Two new triterpenoids from the fruits of Aphanamixis polystachya.

Two new triucallane triterpenoids, polystanin F (1) and polystanin G (2), along with eight known compounds (3-10) were isolated from the fruits of Aphanamixis polystachya. Their structures were established on the basis of extensive spectroscopic analysis. Moreover, eight compounds were evaluated for their in vitro cytotoxicity against three cancer cell lines (liver cancer RT112, colon cancer HCT-116 and breast cancer M231) using the MTT method. Compound 7 showed significant cytotoxic activity against HCT-116 with IC50 1.27 µM.

Development of new dehydrocostuslactone derivatives for treatment of atopic dermatitis via inhibition of the NF-κB signaling pathway.

Atopic dermatitis (AD), a recurrent inflammatory systemic skin disease, is difficult to cure. In the present study, several ethylenediamine-derived dehydrocostuslactone (DHCL) derivatives were prepared to assess their in vitro and in vivo anti-inflammatory activities. The results indicated that DHCL derivatives inhibited NO generation with low cytotoxicity. In particular, compound 5d exhibited the best anti-inflammatory activity. Subsequent experiments revealed that 5d not only inhibited the LPS-induced inflammatory response in RAW264.7 cells via the MAPK-NF-κB signaling pathway inhibition but also significantly decreased Th2-type cytokine levels and inhibited the NF-κB signaling pathway activation in mice with MC903-induced AD. Therefore, DHCL derivatives may be considered as new agents for the treatment of AD.

Cytotoxic sesquiterpene aryl esters from Armillaria gallica 012m.

Objective: To study the chemical constituents of the EtOAc extract of Armillaria gallica 012m. Methods: The chemical constituents of the EtOAc extract of A. gallica 012m were isolated and purified by various column chromatography and their structures were elucidated on the basis of the 1D and 2D NMR spectroscopic and HRESIMS data. Cytotoxicity of all isolates against A549, HCT-116, M231 and W256 human tumor cells was determined by the MTT method. Results: A new sesquiterpene aryl ester, armimelleolide C (1), and eight known ones including armillarivin (2), melleolide F (3), 6'-chloromelleolide F (4), melleolide (5), melleolide K (6), melledonol (7), 13-hydroxydihydromelleolide (8), and armillane (9), were isolated from the EtOAc extract of A. gallica 012m. All isolates showed potential cytotoxic activities against at least one of the human cancer cell lines with IC50 values ranging from (3.17 ± 0.54) to (17.57 ± 0.47) µmol/L. Compound 1 showed significant inhibitory activity against M231 with an IC50 value of (7.54 ± 0.24) µmol/L compared with paclitaxel as the positive control. Compounds 2, 3, and 7, 9 showed obvious inhibitory activity against HCT-116 and were better than that of the positive control. Conclusion: The chemical constituents including a new sesquiterpene aryl ester armimelleolide C (1) from the EtOAc extract of A. gallica 012m have a variety of structures and potential antitumor activities.

Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level.

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments. Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments. Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery. Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.

Risk of fracture following gastric surgery for benign and malignant conditions: A study level pooled analysis of population-based cohort studies.

Background: Metabolic changes may occur following gastric surgery, which has been reported to contribute to bone loss, osteoporosis and even bone fracture. However, the evidence regarding the relationship between gastric surgery for benign and malignant conditions and risk of fracture is controversial. This study was conducted with the aim to evaluate whether gastric surgery is associated with a high risk of fracture. Methods: Major electronic databases were searched from inception through October 2021 for population-based cohort studies investigating the associations between gastric surgery (including bariatric gastric surgeries and surgeries for gastric benign and malignant gastric tumors) and risk of fracture compared with controls. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were derived using the random-effects Mantel-Haenszel model. Multiple subgroup analyses and sensitivity analyses were carried out to test sources of heterogeneity stratified by various study characteristics and the robustness of the results. Results: A total of 14 studies comprising 693134 individuals were identified for analysis. The RR for the risk of fracture in people undergoing gastric surgery was 1.45 [95% confidence interval (CI) 1.23 - 1.72; I2 = 95.8%; P < 0.001] compared with that in control populations, among which the fracture sites of upper limb, spine, lower limb, pelvis and hip showed consistent significant results (all P < 0.05), whereas nonsignificant associations was noted for other fracture sites. Significant associations were also observed for patients having total or subtotal gastrectomy (RR 2.22, 95% CI 1.66 to 3.00), gastric bypass (RR 1.48, 95% CI 1.26 to 1.74), and a similar trend was observed for preserved passage procedures (including sleeve gastrectomy, gastric banding, vertical banded gastroplasty and other procedures that preserved the passage through the duodenum and proximal small bowel, in contrast to gastric bypass), though the difference did not reach statistically significant (RR 1.10, 95% CI 0.95 to 1.26). An evident increased risk in the age range from 40-59 years was observed (40-49 years: RR 1.36, 95% CI 1.19-1.55; 50-59 years: RR 2.48, 95% CI 1.58-3.90). Conclusion: From this large pooled analysis of population-based cohort studies, evidence supports that fracture risk is increased in gastric surgery survivors compared with the control population. Early prevention and effective intervention strategies of bone fracture should be taken from clinicians and health policy makers. Clinical Trial Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291394), identifier CRD42021291394.

Hypothermia preconditioning improves cardiac contractility after cardiopulmonary resuscitation through AMPK-activated mitophagy.

Hypothermia preconditioning (HPC) improves cardiac function after cardiac arrest, yet the mechanism is unclear. We hypothesized that HPC-activated adenosine monophosphate-activated protein kinase (AMPK) activity may be involved. Adult male Wistar rats were randomly divided into normothermia Control, HPC (cooling to 32-34°C for 30 min), and HPC + Compound C (Compound C 10 mg/kg was injected intraperitoneally 30 min before HPC group). The rats underwent 7 min of untreated ventricular fibrillation (VF) followed by cardiopulmonary resuscitation (CPR). Cardiac function and hemodynamic parameters were evaluated at 4 h after return of spontaneous circulation (ROSC). Survival status was determined 72 h after ROSC. Mechanistically, we further examined the AMPK-Unc-51 Like Autophagy Activating Kinase 1 (ULK1)-mitophagy pathway and autophagic flux in vivo and in vitro. Six of twelve rats in the Control group, 10 of 12 rats in the HPC group, and 7 of 12 rats in HPC + Compound C group were successfully resuscitated. The 72-h survival rates were 1 of 12 Control, 6 of 12 HPC, and 2 of 12 HPC + Compound C rats, respectively (P = 0.043). Rats in the HPC group demonstrated greater cardiac contractility and hemodynamic stability which were compromised by Compound C. Furthermore, HPC increased the protein levels of p-AMPKα and p-ULK1 and promoted the expression of mitochondrial autophagy-related genes. Compound C decreased the expression of mitochondrial autophagy-related genes and reduced autophagic flux. Consistent with the observations obtained in vivo, in vitro experiments in cultured neonatal rat cardiomyocytes (CMs) demonstrated that HPC attenuated simulated ischemia-reperfusion-induced CM death, accompanied by increased AMPK-ULK1-mitophagy pathway activity. These findings suggest that AMPK-ULK1-mitophagy pathway was activated by HPC and has a crucial role in cardioprotection during cardiac arrest. Manipulation of mitophagy by hypothermia may merit further investigation as a novel strategy to prevent cardiac ischemia-reperfusion injury.

Percutaneous Coronary Intervention After Return of Spontaneous Circulation Reduces the In-Hospital Mortality in Patients with Acute Myocardial Infarction Complicated by Cardiac Arrest.

BACKGROUND AND OBJECTIVE: The role of percutaneous coronary intervention (PCI) after return of spontaneous circulation (ROSC) in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) is controversial. This study aimed to evaluate the effects of PCI on the in-hospital mortality after ROSC in patients with AMI complicated by CA. METHODS: The clinical data of 66 consecutive patients with ROSC after CA caused by AMI from January 2006 to December 2015 at the First Affiliated Hospital of Sun Yat-sen University were collected. Among these patients, 21 underwent urgent PCI. We analyzed the clinical characteristics of the patients during hospitalization. RESULTS: The patients who underwent PCI had a higher rate of ST-segment elevation, and their initial recorded heart rhythms were more likely to have a shockable rhythm. Further, they had a high PCI success rate of 100%. The in-hospital mortality in the patients who did not undergo PCI was significantly higher than that in the patients who underwent PCI (68.9% vs 9.5%, P<0.05). Multivariate logistic regression analysis showed that cardiogenic shock (odds ratio [OR], 3.537; 95% CI, 1.047-11.945; P=0.042) and Glasgow Coma Scale score of ≤8 after ROSC (OR, 14.992; 95% CI, 2.815-79.843; P=0.002) were the independent risk factors for in-hospital mortality among the patients. Meanwhile, PCI was a protective factor against in-hospital mortality (OR, 0.063; 95% CI, 0.012-0.318; P=0.001). After propensity matching analysis, the results still showed that PCI (OR, 0.226; 95% CI, 0.028-1.814; P=0.0162) was a protective factor for in-hospital death. CONCLUSION: The patients with ROSC after CA caused by AMI who underwent PCI had a lower in-hospital mortality than those who did not undergo PCI.

Flower extract of Caragana sinica. ameliorates DSS-induced ulcerative colitis by affecting TLR4/NF-κB and TLR4/MAPK signaling pathway in a mouse model.

OBJECTIVES: This study aimed to find out the protective effects and preliminary mechanisms of the flower extract of Caragana sinica (FEC) on dextran sulfate sodium salt (DSS)-induced colitis. MATERIALS AND METHODS: The ulcerative colitis models of mice induced by 3% DSS were established and treated with FEC. Body weight changes, disease activity index (DAI), colon histopathological score, anti-oxidant ability, and the level of inflammatory cytokines were determined. The expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) were assessed in colonic tissue by immunohistochemical staining. Western blot was used to analyze the expression of TLR4/ nuclear factor kappa-B (NF-κB) and TLR4/ mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: FEC significantly prevented body weight loss and colonic shortening and reduced the disease activity index and histopathological score (P<0.05). Moreover, FEC treatment remarkably down-regulated the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) and up-regulated the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and interleukin 10 (IL-10) in the colon of DSS mice (P<0.05). Furthermore, the expression of TLR4/NF-κB and TLR4/MAPK pathway-related proteins was inhibited by FEC (P<0.05). CONCLUSION: Our findings demonstrated that FEC could serve as a potential therapeutic agent for treatment of ulcerative colitis.

Effect of Ultrasound Debridement on Serum Inflammatory Factors and bFGF, EGF Expression in Wound Tissues.

OBJECTIVE: To determine the effect of ultrasonic debridement on serum inflammatory factors of procalcitonin (PCT), highsensitivity C-reactive protein (hs-CRP), red blood cell deposition rate (ESR) content, and expression levels of wound tissue basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Emergency, Dongguan People's Hospital, China, from February 2016 to February 2018. METHODOLOGY: A total of 80 patients with limb flap repair were randomly divided into a control group and an observation group, with 40 cases in each group. Control group was treated with conventional surgical debridement, and the observation group was treated with ultrasound debridement technique. The effect was compared between two groups. RESULTS: On the 1st, 3rd, and 7th days after flap repair, Numeric Rating Scale (NRS) scores in observation group were lower than those in control group (all p <0.001). On the 7th day after the flap repair, serum levels of PCT, hs-CRP, and ESR were lower in observation group than those in control group (all p <0.001). On the 7th and 12th day after flap repair, expression levels of bFGF and EGF protein in the wound tissue of observation group were higher than those in control group (all p <0.001). Infection with sinus tract formed after the flap repair in observation group was lower than that in control group (p=0.048). CONCLUSION: Compared with conventional surgical debridement, ultrasound debridement technique can more effectively reduce postoperative inflammatory reactions, reduce postoperative wound infection, relieve pain in patients, promote the bFGF and EGF expression in the wound tissue.