Glycosides from the leaves of Fraxinus Hubeiensis.

Fraxinus hubeiensis is a plant endemic to China and widely used as folk medicine to treat various diseases. However, its chemical constituents have never been reported sufficiently. Thus, the primary objective of this study was to investigate the phytochemical constituents and biological activities of F. hubeiensis leaves. Hence, combined column chromatographic and spectroscopic techniques were used to identify and characterize the secondary metabolites such as a pair of 3-keto-glycoside epimers (1) and (2), along with five known compounds (3 ~ 7). The results of α-glucosidase inhibitory activity exhibited that 1 and 2 had moderate activity with IC50 values of 359.50 and 468.43 µM, respectively, compared to a positive control acarbose with the IC50 value of 164.08 µM. However, Compounds 1-6 were shown to be inactive against the tested microbes.

Chemical Constituents and α-Glucosidase Inhibitory, Antioxidant and Hepatoprotective Activities of Ampelopsis grossedentata.

Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids (1-2) and seventeen known compounds (3-19) were isolated and identified from the dried stems and leaves of A. grossedentata. These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure-activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC50 value of 0.21 µM. In addition, compounds 1-2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.

[Analysis of regularity of acupoint selection and compatibility of acupuncture in the treatment of postpartum depression].

OBJECTIVE: To analyze the regularity of acupoint selection, and compatibility of acupuncture in the treatment of postpartum depression. METHODS: Articles both in English and Chinese published in databases of CNKI, Wanfang, VIP, Chinese biomedical literature database (SinoMed), PubMed, Embase, Cochrane Library from the inception to February of 2021 were retrieved by using key words "acupuncture" or "moxibustion" or "electroacupuncture" or "acupoint application" or " acupoint burying" or "acupoint injection" or "fire needling" and "postpartum depression" or "puerperal depression". The frequencies of selected acupoints and meridians were counted by using data mining technology, and the points with high frequency were analyzed by cluster analysis. RESULTS: A total of 42 articles were included, containing 65 prescriptions and 80 points. The highest frequency of acupoints were Baihui (GV20), Sanyinjiao (SP6), Taichong (LR3), Neiguan (PC6), Zusanli (ST36) and Shenmen (HT7). The most frequently selected channels were Bladder Meridian, Governor Meridian and Liver Meridian. Among the specific points, intersection points, five-shu points, yuan-source points and back-shu points were widely used. Through cluster analysis, four effective cluster groups ï¼»GV20-SP6, LR3-PC6, Xinshu (BL15)-Ganshu (BL18)-Pishu (BL20)-Guanyuan (CV4), Hegu (LI4)-Qihai(CV6)-Qimen (LR14)ï¼½ were obtained, as well as a group of main points (GV20-SP6-LR3-PC6-ST36-HT7) and two groups of matching points ï¼»LI4-CV6-LR14 and BL15-BL18-BL20-CV4-Sishencong (EX-HN1)ï¼½. CONCLUSION: Through data mining technology, this paper summarized the acupoint selection and compatibility law of acupuncture in the treatment of postpartum depression, focusing on regulating Qi, blood and spirit, so as to provide reference for guiding the clinical acupuncture treatment and scientific research of postpartum depression.

[Effect of Gegen Qinlian Decoction on methylation and expression of Scd1gene in adipose tissue of insulin resistant rats and correlations between methylation and physiological and biochemical parameters].

This study aimed to explore the effect of Gegen Qinlian Decoction(GQD) on the methylation and mRNA expression level of stearoyl CoA desaturase(SCD) gene in the adipose tissue of rats with insulin resistance(IR) induced by high-fat diet as well as the correlations between methylation and physiological and biochemical indicators. The animals were divided into seven groups, namely, blank control(C) group, IR model group, low-(1.65 g·kg~(-1)), medium-(4.95 g·kg~(-1)), and high(14.85 g·kg~(-1))-dose GQD(GQDL, GQDM, and GQDH) groups, rosiglitazone(RGN, 5 mg·kg~(-1)) group, and simvastatin(SVT, 10 mg·kg~(-1)) group. The rat epididymal adipose tissue was collected for detecting all the cytosine methylation levels in two fragments of Scd1 gene by bisulfite sequencing PCR(BSP). Scd1-1 was located in CG shores and Scd1-2 in CG islands, including the transcriptional start site(TSS). The Scd1 mRNA level was determined by quantitative real-time PCR(q-PCR). Spearman correlation coefficient was used to analyze the correlations between amplified fragment C methylation and physiological and biochemical indicators. The results showed that GQDM remarkably reversed the elevated CG7 methylation in the TSS upstream region of Scd1-2 triggered by high-fat diet. GQDL significantly reversed the lowered total CG methylation in the downstream region of Scd1-2 induced by the high-fat diet. GQD did not significantly improve the decreased Scd1 mRNA expression caused by high-fat diet. Changes in methylation of the total CG, CG5 and CT11 of Scd1-1 in CG shores exhibited significant negative correlations with the serum triglyceride(TG) but positive correlation with the Scd1 mRNA level. The methylation of several C sites in the TSS upstream region of Scd1-2 was positively correlated with physiological and biochemical parameters. The methylation of several CG sites in the TSS downstream region of Scd1-2 was negatively associated with physiological and biochemical parameters. Besides, the methylation of several CH sites in the downstream fragment was positively correlated with physiological and biochemical parameters. All these have demonstrated that GQD may exert the therapeutic effect by regulating the methylation of CG7 in the TSS upstream region and total CG site in the TSS downstream region of Scd1 gene. The methylation of total CG, CG5 and CT11 sites in CG shores of Scd1 gene may be important targets for regulating Scd1 mRNA level and affecting serum TG.

The traditional ethnic herb Tadehagi triquetrum from China: a review of its phytochemistry and pharmacological activities.

CONTEXT: Tadehagi triquetrum (Linn.) Ohashi (Fabaceae) (TT), is a traditional herbal medicine used especially in China's ethnic-minority communities, such as the Zhuang, Dai, Li and Wa aeras. As an ethnic medicine, it has long been used to treat various diseases. OBJECTIVE: This review summarised the phytochemical and pharmacological progress on TT from 1979 to October, 2021 by highlighting its chemical classification, structural features, pharmacological applications and folk applications to provide inspirations and suggestions for accelerating further research of this traditional phytomedicine. METHODS: The information on TT in this article has been obtained using these multiple scientific databases including Scifinder, Web of Science, ScienceDirect, Wiley, ACS publications, Springer, PubMed, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar and Baidu Scholar. Some information was also collected from classic literature on traditional Chinese medicines. RESULTS: More than 70 compounds have been isolated and reported from TT to date by the comprehensive analysis of the current literature. A large number of traditional uses and pharmacological studies have exhibited diversified bioactivities of various TT extracts and its metabolites, including anti-inflammatory, antimicrobial, anti-hepatitis B virus, hepatoprotective, insecticidal, etc. CONCLUSIONS: As a famous traditional medicine with a long history, TT has various medicinal uses and some of them have been supported by modern pharmacological researches. Further detailed studies on the action mechanisms, pharmacodynamics and structure-function relationships of single compounds or active constituents from TT are also required.

Investigating Mechanisms of Response or Resistance to Immune Checkpoint Inhibitors by Analyzing Cell-Cell Communications in Tumors Before and After Programmed Cell Death-1 (PD-1) Targeted Therapy: An Integrative Analysis Using Single-cell RNA and Bulk-RNA Sequencing Data.

Currently, a significant proportion of cancer patients do not benefit from programmed cell death-1 (PD-1)-targeted therapy. Overcoming drug resistance remains a challenge. In this study, single-cell RNA sequencing and bulk RNA sequencing data from samples collected before and after anti-PD-1 therapy were analyzed. Cell-cell interaction analyses were performed to determine the differences between pretreatment responders and nonresponders and the relative differences in changes from pretreatment to posttreatment status between responders and nonresponders to ultimately investigate the specific mechanisms underlying response and resistance to anti-PD-1 therapy. Bulk-RNA sequencing data were used to validate our results. Furthermore, we analyzed the evolutionary trajectory of ligands/receptors in specific cell types in responders and nonresponders. Based on pretreatment data from responders and nonresponders, we identified several different cell-cell interactions, like WNT5A-PTPRK, EGFR-AREG, AXL-GAS6 and ACKR3-CXCL12. Furthermore, relative differences in the changes from pretreatment to posttreatment status between responders and nonresponders existed in SELE-PSGL-1, CXCR3-CCL19, CCL4-SLC7A1, CXCL12-CXCR3, EGFR-AREG, THBS1-a3b1 complex, TNF-TNFRSF1A, TNF-FAS and TNFSF10-TNFRSF10D interactions. In trajectory analyses of tumor-specific exhausted CD8 T cells using ligand/receptor genes, we identified a cluster of T cells that presented a distinct pattern of ligand/receptor expression. They highly expressed suppressive genes like HAVCR2 and KLRC1, cytotoxic genes like GZMB and FASLG and the tissue-residence-related gene CCL5. These cells had increased expression of survival-related and tissue-residence-related genes, like heat shock protein genes and the interleukin-7 receptor (IL-7R), CACYBP and IFITM3 genes, after anti-PD-1 therapy. These results reveal the mechanisms underlying anti-PD-1 therapy response and offer abundant clues for potential strategies to improve immunotherapy.

[Exploration on the rules of acupoints selection for phlegm disorder treated with acupuncture and moxibustion based on ancient literature study].

OBJECTIVE: To analyze the rules of acupoints selection for phlegm disorder in treatment with acupuncture and moxibustion in ancient literature so as to provide guidance to clinical treatment of phlegm disorder. METHODS: The word "phlegm" was taken as the search term and the relevant articles were retrieved from Zhonghuayidian (Dictionary of Chinese Medicine). According to the inclusion and exclusion criteria, the articles were screened and the database was set up. The analysis was conducted on acupoint selection, the correlation with meridians involved and distribution location, as well as the use frequency of specific points and acupoint combination. RESULTS: It was found that in treatment of phlegm disorder, the highest frequently used acupoints were Zusanli (ST36) and Zhongwan (CV12). The use frequency of three yang meridians was higher than that of three yin meridians. The commonly involved meridians were the Conception Vessel, Bladder Meridian of Foot-taiyang and the Governor Vessel. The acupoints located in the chest and abdomen were highly used. The use frequency of specific points was higher than that of non-specific ones. The sequence of the use frequency of specific points, from high to low, is the crossing point, the front-mu point and luo-connecting point. The combination of Danzhong (CV17) and Zusanli (ST36) is of the high frequency. CONCLUSION: Ancient medical scholars focus on regulating spleen and stomach functions, as well as qi activity in treatment of phlegm disorder with acupuncture and moxibustion, which is coincident with the treatment principle of phlegm disorder in traditional Chinese medicine. In treatment, acupuncture-moxibusiton is characterized as laying the emphasis on the specific points, the local acupoints and the holistic idea as " regulation of yang for yin disorder"．.

Comparison of Structured Nutrition Therapy for Ramadan with Standard Care in Type 2 Diabetes Patients.

(1) Background: Structured nutrition therapy (NT) is essential for the management of type 2 diabetes (T2D), but the optimal delivery during Ramadan fasting remains unclear. The present study aimed to evaluate the effect of structured NT program versus standard care in patients with T2D during Ramadan. (2) Methods: The present study was an 8-week, parallel, non-randomized study with patients' preference design involving 64 patients with T2D. The participants were asked to choose their preferred group, i.e., structured NT (Structured Ramadan NT, sRNT) or standard care (SC). The participants in the sRNT group received a Ramadan-focused nutrition plan, including a diabetes-specific formula throughout the study, whereas the patients in the SC group received standard nutrition care. Study outcomes included clinical outcomes and quality of life (QoL). Data was analyzed using two-way repeated-measures ANOVA and linear mixed-effects model. (3) Results: More than half of the participants (n = 38, 63%) chose sRNT as their preferred group. Both groups had comparable baseline characteristics. After 8-weeks of the respective intervention, participants in the sRNT group had lower levels of fasting plasma glucose (-0.9 ± 0.3 mmol/L vs. 0.2 ± 0.3 mmol/L, p < 0.05), triglycerides (-0.21 ± 0.08 mmol/L vs. 0.20 ± 0.17 mmol/L, p < 0.05), and self-monitoring glucose at pre-dawn (6.9 mmol/L vs. 7.8 mmol/L, p < 0.05) and pre-bedtime (7.6 mmol/L vs. 8.6 mmol/L, p < 0.05) than participants in the SC group. Although not different between groups, HbA1c levels decreased significantly in the sRNT (-0.72 ± 0.16%, p < 0.001) but not in the SC group (-0.35 ± 0.24%, p = 0.155). QoL and satisfaction scores improved significantly in sRNT group, but not in SC group. (4) Conclusions: The structured NT regimen for Ramadan is a feasible and beneficial program for T2D patients observing Ramadan fasting as it showed an improvement in clinical outcomes and QoL.

[In vitro evaluation, cellular uptake and anti-acute myocardial ischemia effect of puerarin PEG-PLGA micelles].

PUE@PEG-PLGA micelles has excellent characteristics such as small particle size, high drug loading and slow drug release. The results of TEM electron microscopy showed that PUE@PEG-PLGA micelles had obvious core-shell structure. The critical micelle concentration(CMC) of PEG-PLGA micelles determined by pyrene assay was about 4.8 mg·L~(-1). Laser confocal experiments showed that PEG-PLGA micelles can enhance the cellular uptake of coumarin-6 and aggregate around the mitochondria; quantitative results of extracellular drug residues also indirectly confirmed that PEG-PLGA micelles can promote cellular uptake of the drug. Acute ischemic myocardial model rats were prepared by coronary artery ligation, and then the model rats were randomly divided into six groups: Sham operation group, model group, puerarin(PUE) group, as well as low-, mid-, and high-dose PUE@PEG-PLGA micelles groups. Drugs were given by iv administration 5 min after the ligation. The ST segment changes in the electrocardiogram were monitored; serum creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), and malondialdehyde(MDA) levels were detected and myocardial infarct size was also measured. Both PUE and PUE@PEG-PLGA micelles can reduce the elevated ST segment, reduce serum CK, LDH, AST and MDA levels, and reduce myocardial infarct size. The efficacy of PUE@PEG-PLGA medium and high dose groups was significantly better than that in the PUE group, and the efficacy in PUE@PEG-PLGA low dose group was basically equivalent to that in the PUE group. PUE@PEG-PLGA micelles can greatly improve the cardiomyocytes uptake of PUE, enhance the anti-acute myocardial ischemia effect of drugs, and reduce its dosage.

Preparation, characterization, and evaluation of antitumor effect of Brucea javanica oil cationic nanoemulsions.

The purpose of this study was to prepare Brucea javanica oil cationic nanoemulsions (BJO-CN) with BJO as drug as well as oil phase and chitosan as cationic inducer, to explore the practical suitability of using cationic nanoemulsions for oral delivery of mixed oil, and to test its bioavailability and antitumor effect. BJO-CN was prepared by chitosan solution stirring method and then characterized physicochemically. The obtained BJO-CN had a spherical morphology with a positive zeta potential of 18.9 mV and an average particle size of 42.36 nm, showing high colloidal stability. The drug loading of BJO-CN was 91.83 mg·mL(-1), determined by high-performance liquid chromatography with precolumn derivatization. Pharmacokinetic studies revealed that, compared with BJO emulsion (BJO-E) (the dosage of BJO-CN and BJO-E was equal to 505 mg·kg(-1), calculated by oleic acid), BJO-CN exhibited a significant increase in the area under the plasma drug concentration-time curve over the period of 24 hours and relative bioavailability was 1.6-fold. Furthermore, the antitumor effect of BJO-CN in the orthotopic mouse model of lung cancer was evaluated by recording the median survival time and the weight of lung tissue with tumor, hematoxylin and eosin staining, and immunohistochemical technique. Results of anticancer experiments illustrated that, even though the administrated dosage in the BJO-CN group was half of that in the BJO-E group, BJO-CN exhibited similar antitumor effect to BJO-E. Moreover, BJO-CN had good synergistic effect in combination therapy with vinorelbine. These results suggested that cationic nanoemulsions are an effective and promising delivery system to enhance the oral bioavailability and anticancer effect of BJO.

A Historical Cohort Study on the Efficacy of Glucocorticoids and Riboflavin Among Patients with Late-onset Multiple Acyl-CoA Dehydrogenase Deficiency.

BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. METHODS: We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. RESULTS: After 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05). There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05). On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. CONCLUSIONS: Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

[Protective effect of yixinshu capsule on myocardial ischemia reperfusion injury in rats].

OBJECTIVE: To observe the protective effect of Yixinshu capsule on myocardial ischemia reperfusion injury (MIRI) in SD rats. METHOD: Sixty healthy SD rats were randomized into six groups: sham group, MIRI model group, Xinsuning capsule group, low, middle or high dose Yixinshu capsule. Acute MIRI rat models were created by reperfusion for 120 min after anterior interventricular branch of the left coronary artery for 30 min. The serum creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and malondialdehyde(MDA), blood viscosity, and infarction area of myocardium were determined. RESULT: Yixinshu capsule could reduce serum CK, LDH, AST and LDH activity, improve the blood viscosity, and reduced the myocardial infarct size. CONCLUSION: Yixinshu capsule can protect against MIRI in rats.

[Stability of PEGylated puerarin under different storage conditions].

OBJECTIVE: To detect the stability of PEGylated puerarin (PEG-PUE), in order to provide experimental basis for storage conditions of PEGylated puerarin. METHOD: First, a method for determining the content of PEG-PUE was established. Next, a system study was conducted for the stability of PEG-PUE affected by different factors such as temperature, humidity, light and light avoidance. RESULT: PEG-PUE was severely degraded under the conditions of high temperature, high humidity and light. It was also seriously degraded under high temperature. CONCLUSION: PEG-PUE shall be stored under low temperature and in a dark and dry environment.

[In vitro dissolution of forsythin in Forsythia suspensa powder of different particle diameter].

OBJECTIVE: To examine the in vitro dissolution of forsythin in Forsythia suspensa powder of different particle diameter, in order to give guidance to the grinding process. METHOD: HPLC was used to determine the in vitro dissolution quantity and dissolution velocity of forsythin coarse powder, fine powder and ultramicroscopic powder. RESULT: The dissolution curves of Forsythia suspensa coarse powder, fine powder and ultramicroscopic powder were basically inconformity to Weibull distribution. Specifically, T50 was 11.8, 10.5 and 6.8 min, respectively, and Q45 was 78.22%, 81.91% and 90.76%, respectively. CONCLUSION: The superfine milling process can significantly increase the dissolution quantity and dissolution velocity of forsythin.