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Objective To explore the active components, targets and possible mechanism of Yishen Tongluo (Kidney-boosting Collateral-unblocking) Formula (YSTLF) in the treatment of diabetic kidney disease (DKD) based on network pharmacology. Methods The effective components and related targets of YXTLF were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform ( TCMSP), The Encyclopedia of Traditional Chinese Medicine ( ETCM) and A Bioinformatics Analysis Tool for Molecular mechanism of Tradition Chinese Medicine (BATMAN-TCM), and further supplemented with literature research. Then these components and targets were associated with the target information related to DKD in GeneCards, OMIM, TTD and DrugBank databases. Based on the protein-protein interaction (PPI) network constructed by String11. 0 software, the key targets corresponding to the main active components in YSTLF were obtained. The "component-disease-target" regulatory network diagram with TCM compounds was constructed by cytoscape 3. 8. 0, and the pharmacodynamic mechanism of YSTLF in the treatment of DKD was preliminarily predicted. At the same time, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analysis were carried out using R language BioConductor and pathview software to reveal the functions of related target genes and pathways. With the mesangial cells ( SV40-MES-13) of mice induced by high glucose as the main research object, the effects of YSTLF on the expression of key target genes and the regulation of related pathways were verified by luciferase reporter gene detection, RT-qPCR and western blot. Results 108 active components of YSTLF with potential therapeutic effect of DKD and 417 corresponding targets were screened. The " component-disease-target" network diagram suggested that kaempferol and astragaloside were the main active components in YSTLF in the treatment of DKD, and Akt and IL-6 were the key targets of the above-mentioned chemical components. The result of GO functional annotation and KEGG pathway enrichment showed that the selected key targets were mainly involved in a series of biological reactions, such as drug immune response, oxidative stress response, inflammatory response, and signal transduction, etc., and were mainly involved in the regulation of AGE-RAGE and PI3K/ AKT signal pathways. The result showed that YSTLF could effectively improve the activation of inflammation related indexes TNF-α and IL-6 and fibrosis related indexes TGF-β1, α-SMA and Col-I in SV40-MES-13 cells in mice induced by high glucose. Conclusion Yishen Tongluo Formula seems to be multi-component, multi-target and multi-pathway in the treatment of DKD. It may play a role in the treatment of DKD by regulating AGE-RAGE and PI3K/ AKT signal pathways, thus inhibiting inflammatory reaction and renal tissue fibrosis. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Danshen and Sanqi Prescription (Dan-Qi) is commonly used to treat cardiovascular diseases (CVD) in China. Since Danshen and Sanqi are reported to ameliorate lipid metabolism disorders at treatment of cardiovascular diseases. Meanwhile, it is reported that co-administration of Danshen and Sanqi exhibited significant pharmacokinetic herb–herb interactions. We reasoned that Danshen and Sanqi combination could be potentially function synergistically in treating diet induced insulin resistance. Materials and methods Using high calori food induced Drosophila and mice models, we assessed Danshen and Sanqi treatment for their anti-diabetic effects. Results The combination of Danshen and Sanqi (Dan-Qi) effectively improved fat and glucose metabolism of the high-sugar and high-fat diet fed fruit flies. More importantly, Dan-Qi significantly ameliorated hyperlipidemia and hyperglycemia phenotype caused in high-fat diet induced obesity (DIO) mouse model. The Dan-Qi treated DIO mice showed lower fasting insulin, triglycerides, total and low-density lipoprotein cholesterol (LDL-C) levels in plasma, much better than Danshen or Sanqi treated alone. It was shown that Dan-Qi prescription reduced fat accumulation in the liver with Sanqi playing the major role. Interestingly, it was not Danshen or Sanqi alone, but the combination markedly increased glycogen deposition in mice liver. Quantitative RT-PCR showed Dan-Qi increased liver glycogen synthesis gene like Glut-1, GK, and Glut-4, reduced fat and cholesterol anabolism genes such as SREBP-1c, ACC, ATP-CL, ACS. Meanwhilpose tissues and muscle tissues, the glucose and fat metabolism genes are changed accordingly to pro-catabolism status. Notably, endogenous plasma metabolites of Dan-Qi treated mice displayed much better overral rectifying effects than the Danshen or Sanqi alone. Conclusions Our data demonstrated that Danshen and Sanqi combination exerted significant anti-diabetic efficacy, and Dan-Qi prescription could be potentially considered as a therapeutic application in diabetes. [ABSTRACT FROM AUTHOR]

A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (>5 mg/mL). Results of in vitro experiments showed that TP-CMCS could relieve TP-induced inhibition on RAW264.7 cells and apoptosis, respectively. Compared with the TP group, TP-CMCS could effectively alleviate the toxicity injury of TP and decreased the mortality rate of the mice (p < 0.05). TP-CMCS did not cause much damage to the liver (AST and ALT) and kidney (BUN and CRE) (p < 0.05). After administration, the levels of IL-6, IL-1β, and TNF-α decreased, and the arthritis detumescence percentages increased significantly, and the bony erosion degree was distinctly decreased in the TP-CMCS groups and TP group. Our results suggested that TP-CMCS was a useful carrier for the treatment of RA, which enhanced aqueous solubility of free TP and reduced drug toxicity in vitro and in vivo. [ABSTRACT FROM AUTHOR]

A method based on enzyme blocking combined with ultrafiltration liquid chromatography–mass spectrometry (LC–MS) has been developed to identify xanthine oxidase (XOD) inhibitors in the roots of Lindera reflexa Hemsl (LR) and determine their binding positions. Allopurinol and febuxostat, known XOD inhibitors, which occupy different binding positions in XOD, were used as blockers and pre‐incubated with XOD. Then the LR extract was incubated without XOD, and with XOD, allopurinol‐blocked XOD and febuxostat‐blocked XOD before ultrafiltration LC–MS was performed. By comparing the chromatographic profiles of the incubation samples, not only the ligands, but also the binding position of these ligands with XOD could be determined. Finally, three compounds, pinosylvin, pinocembrin and methoxy‐5‐hydroxy‐trans‐stilbene, were identified as potential XOD inhibitors and the binding modes of these three compounds were shown to be similar to those of febuxostat. To verify the XOD inhibitory activity of the screened compounds, the microplate method and molecular docking in silico were used to evaluate the enzyme inhibitory activities and the binding positions with XOD. The results showed that the developed method could screen for XOD ligands in LR extracts and also determine the binding positions of the ligands. To our knowledge, this is the first report of the XOD inhibitory activity of these three compounds. [ABSTRACT FROM AUTHOR]

The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p -TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p -mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.

Non-coding RNAs are classified as small non-coding RNAs, long non-coding RNAs and circular RNAs, which are involved in a variety of biological processes, including cell differentiation, proliferation, apoptosis and pathological conditions of various diseases. Many studies have shown that non-coding RNAs are related to spermatogenesis, maturation, apoptosis, function, etc. In addition, the expression of non-coding RNAs in testicular tissue and semen of patients with non-obstructive azoospermia was different. However, the role of non-coding RNAs in the pathogenesis of non-obstructive azoospermia has not been fully elucidated, and the role of non-coding RNAs in non-obstructive azoospermia is rarely reviewed. Here we summarize the research progress of non-coding RNAs in the pathogenesis of non-obstructive azoospermia., 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, Zhang, Zhang, Feng, Xie, Liu, Zhu and Luo.)

Advances in induced pluripotent stem cell (iPSC) techniques have opened up new perspectives in research on developmental biology. Compared with other sources of human cellular models, iPSCs present a great advantage in hosting the unique genotype background of donors without ethical concerns. A wide spectrum of cellular and organoid models can be generated from iPSCs under appropriate in vitro conditions. The pluripotency of iPSCs is orchestrated by external signalling and regulated at the epigenetic, transcriptional and posttranscriptional levels. Recent decades have witnessed the progress of studying tissue-specific expressions and functions of microRNAs (miRNAs) using iPSC-derived models. MiRNAs are a class of short non-coding RNAs with regulatory functions in various biological processes during development, including cell migration, proliferation and apoptosis. MiRNAs are key modulators of gene expression and promising candidates for biomarker in development; hence, research on the regulation of human development by miRNAs is expanding. In this review, we summarize the current progress in the application of iPSC-derived models to studies of the regulatory roles of miRNAs in developmental processes., 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 Chen, Zhang, Zhang, Chen, Zuo, Xie, Zhou, Chen and Chen.)

In this paper, an HPLC peak fractionation approach combined with homogeneous time-resolved fluorescence analysis is proposed for screening epidermal growth factor receptor inhibitors from Rhei Radix et Rhizoma. With this approach, the amount of sample used for a single HPLC run is sufficient for performing a multiple assay due to the miniaturization ability of the homogeneous time-resolved fluorescence technology. This allows for improving the stability and repeatability of the activity assay for each fraction. From a total of 26 fractions collected from the Rhei Radix et Rhizoma extract, 13 fractions exhibit inhibitory activity against the epidermal growth factor receptor. The structures of activity compounds were determined by HPLC-LTQ-Orbitrap MS, revealing the presence of gallic acid, rhein, and emodin with IC 50 values of 21.5, 5.29, and 10.2 µM, respectively. The ligand epidermal growth factor receptor interactions were explored by molecular docking simulations, and the inhibitory effects of the three compounds on A549 cell growth were tested in vitro by an MTT assay. This study demonstrates the suitability of the present screening method for drug discovery in natural products., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknow. etiology and a high mortality rate. Oridonin is a diterpenoid isolated from the Rabdosia rubesecens with diverse biological functions. However, whether oridonin possess potential protective activity on IPF is still unclear. MATERIAL AND METHODS The aim of the present study was to explore the therapeutic effects of oridonin on IPF. First, TGF-β1-induced MRC-5 cells were employed for the evaluation of inhibitory activity in vitro. Then, a bleomycin (BLM)-induced mice pulmonary fibrosis model was used to verify the activity of oridonin in vivo. Several pathological changes, including alveolar space collapse, emphysema, and infiltration of inflammatory cells, were observed in the BLM‑treated mice. RESULTS Oridonin could significantly inhibit the mRNA and protein expression levels of α-SMA and COL1A1 in TGF-β1-induced MRC-5 cells. Oridonin could attenuate pathological changes, including alveolar space collapse, emphysema, and infiltration of inflammatory cells induced by BLM. In addition, oridonin could significantly inhibit BLM-induced upregulation of α-SMA and COL1A1 and the phosphorylation of Smad2/3 in lung tissues of mice. CONCLUSIONS Oridonin could be used as a potential therapeutic agent in treatment for patients with IPF. The mechanisms of anti-fibrosis effect of oridonin might be inhibition of the TGF-β/Smad pathway.