[Meta-analysis and trial sequential analysis of Tanreqing Injection in treatment of severe pneumonia in elderly].

This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.

Zhilong Huoxue Tongyu Capsule regulates the macrophage polarization and inflammatory response via the let-7i/TLR9/MyD88 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhilong Huoxue Tongyu Capsule (ZL) is clinically prescribed for acute ischemic stroke (AIS). However, only a few studies have addressed the mechanisms of ZL in treating AIS. AIM OF THE STUDY: To explore the underlying mechanism of macrophage polarization and inflammation mediated by ZL, and to provide a reference for AIS treatment. MATERIALS AND METHODS: Sixteen SD rats were fed with different dose of ZL (0, 0.4, 0.8, and 1.6 g/kg/d) for 4 days to prepare ZL serum. After 500 ng/mL lipopolysaccharide (LPS) stimulation, RAW264.7 cells were administrated with ZL serum. Then, experiments including ELISA, flow cytometry, real-time quantitative PCR and Western blot were performed to verify the effects of ZL on macrophage polarization and inflammation. Next, let-7i inhibitor was transfected in RAW264.7 cells when treated with LPS and ZL serum to verify the regulation of ZL on the let-7i/TLR9/MyD88 signaling pathway. Moreover, the interaction between let-7i and TLR9 was confirmed by the dual-luciferase assay. RESULTS: ZL serum significantly decreased the expression of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and increased the expression of IL-10 and transforming growth factor ß1 (TGF-ß1) of LPS stimulated-macrophages. Furthermore, ZL serum polarized macrophages toward M2, decreased the expressions of TLR9, MyD88, and iNOS, as well as increased the expressions of let-7i, CHIL3, and Arginase-1. It is worth mentioning that the effect of ZL serum is dose-dependent. However, let-7i inhibitor restored all the above effects in LPS stimulated-macrophages. In addition, TLR9 was the target of let-7i. CONCLUSIONS: ZL targeted let-7i to inhibit TLR9 expression, thereby inhibiting the activation of the TLR9/MyD88 pathway, promoting the M2 polarization, and inhibiting the development of inflammation in AIS.

Research Progress of Cordyceps sinensis and Its Fermented Mycelium Products on Ameliorating Renal Fibrosis by Reducing Epithelial-to-Mesenchymal Transition.

Renal fibrosis is a hallmark and common outcome of various chronic kidney diseases (CKDs) and manifests pathologically as accumulation and deposition of extracellular matrix (ECM) in the kidney. Epithelial-to-mesenchymal transition (EMT) has been shown to be an important mechanism involved in renal fibrosis. Cordyceps sinensis, a traditional Chinese medicine, has long been used for the treatment of renal fibrosis. As research on the mycelium of C. sinensis progressed, a variety of medicines developed from fermented mycelium were used to treat CKD. However, their efficacies and mechanisms have not been fully summarized. In this review, five medicines developed from fermented mycelium of C. sinensis are presented. The pharmacodynamic effects of C. sinensis on different animal models of renal fibrosis are summarized. The in vitro studies and related mechanisms of C. sinensis on renal cells are detailed. Finally, the application and efficacy of these five commercial medicines that meet national standards in different types of CKD are summarized. From this review, it can be concluded that C. sinensis can alleviate various causes of renal fibrosis to some extent, and its mechanism is related to TGF-ß1 dependent signaling, inhibition of inflammation, and improvement of renal function. Further research on rigorously designed, large-sample, clinically randomized controlled trial studies and detailed mechanisms should be conducted.

Zhilong Huoxue Tongyu Capsule attenuates hemorrhagic transformation through the let-7f/TLR4 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hemorrhagic transformation after acute ischemic stroke is a life-threatening disease that currently has no effective chemotherapy. Zhilong Huoxue Tongyu Capsule (ZL) is an empirical prescription of traditional Chinese medicine that is used to prevent and treat cardiovascular and cerebrovascular diseases in China. However, only a few studies have addressed the mechanisms of ZL in treating hemorrhagic transformation. AIM OF THE STUDY: To evaluate the anti-inflammatory effects of ZL on hemorrhagic transformation model rats and lipopolysaccharide (LPS)-induced RAW264.7 macrophages and to explore the underlying molecular mechanisms. MATERIALS AND METHODS: Murine RAW264.7 cells were treated with ZL and LPS (1 µg/mL), and cell viability was detected by cell counting kit-8 assay. RT-qPCR was used to detect the expression of inflammatory chemokines, microRNA let-7a/e/i/f, toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-B (NF-κB) p65. The protein expression levels of TLR4, MyD88, NF-κB p65, and apoptosis related molecules were determined by Western blotting. The apoptosis rate of RAW264.7 macrophages was detected by Annexin V-FITC/PI double staining. A hemorrhagic transformation model in rats was established by intraperitoneal injection of high glucose solution combined with thread embolization. Then, the model rats were observed behaviourally, pathologically, and molecularly. The gene expression of TLR4, MyD88, and NF-κB p65 was measured by RT-qPCR and used to evaluate the protective effect of ZL against hemorrhagic transformation in rats. RESULTS: ZL (5, 20, 40 µg/mL) was beneficial in cell proliferation. LPS (1 µg/mL) stimulated the production of inflammatory chemokines and inhibited the production of let-7a/e/i/f, with let-7f being influenced most strongly. Moreover, overexpression of let-7f decreased the gene and protein levels of TLR4, MyD88, and NF-κB p65, downregulated TLR4, and inhibited its transcriptional activity. ZL (5, 20, and 40 µg·mL-1) inhibited the production of TLR4, MyD88, and NF-κB p65 and promoted the production of let-7f in a concentration-dependent manner. Furthermore, the blockade of TLR4 antagonized the promoting effects of TLR4 pathway activation in cell inflammation and apoptosis by downregulating let-7f. Critically, it was confirmed in vivo and in vitro that ZL upregulated the expression of let-7f and inhibited the gene expression of TLR4, MyD88, and NF-κB p65 to reduce inflammatory cell infiltration, which determined the occurrence of hemorrhagic transformation. CONCLUSIONS: ZL can reduce inflammatory response by upregulating let-7f and subsequently inhibiting the TLR4 signaling pathway, thereby decreasing the occurrence of hemorrhagic transformation.

Traditional Chinese medicine combined with Moxibustion in the treatment of "long-COVID": A protocol for systematic review and meta-analysis.

BACKGROUND: From the end of 2019 to now, COVID-19 is still prevalent, which poses a great threat to international public health. With the increasing number of people infected, the number of patients with COVID-19 sequelae is also increasing, but there is no specific drug for COVID-19 sequelae. In China, traditional Chinese medicine combined with acupuncture has been widely used in COVID-19 sequelae, but there is still a lack of evidence-based medicine evaluation. The purpose of this study was to evaluate the efficacy and safety of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. METHODS: According to the retrieval strategy, the "long COVID" randomized controlled trial of traditional Chinese medicine combined with moxibustion will be search in eight databases composed of PubMed, Embase, Web of Science, China National knowledge Infrastructure Database, China Biomedical Database and China Science and Technology Journal Database, regardless of publication date or language. The study was screened according to the inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to evaluate the quality of the study. Meta-analysis was carried out using RevMan5.3 and STATA12.0 software. Finally, the level of evidence of the results will be evaluated. RESULTS: This study will evaluate whether traditional Chinese medicine combined with moxibustion can effectively treat the symptoms of COVID-19 sequelae. CONCLUSION: This study will provide evidence whether there is benefit of traditional Chinese medicine combined with moxibustion in the treatment of COVID-19 sequelae. At the same time, our research results will provide a reference for clinical decision-making and guiding development in the future.

Leaf Mycobiome and Mycotoxin Profile of Warm-Season Grasses Structured by Plant Species, Geography, and Apparent Black-Stroma Fungal Structure.

Grasses harbor diverse fungi, including some that produce mycotoxins or other secondary metabolites. Recently, Florida cattle farmers reported cattle illness, while the cattle were grazing on warm-season grass pastures, that was not attributable to common causes, such as nutritional imbalances or nitrate toxicity. To understand correlations between grass mycobiome and mycotoxin production, we investigated the mycobiomes associated with five prominent, perennial forage and weed grasses [Paspalum notatum Flügge, Cynodon dactylon (L.) Pers., Paspalum nicorae Parodi, Sporobolus indicus (L.) R. Br., and Andropogon virginicus (L.)] collected from six Florida pastures actively grazed by livestock. Black fungal stromata of Myriogenospora and Balansia were observed on P. notatum and S. indicus leaves and were investigated. High-throughput amplicon sequencing was applied to delineate leaf mycobiomes. Mycotoxins from P. notatum leaves were inspected using liquid chromatography-mass spectrometry (LC-MS/MS). Grass species, cultivars, and geographic localities interactively affected fungal community assemblies of asymptomatic leaves. Among the grass species, the greatest fungal richness was detected in the weed S. indicus. The black fungal structures of P. notatum leaves were dominated by the genus Myriogenospora, while those of S. indicus were codominated by the genus Balansia and a hypermycoparasitic fungus of the genus Clonostachys. When comparing mycotoxins detected in P. notatum leaves with and without M. atramentosa, emodin, an anthraquinone, was the only compound which was significantly different (P < 0.05). Understanding the leaf mycobiome and the mycotoxins it may produce in warm-season grasses has important implications for how these associations lead to secondary metabolite production and their subsequent impact on animal health. IMPORTANCE The leaf mycobiome of forage grasses can have a major impact on their mycotoxin contents of forage and subsequently affect livestock health. Despite the importance of the cattle industry in warm-climate regions, such as Florida, studies have been primarily limited to temperate forage systems. Our study provides a holistic view of leaf fungi considering epibiotic, endophytic, and hypermycoparasitic associations with five perennial, warm-season forage and weed grasses. We highlight that plant identity and geographic location interactively affect leaf fungal community composition. Yeasts appeared to be an overlooked fungal group in healthy forage mycobiomes. Furthermore, we detected high emodin quantities in the leaves of a widely planted forage species (P. notatum) whenever epibiotic fungi occurred. Our study demonstrated the importance of identifying fungal communities, ecological roles, and secondary metabolites in perennial, warm-season grasses and their potential for interfering with livestock health.

LINC00461 Regulates the Recurrence of Large B Cell Lymphoma through the miR-411-5p/BNIP3 Pathway.

Objective: To analyze the mechanism of LINC00461 regulating the recurrence of diffuse large B cell lymphoma (DLBCL) through microRNA (miR)-411-5p/BCL2 interacting protein 3 (BNIP3) pathway. Methods: DLBCL samples in TCGA and GSE12453 were used for differential analysis to find long noncoding RNA (lncRNA) related to DLBCL recurrence. The 4 DLBCL data with the highest and lowest expression levels of LINC00461 in the TCGA database were selected for GSEA enrichment analysis. The targeting relationships of miR-411-5p with LINC00461 and BNIP3 were verified by the dual luciferase report. Blood samples from DLBCL patients were used to analyze the correlation between miR-411-5p and LINC00461 or BNIP3. LINC00461, miR-411-5p, or BNIP3 was overexpressed or silenced by transfection, and a tumor-bearing nude mice model was constructed to detect their effects on proliferation and apoptosis. Results: The level of LINC00461 in DLBCL was significantly higher than that in normal cases, and the level in recurrence DLBCL was significantly higher than that in nonrecurrence. The enrichment analysis results showed that the function of LINC00461 was closely related to apoptosis. The results shown that miR-411-5p bound to LINC00461 and BNIP3 and was negatively correlated with LINC00461 and BNIP3 mRNA in blood of DLBCL patients. Suppressing the level of LINC00461 inhibited cell proliferation and induced apoptosis. The inhibition of LINC00461 or overexpression of miR-411-5p reduced the expression of BNIP3 protein, thereby inducing apoptosis at the in vivo and in vitro levels. Conclusion: LINC00461 may induce miR-411-5p to "sponge," thereby increasing the expression of BNIP3 protein, and exerting the function of inhibiting apoptosis and promoting DLBCL recurrence.

In Vitro Immunomodulatory Effects of Inonotus obliquus Extracts on Resting M0 Macrophages and LPS-Induced M1 Macrophages.

Background: Inonotus obliquus (Chaga) is a parasitic fungus that is distributed mainly in northeast China. Our literature research showed chaga polysaccharides have bilateral effects on tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels when they exert antitumor and antidiabetic activities. The current research tried to explore the influence of chaga extracts on inflammatory factors via macrophage polarization which has bilateral immune-regulation not only on healthy tissue homeostasis but also on pathologies. Methods: Chaga was extracted with 100°C water and precipitated with 80% ethanol. The extracts were studied on RAW264.7 macrophage at resting condition (M0) and lipopolysaccharide (LPS)-activated subtype (classic activated macrophage, M1). The IL-1ß, TNF-α, nitric oxide (NO) level, and the protein expressions of M1 and alternative activated macrophage (M2) markers including IL-1ß, inducible NO synthase (iNOS), mannose receptor (CD206), and arginase (Arg)-1 were compared. Results: The 100 g extracts contained 13.7 g polysaccharides and 1.9 g polyphenols. Compared with M0, the 50 µg/mL extracts increased NO level (P < 0.05) and decreased CD206 and Arg-1 expression significantly (P < 0.05). The extracts at 100-200 µg/mL increased NO and TNF-α level (P < 0.05), but increased iNOS and IL-1ß expression significantly (P < 0.05). Compared with M1, the extracts decreased NO level at 25, 50, 100, and 200 µg/mL and decreased IL-1ß and TNF-α level at 100-200 µg/mL significantly (P < 0.05). At 25-200 µg/mL, the extracts significantly increased CD206 and Arg-1 expression and decreased IL-1ß and iNOS expression separately (P < 0.05). Conclusions: Our research suggested that the bilateral effects of the chaga extracts on iNOS, IL-1ß, and NO level on M0/M1 macrophages might be related with chaga polysaccharides and chaga polyphenols. Some in vivo anticancer and antidiabetic research of purified chaga polysaccharides related to macrophage differentiation should be conducted further.

Antiosteoporosis Studies of 20 Medicine Food Homology Plants Containing Quercetin, Rutin, and Kaempferol: TCM Characteristics, In Vivo and In Vitro Activities, Potential Mechanisms, and Food Functions.

Dietary nutraceutical compounds have been evidenced as backbone for bone health in recent years. It is reported that medicine food homology (MFH) plants have multiple nutraceutical compounds. Based on our literature research, 20 MFH plants caught our attention because they contain three popular antiosteoporosis compounds simultaneously: quercetin, rutin, and kaempferol. According to traditional Chinese medicine (TCM), their characteristics including natures, flavors, attributive to meridian tropism, and efficacies were listed. The relationships between TCM efficacies, such as "heat clearing," "tonic," and "the interior warming," and antiosteoporosis pharmacological actions such as antioxidant and immune regulation were discussed. The in vivo antiosteoporosis effects of the 20 MFH plants were summarized. The in vitro antiosteoporosis activities and related mechanisms of the 20 plants and quercetin, rutin, kaempferol were detailed. The TGF-ß-Smad signaling, fibroblast growth factor, and Wnt/ß-catenin signaling on bone formation and the RANKL signaling, NF-κB signaling, and macrophage-colony-stimulating factor on bone resorption were identified. From food point, these 20 MFH plants could be classified as condiment, vegetable, fruit, tea and related products, beverage, etc. Based on the above discussion, these 20 MFH plants could be used as daily food supplements for the prevention and treatment against osteoporosis.

Pharmacological Actions, Molecular Mechanisms, Pharmacokinetic Progressions, and Clinical Applications of Hydroxysafflor Yellow A in Antidiabetic Research.

Hydroxysafflor yellow A (HSYA), a nutraceutical compound derived from safflower (Carthamus tinctorius), has been shown as an effective therapeutic agent in cardiovascular diseases, cancer, and diabetes. Our previous study showed that the effect of HSYA on high-glucose-induced podocyte injury is related to its anti-inflammatory activities via macrophage polarization. Based on the information provided on PubMed, Scopus and Wanfang database, we currently aim to provide an updated overview of the role of HSYA in antidiabetic research from the following points: pharmacological actions, molecular mechanisms, pharmacokinetic progressions, and clinical applications. The pharmacokinetic research of HSYA has laid foundations for the clinical applications of HSYA injection in diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. The application of HSYA as an antidiabetic oral medicament has been investigated based on its recent oral delivery system research. In vivo and in vitro pharmacological research indicated that the antidiabetic activities of HSYA were based mainly on its antioxidant and anti-inflammatory mechanisms via JNK/c-jun pathway, NOX4 pathway, and macrophage differentiation. Further anti-inflammatory exploration related to NF-κB signaling, MAPK pathway, and PI3K/Akt/mTOR pathway might deserve attention in the future. The anti-inflammatory activities of HSYA related to diabetes and diabetic complications will be a highlight in our following research.

A novel self-crosslinked gel microspheres of Premna microphylla turcz leaves for the absorption of uranium.

Premna microphylla turcz leaves (PMTL) is a resource-rich, biodegradable, renewable biomass. Here, a microsphere adsorbent was prepared from PMTL by a self-crosslinking method without any addition of chemical cross-linking agent, and characterized by SEM, FTIR, and XPS. The influence of preparation methods and conditions on the properties of the microspheres was studied and the self-crosslinking mechanism was analyzed. The effects of temperature, pH, contact time, uranium concentration, and adsorbent dosage on its adsorption performance toward to uranium were systematically explored. The results showed that PMTL endogenous pectin binding with endogenous Ca2+, Mg2+ and other metal ions to form an 'egg box' structure might be the mechanism of its self-crosslinking to form microspheres. The adsorption isotherms fitted well by the Freundlich model and the experimental maximum adsorption capacity of microspheres was 346.65 mg·g-1 at pH of 5, and kinetics data correlated well with the pseudo-second order model. The adsorption mechanism might be the coordination bonding between the uranium and oxygen-containing groups (hydroxyl and carboxyl groups), and the ion exchange between the uranium and metal ions (mainly Ca2+ and Mg2+). The PMTL microspheres are promising in treating uranium-containing wastewater in a more cost-effective and environmentally friendly manner.

A network pharmacology strategy to investigate the anti-inflammatory mechanism of luteolin combined with in vitro transcriptomics and proteomics.

Luteolin, a natural flavonoid exists in various medicinal plants, has strong anti-inflammatory effect. However, anti-inflammatory mechanism of luteolin has not been fully explored. Hence, we systematically investigated druggability and anti-inflammatory mechanism of luteolin based on network pharmacology and in vitro experiments. The absorption, distribution, metabolism and excretion of luteolin were evaluated by TCMSP server. Targets associated with luteolin and inflammation were collected from public databases, and the overlapping targets between luteolin and inflammation were analyzed by Draw Venn diagram. Then the protein-protein interaction network of luteolin against inflammation was constructed. Further, gene function and pathway enrichment analysis were performed. Finally, in vitro experiments were carried out to estimate the accuracy of predicted target genes. ADME results indicated that luteolin has great potential to be developed into a drug. 226 overlapping targets were screened by matching 280 targets of luteolin with 9015 targets of inflammation. 9 core targets of luteolin against inflammation were identified, including MMP9, MAPK1, HSP90AA1, CASP3, ALB, EGFR, SRC, HRAS and ESR1. Gene function were mainly involved in metabolism, energy pathways and signal transduction. Metabolic pathways, pathways in cancer, PI3K-AKT signaling pathway, Ras signaling pathway and so on might be the critical pathways of luteolin against inflammation. RT-qPCR and ELISA results indicated that luteolin decreased the expression of most of core genes at protein and mRNA levels (MMP9, MAPK1, HSP90AA1, EGFR, SRC and HRAS). Luteolin is expounded to have great potential to be developed into a drug and target various genes and pathways to perform anti-inflammatory effect.

Reappraisal on pharmacological and mechanical treatments of heart failure.

Heart failure (HF) is a highly frequent disorder with considerable morbidity, hospitalization, and mortality; thus, it invariably places pressure on clinical and public health systems in the modern world. There have been notable advances in the definition, diagnosis, and treatment of HF, and newly developed agents and devices have been widely adopted in clinical practice. Here, this review first summarizes the current emerging therapeutic agents, including pharmacotherapy, device-based therapy, and the treatment of some common comorbidities, to improve the prognosis of HF patients. Then, we discuss and point out the commonalities and areas for improvement in current clinical studies of HF. Finally, we highlight the gaps in HF research. We are looking forward to a bright future with reduced morbidity and mortality from HF.

Chinese Herbal Medicine Dingji Fumai Decoction for Ventricular Premature Contraction: A Real-World Trial.

BACKGROUND: Chinese herbal medicine Dingji Fumai Decoction (DFD) is widely clinically used for ventricular premature contraction (VPC). This real-word trial was designed to assess the safety and effectiveness of DFD for VPC. METHODS: This was a double-blinded, randomized placebo-controlled trial. Patients with VPC were randomized (1 : 1) to treatment with DFD combined with metoprolol (DFD arm) or metoprolol combined with placebo (MET arm). A primary end point was a composite of clinical symptoms and signs determined by the traditionalChinese medicine syndrome score and the number of VPC determined by the Holter examination. Second outcomes were adverse events, medication compliance, and laboratory examination. RESULTS: 144 patients were randomized to DFD arm (76 patients) or MET arm (68 patients), and 136 cases (71 in DFD arm and 65 in MET arm) finally completed this trial. After a 12-week follow-up, DFD arm significantly decreased traditional Chinese medicine syndrome score and the number of VPC compared with MET arm (P = 0.003 and 0.034, respectively). There was no adverse drug effect and patient medication compliance was good. CONCLUSIONS: Superiority with DFD arm for VPC was demonstrated over MET arm for both the safety and effectiveness end points.

Antiarrhythmic Mechanisms of Chinese Herbal Medicine Dingji Fumai Decoction.

BACKGROUND: Dingji Fumai decoction (DFD) is used to treat ventricular arrhythmia, and it has provided a very good curative effect. However, its cellular electrophysiological mechanism is unknown. METHODS: Electrocardiogram was recorded, and oxidative stress response and ion-channel-related molecules were detected in rats with barium chloride- and aconitine-induced ventricular arrhythmia. Moreover, whole-cell patch-clamp assay was used to investigate the inhibitory effect of DFD on Nav1.5 in Chinese hamster ovary cells. RESULTS: DFD prolonged the occurrence time and shortened the duration of ventricular arrhythmia, decreased the malondialdehyde and increased the superoxide dismutase, and alleviated the activation of Na+-K+-ATPase and connexin-43. DFD suppressed Nav1.5dose-dependently with an IC50 of 24.0 ± 2.4 mg/mL. CONCLUSIONS: The clinical antiarrhythmic mechanisms of DFD are based on its antioxidant potential, alleviation of Na+-K+-ATPase and connexin-43, and class I antiarrhythmic properties by suppressing Nav1.5dose-dependently with an IC50 of 24.0 ± 2.4 mg/mL.

Effects of Chaga Medicinal Mushroom Inonotus obliquus (Agaricomycetes) Extracts on NOS-cGMP-PDE5 Pathway in Rat Penile Smooth Muscle Cells.

Some medicinal mushrooms have effects on sexual dysfunctions. Nitric oxide synthase (NOS)-cyclic gua-nosine monophosphate (cGMP)-phosphodiesterase 5 enzyme (PDE5) pathway is one of the pathophysiological basis of erectile dysfunction (ED). The normal erectile function involves the synthesis of nitric oxide (NO), and the subsequent accumulation of cGMP, whereas cGMP degradation is specifically controlled by PDE5, which promotes corporal smooth muscle cell (SMC) tone and terminates erection. The antioxidant activities of Inonotus obliquus (chaga) water extracts (IO1) and water extraction and alcohol precipitation extracts (IO2) were compared using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and oxygen radical absorbance capacity (ORAC) method. Three subtypes of NOS (nNOS, iNOS, and eNOS) and PDE5 protein expressions were tested by Western blotting, and cGMP was determined by ELISA on a rat corporal primary SMC. The results revealed that IO2, which had a significantly higher polysaccharide content than IO1, showed a significantly higher ORAC value and a significantly lower half inhibitory concentration for DPPH scavenging activity than IO1. We observed that both IO1 and IO2 increased the expression of eNOS and iNOS significantly compared with the control. Furthermore, when compared with the control, IO1 increased PDE5 expression significantly, while IO2 showed no effect. The different impacts on PDE5 might be the reason that IO2, not IO1, showed significant inducible effect on cGMP compared with the control. This is to our knowledge, the first study exploring the effect of I. obliquus on NOS-cGMP-PDE5 pathway on SMC. The results provide a possible selection of I. obliquus for the treatment of ED.

Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate Induces Cell Death with Coexisting Mitotic Arrest and Autophagy in Human Chronic Myelogenous Leukemia K562 Cells.

A natural compound from Wasabia japonica, 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) was investigated for its anti-leukemia activity and mechanism of action. It was found that 6-MITC inhibited the viability of human chronic myelogenous leukemia K562 cells along with extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation. The evidence of autophagy included the validation of autophagosomes with double-layered membranes under transmission electron microscopy, LC3I/II conversion, and the induction of G2/M phase arrest observed with acridine orange staining of treated cells, as well as the elevation of phosphorylated-histone H3 expression at the M phase. With regard to the expression of proteins related to mitosis, the downregulation of p-CHK1, p-CHK2, p-cdc25c, and p-cdc2, as well as the upregulation of cyclin B1, p-cdc20, cdc23, BubR1, Mad2, and p-plk-1 was observed. The knockdown of cdc20 was unable to block the effect of 6-MITC. The differentiation of k562 cells into monocytes, granulocytes, and megakaryocytes was not affected by 6-MITC. The 6-MITC-induced unique mode of cell death through the concurrent induction of mitosis and autophagy may have therapeutic potential. Further studies are required to elucidate the pathways associated with the counteracting occurrence of mitosis and autophagy.

Rivaroxaban for cancer-associated venous thromboembolism: A systematic review and meta-analysis protocol.

BACKGROUND: All cancers increase developing venous thromboembolism risk, and VTE is the second-leading cause of death among cancer patients. The anticoagulant drugs are considered to be the optimal treatment for patients with cancer-associated VTE. However, there is still controversy whether rivaroxaban, a new oral anticoagulant, can lead to better outcomes globally. METHODS: We will search PubMed, Web of Science, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure for relevant published studies before 1 September, 2019, without any language restrictions. Only published randomized controlled trials that meet the inclusion criteria will be included. Subgroup analysis of the type of cancer, the type of VTE, cancer stage, age, sex, ethnicity, history of smoking and drinking as well as the mean, dose and duration of anticoagulants will be performed. DISCUSSION: Our study aims to estimate the efficacy and safety of rivaroxaban for patients with cancer-associated VTE and to provide recommendations to key stakeholders. TRIAL REGISTRATION: PROSPERO, October 23, 2019, CRD42019143265, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=143265.

Marinobacter sp. Stable Hydrous Titanium Oxide-Functionalized Bovine Serum Albumin Nanospheres for Uranium Capture from Spiked Seawater.

A novel nanospherical hydrous titanium oxide adsorbent (hydrous titanium oxide-immobilized bovine serum albumin nanospheres, HTO-BSA-NSs) was prepared by immobilizing HTOs with a manipulated molecular mass and number of active sites for uranium on the surface of BSA-NSs. The adsorption performances of HTO-BSA-NSs were investigated in spiked natural seawater with extra 8 ppm uranium. The results demonstrated that HTO-BSA-NSs are capable of uranium capture from a complex aqueous matrix with a low uranium concentration. Meanwhile, the microbial stability of HTO-BSA-NSs in sterilized natural seawater with Marinobacter sp. was investigated and observed through an optical microscope and TEM, revealing that the wrapped HTOs could protect the BSA-NSs from the decomposition of microorganisms, and the structure and functional groups of HTO-BSA-NSs remain stable compared with the BSA-NSs. In addition, the uranium adsorption mechanism of HTO-BSA-NSs is mainly recognized as dehydrated complexation, which was concluded from characterization analysis, adsorption model fitting, and theoretical calculations based on density functional theory. The remarkable uranium adsorption performance and microbial stability of HTO-BSA-NSs indicated that they have the potential to be a low-cost and environmentally friendly adsorbent for uranium extraction from complex environments such as seawater or uranium-containing industrial wastewater.

Antioxidant, metabolic enzymes inhibitory ability of Torreya grandis kernels, and phytochemical profiling identified by HPLC-QTOF-MS/MS.

In this study, the antioxidant activities, α-glucosidase and tyrosinase inhibitory ability of Torreya grandis kernels (TGK) were performed. Samples were extracted with various polarity of ethanol, and the major phytochemical profile was characterized. The results showed that 70% of ethanol extract gave the richest phenolics and flavonoids. The strongest DPPH· and ABTS·+ scavenging ability, as well as the best inhibition on tyrosinase and α-glucosidase was also detected on 70% of ethanol extract. Among the fractions of 70% of ethanol extract, the ethyl acetate fraction (EAF) owned the highest phenolics, flavonoids, and the best DPPH· and ABTS·+ scavenging ability, and tyrosinase inhibition. Unexpectedly, the dichloromethane fraction possessed the strongest inhibition on α-glucosidase, which was much greater than that of acarbose. HPLC-QTOF-MS/MS analysis result to the characterization of 19 compounds from EAF. The results implied that TGK can be a potential source of natural antioxidants, α-glucosidase and tyrosinase inhibitors. Practical applications The kernels of T. grandis are one of the precious nuts in the world, and the extracts were advertised to show a variety of biological activities and pharmacological effects. However, researches on the phytochemical constituents and bioactivities are fewer. In this study, TGK was found to show good potency in antioxidant, α-glucosidase and tyrosinase inhibitory activities. The 70% ethanol is the best solvent for extracting above mentioned active components, and ethyl acetate can be the suitable enriching solvent. In addition, the predominant phytochemical compounds in EAF were characterized. Therefore, this research can help to the performance of further research and application of TGK in functional products.