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The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 µg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time.
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ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.
Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Saponins , Animals , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Mice , Saponins/pharmacology , Saponins/isolation & purification , Spirostans/pharmacology , Spirostans/isolation & purification , Biofilms/drug effects , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Female , Fishes , MaleABSTRACT
BACKGROUND: To describe the diagnostic criteria used and their application accuracy in the practice of polycystic ovary syndrome (PCOS) caring among obstetricians and gynaecologists across China. METHODS: This was an Online cross-sectional survey of Obstetricians and gynecologists involved in PCOS caring conducted via the largest continuing education platform of obstetrics and gynecology across China from September 2019 to November 2019. RESULTS: A total of 2,328 respondents were eligible for the final analysis. Of these, 94.5 % were general obstetricians and gynaecologists (Ge-ObGyn), and 5.5 % were reproductive endocrinologists (Re-ObGyn). Overall, the most frequently used criteria were the Androgen Excess and Polycystic Ovary Syndrome Society (AE-PCOS) criteria (48.2 %), followed by the Rotterdam criteria (35.7 %) and NIH criteria (12.1 %). Of the respondents, 31.3 % used their diagnostic criteria in their clinical practice. More respondents who chose the Rotterdam criteria could accurately apply the diagnostic criteria than those who chose the AE-PCOS criteria (41.2 % vs. 32.1 %, P < 0.001). Compared with Ge-ObGyn, Re-ObGyn were less likely to use the AE-PCOS criteria (adjusted odds ratio, 0.513; 95 % CI, 0.328-0.802; P < 0.05) and 1.492 times more likely to accurately use their criteria (95 % CI, 1.014-2.196; P < 0.05). CONCLUSIONS: Less than one-third of obstetricians and gynaecologists across China could accurately use the diagnostic criteria they choose to diagnose PCOS. There is an urgent need to train obstetricians and gynaecologists on PCOS diagnosis in an effort to improve the medical care quality of patients with PCOS.
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Clinical Competence , Gynecology , Obstetrics , Polycystic Ovary Syndrome/diagnosis , Practice Patterns, Physicians' , Adult , China , Endocrinology , Female , Humans , Male , Middle Aged , Odds Ratio , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND@#Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.@*METHODS@#Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.@*RESULTS@#Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.@*CONCLUSIONS@#COM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272.
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Female , Humans , Exenatide/therapeutic use , Metformin/therapeutic use , Obesity/drug therapy , Overweight , Polycystic Ovary Syndrome/drug therapyABSTRACT
OBJECTIVE@#To evaluate the effects of Chinese medicine Dingkun Pill () alone or in combination with Diane-35 on patients with polycystic ovary syndrome (PCOS).@*METHODS@#This is a prospective randomized controlled trial conducted at Peking Union Medical College Hospital Beijing, China, from December 2016 to September 2017. Totally 117 PCOS patients were randomly assigned to the Dingkun Pill group (38 cases), Diane-35 group (40 cases), or combined group (39 cases). Patients in the Dingkun Pill group or Diane-35 group took daily 7 g of oral Dingkun Pill or 1 tablet of oral Diane-35, respectively, for 21 consecutive days followed by 7 drug-free days. And the combined group received a combination of Dingkun Pill and Diane-35. The treatment course was 3 months. Fasting plasma glucose and insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), free fatty acids (FFA) and sex hormones were analyzed, quantitative insulin sensitivity check index (QUICKI) was calculated, and menstruation and acne scores were recorded at baseline and after 3-month treatment.@*RESULTS@#Compared with before treatment, QUICKI decreased significantly in the Dingkun Pill and combined groups after 3-month treatment (P0.05).@*CONCLUSIONS@#Dingkun Pill showed better effects than Diane-35 in improving insulin sensitivity, lowering TC and FFA. Diane-35 was more efficient in regulating menstruation and lowering androgen than Dingkun Pill. Combination of Dingkun Pill and Diane-35 may be a better choice to regulate menstruation, lower androgens while improve glucose metabolism in PCOS patients. (Registered on ClinicalTrials.gov, registration No. NCT03264638).
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OBJECTIVE@#To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS).@*METHODS@#A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated.@*RESULTS@#Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05).@*CONCLUSION@#DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).