The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology.

Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis. SOI has a serious impact on women's physical and mental health and family harmony, and it is a clinical problem that needs to be solved urgently.

Objective: The purpose of the present study was to explore the potential pharmacological mechanisms of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.

Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed through the STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation, Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of tubal inflammation and to validate the predictions of network pharmacology and the therapeutic efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes. TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected by western blot.

Results: Through database analysis, it was found that YJP shared 105 identical targets with the disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5 core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved. The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue, inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore, YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated ESR1.

Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.

Potent anti-angiogenic component in Kaempferia galanga L. and its mechanism of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the roots of Kaempferia galanga has been used to treat high blood pressure, chest pain, headache, toothache, rheumatism, indigestion, cough, inflammation and cancer in Asia. Nevertheless, most of its pharmacological studies were focused on ethanolic extracts and volatile oils. The exact active chemical constituents and their underlying mechanisms are still poorly understood, especially towards its anti-cancer treatment. Inhibition of angiogenesis is an important atrategy to inhibit tumor growth. It has been reported that the low polar component of the plant possessed anti-angiogenic activity. Yet, the potent compound which is responsible for the effect and its molecular mechanism has not been reported. AIM OF THE STUDY: To determine the potent anti-angiogenic component in K.galanga and its mechanism of action. MATERIAL AND METHODS: The low polar components of the plant were concentrated using the methods of supercritical fluid extraction (SFE), subcritical extraction (SCE) and steam distillation (SD). The anti-angiogenic activity of the three extracts was evaluated using a zebrafish model. The content of the active compound in those extracts was determined with HPLC analysis. The in-vitro and in-vivo activity of the isolated compound was evaluated using human umbilical vein endothelial cells (HUVECs) model, the aortic ring assay and the matrigel plug assay, respectively. Its molecular mechanism was further studied by the western blotting assay and computer-docking experiments. Besides, its cytotoxicity on cancer and normal cell lines was evaluated using the cell-counting kit. RESULTS: HPLC results showed that trans-ethyl p-methoxycinnamate (TEM) was the major component of the extracts. The extract of SFE showed the best effect as it has the highest content of TEM. TEM could inhibit vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. Moreover, it inhibited VEGF-induced sprout formation ex vivo and vessel formation in vivo. Mechanistic study showed that it could suppress tyrosine kinase activity of the receptor of VEGF (VEGFR2) and alter its downstream signaling pathways. In addition, the molecular docking showed that the binding of TEM and VEGFR2 is stable, which mainly attributed to the non-covalent binding interaction. Beside, TEM possessed little toxicity to both cancer and normal cells. CONCLUSION: TEM is the major anti-angiogenic component present in K. galanga and its anti-angiogenic property rather than toxicity provides scientific basis for the traditional use of K. galanga in cancer treatment.

NPASS database update 2023: quantitative natural product activity and species source database for biomedical research.

Quantitative activity and species source data of natural products (NPs) are important for drug discovery, medicinal plant research, and microbial investigations. Activity values of NPs against specific targets are useful for discovering targeted therapeutic agents and investigating the mechanism of medicinal plants. Composition/concentration values of NPs in individual species facilitate the assessments and investigations of the therapeutic quality of herbs and phenotypes of microbes. Here, we describe an update of the NPASS natural product activity and species source database previously featured in NAR. This update includes: (i) new data of ∼95 000 records of the composition/concentration values of ∼1 490 NPs/NP clusters in ∼390 species, (ii) extended data of activity values of ∼43 200 NPs against ∼7 700 targets (∼40% and ∼32% increase, respectively), (iii) extended data of ∼31 600 species sources of ∼94 400 NPs (∼26% and ∼32% increase, respectively), (iv) new species types of ∼440 co-cultured microbes and ∼420 engineered microbes, (v) new data of ∼66 600 NPs without experimental activity values but with estimated activity profiles from the established chemical similarity tool Chemical Checker, (vi) new data of the computed drug-likeness properties and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties for all NPs. NPASS update version is freely accessible at http://bidd.group/NPASS.

Injectable carboxymethyl chitosan-genipin hydrogels encapsulating tea tree oil for wound healing.

Injectable hydrogel is of interesting for wound healing due to it can be used as carriers of bioactive molecules for the reparation of tissues with minimal invasiveness. However, the integration of lipid-soluble substances into hydrogel network is difficult because of the polarity differences. Here, the tea tree oil (TTO) is encapsulated into the hydrogel network via a previous emulsification process, and a tough and antibacterial injectable hydrogel is synthesized by the Schiff base reaction between carboxymethyl chitosan (CMCS) and genipin (GP). CMCS is served as both an emulsifier and a gel-forming material to construct the heterogeneous hydrogel. The obtained hydrogels present high adhesive strength (∼162.75 kPa), great antibacterial properties (over 90 %) and excellent biocompatibility. Moreover, an anal fistula-like wound healing experiment concluded that the heterogeneous hydrogel has good slow-release properties of TTO for an accelerate healing process, this hydrogel shows great potential for the treatment of complex anal fistula wounds.

Effects and parameters of community-based exercise on motor symptoms in Parkinson's disease: a meta-analysis.

BACKGROUND: Community-based exercise is a continuation and complement to inpatient rehabilitation for Parkinson's disease and does not require a professional physical therapist or equipment. The effects, parameters, and forms of each exercise are diverse, and the effect is affected by many factors. A meta-analysis was conducted to determine the effect and the best parameters for improving motor symptoms and to explore the possible factors affecting the effect of community-based exercise.  METHODS: We conducted a comprehensive search of six databases: PEDro, PubMed/Medline, CENTRAL, Scopus, Embase, and WOS. Studies that compared community-based exercise with usual care were included. The intervention mainly included dance, Chinese martial arts, Nordic walking, and home-based exercise. The primary outcome measure was the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The mean difference (95% CI) was used to calculate the treatment outcomes of continuous outcome variables, and the I2 statistic was used to estimate the heterogeneity of the statistical analysis. We conducted subgroup analysis and meta-regression analysis to determine the optimal parameters and the most important influencing factors of the exercise effect.  RESULTS: Twenty-two studies that enrolled a total of 809 subjects were included in the analysis. Exercise had a positive effect on the UPDRS-III (MD = -5.83; 95% CI, -8.29 to -3.37), Timed Up and Go test (MD = -2.22; 95% CI -3.02 to -1.42), UPDRS ((MD = -7.80; 95% CI -10.98 to -6.42), 6-Minute Walk Test (MD = 68.81; 95% CI, 32.14 to 105.48), and Berg Balance Scale (MD = 4.52; 95% CI, 2.72 to 5.78) scores. However, the heterogeneity of each included study was obvious. Weekly frequency, age, and duration of treatment were all factors that potentially influenced the effect. CONCLUSIONS: This meta-analysis suggests that community-based exercise may benefit motor function in patients with PD. The most commonly used modalities of exercise were tango and tai chi, and the most common prescription was 60 min twice a week. Future studies should consider the influence of age, duration of treatment, and weekly frequency on the effect of exercise. PROSPERO TRIAL REGISTRATION NUMBER: CRD42022327162.

Chinese herbal medicine combined with oxaliplatin-based chemotherapy for advanced gastric cancer: A systematic review and meta-analysis of contributions of specific medicinal materials to tumor response.

Introduction: The incidence and mortality of gastric cancer ranks among the highest, and the 5-year survival rate of advanced gastric cancer (AGC) is less than 10%. Currently, chemotherapy is the main treatment for AGC, and oxaliplatin is an important part of the commonly used chemotherapy regimen for AGC. A large number of RCTs have shown that Chinese herbal medicine (CHM) combined with oxaliplatin-based chemotherapy can improve objective response rate (ORR) and disease control rate (DCR), reduce the toxic and side effects of chemotherapy. There is currently a lack of systematic evaluation of the evidence to account for the efficacy and safety of CHM combined with oxaliplatin-based chemotherapy in AGC. Therefore, we carried out this study and conducted the sensitivity analysis on the herbal composition to explore the potential anti-tumor efficacy. Methods: Databases of PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Wanfang database, and the Chinese Scientific Journals Database were searched from their inception to April 2022. RCTs evaluating the efficacy of CHM combined with oxaliplatin-based chemotherapy on AGC were included. Stata 16 was used for data synthesis, RoB 2 for quality evaluation of included RCTs, and GRADE for quality of synthesized evidence. Additional sensitivity analysis was performed to explore the potential anti-tumor effects of single herbs and combination of herbs. Results: Forty trials involving 3,029 participants were included. Most included RCTs were assessed as "Some concerns" of risk of bias. Meta-analyses showed that compare to oxaliplatin-based chemotherapy alone, that CHM combined with oxaliplatin-based chemotherapy could increase the objective response rate (ORR) by 35% [risk ratio (RR) = 1.35, 95% confidence intervals (CI) (1.25, 1.45)], and disease control rate (DCR) by 12% [RR = 1.12, 95% CI (1.08, 1.16)]. Subgroup analysis showed that compare to SOX, FOLFOX, and XELOX regimens alone, CHM plus SOX, CHM plus FOLFOX, and CHM plus XELOX could significantly increase the ORR and DCR. Sensitivity analysis identified seven herbs of Astragalus, Liquorice, Poria, Largehead Atractylodes, Chinese Angelica, Codonopsis, and Tangerine Peel with potentials to improve tumor response of oxaliplatin-based chemotherapy in AGC. Conclusion: Synthesized evidence showed moderate certainty that CHM plus oxaliplatin-based chemotherapy may promote improvement in tumor response in AGC. CHM treatment is safe for AGC. Due to the poor quality of included RCTs and small samplesizes, the quality of synthesized evidence was not high. Specific combinations of herbs appeared to produce higher contributions to ORR than the herb individually. Each of this seven above mentioned herbs has been shown in experimental studies to potentially contribute to the improvement of tumor response. To support this conclusion, these seven herbs are worthy of further clinical research. Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262595], identifier [CRD42022262595].

Metal-organic framework on porous TiO2 thin film-coated alumina beads for fractional distillation of plant essential oils.

Fractionation of essential oils is technically challenging due to enormous scaffold diversities and structural complexities as well as difficulties in the implementation of the fractionation in the gas phase. Packing beads with multi-dimensional hierarchical nanostructures have been developed herein to pack fractional columns for atmospheric distillations. Activated alumina beads were coated with a porous TiO2 thin film. Growth of Cu-BTC (benzene-1,3,5-tricarboxylate) crystals in resultant porous surfaces leads to the generation of new nanopores and increased metal centers for differential coordination with diverse components of essential oils. The TiO2 thin film is not only an integral part of the composites but also induces the oriented growth of Cu-BTC metal organic framework (MOF) crystals through coordinative interactions. These Al2O3@TiO2@Cu-BTC MOF beads show very strong absorptive capability for major components of essential oils, except for a single cyclic ether eucalyptol with steric hindrances. The eucalyptol was fractionated by using the column packed with those modified alumina beads from raw materials of Artemisia argyi, and Rosmarinus officinalis with high purities up to 96% and 93%, respectively.

N-Acetylcysteine's Renoprotective Effect in Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To examine N-acetylcysteine's (NAC's) renoprotective effect in adult cardiac surgeryMethods: PubMed, Ovid Medline, and Embase were searched for randomized controlled trials published between January 1990 and May 2021 that investigated the effect of NAC in preventing acute kidney injury (AKI) in patients undergoing cardiac surgery. The inclusion criterion was studies that assessed the effect of NAC in comparison to placebo by measuring the incidence of AKI. RESULTS: Overall meta-analytic estimates of all 10 included trials showed that NAC did not have a significant effect (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.64-1.10) on AKI. Further subgroup analysis did not show a significant benefit of NAC in preventing AKI. CONCLUSION: This meta-analysis suggests that NAC does not have a significant effect in reducing the incidence of AKI. However, there is notable heterogeneity among the included studies that could possibly account for the non-significant effect observed. It is worth noting that only one trial administered NAC high dosages perioperatively, and it is the only included trial to show a significant benefit in reducing the incidence of AKI (OR: 0.30, 95% CI: 0.11-0.81). Further studies on this dosage and duration of administration should be conducted to best elucidate the effect of administering NAC.

Effects of ShenLing BaiZhu San Supplementation on Gut Microbiota and Oxidative Stress in Rats with Ulcerative Colitis.

The aim of this study was to evaluate the effect of gut microbiota and antioxidation of Shenling Baizhu San (SLBZS) as a supplement in a rat model of ulcerative colitis (UC) induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Acute intestinal inflammation was induced in 40 male SD rats aged 4 weeks with 100 mg/kg TNBS, and then three dosages of SLBZS (0.5 g/kg, 1 g/kg, and 1.5 g/kg) were administered for eight days, respectively. Faecal microbiome composition was assessed by 16S rRNA high-throughput sequencing. The result indicated that SLBZS could reduce the diversity of gut microbiota and increased its abundance. At the genus level, the relative abundance of SCFAs producing bacteria including Prevotella and Oscillospira increased, while the relative abundance of opportunistic pathogens including Desulfovibrio and Bilophila decreased. Meanwhile, SLBZS could improve the lesions of colon and significantly reduce the level of MPO, increase the levels of SOD and CAT in rats' serum. These findings revealed that SLBZS was effective and possessed anticolitic activities in a rat model of UC by reducing macroscopical and microscopical colon injury, enhancing antioxidant capacity, and regulating gut microbiota.

Main Active Components and Cell Cycle Regulation Mechanism of Astragali Radix and Angelicae Sinensis Radix in the Treatment of Ox-LDL-Induced HUVECs Injury and Inhibition of Their Cell Cycle.

To explore the main active components and effects of cell cycle regulation mechanism of Astragali radix (AR) and Angelicae sinensis radix (ASR) on oxidative damage in vascular endothelial cells, a model of oxidative damage in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL) treatment was developed. Based on the "knock-out/knock-in" model of the target component, cell viability, intracellular reactive oxygen species (ROS), and lactate dehydrogenase (LDH) leakage were assessed by Cell Counting Kit-8 assay, fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA), and colorimetric assay, respectively, to evaluate the protective effect of the active components of AR and ASR (astragaloside IV (AS IV), astragaloside I (AS I), formononetin (FRM), calycosin (CAL), calycosin-7-O-ß-D glucoside (CLG), and ferulic acid (FRA)) against oxidative damage. The cell cycle and expression of genes encoding cyclins and cyclin-dependent kinases (CDKs) were observed using flow cytometry and quantitative real-time polymerase chain reaction. The results showed that the combination of active components (ACC) significantly inhibited the decrease in cell viability as well as the increase in ROS and LDH release in HUVECs induced by ox-LDL treatment. AS IV and FRM promoted the proliferation of HUVECs but the proliferation index was decreased in the AS I and FRA groups; this inhibitory effect was counteracted by the ACC. The ACC reduced and increased the proportion of positive cells in G1 and S phases, respectively, followed by the upregulation of cyclin A (CCNA), cyclin E (CCNE), and CDK2 mRNA expression and downregulation of cyclin B (CCNB), cyclin D1 (CCND1), CDK1, CDK4, and CDK6 mRNA expression, which significantly mitigated inhibition of HUVECs proliferation induced by ox-LDL treatment. Taken together, AS IV, AS I, FRM, CAL, CLG, and FRA were the primary pharmacodynamic substances of AR and ASR that alleviated oxidative injury in HUVECs. ACC mitigated the upregulation of intracellular ROS levels and LDH release induced by ox-LDL treatment, which promoted the cell cycle procession of HUVECs by regulating the expression of genes encoding cyclins and CDKs and thus preventing oxidative damage in HUVECs.

[Electroacupuncture at "Taichong"(LR3) improves baroreflex sensitivity and α2-adrenergic receptor activity in nucleus tractus solitarii of hypertensive rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Taichong"(LR3) on blood pressure, sympathetic nerve activity, baroreflex sensitivity, and α 2-adrenergic receptor (α2AR) expression in nucleus tractus solitarii (NTS) in hypertensive rats, so as to reveal its mechanisms underlying improvement of hypertension. METHODS: Male Sprague Dawley rats were randomly divided into 4 groups: sham-operation, model, EA, and sham-EA (non-acupoint) groups, with 12 rats in each group. The hypertension model was established by occlusion of the right renal aorta (two-kidney-one clip method). Rats of the sham-operation group received the same surgery but without occlusion of the renal artery. EA (2 Hz/15 Hz, 2 mA) was applied to bilateral LR3 for 30 min, once a day for 28 days, and sham EA was applied to the skin of the rat tail near the buttock on both sides. The mean arterial pressure (MAP) of the abdominal aorta and heart rate (HR) were recorded. The autonomic nerve function was assessed by using frequency domain analysis of heart rate variability (HRV), and the baroreflex sensitivity detected by sequential method. Plasma norepinephrine (NE) level was measured by ELISA, and the α2AR positive neurons and α2AR protein expression in NTS were detected by using fluorescence immunohistochemistry and Western blot, respectively. The functions of α2AR within the NTS in modulating MBP and HR were verified by microinjection of its agonist (clonidine) and antagonist (yohimbine) separately. RESULTS: Compared to the sham operation rats, the hypertension rats displayed significant increases in the MAP (P<0.01), plasma norepinephrine content (P<0.01), ratios of low frequency/total power (LF/TP) and low frequency/high frequency (LF/HF) (P<0.01), and significant reduction in the overall gain, uplink sequence gain and downlink sequence gain of baroreflex (P<0.01), the number α2AR positive neurons and α2AR protein expression level in NTS (P<0.01). The rats in the EA group (rather than in the sham-EA group) showed significant reduction in MAP at the 3rd and 4th week, plasma NE content, LF/TP and LF/HF (P<0.01), and obvious increase in the overall gain, uplink sequence gain and downlink sequence gain of baroreflex (P<0.01), and the number of α2AR positive neurons and α2AR protein expression in comparison (P<0.05) with those of the model group. Microinjection of clonidine into NTS induced an evident decrease in both MAP and HR in the model group relevant to the sham operation group (P<0.01), while the MAP and HR changes of the EA (not sham EA) group were considerably bigger than those of the model group (P<0.05), being similar to those of the sham-operation group (P>0.05), which suggested an elimination of the BP-lowering effect of clonidine after EA. CONCLUSION: EA at LR3 can reduce MBP, sympathetic activities, improve baroreflex sensitivity in renovascular hypertensive rats, which may be associated with its effects in up-regulating the decreased NTS α2AR expression and functional activities.

Complementary and alternative medicine therapies for uremic pruritus - A systematic review of randomized controlled trials.

INTRODUCTION: Uremic pruritus (UP) is one of the most bothersome symptoms among chronic kidney disease (CKD) patients. The pathophysiology of UP remains elusive, resulting in limited treatment options. The inability of standard medical treatments to provide effective relief has piqued interest in complementary and alternative medicine (CAM). METHODOLOGY: A systematic review of randomized controlled trials (RCTs) summarizing the efficacy and safety profile of CAM used for UP in CKD patients was performed. CAM interventions were classified using categories proposed by the National Center for Complementary and Integrative Health. The efficacy of each CAM was determined from changes in UP severity and all reported adverse effects were extracted. RESULTS: Of 5242 articles screened, 34 RCTs were included, with 15 (44.1 %) studies having a sample size greater than 50. The studies considered 21 treatments including omega-3 fatty acid supplementation (n=5), acupuncture (n=5), topical capsaicin (n=4) and acupressure (n=3). Acupuncture, acupressure and topical capsaicin were shown to be effective in improving uremic pruritus. Interventions which include oral omega-3 fatty acid and zinc supplementation demonstrated mixed efficacy. Other therapies such as evening primrose oil, turmeric, vitamin B3, vitamin D and thermal therapy were not effective for treatment of UP. Common adverse effects reported with topical capsaicin included mild burning sensations (50.0-88.2 %) or erythema (6.7-22.7%) while that of acupuncture included soreness (7.5 %), bleeding (6.0-7.5%) and hematoma (1.9 %). CONCLUSIONS: Acupuncture, acupressure and topical capsaicin have the largest body of evidence for efficacy in the treatment of UP. Larger and higher quality RCTs are required to examine the efficacy and safety of promising CAM.

Cardioprotective effects of polydatin against myocardial injury in diabetic rats via inhibition of NADPH oxidase and NF-κB activities.

BACKGROUND: Diabetic cardiomyopathy is a main cause of the increased morbidity in diabetic patients, no effective treatment is available so far. Polydatin, a resveratrol glucoside isolated from the Polygonum cuspidatum, was found by our and others have antioxidant and cardioprotective activities. Therapeutic effects of polydatin on diabetic cardiomyopathy and the possible mechanisms remains unclear. This study aimed to investigate the cardioprotective effects and underlying mechanisms of polydatin on myocardial injury induced by hyperglycemia. METHODS: Diabetes in rats was made by high-fat diet combined with multiple low doses of streptozotocin, and then treated with polydatin (100 mg·kg-1·day-1, by gavage) for 8 weeks. Cardiac function was examined by echocardiography. Myocardial tissue and blood samples were collected for histology, protein and metabolic characteristics analysis. In cultured H9c2 cells with 30 mM of glucose, the direct effects of polydatin on myocyte injury were also observed. RESULTS: In diabetic rats, polydatin administration significantly improved myocardial dysfunction and attenuated histological abnormalities, as evidenced by elevating left ventricular shortening fraction and ejection fraction, as well as reducing cardiac hypertrophy and interstitial fibrosis. In cultured H9c2 cells, pretreatment of polydatin dose-dependently inhibited high glucose-induced cardiomyocyte injury. Further observation evidenced that polydatin suppressed the increase in the reactive oxygen species levels, NADPH oxidase activity and inflammatory cytokines production induced by hyperglycemia in vivo and in vitro. Polydatin also prevented the increase expression of NOX4, NOX2 and NF-κB in the high glucose -stimulated H9c2 cells and diabetic hearts. CONCLUSIONS: Our results demonstrate that the cardioprotective effect of polydatin against hyperglycemia-induced myocardial injury is mediated by inhibition of NADPH oxidase and NF-κB activity. The findings may provide a novel understanding the mechanisms of the polydatin to be a potential treatment of diabetic cardiomyopathy.

Effects of Huaier Extract on Ameliorating Colitis-Associated Colorectal Tumorigenesis in Mice.

BACKGROUND: Huaier extract has been a part of traditional Chinese medicine (TCM) for roughly 1600 years and may serve as a potential anti-cancer drug as it is associated with good efficacy and low toxicity. Individuals with inflammatory bowel disease (IBD) are at a higher chance of being diagnosed with colorectal cancer (CRC) and as Huaier extract may potentially influence tumorigenesis, we set out to determine the effect of Huaier extract on colitis-associated CRC. METHODS: The CRC mouse model, established through azoxymethane (AOM) and dextran sulfate sodium (DSS), was administered Huaier extract. Weight loss, colon length, tumor number and tumor size were evaluated macroscopically. Pro-inflammatory cytokine expression and STAT3 phosphorylation were assessed in the colon using ELISA, Western blot and/or immunohistochemistry. RESULTS: Huaier extract improved the severity of colitis-associated tumorigenesis compared with control group, with attenuated weight loss and longer colons. Tumor number, size and load were drastically decreased in mice treated with Huaier. Histological assessment suggested that Huaier could decrease histological injury of the colon tissue. Additionally, Huaier extract treatment led to reduced pro-inflammatory cytokine levels (TNF-α, IL-6, IFN-γ and IL-1ß) and a decrease of STAT3 phosphorylation in colon tissue. Additionally, present findings demonstrated that Huaier extract inhibited cell proliferation and induced apoptosis in CRC cells HCT116 and HCT8. The migration and invasion of CRC cells were markedly inhibited upon exposure to Huaier treatment. The apoptosis-associated protein levels (P53, Bax, Bcl-2, pro-caspase-3 and cleavage caspase-3) showed significant differences after the administration of Huaier extract in HCT116 and HCT8 cells. In vivo, the administration of Huaier extract to mice inhibited tumor growth and yielded a similar profile of apoptotic proteins expression p53, Bcl-2, pro-caspase-3 and cleaved caspase-3 while no significant differences in Bax were observed. Moreover, the ratio of TUNEL-positive/apoptotic cells was markedly increased in the Huaier-treated mice. CONCLUSION: Huaier extract may reduce the IBD-associated tumor development by suppressing pro-inflammatory cytokine levels and STAT3 stimulation.

[Identification and attribution of chemical constituents of Qingfei Paidu Decoction based on UHPLC-LTQ-Orbitrap-MS technology].

UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 µm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.

Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice.

The brain has evolved in an environment where food sources are scarce, and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity or overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood. Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the lateral/perifonical hypothalamus (LH) are critical for homeostatic regulation, reward seeking, stress response, and cognitive functions. In this study, we examined adaptations in Hcrt cells regulating behavioral responses to salient stimuli in diet-induced obese mice. Our results demonstrated changes in primary cilia, synaptic transmission and plasticity, cellular responses to neurotransmitters necessary for reward seeking, and stress responses in Hcrt neurons from obese mice. Activities of neuronal networks in the LH and hippocampus were impaired as a result of decreased hypocretinergic function. The weakened Hcrt system decreased reward seeking while altering responses to acute stress (stress-coping strategy), which were reversed by selectively activating Hcrt cells with chemogenetics. Taken together, our data suggest that a deficiency in Hcrt signaling may be a common cause of behavioral changes (such as lowered arousal, weakened reward seeking, and altered stress response) in obese animals.

Thermoresponsive starch-based particle-stabilized Pickering high internal phase emulsions as nutraceutical containers for controlled release.

Pickering high internal phase emulsions (HIPEs) stabilized solely by bioderived starch-based particles hold potential for application in the food and pharmaceutical fields. This paper reports the use of a thermoresponsive 2-hydroxy-3-butoxypropyl starch (HBPS) particle as a representative natural biocompatible material for use as an effective stabilizer for HIPE formation. HBPS is synthesized by using butyl glycidyl ether as a hydrophobic reagent to change the hydrophobic-hydrophilic balance of starch, and then starch-based particles are fabricated by a simple nanoprecipitation procedure. The size of particles increased with an increase in temperature, and the particles are essentially monodisperse with a PDI of about 0.1 when the temperature was above 15 °C. These HBPS particles were subsequently used as an effective stabilizer to fabricate stable oil-in-water (o/w) Pickering HIPEs with an internal phase volume of 80% at different stabilizer concentrations. The results demonstrated that increasing the particle concentration is conducive to the formation of stable Pickering HIPEs with greater stiffnesses. In addition, the nutraceutical material (ß-carotene) was encapsulated into HIPEs and in vitro release experiments revealed that the release in this system can be controlled by adjusting the temperature.

Inhibitory effect of melatonin on Mst1 ameliorates myocarditis through attenuating ER stress and mitochondrial dysfunction.

Viral myocarditis has been found to be one of the leading causes of sudden death in young adults. However, no effective drugs have been developed to intervene the progression of myocarditis. Accordingly, the present study is carried out to explore the protective role played by melatonin in the setting of viral myocarditis with a focus on Mst1-Hippo pathway, mitochondrial dysfunction and ER stress. Cardiac function was determined via echocardiographic examination. Mitochondrial function and ER stress were detected via ELISA, western blots, and immunofluorescence. Our data demonstrated that virus injection induced cardiac dysfunction as evidenced by reduced contractile function in myocardium. Besides, LDH release assay and western blotting analysis demonstrated that cardiomyocyte death was activated by virus injection. Interestingly, melatonin treatment improved cardiac function and repressed virus-mediated cardiomyocyte apoptosis. At the molecular levels, mitochondrial dysfunction was induced by virus infection, as indicated by mitochondrial membrane potential reduction, mPTP opening rate elevation and caspase-9-related apoptosis activation. Besides, ER stress parameters were also elevated in virus-treated cardiomyocytes. Interestingly, melatonin treatment maintained mitochondrial dysfunction and repressed ER stress. To the end, we found that Mst1 was upregulated by virus infection; this effect was attenuated through supplementation with melatonin. However, Mst1 overexpression reduced the beneficial impact exerted by melatonin on cardiomyocyte viability, mitochondrial function and ER homeostasis. Our study illustrated that melatonin treatment attenuated viral myocarditis via sustaining cardiomyocyte viability, repressing mitochondrial dysfunction and inhibiting ER stress in a manner dependent on Mst1 inhibition.

Orexin Receptor-1 in the Rostral Ventrolateral Medulla Mediates the Antihypertensive Effects of Electroacupuncture.

Electroacupuncture (EA) has been used to treat numerous diseases, including hypertension. This study aimed to investigate the long-term effect and underlying mechanisms of EA stimulation at the LI11 point on the hypertension and sympathetic nerve activity in two-kidney, one-clip (2K1C) hypertensive rats. EA (0.1-0.4 mA, 2 and 15 Hz) was applied to the acupoints LI11 overlying the deep radial nerve once a day for 6 weeks. The mean arterial pressure (MAP) and heart rate (HR) were determined by radiotelemetry, and the sympathetic nerve activity was evaluated by telemetric analyses of the low-frequency component of blood pressure (BP) and by plasma epinephrine and norepinephrine levels. The results showed 6 weeks of EA significantly lowered the increased BP effectively, inhibited the enhanced sympathetic nerve activities and attenuated cardiac hypertrophy in 2K1C hypertensive rats. The level of orexin receptor-1 (OX1R) in the rostral ventrolateral medulla (RVLM) after EA treatment was markedly reduced in 2K1C rats, while there was no difference in the RVLM expression of orexin receptor-2 (OX2R) in 2K1C and 2K1C+EA rats. Moreover, the increased pressor and depressor responses to microinjection of orexin A or OX1R antagonist SB408124 into the RVLM of 2K1C rats were significantly blunted by the EA treatment. These findings suggest that BP-lowering effect of EA on renovascular hypertension may be through inhibition of central sympathetic activities and modulation of functional orexin receptors in the RVLM.