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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: Alzheimer's disease (AD) is a common progressive neurodegenerative disease characterized by memory impairments, and there is no effective therapy. Neural stem/progenitor cell (NSPC) has emerged as potential novel therapy for AD, and we aim to explore whether neural stem/progenitor cell therapy was effective for rodent models of AD. Methods: We searched PubMed, Embase, Cochrane Library and Web of Science up to December 6, 2022. The outcomes included cognitive function, pathological features and BDNF. The GetData Graph Digitizer software (version 2.26) was applied to extract numerical values, and RevMan 5.3 and Stata 16 were used to analyze data. The SYRCLE risk of bias tool was used to assess study quality. Results: We evaluated 22 mice studies and 8 rat studies. Compared to control groups, cognitive function of NSPC groups of both mice studies (SMD = − 1.96, 95% CI − 2.47 to − 1.45, I2 = 75%, P < 0.00001) and rat studies (SMD = − 1.35, 95% CI − 2.11 to − 0.59, I2 = 77%, P = 0.0005) was apparently improved. In mice studies, NSPC group has lower Aβ deposition (SMD = − 0.96, 95% CI − 1.40 to − 0.52, P < 0.0001) and p-tau level (SMD = − 4.94, 95% CI − 7.29 to − 2.95, P < 0.0001), higher synaptic density (SMD = 2.02, 95% CI 0.50–3.55, P = 0.009) and BDNF (SMD = 1.69, 95% CI 0.61–2.77, P = 0.002). Combined with nanoformulation (SMD = − 1.29, 95% CI − 2.26 to − 0.32, I2 = 65%, P = 0.009) and genetically modified (SMD = − 1.29, 95% CI − 1.92 to − 0.66, I2 = 60%, P < 0.0001) could improve the effect of NSPC. In addition, both xenogeneic and allogeneic transplant of NSPC could reverse the cognitive impairment of AD animal models. Conclusions: Our results suggested that NSPC therapy could improve the cognitive function and slow down the progression of AD. Due to the limitations of models, more animal trials and clinical trials are needed. [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]

The objective of this study was to identify the metabolites of rotundic acid after oral administration to rats and compare the similarities with its biotransformation by Syncephalastrum racemosum AS 3.264 using ultra-high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry. A total of fourteen metabolites were determined based on the mass spectrometry and chromatographic behaviors, among which eleven (M1–M3, M7–M14) and six (M2, M4–M8) metabolites were identified in rats and S. racemosum , respectively. Three identical metabolites (M2, M7 and M8) were found in rats and S. racemosum , indicating that there were metabolic similarities. Moreover, to confirm the results of mass spectrometry, three (M2, M4 and M7) metabolites were obtained by the means of amplifying incubation and their structures were determined by various spectroscopic analyses, and M4 was proved to be a previously undescribed compound. This results showed that in vitro assisted preparation by microbial transformation is a feasible and effective method of obtaining metabolites which are in low amounts and difficult to be prepared in vivo . [ABSTRACT FROM AUTHOR]