Xingbei antitussive granules ameliorate cough hypersensitivity in post-infectious cough guinea pigs by regulating tryptase/PAR2/TRPV1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xingbei antitussive granules (XB) is a classic Chinese Medicine prescription for treating post-infectious cough(PIC), based on the Sanao Decoction from Formularies of the Bureau of People's Welfare Pharmacies in the Song Dynasty and Jiegeng decoction from Essentials of the Golden Chamber in the Han Dynasty. However, the therapeutic effects and pharmacological mechanisms are still ambiguous. In the present study, we endeavored to elucidate these underlying mechanisms. AIMS OF THE STUDY: This study aimed to explore the potential impact and mechanism of XB on PIC, and provide a scientific basis for its clinical application. MATERIALS AND METHODS: Cigarette smoking (CS) combined with lipopolysaccharide (LPS) nasal drops were administered to induce the PIC guinea pig with cough hypersensitivity status. Subsequently, the model guinea pigs were treated with XB and the cough frequency was observed by the capsaicin cough provocation test. The pathological changes of lung tissue were assessed by HE staining, and the levels of inflammatory mediators, mast cell degranulating substances, and neuropeptides were detected. The protein and mRNA expression of transient receptor potential vanilloid type 1(TRPV1), proteinase-activated receptor2(PAR2), and protein kinase C (PKC) were measured by Immunohistochemical staining, Western blot, and RT-qPCR. Changes in the abundance and composition of respiratory bacterial microbiota were determined by 16S rRNA sequencing. RESULTS: After XB treatment, the model guinea pigs showed a dose-dependent decrease in cough frequency, along with a significant alleviation in inflammatory infiltration of lung tissue and a reduction in inflammatory mediators. In addition, XB high-dose treatment significantly decreased the levels of mast cell Tryptase as well as ß-hexosaminidase (ß-Hex) and downregulated the expression of TRPV1, PAR2, and p-PKC. Simultaneously, levels of neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and nerve growth factor (NGF) were improved. Besides, XB also can modulate the structure of respiratory bacterial microbiota and restore homeostasis. CONCLUSION: XB treatment alleviates cough hypersensitivity and inflammatory responses, inhibits the degranulation of mast cells, and ameliorates neurogenic inflammation in PIC guinea pigs whose mechanism may be associated with the inhibition of Tryptase/PAR2/PKC/TRPV1 and the recovery of respiratory bacterial microbiota.

Five Tibetan patent medicines orally for ischemic stroke: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tibetan Patent Medicines (TPMs) have unique advantages in the treatment of ischemic stroke (IS) with the features of multi-component, multi-channel, and multi-target. In China, five TPMs mainly consisting of precious medicinal materials such as gold, pearls, and agate are widely utilized to treat IS and have achieved good results according to the current clinical practice. AIM OF THE STUDY: To systematically evaluate the efficacy and safety of the five TPMs orally in treating IS and provide a reference for future clinical application and research. MATERIALS AND METHODS: We searched the following 24 databases up to December 11, 2022: China National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, Chinese Biomedical Database (CBM), PubMed, Embase, Web of Science, MEDLINE, Scopus, the Cochrane Library, ScienceDirect, etc. Comprehensive searches for randomized controlled trials (RCTs) of the five TPMs for IS were conducted. Outcome measures included clinical effective rate, neurological impairment score, activities of daily living (ADL), hematologic indices, and adverse events (AEs). The meta-regression, subgroup analyses, and sensitivity analyses were conducted to explore the sources of heterogeneity. We assessed the evidence grade of outcomes via the GRADE system. TSA software was used for trial sequential analyses of the clinical effective rate, neurological impairment score, and ADL. RESULTS: 17 RCTs (1603 patients) met our criteria. Compared with the control groups, the five TPMs showed greater improvement in clinical effective rate (RR = 1.23, 95% CI 1.17 to 1.29, P < 0.00001), neurological impairment score (SMD = -1.71, 95% CI -2.31 to -1.10, P < 0.00001), ADL (SMD = 1.97, 95% CI 1.26 to 2.68, P < 0.00001), hematocrit (MD = -1.56, 95% CI -2.83 to -0.29, P = 0.02), and hypersensitive-c-reactive-protein (MD = -2.96, 95% CI -3.30 to -2.61, P < 0.00001). AEs were reported in four RCTs and there was no statistical difference between groups (RD = -0.00, 95% CI -0.04 to 0.03, P = 0.82). The quality of evidence of the outcomes was rated as low to very low according to the GRADE system. The results of TSA provided firm evidence for the significant effect of the five TPMs on clinical effective rate, neurological impairment score, and ADL. CONCLUSIONS: This review showed that the five TPMs were beneficial in improving clinical effective rate, neurological impairment scores, and ADL. However, no definite conclusions for hematologic indices and AEs were drawn due to insufficient studies. Further high-quality clinical trials are required to confirm these findings.

Enhanced Anti-Rheumatoid Arthritis Activity of Total Alkaloids from Picrasma Quassioides in Collagen-Induced Arthritis Rats by a Targeted Drug Delivery System.

New drug delivery systems have rarely been used in the formulation of traditional Chinese medicine, especially those that are crude active Chinese medicinal ingredients. In the present study, hyaluronic acid decorated lipid-polymer hybrid nanoparticles were used to prepare a targeted drug delivery system (TDDS) for total alkaloid extract from Picrasma quassioides (TAPQ) to improve its targeting property and anti-inflammatory activity. Picrasma quassioides, a common-used traditional Chinese medicine (TCM), containing a series of hydrophobic total alkaloids including ß-carboline and canthin-6-one alkaloids show great anti-inflammatory activity. However, its high toxicity (IC50= 8.088±0.903 µg/ml), poor water solubility (need to dissolve with 0.8% Tween-80) and poor targeting property severely limits its clinical application. Herein, hyaluronic acid (HA) decorated lipid-polymer hybrid nanoparticles loaded with TAPQ (TAPQ-NPs) were designed to overcome above mentioned deficiencies. TAPQ-NPs have good water solubility, strong anti-inflammatory activity and great joint targeting property. The in vitro anti-inflammatory activity assay showed that the efficacy of TAPQ-NPs was significantly higher than TAPQ(P<0.001). Animal experiments showed that the nanoparticles had good joint targeting property and had strong inhibitory activity against collagen-induced arthritis (CIA). These results indicate that the application of this novel targeted drug delivery system in the formulation of traditional Chinese medicine is feasible.

Supplementation of mitochondria from endometrial mesenchymal stem cells improves oocyte quality in aged mice.

Maternal ageing is one of the major causes of reduced ovarian reserve and low oocyte quality in elderly women. Decreased oocyte quality is the main cause of age-related infertility. Mitochondria are multifunctional energy stations that determine the oocyte quality. The mitochondria in aged oocytes display functional impairments with mtDNA damage, which leads to reduced competence and developmental potential of oocytes. To improve oocyte quality, mitochondrial supplementation is carried out as a potential therapeutic approach. However, the selection of suitable cells as the source of mitochondria remains controversial. We cultivated endometrial mesenchymal stem cells (EnMSCs) from aged mice and extracted mitochondria from EnMSCs. To improve the quality of oocytes, GV oocytes were supplemented with mitochondria via microinjection. And MII oocytes from aged mice were fertilized by intracytoplasmic sperm injection (ICSI), combining EnMSCs' mitochondrial microinjection. In this study, we found that the mitochondria derived from EnMSCs could significantly improve the quality of aged oocytes. Supplementation with EnMSC mitochondria significantly increased the blastocyst ratio of MII oocytes from aged mice after ICSI. We also found that the birth rate of mitochondria-injected ageing oocytes was significantly increased after embryo transplantation. Our study demonstrates that supplementation with EnMSC-derived mitochondria can improve the quality of oocytes and promote embryo development in ageing mice, which might provide a prospective strategy for clinical treatment.

The Role of Dehydroepiandrosterone in Improving in vitro Fertilization Outcome in Patients with DOR/POR: A Systematic Review and Meta- Analysis.

BACKGROUND AND OBJECTIVE: Although many trials have evaluated the use of dehydroepiandrosterone to improve outcomes in poor responders undergoing assisted reproductive technology treatment, evidence supporting this approach is controversial. We aimed to conduct a systematic review and meta-analysis of existing published data to further elucidate and supplement the use of Dehydroepiandrosterone (DHEA) to improve the effectiveness of vitro fertilization in patients with diminished ovarian reserve or adverse ovarian reactions. METHODS: PubMed, Embase, Cochrane Library, and the Web of Science databases were searched through December 2020. Oocyte yield, metaphase II oocytes, fertilized oocytes, top-quality embryos, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were analyzed as relative outcomes. Meta-analysis was performed and fitted to both fixed-effects models and random-effects models. RESULTS: Eight prospective randomized controlled studies, five prospective case-control studies, and three retrospective cohort studies were conducted with a total of 1998 participants. Meta-analyses of these studies showed a significantly higher number of oocytes retrieved (WMD 1.09, 95% CI 0.38 to 1.80), metaphase II oocytes (WMD 0.78, 95% CI 0.16 to 1.40), fertilized oocytes (WMD 0.84, 95% CI 0.42 to 1.26), top-quality embryos (WMD 0.60, 95% CI 0.34 to 0.86), clinical pregnancy rate (RR 1.35, 95% CI 1.13 to 1.61), and ongoing pregnancy rate (RR 1.82, 95% CI 1.34 to 2.46), although there was no difference in live birth rate (RR 1.35, 95% CI 0.94 to 1.94) in the DHEA supplementation groups compared with that in the control groups. CONCLUSION: Oral DHEA supplementation appears to improve some IVF outcomes. On the basis of this limited evidence, we conclude that further studies are required to provide sufficient data.

The Role of Alternative Splicing in Cancer: Regulatory Mechanism, Therapeutic Strategy, and Bioinformatics Application.

[Formula: see text] Alternative splicing (AS) can generate distinct transcripts and subsequent isoforms that play differential functions from the same pre-mRNA. Recently, increasing numbers of studies have emerged, unmasking the association between AS and cancer. In this review, we arranged AS events that are closely related to cancer progression and presented promising treatments based on AS for cancer therapy. Obtaining proliferative capacity, acquiring invasive properties, gaining angiogenic features, shifting metabolic ability, and getting immune escape inclination are all splicing events involved in biological processes. Spliceosome-targeted and antisense oligonucleotide technologies are two novel strategies that are hopeful in tumor therapy. In addition, bioinformatics applications based on AS were summarized for better prediction and elucidation of regulatory routines mingled in. Together, we aimed to provide a better understanding of complicated AS events associated with cancer biology and reveal AS a promising target of cancer treatment in the future.

Modulating the structure of lamb myofibrillar protein gel influenced by psyllium husk powder at different NaCl concentrations: Effect of intermolecular interactions.

In this study, a strategy involving psyllium husk powder (PHP) was proposed to alleviate the textural deterioration of protein gels under low-sodium conditions. Results revealed that myofibrillar protein (MP) in 0.3 M NaCl could accommodate more PHP to achieve better gels properties compared with that of 0.6 M NaCl. The 3 % addition of PHP could lessen the textural deterioration of gels at 0.3 M NaCl because of the insertion of PHP into the hydrophobic cavity of MP. Consequently, the reduction in protein viscoelasticity and the thermal stability of the head and tail of myosin improved. α-Helix structures unfolded, intermolecular forces formed, and proteins aggregated. Molecular docking predicted hydrogen bonds and hydrophobic interactions as the main forces to stabilize the conformation of composites. Experiments further verified that hydrophobic interactions and disulfide bonds were the main forces that stabilized the structure of MP-PHP composite gels.

Effects of Qidantang Granule on early stage of diabetic kidney disease in rats.

Diabetic kidney disease (DKD), is one of the most common vascular diseases caused by diabetes, eventually progressing into glomerular sclerosis. Qidantang Granule is a traditional Chinese medicine that is commonly used for DKD. However, there is still no experimental evidence for its effectiveness on DKD. 8-week-old Sprague Dawley male rats were fed on high-fat and high-sugar diet for 4 weeks, and then intraperitoneally injected with 35 mg/kg streptozotocin (STZ) to induce diabetes. Diabetic rats were randomly divided into three groups, and orally administrated with vehicle, 50 mg/kg or 200 mg/kg Qidantang Granule respectively, once daily for 9 weeks. Qidantang Granule effectively reduced food and water intake, body weight and fasting blood glucose, decreased inflammation and oxidative stress, ameliorated renal injury through suppressing PI3K signaling pathway in STZ-induced DKD rats. Our results provide experimental evidence to demonstrate the pharmacological mechanism of Qidantang Granule in the treatment of DKD.

A sponge heated by electromagnetic induction and solar energy for quick, efficient, and safe cleanup of high-viscosity crude oil spills.

Frequent oil spills have caused severe environmental and ecological damage. Effective cleanup has become a complex challenge owing to the poor flowability of viscous crude oils. The current method of solar heating to reduce the viscosity of heavy oil is only suitable during sunny days, while the use of Joule heating is limited by the risk of direct exposure to high-voltage electricity. Herein, we demonstrate a noncontact electromagnetic induction and solar dual-heating sponge for the quick, safe, and energy-saving cleanup of ultrahigh-viscosity heavy oil. The resulting sponge with magnetic, conductive, and hydrophobic properties can be rapidly heated to absorb heavy oil under alternating magnetic fields, solar irradiation, or both of these conditions. By constructing theoretical models and fitting the actual data, an in-depth analysis of induction and solar heating processes is carried out. The sponge has excellent resilience and stability, indicating its reusability, fast and continuous adsorption (16.17 g in 10 s), and large capacity (75-81 g/g, the highest value ever) for soft asphalt (a highly viscous crude oil). This work provides a new noncontact dual-heating strategy for heavy oil cleanup, in which absorbents use induction heating during an emergency and then switch to partial or full solar heating to save energy in sunny conditions. ENVIRONMENTAL IMPLICATION: Heavy oils stranded on the beach or floating on water can kill underwater plants by blocking sunlight, or trap water birds and other animals. Heavy oil also contains aromatic substances that are toxic to aquatic organisms. Although oil spills near shallow water cannot be cleaned up by fences or other machinery, an oil adsorbent can deal with this problem. However, common adsorbents cannot effectively absorb high-viscosity oils, such as heavy oil. In this paper, an induction and solar dual-heating sponge is developed for the effective cleanup of high-viscosity oil.

Notoginsenoside R1 ameliorates mitochondrial dysfunction to circumvent neuronal energy failure in acute phase of focal cerebral ischemia.

Due to sudden loss of cerebral blood circulation, acute ischemic stroke (IS) causes neuronal energy attenuation or even exhaustion by mitochondrial dysfunction resulting in aggravation of neurological injury. In this study, we investigated if Notoginsenoside R1 ameliorated cerebral energy metabolism by limiting neuronal mitochondrial dysfunction in acute IS. Male Sprague-Dawley rats (260-280 g) were selected and performed by permanent middle cerebral artery occlusion model. In vitro, the oxygen glucose deprivation (OGD) model of Neuro2a (N2a) cells was established. We found Notoginsenoside R1 treatment reduced rats' cerebral infarct volume and neurological deficits, with increased Adenosine triphosphate (ATP) level together with upregulated expression of glucose transporter 1/3, monocarboxylate transporter 1 and citrate synthase in brain peri-ischemic tissue. In vitro, OGD-induced N2a cell death was inhibited, cell mitochondrial morphology was improved. Mitochondrial amount, mitochondrial membrane potential, and mitochondrial DNA copy number were increased by Notoginsenoside R1 administration. Furthermore, mitochondrial energy metabolism-related mRNA array found Atp12a and Atp6v1g3 gene expression were upregulated more than twofold, which were also verified in rat ischemic tissue by quantitative polymerase chain reaction (qPCR) assay. Therefore, Notoginsenoside R1 administration increases cerebral glucose and lactate transportation and ATP levels, ameliorates neuronal mitochondrial function after IS. Notoginsenoside R1 may be a novel protective agent for neuronal mitochondria poststroke.

Overview of therapeutic potentiality of Angelica sinensis for ischemic stroke.

BACKGROUND: Ischemic stroke is a common cerebrovascular disease. Due to sudden interruption of blood flow by arterial thrombus, amounts of neurons in ischemic central and penumbral regions occur necrosis and apoptosis resulting in serious injury of neurological function. Chinese medicines have a great advantage in ischemic stroke treatment and recovery, especially Angelica sinensis. PURPOSE: There are a large number of studies reported that Angelica injection and A. sinensis active compounds. We systematically reviewed the effects and mechanisms of A. sinensis in recent years according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements, and excavated its therapeutic potentiality for exploring more effective and safe compounds for ischemic stroke precision treatment. RESULTS: A. sinensis extracts and active compounds, such as Z-ligustilide, 3-n-Butylphthalide, and ferulic acid have significant effects of anti-inflammation, anti-oxidative stress, angiogenesis, neurogenesis, anti-platelet aggregation, anti-atherosclerosis, protection of vessels, which contributes to improvement of neurological function on ischemic stroke. CONCLUSION: A. sinensis is a key agent for ischemic stroke treatment, and worth deeply excavating its therapeutic potentiality with the aid of pharmacological network, computer-aided drug design, artificial intelligence, big data and multi-scale modelling techniques.

Notoginsenoside R1 intervenes degradation and redistribution of tight junctions to ameliorate blood-brain barrier permeability by Caveolin-1/MMP2/9 pathway after acute ischemic stroke.

BACKGROUND: The leakage of blood-brain barrier (BBB) is main pathophysiological change in acute stage of ischemic stroke, which not only deteriorates neurological function, but also increases the risk of hemorrhagic transformation after thrombolysis. PURPOSE/STUDY DESIGN: This article investigates the efficacy of Notoginsenoside R1, an active ingredient of Panax notoginseng, on BBB permeability and explores related mechanisms after acute ischemic stroke. METHODS: In vivo, male Sprague-Dawley rats (260-280 g) were selected and randomly divided into 6 groups: sham group, model group, low, middle and high doses of Notoginsenoside R1 groups and positive drug Dl-3-n-Butylphthalide group. Except for sham group, rats were performed with permanent middle cerebral artery occlusion model in each group. Twelve hours later, rats were evaluated for Bederson neurological function, and BBB integrity by Evans blue leak imaging; Triphenyltetrazolium chloride staining was used to detect the volume of cerebral infarction. Frozen sections of rats' brain tissue were prepared for detection of MMPs activity in situ zymography. Peripheral tissue of cerebral infarction was collected and tested the expression of MMP2, 9 and tight junction proteins (zo1, claudin5, occludin) by western blot. In vitro, transwell endothelial barrier model was established by bEnd.3 cells. Oxygen glucose deprivation (OGD) was chosen to simulate the hypoxic environment. Suitable OGD stimulation time as well as Notoginsenoside R1 and Dl-3-n-Butylphthalide optimal dose concentrations were determined through transwell leakage and CCK8 assay. Furthermore, endothelial subcellular component proteins were extracted. The change of zo1, claudin5, occludin and caveolin1 was detected by western blot. RESULTS: Notoginsenoside R1 treatment significantly reduced BBB leakage and cerebral infarction volume, weakened neurological deficits in post-stroke rats. Moreover, it inhibited the activity of MMPs in infarcted cortex and striatum, down-regulated MMP2, 9 and up-regulated zo1 and claudin5 expressions in penumbra. In vitro, Notoginsenoside R1 treatment decreased OGD-induced endothelial barrier permeability, restored expressions of zo1, claudin5 on cellular membrane and cytoplasm, as well as mediated membrane redistribution of occludin and caveolin1 from actin cytoskeletal fraction. CONCLUSIONS: Notoginsenoside R1 treatment attenuates BBB permeability, cerebral infarction volume and neurological impairments in rats with acute cerebral ischemia. The mechanisms might be related to intervening degradation and redistribution of zo1, caludin5 and occludin by caveolin1/ MMP2/9 pathway. More effects and mechanisms of Notoginsenoside R1 on rehabilitation of stroke are worthy to be explored in the future.

Traditional Chinese Medicine Constitution Correlated with Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the correlation between traditional Chinese medicine (TCM) body constitution and ischemic stroke (IS). METHODS: Literature search was conducted in databases including Wanfang database, Chongqing VIP, China National Knowledge Infrastructure, Embase, and PubMed from inception to November 16, 2020. Observational studies evaluating the association between TCM body constitution and IS were included for analysis. The distribution of body constitutional types in IS patients was pooled into meta-analysis. The correlation between constitution and IS was presented by the odds ratio (OR) and 95% CI through the comparison between IS and the general population. RESULTS: 41 studies involving 11,211 participants were included. Among the nine constitution types, qi-deficiency constitution (QDC), phlegm-dampness constitution (PDC), and blood stasis constitution (BSC) are the common types, accounting for 25% [0.22, 0.29], 23% [0.20, 0.29], and 17% [0.13, 0.22], respectively, in IS patients. The proportion of PDC and QDC among IS patients is 2.34 times and 3.47 times higher than that in the general population, respectively (OR and 95% CI: 2.34 [1.39, 3.94], 3.47 [1.61, 7.50], respectively). CONCLUSION: PDC and QDC are the common constitutions in IS patients and may have a potential correlation with the incidence of IS. Due to the low or moderate quality of included studies, more well-designed prospective studies are warranted to further evaluate the relationship between TCM constitutions and IS.

The Extracts of Angelica sinensis and Cinnamomum cassia from Oriental Medicinal Foods Regulate Inflammatory and Autophagic Pathways against Neural Injury after Ischemic Stroke.

The study indicates inflammation and autophagy are closely related to neural apoptosis in the pathology of ischemic stroke. In the study, we investigate the effects and mechanisms of the extracts of Angelica sinensis and Cinnamomum cassia (AC) from oriental medicinal foods on inflammatory and autophagic pathways in rat permanent middle cerebral artery occlusion model. Three doses of AC extract were, respectively, administered for 7 days. It suggests that AC extract treatment ameliorated scores of motor and sensory functions and ratio of glucose utilization in thalamic lesions in a dose-dependent manner. Expression of Iba1 was decreased and CD206 was increased by immunofluorescence staining, western blotting results showed expressions of TLR4, phosphorylated-IKKß and IκBα, nuclear P65, NLRP3, ASC, and Caspase-1 were downregulated, and Beclin 1 and LC3 II were upregulated. Low concentrations of TNF-α, IL-1ß, and IL-6 were presented by ELISA assay. Additionally, caspase 8 and cleaved caspase-3 expressions and the number of TUNEL positive cells in ipsilateral hemisphere were decreased, while the ratio of Bcl-2/Bax was increased. Simultaneously, in LPS-induced BV2 cells, it showed nuclear P65 translocation and secretion of proinflammatory cytokines were suppressed by AC extract-contained cerebrospinal fluid, and its intervened effects were similar to TLR4 siRNA treatment. Our study demonstrates that AC extract treatment attenuates inflammatory response and elevates autophagy against neural apoptosis, which contributes to the improvement of neurological function poststroke. Therefore, AC extract may be a novel neuroprotective agent by regulation of inflammatory and autophagic pathways for ischemic stroke treatment.

Effect of calcinated pyrite on simultaneous ammonia, nitrate and phosphorus removal in the BAF system and the Fe2+ regulatory mechanisms: Electron transfer and biofilm properties.

To efficiently remove nitrogen and phosphorus from secondary effluent with low values of COD/TN, a novel biological aerated filter (BAF) utilizing calcined pyrite with a large specific surface area (SSA) and pore diameter (PD) was designed to address this challenge. From the perspective of nutrients removal performance, and the corresponding effluent total nitrogen (TN) and PO43--P in the calcined pyrite autotrophic denitrification (CPAD) process decreased from 40.21 to 1.07 mg/L to 1.22 and 0.14 mg/L, respectively. Furthermore, the nutrients removal kinetics analysis showed that the CPAD and pyrite autotrophic denitrification (PAD) processes could be fitted with Half-order and Zero-order reactions via kinetics analysis, respectively, indicating that the TN removal performance of CPAD processes was better than that of the PAD process. Moreover, CPAD combined with sulfur autotrophic denitrification (SAD) processes was fitted by First-order reaction, and the TN removal performance was further enhanced over the CPAD process. From the perspective of microregulation, Fe2+ production in the PAD and CPAD processes could accelerate the electron transfer rate by increasing electron transport system activity (ETSA) and reducing electrochemical impedance spectroscopy (EIS). Moreover, Fe2+ stimulated microbes to produce more proteins (PN) and C10-HSL, which improved biofilm stability and interspecific communication processes. Notably, nitrifiers and autotrophic denitrifiers were simultaneously enriched via detection of high-throughput sequencing of 16 S rRNA genes, which verified the feasibility of simultaneous nitrification and autotrophic denitrification. Therefore, BAF with calcined pyrite and sulfur as composite fillers have a considerable advantage in nutrients removal.

Identification and verification of effective components of Huanghuai for dysfunctional uterine bleeding based on network pharmacology and molecular docking.

Objective: The Huanghuai (HH), which is made from the dried roots of Scutellaria baicalensis (Huangqin in Chinese) and the dried flowers and buds of Sophora japonica (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect. Methods: TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.7.2 were utilized for the construction of a compound-target-pathway network. Docking the potential effective components with potential targets. The HPLC analysis of the potential effective components was performed. In vivo, the hot plate test model was used to study the analgesic activity, the egg white was used to study the swollen reaction in the sole in mice, and the hemostasis effect was studied by the capillary method, tail-breaking method and abortion uterus test. Results: The results showed that six compounds (acacetin, beta-sitosterol, wogonin, baicalein, kaempferol and quercetin) and four potential targets (PTGS2, AKT1, TP53 and TNF) in the compound-target-pathway network were the potential material basis for HH to treat DUB. It can be seen that the binding energy of the acacetin, wogonin, baicalein, beta-sitosterol, kaempferol and quercetin in HH docked with the receptor proteins PTGS2, AKT1, TP53, and TNF were far less than -5.0 kJ/mol, which means the molecules have low conformational energy, stable structure and high binding activity. And the result of HPLC analysis showed that acacetin, wogonin, baicalein, kaempferol and quercetin were the potential effective components of the hemostasis mechanism of HH, beta-sitosterol was removed due to low content. In vivo testing of the potential effective components, it revealed that the group of potential effective components identified by HPLC could increase the pain threshold, inhibit the swelling hind paws of mice induced by egg white, reduce the bleeding time and clotting time, reduce uterine bleeding, decrease the uterine weight, increase the content of Ca and ET-1, and reduce the content of NO in uterine homogenate tissue, and decrease of E2 and P content in uterine serum in aborted rats, whose efficacy was equal to HH. Conclusion: The results indicated that HH and potential active ingredient groups obtained from network pharmacology can treat DUB and play a hemostatic effect. The results obtained by network pharmacology have certain reliability. This study provides new indications for further mechanism research of HH on DUB and the development of HH or its components as an alternative therapy for patients with DUB. At the same time, the application of network pharmacology strategy may provide a powerful tool for exploring the mechanism of traditional Chinese medicine and discovering new biologically active ingredients.

Mechanisms and Active Compounds Polysaccharides and Bibenzyls of Medicinal Dendrobiums for Diabetes Management.

BACKGROUND: Medicinal dendrobiums are used popularly in traditional Chinese medicine for the treatment of diabetes, while their active compounds and mechanism remain unclear. This review aimed to evaluate the mechanism and active compounds of medicinal dendrobiums in diabetes management through a systematic approach. METHODS: A systematic approach was conducted to search for the mechanism and active phytochemicals in Dendrobium responsible for anti-diabetic actions using databases PubMed, Embase, and SciFinder. RESULTS: Current literature indicates polysaccharides, bibenzyls, phenanthrene, and alkaloids are commonly isolated in Dendrobium genusin which polysaccharides and bibenzyls are most aboundant. Many animal studies have shown that polysaccharides from the species of Dendrobium provide with antidiabetic effects by lowering glucose level and reversing chronic inflammation of T2DM taken orally at 200 mg/kg. Dendrobium polysaccharides protect pancreatic ß-cell dysfunction and insulin resistance in liver. Dendrobium polysaccharides up-regulate the abundance of short-chain fatty acid to stimulate GLP-1 secretion through gut microbiota. Bibenzyls also have great potency to inhibit the progression of the chronic inflammation in cellular studies. CONCLUSION: Polysaccharides and bibenzyls are the major active compounds in medicinal dendrobiums for diabetic management through the mechanisms of lowering glucose level and reversing chronic inflammation of T2DM by modulating pancreatic ß-cell dysfunction and insulin resistance in liver as a result from gut microbita regulation.

A Targeted Computational Screen of the SWEETLEAD Database Reveals FDA-Approved Compounds with Anti-Dengue Viral Activity.

Affordable and effective antiviral therapies are needed worldwide, especially against agents such as dengue virus that are endemic in underserved regions. Many antiviral compounds have been studied in cultured cells but are unsuitable for clinical applications due to pharmacokinetic profiles, side effects, or inconsistent efficacy across dengue serotypes. Such tool compounds can, however, aid in identifying clinically useful treatments. Here, computational screening (Rapid Overlay of Chemical Structures) was used to identify entries in an in silico database of safe-in-human compounds (SWEETLEAD) that display high chemical similarities to known inhibitors of dengue virus. Inhibitors of the dengue proteinase NS2B/3, the dengue capsid, and the host autophagy pathway were used as query compounds. Three FDA-approved compounds that resemble the tool molecules structurally, cause little toxicity, and display strong antiviral activity in cultured cells were selected for further analysis. Pyrimethamine (50% inhibitory concentration [IC50] = 1.2 µM), like the dengue proteinase inhibitor ARDP0006 to which it shows structural similarity, inhibited intramolecular NS2B/3 cleavage. Lack of toxicity early in infection allowed testing in mice, in which pyrimethamine also reduced viral loads. Niclosamide (IC50 = 0.28 µM), like dengue core inhibitor ST-148, affected structural components of the virion and inhibited early processes during infection. Vandetanib (IC50 = 1.6 µM), like cellular autophagy inhibitor spautin-1, blocked viral exit from cells and could be shown to extend survival in vivo Thus, three FDA-approved compounds with promising utility for repurposing to treat dengue virus infections and their potential mechanisms were identified using computational tools and minimal phenotypic screening.IMPORTANCE No antiviral therapeutics are currently available for dengue virus infections. By computationally overlaying the three-dimensional (3D) chemical structures of compounds known to inhibit dengue virus over those of compounds known to be safe in humans, we identified three FDA-approved compounds that are attractive candidates for repurposing as antivirals. We identified targets for two previously identified antiviral compounds and revealed a previously unknown potential anti-dengue compound, vandetanib. This computational approach to analyze a highly curated library of structures has the benefits of speed and cost efficiency. It also leverages mechanistic work with query compounds used in biomedical research to provide strong hypotheses for the antiviral mechanisms of the safer hit compounds. This workflow to identify compounds with known safety profiles can be expanded to any biological activity for which a small-molecule query compound has been identified, potentially expediting the translation of basic research to clinical interventions.

Evaluation of the efficacy and safety of the use of acupuncture for the adjuvant treatment of patients with post-stroke cognitive impairment: protocol for a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is a series of syndromes that meet the diagnostic criteria for cognitive impairment that appear after a stroke. The treatment of PSCI with oral drugs alone is not ideal and has obvious side effects. Therefore, complementary and alternative treatments are needed for patients with insufficient or significant side effects of oral medications. Therefore, we will evaluate the clinical effectiveness and safety of acupuncture in the treatment of PSCI. METHODS/DESIGN: In this study, patients will be randomly divided into two groups. Intervention group: acupuncture combined with oral medication. CONTROL GROUP: Western medicine treatment plan. All participants will continue to receive conventional drug treatment. The selection of outcomes will be evaluated by Mini Mental State Examination Scale (MMSE) at week 12. The scale will be conducted by two well-trained reviewers who will conduct joint MMSE inspections on participants. The test time will be selected 3 days before treatment and once 4 weeks after treatment. After the MMSE test, the two raters scored independently, and the average of the two was used as the final score. DISCUSSION: This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with PSCI. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000029926. Registered on 17 February 2020 http://www.chictr.org.cn/showproj.aspx?proj=49356.

Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID-19): an empirical study from Wuhan, Hubei Province, China.

BACKGROUND: A novel coronavirus was identified in December, 2019 in Wuhan, China, and traditional Chinese medicine (TCM) played an active role in combating the novel coronavirus pneumonia (NCP) caused by this fast-spreading virus COVID-19. Thus, we aimed to explore TCM characteristics of clinical efficacy to NCP, as well as to optimize Qingfei Paidu decoction (QFPDD) and the recommended formulas to NCP by National Health Commission (NHC). METHODS: Chinese medical sciences theory and clinical application of TCM were analyzed. A total of 54 NCP patients were observed in a hospital from Wuhan, whose clinical characteristics and utilization of Chinese Medicines (CMs) were described. Paired t test was used to measure the change of patients' hemogram during hospitalization period, indicating the effect of CMs. Multiple linear regression analysis was applied to explore the factors affecting the length of hospital stay. Network pharmacology analysis was applied to figure out the performance of NHC-recommended formulas of five disease stages at levels of compounds, targets and pathways. RESULT: The average length of hospital stay was 8.96 days. Patients over 45 stayed 9.79 days in hospital in average, longer than 7.64 days of patients under 45. Comparing the hemograms between admission and discharge of hospital, the number of leukocytes, neutrophil, lymphocyte and platelet increased, while the numbers of erythrocytes, hemoglobin concentration and hematocrit decreased. According to the standard coefficients of regression, the factor affecting the length of stay for the most was CMs in category of invigorating spleen and removing dampness (ISRD), followed by administrating CMs, male, and cough. Thirty-two CMs were screened after deleting duplication from QFPDD and NHC-recommended formulas. Compound quercetin, luteolin, kaempferol, acacetin etc., were all involved in the treatment of various disease stages on the compound level both in generality and individuality. CONCLUSION: TCM has a systemic theoretical understanding on the pathological evolution and a positive clinical efficacy on NCP. The CMs of ISRD improved patients' recovery, suggesting the importance of regulating intestinal function and keeping microenvironmental balance in TCM treatment of NCP. The active compounds from QFPDD and NHC-recommended formulas contribute to recovery of varied disease progresses during TCM treating NCP.