Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs. Among 1430 patients receiving anti-TB therapy, 440 (30.77%) patients showed at least 1 ADR induced by anti-TB drugs. Hyperuricemia was the most common ADR, followed by hepatic function test abnormality, liver damage and gastrointestinal reactions. Significant differences (P < .05) were also seen in diabetes, age, treatment duration, type of TB (extrapulmonary) and some therapeutic regimens between ADR group and non-ADR group, respectively. Multivariate logistic regression analysis showed that treatment duration (OR = 1.029, 95%CI[1.018-1.040], P = .000), type of TB (extrapulmonary, OR = 1.487, 95%CI[1.134-1.952], P = .004) and some therapeutic regimens (HREZ, OR = 1.425, 95%CI[0.922-2.903], P = .001; HRZS, OR = 2.063, 95% CI[1.234-3.449], P = .006; HRZ, OR = 3.623, 95%CI[2.289-5.736], P = .000) were risk factors for ADRs induced by anti-TB drugs. Anti-TB drugs usually induced the occurrence of severe and frequent adverse effects, such as hyperuricemia. Treatment duration, HREZ, HRZS and HRZ regimens, and type of TB (extrapulmonary) should be considered as high-risk factors. Thus, it should be recommended to consider optimum management during anti-TB therapy, particularly hyperuricemia monitoring and hepatic function test.

Inhibition of Sema4D attenuates pressure overload-induced pathological myocardial hypertrophy via the MAPK/NF-κB/NLRP3 pathways.

Sema4D (CD100) is closely related to pathological and physiological processes, including tumor growth, angiogenesis and cardiac development. Nevertheless, the role and mechanism of Sema4D in cardiac hypertrophy are still unclear to date. To assess the impact of Sema4D on pathological cardiac hypertrophy, TAC surgery was performed on C57BL/6 mice which were transfected with AAV9-mSema4D-shRNA or AAV9-mSema4D adeno-associated virus by tail vein injection. Our results indicated that Sema4D knockdown mitigated cardiac hypertrophy, fibrosis and dysfunction when exposed to pressure overload, and Sema4D downregulation markedly inhibited cardiomyocyte hypertrophy induced by angiotensin II. Meanwhile, Sema4D overexpression had the opposite effect in vitro and in vivo. Furthermore, analysis of signaling pathways showed that Sema4D activated the MAPK pathway during cardiac hypertrophy induced by pressure overload, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed Sema4D overexpression-induced deteriorated phenotype, resulting in improved cardiac function. Further research indicated that myocardial hypertrophy induced by Sema4D was closely related to the expression of the pyroptosis-related proteins PP65, NLRP3, caspase-1, ASC, GSDMD, IL-18 and IL-1ß. In conclusion, our study demonstrated that Sema4D regulated the process of pathological myocardial hypertrophy through modulating MAPK/NF-κB/NLRP3 pathway, and Sema4D may be the promising interventional target of cardiac hypertrophy and heart failure.

Galangin delivered by retinoic acid-modified nanoparticles targeted hepatic stellate cells for the treatment of hepatic fibrosis.

Hepatic fibrosis (HF) is a chronic hepatic pathological process induced by various liver injuries, with few available therapies. Previous research studies revealed that HF is characterized by the accumulation of excess extracellular matrix in the liver, mainly overexpressed by activated hepatic stellate cells (HSC). Therefore, HSC have been targeted in clinical trials for the management of HF. The aim of the present study was to develop an anti-HF drug delivery system with acrylic resin (Eudragit® RS100, Eud RS100) nanoparticles (NPs) through modification by retinoic acid (RA), modified for binding the retinol-binding protein reporter (RBPR) in HSC. Galangin (GA), is a multiple effects flavonoid which has demonstrated an anti-HF effect in our previous studies. In this study, GA was utilized for the treatment of HF. The results revealed that the NPs were well formed (diameter: 70 nm), spherical in shape, and exhibited uniform distribution and a high encapsulation efficiency. Moreover, a prominent controlled release effect and a significant increase in bioavailability was observed following the encapsulation of GA in NPs. These findings indicated that the limitation of low bioavailability due to the hydrophobic feature of GA was overcome. Furthermore, the pharmacodynamics studies demonstrated that NPs could drastically influence the anti-HF effects of GA after modification with retinoic acid. The results of the present study suggested that retinoic acid-modified GA NPs represent a promising candidate in the development of an anti-HF drug delivery system for the treatment of HF.

Crebanine induces ROS-dependent apoptosis in human hepatocellular carcinoma cells via the AKT/FoxO3a signaling pathway.

Background: Hepatocellular carcinoma (HCC), as an aggressive cancer with a high mortality rate, needs high-efficiency and low-toxicity drug therapy. Natural products have great potential as candidate lead compounds for the development of new HCC drugs. Crebanine is an isoquinoline alkaloid derived from Stephania with various potential pharmacological effects such as anti-cancer. However, the molecular mechanism underlying crebanine-induced liver cancer cells apoptosis has not been reported. Here, we investigated the effect of crebanine on HCC and identified a potential mechanism of action. Methods: In this paper, we intend to detect the toxic effects of crebanine on hepatocellular carcinoma HepG2 cells through a series of in vitro experiments, including detecting the effects of crebanine on the proliferation of HepG2 cells using the CCK8 method and plate cloning assay, observing the growth status and morphological changes of crebanine on HepG2 cells by inverted microscopy; and using the Transwell method to determine the the effect of crebanine on the migration and invasion ability of HepG2 cells; using Hoechst 33258 assay to stain cancer cells, thus observing the effect of crebanine on the morphology of HepG2 apoptotic cells, and detecting the apoptotic state and level of HepG2 cells by flow cytometry; using ROS kit and JC-1 assay kit to detect the changes of reactive oxygen species and mitochondrial membrane potential of HepG2 The immunofluorescence assay was taken to verify whether crebanine had an effect on the expression of p-FoxO3a in cancer cells; the Wetern blot assay was also used to examine the effect of crebanine on proteins related to the mitochondrial apoptotic pathway and its effect on the regulation of the relative protein expression of AKT/FoxO3a axis; after this, NAC and AKT inhibitor LY294002 were used to cells were pretreated with NAC and AKT inhibitor LY294002, respectively, in order to further validate the inhibitory effect of crebanine. Results: It was shown that crebanine effectively inhibited the growth and capacity of HepG2 cells migration and invasion in a dose-dependent manner. Furthermore, the effect of crebanine on the morphology of HepG2 cells was observed through microscopy. Meanwhile, crebanine induced apoptosis by causing reactive oxygen species (ROS) burst and mitochondrial membrane potential (MMP) disrupt. We found that crebanine could down-regulate Bcl-2 and up-regulate Bax, cleaved-PARP, cleaved-caspase-3 and cleaved-caspase-9, but these effects were overturned by ROS inhibitor N-acetylcysteine (NAC). Crebanine also down-regulated p-AKT and p-FoxO3a, and the PI3K inhibitor LY294002 significantly enhances this effect. We also found that the expression of AKT/FoxO3a signaling pathway was ROS-dependent. As shown by Western blots, NAC could partially attenuate the inhibitory effect of crebanine on AKT and FoxO3a phosphorylation. Conclusion: Based on our results, our results suggest that crebanine, as a compound with potential anticancer activity, has significant cytotoxic effects on hepatocellular carcinoma,and it likely induces apoptosis via ROS in the mitochondrial pathway and simultaneously affects the biological function of HCC via the ROS-AKT-FoxO3a signaling axis.

Galangin inhibits neointima formation induced by vascular injury via regulating the PI3K/AKT/mTOR pathway.

Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in the pathological process of neointima formation after vascular injury. Galangin, an extract of the ginger plant galangal, is involved in numerous biological activities, including inhibiting the proliferation and migration of tumor cells, but its effect on VSMCs is unknown. This study focused on the role and mechanism of galangin in the neointima formation induced by vascular injury. Methods and results: In this study, we found that galangin restrained the PDGF-BB-induced proliferation, migration and phenotypic switching of VSMCs in a concentration-dependent manner. In vivo, we established a model of carotid artery balloon injury in rats, followed by intragastric administration of galangin (40 mg kg-1 day-1 or 80 mg kg-1 day-1) for 14 or 28 consecutive days. Then, the degree of neointima hyperplasia was evaluated by H&E staining, and the level of relevant protein expression was assessed by immunofluorescence and western blotting. In vitro, we isolated and grew primary rat aortic smooth muscle cells, which were treated with PDGF-BB and different doses of galangin, and then CCK-8 assay, wound healing assay, transwell assay, western blotting and immunofluorescence assays were performed. We found that galangin significantly inhibited PDGF-BB-induced proliferation, migration, and phenotypic switching of VSMCs and promoted autophagy in VSMCs in vitro, and galangin significantly inhibited neointimal hyperplasia after the common carotid artery balloon injury in rats. In terms of mechanisms, galangin inhibited the PI3K/AKT/mTOR pathway, thereby suppressing VSMC's switch from a contractile to a synthetic phenotype, inhibiting VSMC proliferation, migration and phenotypic switching and upregulating the Beclin1 protein expression levels and the ratio of LC3BII/I, promoting VSMC autophagy, and thereby inhibiting neointimal hyperplasia after vascular injury. Conclusion: Our study suggests that galangin inhibits neointimal hyperplasia after vascular injury by inhibiting smooth muscle cell proliferation, migration and phenotypic switching and by promoting autophagy, and that galangin may be a promising drug for the prevention and treatment of vascular restenosis after PCI.

Galangin Reverses Hepatic Fibrosis by Inducing HSCs Apoptosis via the PI3K/Akt, Bax/Bcl-2, and Wnt/ß-Catenin Pathway in LX-2 Cells.

Hepatic fibrosis (HF) is a common disease, with currently no available treatment. Galangin, a natural flavonoid extracted from Alpinia officinaruim Hance, has multiple effects demonstrated in previous studies. The aim of the present study was to explore the anti-fibrogenic effect of galangin in vitro, and research its potential molecular mechanisms. LX-2 cells were chosen as an in vitro HF model, and were treated with galangin in different concentrations. Cell viability was analyzed using Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was measured using flow cytometry, and the anti-fibrogenic effect of galangin was determined using RT-quantitative (q)PCR, immunofluorescence, and Western blotting. The results show that the proliferation of LX-2 cells was efficiently inhibited by galangin, and apoptosis was induced in a dose-dependent manner. Both the mRNA and protein expression of alpha-smooth muscle actin (α-SMA) and collagen I were markedly downregulated. Galangin also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt and Wnt/ß-catenin signaling pathways and increased the Bax/Bcl-2 ratio. The results of this study suggest that galangin has an anti-fibrogenic effect and may represent a promising agent in the treatment of hepatic fibrosis.

Wuchang Fangcang Shelter Hospital: Practices, Experiences, and Lessons Learned in Controlling COVID-19.

In early January 2020, the outbreak of the new corona virus pneumonia (Corona Virus Disease 2019, COVID-19) occurred. Wuhan, the capital city of Hubei province, became the epicenter of the disease in China. The rapid growth of patients had exceeded the maximum affordability of local medical resources. A large comprehensive gymnasium was converted into Wuchang Fangcang Shelter Hospital in order to provide adequate medical beds and appropriate care for the confirmed patients with mild to moderate symptoms. For these hospitalized patients with COVID-19, medication became the mainstay of therapy. From 5th February to 10th March, a team of pharmacists successfully completed drug supplies and pharmaceutical services for 1124 patients and approximately 800 medical staff, and, while doing so, received zero complaint, and experienced zero disputes and zero pharmacist infection. This paper summarizes the development and construction of the pharmacy, human resource allocation of pharmacists, pharmacy administration, and pharmaceutical services. It aims to review a 34-day period of pharmaceutical practice and serve as a reference for other health professionals working on COVID-19 prevention and treatment in other regions.