. It also has anticancer effects via the induction of apoptosis and cell cycle arrest. However, the effects of SB on cervical cancer cells through mitochondrial fission have not been studied. Here, we showed that SB markedly suppressed cervical cell proliferation by inducing G2/M cell cycle arrest via the activation of dynamin-related protein 1 (Drp1), which in turn mediated the mitochondrial fission dysfunction both in vitro and in vivo. SB decreased the ATP content, mitochondrial membrane potential, and mtDNA copy number, as well as reduced the reactive oxygen species levels in cervical cells. Furthermore, SB induced excessive mitochondrial fragmentation and reduced tubule formation. Further study showed that knockdown of Drp1 abolished the SB-induced G2/M cell cycle arrest in cervical cancer cells by inhibiting the mitochondrial fission pathway. More importantly, SB inhibited Hela cell growth in vivo model. In conclusion, we are the first to demonstrate that SB induces cervical cancer cell G2/M cell cycle arrest by activating Drp1-dependent mitochondrial fission dysfunction. This study suggests the strategy of inducing Drp1-dependent mitochondrial fission for cervical cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Ilex pubescens Hook et Arn mainly contains triterpenoids that possess antithrombotic, anti‐inflammatory and analgesic effects. Quantitative and qualitative analyses of the triterpenoids in I. pubescens can be useful for determining the authenticity and quality of raw materials and guiding its clinical preparation. Objectives: To establish a method for rapid and comprehensive analysis of triterpenoids in I. pubescens using ultra‐high‐performance liquid chromatography coupled to electrospray ionisation and quadrupole time‐of‐flight‐mass spectrometry (UPLC‐ESI‐QTOF‐MS), which will also be applied to evaluate the contents of nine triterpenoids among root, root heartwood and root bark of I. pubescens to judge the value of the root bark to avoid wastage. Methods: UPLC‐ESI‐QTOF‐MS data from the extracts of I. pubescens in negative mode were analysed using Peakview and Masterview software that provided molecular weight, mass errors, isotope pattern fit and MS/MS fragments for the identification of triterpenoids. The quantification of nine investigated compounds of I. pubescens was accomplished using MultiQuant software. Results: A total of 33 triterpenoids, five phenolic acids, two lignans and a flavonol were characterised in only 14 min. The total content of the nine compounds in the root bark was generally slightly higher than that of the root and root heartwood, which has not been reported before. Conclusion: The developed UPLC‐ESI‐QTOF‐MS method was proven to be rapid and comprehensive for simultaneous qualitative and quantitative analyses of the characteristic triterpenoids in I. pubescens. The results may provide a basis for holistic quality control and metabolic studies of I. pubescens, as well as serve as a reference for the analysis of other Ilex plants. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Symmetrical solid oxide fuel cells (SSOFCs) with identical anode and cathode have many benefits compared with traditional SOFCs. However, it is still a challenge to find high performance electrode materials with excellent catalytic activity and preferable stability under both reducing and oxidizing atmosphere. Here, a novel Ba 0.9 La 0.1 Co 0.7 Fe 0.2 Nb 0.1 O 3-δ (BLCFN) perovskite electrode has been developed as promising symmetrical electrode material for SSOFCs. The A-site non-stoichiometry introduced in BLCFN simultaneously enhances both the cathode and anode electrocatalytic performance. The cathode polarization resistance of BLCFN with 5% deficiency is decreased by 28.6% to 0.05 Ω·cm2 at 750°C in air, which can be mainly attributed to the increase of oxygen vacancy concentration via partial ionic defect. The BLCFN anode polarization resistance is reduced by 42.1% to 0.11 Ω·cm2 at 750°C in 5% H 2 /N 2. The promoted hydrogen oxidation reaction activity of BLCFN is related to the exsolved homogeneous Co-Fe nanoparticles from BL95CFN substrate in reducing atmosphere. The full cell with BL95CFN symmetrical electrodes displays high redox stability through reversing the flow of wet hydrogen and ambient air. Additionally, this SSOFCs with strong anchor characteristic of exsolved Co-Fe nanoparticles shows excellent coking-tolerance using methane fuel compared with traditional Ni-SDC anode. This work provides a potential way towards the development of high-performance, excellent redox-stable and coking-tolerant SSOFCs. [ABSTRACT FROM AUTHOR]

Background. Chinese herbal medicines are widely used to lower serum uric acid levels. However, no systemic review summarizes and evaluates their efficacies and the underlying mechanisms of action. Objectives. To evaluate the clinical and experimental evidences for the effectiveness and the potential mechanism of Chinese herbal medicines in lowering serum uric acid levels. Methods. Four electronic databases PubMed, Wed of Science, the Cochrane Library and Embase were used to search for Chinese herbal medicines for their effects in lowering serum uric acid levels, dated from 1 January 2009 to 19 August 2020. For clinical trials, randomized controlled trials (RCTs) were included; and for experimental studies, original articles were included. The methodological quality of RCTs was assessed according to the Cochrane criteria. For clinical trials, a meta-analysis of continuous variables was used to obtain pooled effects. For experimental studies, lists were used to summarize and integrate the mechanisms involved. Results. A total of 10 clinical trials and 184 experimental studies were included. Current data showed that Chinese herbal medicines have promising clinical efficacies in patients with elevated serum uric acid levels (SMD: −1.65, 95% CI: −3.09 to −0.22; p = 0.024). There was no significant difference in serum uric acid levels between Chinese herbal medicine treatments and Western medicine treatments (SMD: −0.13, 95% CI: −0.99 to 0.74; p = 0.772). Experimental studies revealed that the mechanistic signaling pathways involved in the serum uric acid lowering effects include uric acid synthesis, uric acid transport, inflammation, renal fibrosis and oxidative stress. Conclusions. The clinical studies indicate that Chinese herbal medicines lower serum uric acid levels. Further studies with sophisticated research design can further demonstrate the efficacy and safety of these Chinese herbal medicines in lowering serum uric acid levels and reveal a comprehensive picture of the underlying mechanisms of action. [ABSTRACT FROM AUTHOR]

Background: The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown., Results: A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3 -/- ) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated., Conclusion: Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract., (© 2024. The Author(s).)

Purpose: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice., Methods: PCCL was orally administered at a dose of 20 mg·kg-1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg-1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1β levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2., Results: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression., Conclusions: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.

Background: Lung cancer is the leading cause of cancer-associated mortality worldwide, and most lung cancers are classified as non-small cell lung cancer (NSCLC). MiR-328 influence the progression of multiple tumors, but the role of miR-328-5p in NSCLC has not been elucidated. The aim of this study was to illuminate the oncogenic role and potential molecular mechanisms of the miR-328-5p and lysyl oxidase like 4 (LOXL4) in NSCLC., Methods: Expression of miR-328-5p was detected by real-time quantitative polymerase chain reaction (qRT-PCR) in tumor and non-tumor adjacent tissues. After Lentivirus-miR-328-5p was employed to intervene this miRNA in NSCLC cell lines, RT-qPCR was used to detect the expression levels of miR-328-5p. Cell Counting Kit-8 (CCK-8), cell colony formation, flow cytometry, wound healing, Transwell assays were used to determine the malignant phenotypes of NSCLC cells. Nude mice models of subcutaneous tumors were established to observe the effect of miR-328-5p on tumorigenesis. Targeting the 3'UTR of LOXL4 by miR-328-5p was verified by integrated analysis including transcriptome sequencing, dual-luciferase and western-blot assays., Results: High miR-328-5p level was observed in NSCLC cells from The Cancer Genome Atlas (TCGA) database and tumor tissues collected from NSCLC patients. Overexpressed miR-328-5p promoted NSCLC cell proliferation, survival, and migration, and promoted tumor growth in vivo . Knockdown of miR-328-5p suppressed tumorigenic activities. Transcriptome sequencing analysis revealed that LOXL4 was downregulated by miR-328-5p, which was confirmed by dual-luciferase reporter and western-blot assays., Conclusions: miR-328-5p showed targeted regulation of LOXL4 to promote cell proliferation and migration in NSCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-345/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Intestinal microbial colonization in early life plays a crucial role in immune development and mucosal homeostasis in later years. Antibiotic exposure in early life increases the risk of inflammatory bowel disease (IBD). Ginger acts like a prebiotic and has been used in traditional Chinese medicine for colitis. We investigated the protective effect of ginger against dextran sulfate sodium (DSS)-induced colitis in mice exposed to antibiotic in their early years. Methods: A weaned mouse model exposed to azithromycin (AZT) for 2 weeks was used to mimic antibiotic exposure in childhood among humans. A diet containing ginger extract was administered to mice for 4 weeks after antibiotic exposure. The susceptibility to DSS-induced colitis was evaluated in terms of weight loss, disease activity index (DAI) score, colon length, colitis biomarkers, and intestinal barrier function. The gut microbiota was analyzed in terms of 16S rRNA levels. Results: Ginger extract prevented weight loss, colon shortening, inflammation, and intestinal barrier dysfunction in mice exposed to antibiotics in early life. Ginger increased the bacterial diversity and changed the abundance of bacterial belonging to family Peptococcaceae and Helicobacter species to modulate microbiota structure and composition adversely affected by early antibiotic exposure. Conclusion: Ginger has a protective effect in potentially decreasing the susceptibility to colitis in mice exposed to antibiotics early in life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Liu, He, Wang, Lu, You, Chen, Cheng, Li, Fu, Kwan, Zhou and Zhao.)

Heart, liver, and kidney, which are known as the essential organs for metabolism, possess the unique ability to regulate the proliferation function of the body against injury. Silibinin (SB), a natural polyphenolic flavonoid extracted from traditional herb Silybum marianum L., has been used to protect hepatocytes. Whether SB can regulate mitochondrial fission in normal cells and the underlying mechanisms remain unclear. Here, we showed that SB markedly promoted cell proliferation by facilitating G1/S transition via activating dynamin-related protein 1 (Drp1), which in turn mediated mitochondrial fission in these normal cells. SB dose-dependently increased the mitochondrial mass, mtDNA copy number, cellular adenosine triphosphate production, mitochondrial membrane potential, and reactive oxygen species in normal cells. Furthermore, SB dose-dependently increased the expression of Drp1. Blocking Drp1 abolished SB-induced mitochondrial fission. In conclusion, we demonstrate that SB promotes cell proliferation through facilitating G1/S transition by activating Drp1-mediated mitochondrial fission. This study suggests that SB is a potentially useful herbal derivative for the daily prevention of various diseases caused by impaired mitochondrial fission.

Introduction: Ilex pubescens Hook et Arn mainly contains triterpenoids that possess antithrombotic, anti-inflammatory and analgesic effects. Quantitative and qualitative analyses of the triterpenoids in I. pubescens can be useful for determining the authenticity and quality of raw materials and guiding its clinical preparation., Objectives: To establish a method for rapid and comprehensive analysis of triterpenoids in I. pubescens using ultra-high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS), which will also be applied to evaluate the contents of nine triterpenoids among root, root heartwood and root bark of I. pubescens to judge the value of the root bark to avoid wastage., Methods: UPLC-ESI-QTOF-MS data from the extracts of I. pubescens in negative mode were analysed using Peakview and Masterview software that provided molecular weight, mass errors, isotope pattern fit and MS/MS fragments for the identification of triterpenoids. The quantification of nine investigated compounds of I. pubescens was accomplished using MultiQuant software., Results: A total of 33 triterpenoids, five phenolic acids, two lignans and a flavonol were characterised in only 14 min. The total content of the nine compounds in the root bark was generally slightly higher than that of the root and root heartwood, which has not been reported before., Conclusion: The developed UPLC-ESI-QTOF-MS method was proven to be rapid and comprehensive for simultaneous qualitative and quantitative analyses of the characteristic triterpenoids in I. pubescens. The results may provide a basis for holistic quality control and metabolic studies of I. pubescens, as well as serve as a reference for the analysis of other Ilex plants. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)