Uncovering the pharmacological mechanism of Shou Tai Wan on recurrent spontaneous abortion: A integrated pharmacology strategy-based research.

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.

Efficacy of vitamin and antioxidant supplements for treatment of diabetic peripheral neuropathy: systematic review and meta-analysis of randomized controlled trials.

ABSTRACTThe results of treatment effect of vitamin or antioxidant intake on diabetic peripheral neuropathy (DPN) was inconsistent. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to examine whether these supplements are effective in DPN treatment. We searched seven databases from inception to October 2021. All RCTs of DPN treatments with vitamin and antioxidant supplements were included. We performed sensitivity and subgroup analysis, and also tested for publication bias by the funnel plot and Egger's test. A total of 14 studies with 1384 patients were included in this systematic review. Three high-quality trials showed that vitamin and antioxidant supplements significantly increased sensory nerve conduction velocity (SNCV) of the sural nerve (MD = 2.66, 95%CI (0.60, 4.72), P < 0.05, I2 = 0%). Seven studies (758 participants) suggested that these supplements might have improvement on motor nerve conduction velocity (MNCV) of the peroneal nerve in DPN patients with the random-effect model (MD = 0.60, 95%CI (0.28, 0.92), P < 0.05, I2 = 65%). In four studies, these supplements could have improved on MNCV of the median nerve with the fixed-effect model (MD = 4.22, 95%CI (2.86, 5.57), P < 0.05, I2 = 0%). However, ten studies (841 participants) have suggested that vitamin and antioxidant supplements have not decreased glycosylated haemoglobin (HbA1c). Vitamin and antioxidant supplements may improve the conduction velocity of nerves, including median, sural and peroneal nerves of patients with DPN. But these supplements have not decreased HbA1c in DPN patients. Several trials with a large sample size are needed to provide evidence support for clinical practice in the future.

[Phosphorus Enrichment Efficiency of CaO2@FA Composites and the Effect of Its Recovered Material on Soil Improvement].

To explore the resource utilization of phosphorus (P) in wastewater and industrial waste fly ash, we used an efficient composite material (CaO2@FA) for phosphorus removal by loading nano-CaO2 on the surface of fly ash as well as in the pores using the surface precipitation method. The results showed that the material had a larger specific surface area and porosity after loading CaO2 on the fly ash surface. The specific surface area increased to 4.641 m2·g-1, and the total pore volume was up to 0.025 cm3·g-1. The adsorption process of CaO2@FA on P could be described using the Langmuir isothermal adsorption model, and its maximum adsorption capacity was 185.776 mg·g-1(20℃). The adsorption mechanism was attributed to chemical precipitation, mainly the formation of calcium hydroxyphosphate. The enrichment efficiency of CaO2@FA composites on P was significantly higher than that of fly ash, and the efficiency was increasing with the increase in the dosage added. HCO3- and CO32- in the coexisting ions had a negative effect on P adsorption by the composites. The enrichment rate of P in domestic wastewater was up to 93% when the dosage of CaO2@FA composites was 2.0 g·L-1. The content of biological P in the recovered precipitates reached 1.658 mg·g-1. The soil improvement test showed that the biological P content in soil increased by 102.9% when the recovered precipitates were added into the soil. This indicated that the operating cost of recovering 100 mg of P by this composite was as low as 0.76 yuan.

Comparative study of antimicrobial action of aloe vera and antibiotics against different bacterial isolates from skin infection.

Aloe vera is reputed to have medicinal properties. For centuries, it has been used for an array of ailments such as mild fever, wounds and burns, gastrointestinal disorders, diabetes, sexual vitality and fertility problems to cancer, immune modulation, AIDS and various skin infections. In present study, antibacterial activity of aloe vera gel extracts was tested against some common skin infection pathogens, that is, Escherichia coli, Shigella, Salmonella spp. and Staphylococcus aureus all were recorded positive. Antibiotic resistance and susceptibility pattern of above isolates were also studied against 10 clinically significant antibiotics (ampicillin [AMC], amoxicillin, augmentin, cefotaxime, ceftazidime [CAZ], cefuroxime [CXM], ciprofloxaci, tetracycline, cefpodoxime and imipenem). AMC and CXM were found to be most effective antibiotic followed by CXM with highest efficacy against Gram-negative bacteria. In case of CAZ showed highest efficacy was showed against Gram-positive bacteria. Aloe vera leave gel was extracted with four different solvent-like aloe vera leaf extract, root extract, leaf ethanol extract and root ethanol extract; however, Gram-negative as well Gram-positive isolates was found highest susceptibility with aloe leaf and aloe root ethanol extract. Moderate sensitivity observed with aloe leaf extract and aloe root extract against both Gram-positive as well as Gram-negative bacterial isolates. This result showed that ethanol extracts of aloe vera both leaf and root can be used alongside conventional antibiotics to fight agents of infections that are so prevalent in the skin infection.

Microalgae aqueous extracts exert intestinal protective effects in Caco-2 cells and dextran sodium sulphate-induced mouse colitis.

Microalgae are emerging as a good source of natural nutraceuticals. Here, we examined the intestinal protective effects of microalgae aqueous extracts (MAEs) from Chlorella pyrenoidosa, Spirulina platensis, and Synechococcus sp. PCC 7002 in human intestinal epithelial Caco-2 cells and dextran sodium sulphate (DSS)-induced colitis in C57BL/6 mice. MAEs displayed intestinal barrier-protective activities in Caco-2 cells by increasing the expression of heat shock protein (Hsp)-27 and tight junction proteins of occludin and claudin-4 and attenuating the H2O2-induced intracellular reactive oxygen species production, plasma membrane impairment and apoptosis. They also showed anti-inflammatory potential in tumor necrosis factor (TNF)-α-, interleukin (IL)-1ß- and H2O2-stimulated Caco-2 cells by suppressing the secretion of IL-8 and the expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). The 8 d daily intragastric administration of MAEs during and after 4 d DSS exposure effectively alleviated colitis symptoms of weight loss, diarrhea, rectal bleeding, and colon shortening and histopathology, protected intestinal barrier function by increasing colonic Hsp-25, occludin and claudin-4, and attenuated colonic and systemic inflammation by suppressing colonic myeloperoxidase activity, production of TNF-α, IL-1ß and IL-6, expression of COX-2 and iNOS, and peripheral leukocytosis, monocytosis and granulocytosis. Microalgae can thus serve as a functional food to maintain gut health.

Cordycepin reduces weight through regulating gut microbiota in high-fat diet-induced obese rats.

BACKGROUND: An increasing number of studies have shown that obesity is the key etiological agent of cardiovascular diseases, nonalcoholic fatty liver disease, type 2 diabetes and several kinds of cancer and that gut microbiota change was one of the reasons suffering from obesity. At present, the gut microbiota has gained increased attention as a potential energy metabolism organ. Our recent study reported that cordycepin, a major bioactive component separated from Cordyceps militaris, prevented body weight gain in mice fed a high-fat diet directly acting to adipocytes, however, the effect of cordycepin regulating gut microbiota keeps unknown. METHODS: In this research, we synthesized cordycepin (3-deoxyadenosine) by chemical methods and verified that cordycepin reduces body weight gain and fat accumulation around the epididymis and the kidneys of rats fed a high-fat diet. Furthermore, we used high-throughput sequencing on a MiSeq Illumina platform to test the species of intestinal bacteria in high-fat-diet-induced obese rats. RESULTS: We found that cordycepin modifies the relative abundance of intestinal bacteria in high-fat-diet-induced obese rats. However, cordycepin did not alter the variety of bacteria in the intestine. Cordycepin treatment dramatically reversed the relative abundance of two dominant bacterial phyla (Bacteroidetes and Firmicutes) in the high-fat-diet-induced obese rats, resulting in abundance similar to that of the chow diet group. CONCLUSION: Our study suggests that cordycepin can reduce body weight and microbiome done by cordycepin seems be a result among its mechanisms of obesity reduction.

Glabridin inhibits migration, invasion, and angiogenesis of human non-small cell lung cancer A549 cells by inhibiting the FAK/rho signaling pathway.

This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non-small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin's inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανß3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.

Dehydrocostuslactone, a medicinal plant-derived sesquiterpene lactone, induces apoptosis coupled to endoplasmic reticulum stress in liver cancer cells.

This study is the first to investigate the anticancer effect of dehydrocostuslactone [DHE (3aS,6aR,9aR,9bS)-decahydro-3,6,9-tris(methylene) azuleno[4,5-b]furan-2(3H)-one)], a medicinal plant-derived sesquiterpene lactone, on hepatocellular carcinoma. Our results showed that DHE inhibits the proliferation of HepG2 and PLC/PRF/5 cells by inducing apoptosis. DHE induces up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, and nuclear relocation of the mitochondrial factors apoptosis-inducing factor (AIF) and endonuclease G (Endo G). DHE triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol-calcium levels, double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase phosphorylation, inositol-requiring protein 1 (IRE1) and CHOP/GADD153 up-regulation, X-box transcription factor-1 mRNA splicing, and caspase-4 activation. Enhancement of ER stress by DHE is through p38 and extracellular signal-regulated kinase 1/2-dependent manners and subsequently causes c-Jun NH(2)-terminal kinase activation, resulting in AIF and Endo G nuclear relocation. Both of IRE1 small interfering RNA transfection and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester pretreatment inhibit DHE-mediated apoptosis, supporting the hypothesis that DHE induces cell death through ER stress. It is noteworthy that animal studies have revealed a dramatic 50% reduction in tumor volume after 45 days of treatment. This study demonstrates that DHE may be a novel anticancer agent for the treatment of liver cancer.