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Some domestic scholars revealed the effectiveness of Wenshen Yiqi Keli (WSYQKL) on chronic obstructive pulmonary disease (COPD). However, the exact mechanism of WSYQKL on COPD is fuzzy and needs further research. We adopted UPLC-Q/TOF-MS to analyze the chemical components of WSYQKL. In in vitro experiments, human airway smooth muscle cells (hASMCs) were intervened with 2.5% cigarette smoke extract (CSE), medicine serum of WSYQKL, miR-155 mimic, and FoxO3a silencing. Cell viability, proliferation, migration, and the expressions of miR-155, PCNA, Ki67, p21, p27, and FoxO3a were examined by cell counting kit-8, EdU staining, Transwell assay, scarification assay, qRT-PCR, immunol cytochemistry, and western blot, respectively. The association between miR-155 and FoxO3a was assessed by database and luciferase reporter gene analysis. We identified 47 kinds of chemical compositions of WSYQKL in ESI+ mode and 42 kinds of components of WSYQKL in ESI− mode. The medicine serum of WSYQKL strongly alleviated the proliferation and migration of hASMCs induced by CSE in a concentration-dependent manner. The medicine serum of WSYQKL enhanced the levels of p21, p27, and FoxO3a and weakened PCNA and Ki67 levels in hASMCs induced by CSE with the increase of concentration. MiR-155 mimic or FoxO3a silencing notably advanced CSE-treated HASMC viability, proliferation, migration, and the levels of PCNA and Ki67 and downregulated the levels of p21, p27, and FoxO3a in CSE-triggered hASMCs, which was reversed by WSYQKL-containing serum. Our results described that WSYQKL alleviated the proliferation and migration of hASMCs induced by CSE by modulating the miR-155/FoxO3a axis. [ABSTRACT FROM AUTHOR]

Objective. The objective of this study was to observe the protective effect of Rhodiola wallichiana drops in a rat model of fine particulate matter (PM2.5) lung injury. Methods. Forty male Wistar rats were randomly divided into blank control (NC), normal saline (NS), PM2.5-infected (PM), and Rhodiola wallichiana (RW) groups. Rats in the NC group were not provided any interventions, whereas those in the NS and PM groups were administered normal saline and PM2.5 suspension by trachea drip once a week for four weeks. Rats in the RW group were intraperitoneally administered Rhodiola wallichiana for 14 days and then administered PM2.5 suspension by trachea drip 7 days after drug delivery. The levels of inflammatory factors such as interleukin-6, interleukin-1β, and tumor necrosis factor-alpha and oxidative stress biomarkers such as 8-hydroxy-2′-deoxyguanosine, 4-hydroxynonenal, and protein carbonyl content were determined in the serum and bronchoalveolar lavage fluid by ELISA. The level of 4-hydroxynonenal in the lung was also determined using Western blotting and immunohistochemical staining. Results. Levels of inflammatory factors and oxidative stress biomarkers were all increased in the PM group but decreased in the RW group. Western blotting revealed increased 4-hydroxynonenal levels in the PM group but decreased levels in the RW group. Immunohistochemical staining also provided similar results. Conclusion. Rhodiola wallichiana could protect rats from inflammation and oxidative stress injury caused by PM2.5. [ABSTRACT FROM AUTHOR]

Objectives. The incidence of hyperuricemia (HUA) is increasing year by year, and there are no ideal drugs for the treatment; the existing ones can cause serious liver and kidney damage. We have confirmed that the water extract of Dendrobium candidum leaves could reduce the level of uric acid in rats, but the active ingredients remain unknown, and the mechanism is not well understood. This research investigated the therapeutic effect of the macroporous resin extract of the Dendrobium candidum leaf (DLE) on hyperuricemia. In this study, hyperuricemia was induced in rats by a 5-week high-purine diet. After that, DLE was administered continuously for 9 weeks. The result showed that biochemical parameters of liver and kidney function, especially serum uric acid (UA) levels, were significantly improved with DLE, which may relate to the reduction of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the liver. Moreover, DLE could significantly prevent kidney and liver from damage, and intestinal injury and reduce inflammation in hyperuricemic rats by inhibiting the expression of both NF-κB and TLR4 proteins. These results showed that the macroporous resin extract of the Dendrobium candidum leaves may be effective for the treatment of hyperuricemia in rats by inhibiting uric acid production and decreasing inflammation. [ABSTRACT FROM AUTHOR]

At present, the global prevalence of peripheral arterial disease is increasing year by year, and it has become a worldwide disease. Studies have shown that transplanting endothelial progenitor cells (EPCs) into ischemic tissues can improve the tissue ischemia, thereby having a therapeutic effect on peripheral arterial diseases. This indicates that EPCs play a therapeutic effect in peripheral arterial disease. Recent studies have shown that peptidylarginine deiminase (PAD) is involved in the regulation of epigenetics and its inhibitor Cl-amidine can improve endothelium-dependent vasodilation and significantly reduce the formation of arterial thrombosis. It can also play a role in hematopoietic stem cells that share the same origin with EPCs. Therefore, we speculate that PAD4 may also have an effect on EPCs through a similar mechanism, thereby participating in the damage and repair of peripheral arterial disease. Therefore, we first detected the expression of PAD4 in EPCs of peripheral arterial disease and detected changes in the number and function of endothelial progenitor cells in peripheral blood after injecting the PAD4 inhibitor Cl-amidine into mice. A mouse model of lower limb ischemia was established to explore the effect of PAD4 on the function of EPCs in peripheral arterial disease. The results show that PAD4 is highly expressed in peripheral arterial diseases and the PAD4 inhibitor Cl-amidine can increase the number of EPCs and can treat peripheral arterial diseases by improving the proliferation, migration, and vascularization of EPCs. [ABSTRACT FROM AUTHOR]

Objectives. Fatty liver disease (FLD) is a major cause of morbidity and mortality worldwide. Dietary cholesterol and alcohol consumption are important risk factors for the progression of FLD, but whether and how alcohol induces more severe FLD with cholesterol ingestion remain unclear. Herein, we mainly used the Lieber-DeCarli diet to establish the FLD mouse model to investigate the synergistic effects of alcohol and cholesterol metabolism on liver damage. The indices of aspartate transaminase (AST), alanine transaminase (ALT), low-density lipoprotein cholesterol (LDL-c), and total cholesterol (TC) levels, inflammation foci, and pathogenesis by hematoxylin and eosin (H&E) and Oil Red O staining revealed that alcohol induces more severe liver damage by influencing cholesterol metabolism, which might be primarily related to the influence of cholesterol absorption, synthesis, and excretion on the liver or small intestine. Moreover, inhibition of absorption of intestinal cholesterol, but not of fat, sucrose, and alcohol, absorption into the body's metabolism by Ezetimibe, significantly improved FLD in rats fed with the high fat-cholesterol-sucrose and alcohol diet. These results showed that alcohol plays an important role in cholesterol metabolism in FLD. [ABSTRACT FROM AUTHOR]

Objective. Considering the role of lncRNAs reported as regulators in acute myeloid leukemia (AML) progression, the current research aims to investigate the role of PAX8-AS1 in chemo-resistant AML. Methods. Human AML cells HL60 and human doxorubicin (ADM)-resistant AML cells (HL60/ADM cells) were used to establish in vitro models of chemo-sensitive AML and refractory/recurrent AML, respectively. CCK-8 assay and flow cytometry were used to determine cell resistance to ADM, viability, and apoptosis. PAX8-AS1, miR-378g, and ERBB2 expressions in the models and/or AML patients were quantified via qRT-PCR or Western blot. The miRNA/mRNA axis targeted by PAX8-AS1 was analyzed using Starbase, TargetScan, or GEO and validated through a dual-luciferase reporter assay. The expressions of Bcl-2, Bax, and C Caspase-3 in cells were quantitated by Western blot. Results. The highly expressed PAX8-AS1 was observed in AML patients and HL60 cells, which was more evident in refractory/recurrent AML patients and HL60/ADM cells. Compared with that in ADM-treated parental HL60 cells, the viability of ADM-treated HL60/ADM cells remained strong. PAX8-AS1 overexpression increased viability and Bcl-2 expression, while diminishing apoptosis, Bax, and C Caspase-3 expressions in HL60 cells. However, the abovementioned aspects were oppositely impacted by PAX8-AS1 silencing in HL60/ADM cells. PAX8-AS1 directly targeted miR-378g, whose expression pattern is opposite to that of PAX8-AS1 in AML. MiR-378g upregulation abrogated the effects of PAX8-AS1 overexpression on HL60 cells. MiR-378g downregulation offset PAX8-AS1 silencing-induced effects on HL60/ADM cells. Moreover, ERBB2 was recognized as the target of miR-378g, with a higher expression in HL60/ADM cells than in HL60 cells. Conclusion. PAX8-AS1 silencing decreases cell viability, enhances apoptosis, and suppresses ADM resistance in AML via regulating the miR-378g/ERBB2 axis. [ABSTRACT FROM AUTHOR]

Objective. Tripterygium wilfordii polyglycosides tablet (TGt) is an oral preparation extracted from plant Tripterygium wilfordii. It has the effects of anti-inflammation and inhibition of cellular and humoral immunity. However, many reports of adverse reactions caused by TGt have limited its application. In this paper, the clinical efficacy and safety of TGt in the treatment of chronic kidney disease (CKD) were verified by data mining and analysis, so as to provide theoretical data support for the application and development of TGt. Methods. A computer search of the following databases was conducted: PubMed, Web of Science, CBM, VIP, Wanfang Data, and CNKI. The search time limit is from the establishment of the database to September 2020. We searched for clinical randomized controlled trials of TGt in the treatment of CKD. The main types of CKD involved are nephrotic syndrome (NS), primary nephrotic syndrome (PNS), refractory nephrotic syndrome (RNS), and IgA nephropathy (IgAN). RevMan 5.2 and Stata 12.0 software were used to evaluate the literature quality and analyze the data. Finally, GRADEpro software was used to evaluate the quality of evidence. Results. According to the inclusion and exclusion criteria, 75 articles with a total of 6418 subjects were included. The results of the meta-analysis showed that TGt could reduce 24-hour urinary protein, increase serum albumin, improve clinical efficacy, and reduce disease recurrence rate in patients (P < 0.05) with CKD compared with adrenocortical hormones or immunosuppressants. TGt could significantly reduce the level of serum creatinine (Scr) in patients with CKD (P < 0.05), but it was not significant in reducing the level of blood urea nitrogen (P > 0.05). In terms of safety evaluation, in patients with CKD, it could significantly reduce the incidence of gastrointestinal adverse reactions and neurogenic dizziness and headache (P < 0.05). However, in terms of adverse reactions such as liver injury, respiratory infection, and leukopenia, TGt was as harmful as corticosteroids or immunosuppressants (P < 0.05). The quality of the evidence was evaluated with GRADEpro software, and the results showed that TGt was strongly recommended for the treatment of CKD. Conclusion. TGt has certain efficacy in the treatment of CKD and has fewer side effects in certain types of diseases. The effect of TGt combined with other drugs is better than that of single use. This paper also has some limitations. Due to the limited number of the included studies, with all being from China, there may be methodological differences. Therefore, more high-quality literature data from different countries are needed. [ABSTRACT FROM AUTHOR]

The Ge-Gen-Jiao-Tai-Wan (GGJTW) formula has been used to treat type 2 diabetes mellitus (T2DM) in China for a long time. Our previous study has proved that GGJTW could alleviate the type 2 diabetic symptoms, but the underlying mechanisms are still unclear. This study aimed to investigate the changes in gut microbiota and primary bile acids (PBAs) to determine the potential mechanisms of GGJTW in treating T2DM.The fecal transplant method and pseudogerm-free rats were used in our study.The16S rRNA gene sequencing method was used to analyze the changes in the intestinal flora, and PBAs in the colon contents were detected. Finally, the expression of farnesoid X receptor (FXR), G protein-coupled membrane receptor 5 (TGR5), and glucagon-like peptide-1 (GLP-1) was assessed. Following GGJTW treatment, we observed a decrease in blood glucose levels and improvements in glucose tolerance and serum lipid levels. Furthermore, we found that GGJTW could regulate the composition of the gut microbiota and upregulate the diabetic beneficial phylum Firmicutes and bile-acid-related genus Lactobacillus. PBAs in the colon contents were increased in the GGJTW-treated group, accompanied by upregulated expression of the bile acid receptors FXR and TGR5 and increased concentrations of GLP-1. These results indicated that GGJTW could alleviate symptoms of type 2 diabetic rats by regulating the gut microbiota, promoting the production of PBAs, and upregulating the PBA-FXR/TGR5-GLP-1 pathway. [ABSTRACT FROM AUTHOR]

Resveratrol, a polyphenolic plant antitoxin, has a wide range of pharmacological activities. In this study, we systematically evaluated the effects of resveratrol dry suspension (RDS) on immune function in piglets that were treated with different doses of RDS for 2 weeks. The results showed that the RDS has significant effects on the development, maturation, proliferation, and transformation of T lymphocytes. RDS could regulate humoral immune responses by upregulating the release of IFN-γ and downregulating the release of TNF-α. After piglets were vaccinated against classical swine fever virus and foot-and-mouth disease virus, the antibody titers were significantly increased. RDS treatment showed an excellent resistance to enhance T-SOD activity. Values of blood routine and blood biochemistry showed no toxicity. These results suggested that RDS could be considered as an adjuvant to enhance immune responses to vaccines, as well as dietary additives for animals to enhance humoral and cellular immunity. [ABSTRACT FROM AUTHOR]