[Comparative study on excretion of Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats].

Scutellariae Radix extract is one of the important components in Shuganning Injection. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for simultaneously determining five components in Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats, so as to reveal the difference in the excretion process of Shuganning Injection and Scutellariae Radix extract in rats and explore the law of the excretion process of the five components in vivo before and after the compatibility of Scutellariae Radix. Rats were injected with Shuganning Injection and Scutellariae Radix extract(4.2 mL·kg~(-1)), respectively, and the excretion of baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin in bile, urine, and feces of rats in 24 h was observed. The results showed that except for baicalin, the other four index components were excreted as prototype components in a high proportion after intravenous injection of Shuganning Injection and Scutellariae Radix extract in rats, respectively. The excretion of each component was relatively high in urine and less in feces and bile. After the compatibility of Scutellariae Radix extract, the accumulative excretion of five index components in rats all decreased. Among them, the cumulative excretion of baicalein in bile, urine, and feces significantly decreased by 26.67%, 48.11%, and 31.01%. The cumulative excretion of baicalin in bile, urine, and feces decreased significantly by 70.69%, 19.43%, and 31.22%. The result showed that the five index components in Scutellariae Radix extract were mainly excreted by the kidneys, and other components in Shuganning Injection delayed the excretion process and prolonged the residence time. This study is of great significance for elucidating the compatibility rationality of Shuganning Injection.

Bromine Substitution Improves the Photothermal Performance of π-Conjugated Phototheranostic Molecules.

NIR-II fluorescence imaging-guided photothermal therapy (PTT) has been widely investigated due to its great application potential in tumor theranostics. PTT is an effective and non-invasive tumor treatment method that can adapt to tumor hypoxia; nevertheless, simple and effective strategies are still desired to develop new materials with excellent PTT properties to meet clinical requirements. In this work, we developed a bromine-substitution strategy to enhance the PTT of A-D-A'-D-A π-conjugated molecules. The experimental results reveal that bromine substitution can notably enhance the absorptivity (ϵ) and photothermal conversion efficiency (PCE) of the π-conjugated molecules, resulting in the brominated molecules generating two times more heat (ϵ808 nm ×PCE) than their unsubstituted counterpart. We disclose that the enhanced photothermal properties of bromine-substituted π-conjugated molecules are a combined outcome of the heavy-atom effect, enhanced ICT effect, and more intense bromine-mediate intermolecular π-π stacking. Finally, the NIR-II tumor imaging capability and efficient PTT tumor ablation of the brominated π-conjugated materials demonstrate that bromine substitution is a promising strategy for developing future high-performance NIR-II imaging-guided PTT agents.

Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives.

Cancer is a leading cause of death worldwide. The burden of cancer incidence and mortality is increasing rapidly. New approaches to cancer prevention and treatment are urgently needed. Natural products are reliable and powerful sources for anticancer drug discovery. Baicalin and baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, a multi-purpose traditional medicinal plant in China, exhibit anticancer activities against multiple cancers. Of note, these phytochemicals exhibit extremely low toxicity to normal cells. Besides their cytotoxic and cytostatic activities toward diverse tumor cells, recent studies demonstrated that baicalin and baicalein modulate a variety of tumor stromal cells and extracellular matrix (ECM) in the tumor microenvironment (TME), which is essential for tumorigenesis, cancer progression and metastasis. In this review, we summarize the therapeutic potential and the mechanism of action of baicalin and baicalein in the regulation of tumor microenvironmental immune cells, endothelial cells, fibroblasts, and ECM that reshape the TME and cancer signaling, leading to inhibition of tumor angiogenesis, progression, and metastasis. In addition, we discuss the biotransformation pathways of baicalin and baicalein, related therapeutic challenges and the future research directions to improve their bioavailability and clinical anticancer applications. Recent advances of baicalin and baicalein warrant their continued study as important natural ways for cancer interception and therapy.

Effect of transvaginal Lactobacillus supplementation on reversing lower genital tract dysbiosis and improving perinatal outcomes in PCOS patients after IVF-FET: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization-frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. METHODS/DESIGN: This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography-mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. DISCUSSION: This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. ETHICS AND DISSEMINATION: Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. TRIAL REGISTRATION: ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

[Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS].

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-ß-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.

Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1ß)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation.

Effective components and related target genes of Folium Artemisiae argyi were screened from Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform. The therapeutic targets of atherosclerosis were searched in the MalaCards and OMIM databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in WebGestalt online and verified according to ClueGo and Pedia apps in Cytoscape. Then, the protein-protein interaction network was analyzed using the STRING database and constructed using Cytoscape. Differential expression of target genes was identified in GSE9128 and GSE71226 by GEO2R. And then, molecular docking was performed using the Molecular Operating Environment. Finally, we validated the protein expression of Interleukin-6 (IL-6)/IL-1ß /MMP9 by qRT-PCR and Western blot in Raw264.7 which was induced by LPS. A total of 232 potential target genes and 8 ingredients of Folium Artemisiae argyi were identified. Quercetin and naringenin are potential candidate bioactive agents in treating atherosclerosis. Vascular endothelial growth factor (VEGFA), MMP9 and IL-1ß could be potential target genes. KEGG analysis demonstrated that the fluid shear stress and atherosclerosis pathway play a crucial role in the anti-atherosclerosis effect of Folium Artemisiae argyi. Gene Expression Omnibus (GEO) validation demonstrated that VEGFA was downregulated, while MMP9 and IL-1ß were upregulated in patients with atherosclerosis. Molecular docking suggested that only MMP9 had a good combination with quercetin. The cell experiment results suggested that naringenin and quercetin have strong anti-inflammation effects, and significantly inhibit the expression of MMP9. Practical ApplicationsArtemisiae argyi is a traditional Chinese herbal medicine that has been widely used for its antibacterial and anti-inflammatory effects. This research demonstrated the bioactive ingredients, potential targets, and molecular mechanism of Folium Artemisiae argyi in treating atherosclerosis. It also suggests a reliable approach in investigating the therapeutic effect of traditional Chinese herbal medicine in treating Atherosclerotic cardiovascular disease (ASCVD).

Incorporating EEG and fNIRS Patterns to Evaluate Cortical Excitability and MI-BCI Performance During Motor Training.

As electroencephalography (EEG) is nonlinear and nonstationary in nature, an imperative challenge for brain-computer interfaces (BCIs) is to construct a robust classifier that can survive for a long time and monitor the brain state stably. To this end, this research aims to improve BCI performance by incorporation of electroencephalographic and cerebral hemodynamic patterns. A motor imagery (MI)-BCI based visual-haptic neurofeedback training (NFT) experiment was designed with sixteen participants. EEG and functional near infrared spectroscopy (fNIRS) signals were simultaneously recorded before and after this transient NFT. Cortical activation was significantly improved after repeated and continuous NFT through time-frequency and topological analysis. A classifier calibration strategy, weighted EEG-fNIRS patterns (WENP), was proposed, in which elementary classifiers were constructed by using both the EEG and fNIRS information and then integrated into a strong classifier with their independent accuracy-based weight assessment. The results revealed that the classifier constructed on integrating EEG and fNIRS patterns was significantly superior to that only with independent information (  âˆ¼  10% and  âˆ¼  18% improvement respectively), reaching  âˆ¼  89% in mean classification accuracy. The WENP is a classifier calibration strategy that can effectively improve the performance of the MI-BCI and could also be used to other BCI paradigms. These findings validate that our proposed methods are feasible and promising for optimizing conventional motor training methods and clinical rehabilitation.

Motor Imagery and Action Observation Induced Electroencephalographic Activations to Guide Subject-Specific Training Paradigm: A Pilot Study.

Brain-computer interface (BCI)-based motor rehabilitation feedback training system can facilitate motor function reconstruction, but its rehabilitation mechanism with suitable training protocol is unclear, which affects the application effect. To this end, we probed the electroencephalographic (EEG) activations induced by motor imagery (MI) and action observation (AO) to provide an effective method to optimize motor feedback training. We grouped subjects according to their alpha-band sensorimotor cortical excitability under MI and AO conditions, and investigated the EEG response under the same paradigm between groups and different motor paradigms within group, respectively. The results showed that there were significant differences in sensorimotor activations between two groups of subjects. Specifically, the group with weaker MI induced EEG features, could achieve stronger sensorimotor activations in AO than that of other conditions. The group with stronger MI induced EEG features, could achieve stronger sensorimotor activations in the MI+AO than that of other conditions. We also explored their classification and brain network differences, which might try to explain the EEG mechanism in different individuals and help stroke patients to choose appropriate subject-specific motor training paradigm for their rehabilitation and better treatment outcomes.

Potential Involvement of Organic Anion Transporters in Drug Interactions with Shuganning Injection, a Traditional Chinese Patent Medicine.

Traditional Chinese medicine injections have been widely used in China for the treatment of various diseases. Transporter-mediated drug-drug interactions are a major contributor to adverse drug reactions. However, the research on transporter-mediated Traditional Chinese medicine injection-drug interactions is limited. Shuganning injection is a widely used Traditional Chinese medicine injection for treating various liver diseases. In this study, we investigated the inhibitory effect of Shuganning injection and its four main ingredients (baicalin, geniposide, chlorogenic acid, and oroxylin A) on 9 drug transporters. Shuganning injection strongly inhibited organic anion transporter 1 and organic anion transporter 3 with IC50 values < 0.1% (v/v), and moderately inhibited organic anion transporter 2, organic anion transporting-polypeptide 1B1, and organic anion transporting-polypeptide 1B3 with IC50 values < 1.0%. Baicalin, the most abundant bioactive ingredient in the Shuganning injection, was identified as both an inhibitor and substrate of organic anion transporter 1, organic anion transporter 3, and organic anion transporting-polypeptide 1B3. Oroxylin A had the potential to act as both an inhibitor and substrate of organic anion transporting-polypeptide 1B1 and organic anion transporting-polypeptide 1B3. In contrast, geniposide and chlorogenic acid had no significant inhibitory effect on drug transporters. Notably, Shuganning injection markedly altered the pharmacokinetics of furosemide and atorvastatin in rats. Using Shuganning injection as an example, our findings support the implementation of transporter-mediated Traditional Chinese medicine injection-drug interactions in the development of Traditional Chinese medicine injection standards.

Active compounds and potential targets of Shuganning injection in the treatment of hepatocellular carcinoma by network pharmacology and in vitro validation.

Shuganning injection (SGNI), a TCM (traditional Chinese medicine) injection with good hepatoprotective effects, exerted therapeutic effects on hepatocellular carcinoma (HCC). However, the active compounds and effects of SGNI on HCC remain unclear. The objective of this study was to investigate the active compounds and potential targets of SGNI in the treatment of HCC, and explore the molecular mechanisms of main compounds. Network pharmacology was applied to predict the active compounds and targets of SGNI on cancer. The interactions between active compounds and target proteins were validated by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and pull-down assay. The in vitro test of the effects and mechanism of vanillin and baicalein was elucidated by MTT, western blot, immunofluorescence, and apoptosis analysis. According to compound characteristics, targets, etc., two typical active ingredients (vanillin and baicalein) were selected as representatives to explore the effects on HCC. Vanillin (an important food additive) bound to NF-κB1 and baicalein (a bioactive flavonoid) bound to FLT3 (FMS-like tyrosine kinase 3) were confirmed in this study. Vanillin and baicalein both inhibited cell viability and promoted apoptosis of Hep3B and Huh7 cells. In addition, both vanillin and baicalein could enhance the activation of the p38/MAPK (mitogen-activated protein kinase) signaling pathway, which may partially explain the anti-apoptosis effects of the two compounds. In conclusion, two active compounds of SGNI, vanillin and baicalein, promoted apoptosis of HCC cells via binding with NF-κB1 or FLT3, and regulating the p38/MAPK pathway. Baicalein and vanillin may be good candidates for HCC treatment on drug development.

Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides.

Polygonati Rhizoma, a typical homology of medicine and food, possesses remarkable anti-fatigue, anti-aging, metabolic regulatory, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetes, and anti-cancer effects. Among bioactive phytochemicals in Polygonati Rhizoma, polysaccharides play important roles in the health-promoting activities through the mechanisms mentioned above and potential synergistic effects with other bioactives. In this review, we briefly introduce the updated biosynthesis of polysaccharides, the purification method, the structure characterization, and food applications, and discuss in detail the biological activities of Polygonati Rhizoma polysaccharides and associated mechanisms, aiming at broadening the usage of Polygonati Rhizoma as functional food and medicine.

Transporter-mediated Natural Product-Drug Interactions.

The increasing use of natural products in clinical practice has raised great concerns about the potential natural product-drug interactions (NDIs). Drug transporters mediate the transmembrane passage of a broad range of drugs, and thus are important determinants for drug pharmacokinetics and pharmacodynamics. Generally, transporters can be divided into ATP binding cassette (ABC) family and solute carrier (SLC) family. Numerous natural products have been identified as inhibitors, substrates, inducers, and/or activators of drug transporters. This review article aims to provide a comprehensive summary of the recent progress on the research of NDIs, focusing on the main drug transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter 1 and 3 (OAT1/OAT3), organic anion-transporting polypeptide 1B1 and 1B3 (OATP1B1/OATP1B3), organic cation transporter 2 (OCT2), multidrug and toxin extrusion protein 1 and 2-K (MATE1/MATE2-K). Additionally, the challenges and strategies of studying NDIs are also discussed.

Rewiring of the seed metabolome during Tartary buckwheat domestication.

Crop domestication usually leads to the narrowing genetic diversity. However, human selection mainly focuses on visible traits, such as yield and plant morphology, with most metabolic changes being invisible to the naked eye. Buckwheat accumulates abundant bioactive substances, making it a dual-purpose crop with excellent nutritional and medical value. Therefore, examining the wiring of these invisible metabolites during domestication is of major importance. The comprehensive profiling of 200 Tartary buckwheat accessions exhibits 540 metabolites modified as a consequence of human selection. Metabolic genome-wide association study illustrates 384 mGWAS signals for 336 metabolites are under selection. Further analysis showed that an R2R3-MYB transcription factor FtMYB43 positively regulates the synthesis of procyanidin. Glycoside hydrolase gene FtSAGH1 is characterized as responsible for the release of active salicylic acid, the precursor of aspirin and indispensably in plant defence. UDP-glucosyltransferase gene FtUGT74L2 is characterized as involved in the glycosylation of emodin, a major medicinal component specific in Polygonaceae. The lower expression of FtSAGH1 and FtUGT74L2 were associated with the reduction of salicylic acid and soluble EmG owing to domestication. This first large-scale metabolome profiling in Tartary buckwheat will facilitate genetic improvement of medicinal properties and disease resistance in Tartary buckwheat.

Dachaihu decoction inhibits hypernutrition-induced liver metastasis from colorectal cancer by maintaining the gut vascular barrier.

Background: Colorectal cancer (CRC) is the third most common malignancy and the second deadliest cancer worldwide. Metastasis to the liver, the most common metastatic site in CRC, is the leading cause of death in patients with CRC. Hyperlipidemia, which is common in patients with CRC, promotes CRC progression and metastasis. Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition. The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear, and there is an unmet need for effective and low-cost treatments for patients with CRC. Methods: A mouse cecum orthotopic CRC model combined with high-fat diet (HFD) feeding, was established to mimic liver metastasis in CRC in obese patients. The effects of Dachaihu decoction (DCHD), a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease, and of the conventional prescription medicine obeticholic acid (OCA) were evaluated. HFD-induced obesity, hyperlipidemia, and CRC liver metastasis were assessed, along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues. The effects of DCHD and OCA on HFD-induced outcomes were evaluated, and human umbilical vein endothelial cells (HUVECs) treated with bile acids (BAs) and DCHD were used to study the underlying mechanisms in vitro. Results: HFD-mediated obesity and hyperlipidemia promoted CRC metastasis, accompanied by disruption of the gut vascular barrier (GVB) and altered bile acid (BA) metabolism. DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC, improving overall survival. Those effects of DCHD were equivalent to or better than those of OCA. DCHD regulated the expression of genes of BA metabolism and tight junctions (TJ) to prevent HFD-induced disruption of the GVB. In HUVECs, DCHD prevented the increases in intracellular Ca2+ and accumulation of reactive oxygen species induced by primary conjugated BAs, assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins, thereby maintaining the integrity of the endothelial barrier. Conclusions: The data provide a link between hypernutrition and GVB disruption, which contributes to high liver metastasis in patients with CRC. DCHD may represent a novel therapy in CRC, and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.

Regulating Th17/Treg Balance Contributes to the Therapeutic Effect of Ziyuglycoside I on Collagen-Induced Arthritis.

To investigate the therapeutic effect and primary pharmacological mechanism of Ziyuglycoside I (Ziyu I) on collagen-induced arthritis (CIA) mice. CIA mice were treated with 5, 10, or 20 mg/kg of Ziyu I or 2 mg/kg of methotrexate (MTX), and clinical manifestations, as well as pathological changes, were observed. T cell viability and subset type were determined, and serum levels of transforming growth factor-beta (TGF-ß) and interleukin-17 (IL-17) were detected. The mRNA expression of retinoid-related orphan receptor-γt (RORγt) and transcription factor forkhead box protein 3 (Foxp3) in mouse spleen lymphocytes was ascertained by the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Molecular docking was used to detect whether there was a molecular interaction between Ziyu I and protein kinase B (Akt). The activation of mechanistic target of rapamycin (mTOR) in T cells was verified by Western blotting or immunofluorescence. Ziyu I treatment effectively alleviated arthritis symptoms of CIA mice, including body weight, global score, arthritis index, and a number of swollen joints. Similarly, pathological changes of joints and spleens in arthritic mice were improved. The thymic index, T cell activity, and RORγt production of Ziyu I-treated mice were significantly reduced. Notably, through molecular docking, western blotting, and immunofluorescence data analysis, it was found that Ziyu I could interact directly with Akt to reduce downstream mTOR activation and inhibit helper T cell 17 (Th17) differentiation, thereby regulating Th17/regulatory T cell (Treg) balance and improving arthritis symptoms. Ziyu I effectively improves arthritic symptoms in CIA mice by inhibiting mTOR activation, thereby affecting Th17 differentiation and regulating Th17/Treg balance.

Sodium New Houttuyfonate Inhibits Cancer-Promoting Fusobacterium nucleatum (Fn) to Reduce Colorectal Cancer Progression.

Colorectal cancer (CRC) is a major cause of morbidity and mortality worldwide. Recent studies showed that the common anaerobe Fusobacterium nucleatum (Fn) is closely associated with a higher risk for carcinogenesis, metastasis, and chemoresistance of CRC. However, there is no specific antimicrobial therapy for CRC treatment. Herbal medicine has a long history of treating diseases with remarkable effects and is attracting extensive attention. In this study, we tested six common phytochemicals for their antimicrobial activities against Fn and whether anti-Fn phytochemicals can modulate CRC development associated with Fn. Among these antimicrobials, we found that SNH showed the highest antimicrobial activity and little cytotoxicity toward cancer cells and normal cells in vitro and in vivo. Mechanistically, SNH may target membrane-associated FadA, leading to FadA oligomerization, membrane fragmentation and permeabilization. More importantly, SNH blocked the tumor-promoting activity of Fn and Fn-associated cancer-driven inflammation, thus improving the intestinal barrier damaged by Fn. SNH reduced Fn load in the CRC-cells-derived mice xenografts with Fn inoculation and significantly inhibited CRC progression. Our data suggest that SNH could be used for an antimicrobial therapy that inhibits Fn and cancer-driven inflammation of CRC. Our results provide an important foundation for future gut microbiota-targeted clinical treatment of CRC.

Low frequency pulsed electromagnetic fields exposure alleviate the abnormal subchondral bone remodeling at the early stage of temporomandibular joint osteoarthritis.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is characterized by abnormal subchondral bone remodeling and cartilage degeneration. As a non-invasive biophysical technology, pulsed electromagnetic field (PEMF) treatment has been proven to be efficient in promoting osteogenesis. However, the potential bone protective effect and mechanism of PEMF on abnormal subchondral bone remodeling in TMJOA are unknown. METHODS: Unilateral anterior crossbite (UAC) was used to create TMJOA model in rats, and 17ß-estradiol (E2) were injected daily to mimic patients with high-physiological levels of estrogen. Mouse osteoblast-like MC3T3-E1 cells treated with recombinant murine IL-1ß was used to establish inflammatory environment in vitro. The treatment group were subjected to PEMF (2.0mT, 15 Hz, 2 h/d). Micro-CT scanning, histological staining, real-time PCR and western blotting assays were preformed to observe the changes in the subchondral bone. RESULTS: Abnormal resorption of subchondral bone induced by UAC, characterized by decreased bone mineral density, increased osteoclast activity and expression of osteoclast-related factors (RANKL) and down-regulated expression of osteogenesis-related factors (OPG, ALP, Runx2 and OCN) at the early stage, could be reversed by PEMF exposure, which was similar to the effect of estrogen. In addition, PEMF exposure and E2 supplement may have a synergistic effect to some extent. Moreover, PEMF exposure could promote the ALP activity and osteogenic mineralization ability of MC3T3-E1 cells. PEMF promoted the expression of factors related to Wnt/ß-Catenin signal pathway both in vivo and in vitro. CONCLUSIONS: Appropriate PEMF exposure have a protective effect on subchondral bone in TMJOA at early stage, in which canonical Wnt/ß-Catenin pathway may be involved. PEMF may be a promising biophysical approach for early intervention of TMJOA in clinic.

Clinical Efficacy and Safety of Tenofovir in the Treatment of Patients with Chronic Hepatitis B.

The negative rate of serum HBV DNA, HBeAg, and ALT in the tenofovir group was significantly higher than that in the entecavir group (86.67%, 3.33%, and 80.00%) (all P < 0.05). In the tenofovir group, 2cases were considered. Objective. The aim of this study is to analyze the clinical effect and safety of tenofovir in the treatment of chronic hepatitis B (CHB) patients. Methods. A total of 60 patients with CHB who were admitted and treated in Anqing First People's Hospital Affiliated to Anhui Medical University from January 2019 to July 2020 were randomly assigned at a ratio of 1 : 1 into the tenofovir group (treated with tenofovir) and the entecavir group (treated with entecavir) via the random number table method. The clinical therapeutic effect and safety of the two groups were compared. Results. The serum hepatitis B virus (HBV) DNA levels in the two groups decreased after treatment, but there was no significant difference. Ths (2.50%) had nausea, 1 (1.25%) had headache, and 0 had an elevated creatine kinase. In the tenofovir group,1(3.33%) had nausea, 0 had headache, and 0 had an elevated creatine kinase. In the entecavir group, there were 3 (10.00%) cases of nausea, 2 (6.67%) cases of headache, and 1 (3.33%) case of elevated creatine kinase. The overall incidence of adverse reactions in the tenofovir group (3.33%) was significantly lower than that in the entecavir group (20.00%) (all P < 0.05). Conclusion. Tenofovir is more effective than entecavir in the treatment of patients with CHB due to low incidence of adverse events and a good safety profile.

Applying systems thinking to identify enablers and challenges to scale-up interventions for hypertension and diabetes in low-income and middle-income countries: protocol for a longitudinal mixed-methods study.

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and diabetes outcomes. A systematic inquiry of these projects will provide necessary scientific insights into the enablers and challenges in the scale up of complex NCD interventions. METHODS AND ANALYSIS: We will apply systems thinking (a holistic approach to analyse the inter-relationship between constituent parts of scaleup interventions and the context in which the interventions are implemented) and adopt a longitudinal mixed-methods study design to explore the planning and early implementation phases of scale up projects. Data will be gathered at three time periods, namely, at planning (TP), initiation of implementation (T0) and 1-year postinitiation (T1). We will extract project-related data from secondary documents at TP and conduct multistakeholder qualitative interviews to gather data at T0 and T1. We will undertake descriptive statistical analysis of TP data and analyse T0 and T1 data using inductive thematic coding. The data extraction tool and interview guides were developed based on a literature review of scale-up frameworks. ETHICS AND DISSEMINATION: The current protocol was approved by the Monash University Human Research Ethics Committee (HREC number 23482). Informed consent will be obtained from all participants. The study findings will be disseminated through peer-reviewed publications and more broadly through the GACD network.

New Sorbicillinoids with Tea Pathogenic Fungus Inhibitory Effect from Marine-Derived Fungus Hypocrea jecorina H8.

Four new dimeric sorbicillinoids (1-3 and 5) and a new monomeric sorbicillinoid (4) as well as six known analogs (6-11) were purified from the fungal strain Hypocrea jecorina H8, which was obtained from mangrove sediment, and showed potent inhibitory activity against the tea pathogenic fungus Pestalotiopsis theae (P. theae). The planar structures of 1-5 were assigned by analyses of their UV, IR, HR-ESI-MS, and NMR spectroscopic data. All the compounds were evaluated for growth inhibition of tea pathogenic fungus P. theae. Compounds 5, 6, 8, 9, and 10 exhibited more potent inhibitory activities compared with the positive control hexaconazole with an ED50 of 24.25 ± 1.57 µg/mL. The ED50 values of compounds 5, 6, 8, 9, and 10 were 9.13 ± 1.25, 2.04 ± 1.24, 18.22 ± 1.29, 1.83 ± 1.37, and 4.68 ± 1.44 µg/mL, respectively. Additionally, the effects of these compounds on zebrafish embryo development were also evaluated. Except for compounds 5 and 8, which imparted toxic effects on zebrafish even at 0.625 µM, the other isolated compounds did not exhibit significant toxicity to zebrafish eggs, embryos, or larvae. Taken together, sorbicillinoid derivatives (6, 9, and 10) from H. jecorina H8 displayed low toxicity and high anti-tea pathogenic fungus potential.