The effects of P2 segment of posterior cerebral artery to thalamus blood supply pattern on gait in cerebral small vessel disease: A 7 T MRI based study.

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.

Evaluation of the effects of vitamin D deficiency and cigarette smoking on insulin resistance in type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

There are contradictory findings regarding the effects of vitamin D supplementation and cigarette smoking on glucose metabolism in individuals with type 2 diabetes mellitus (T2DM). Consequently, this meta-analysis focused on the association between vitamin D interventions and smoking cessation on glycemic control in T2DM patients. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane Library, EMBASE and PubMed databases were used for a language-inclusive literature search until November 2022. The primary outcomes of this meta-analysis were changes in glycated hemoglobin (HbA1c) level, vitamin D concentration and body mass index (BMI) values. This meta-analysis included 14 randomized controlled trials (RCTs) with a total of 23,289 individuals with T2DM. Nine RCTs were related to vitamin D supplementation interventions, and 5 RCTs were related to smoking cessation interventions. The studies on vitamin D supplementation showed a substantial change in the intervention group, with a risk ratio (RR) of 0.72 (95% confidence interval (95% CI): 0.58, 0.88; p = 0.001) and an odds ratio (OR) of 0.52 (95% CI: 0.34, 0.78; p = 0.002); high heterogeneity was observed (I2 ≥ 95%). Similarly, the smoking cessation studies showed a substantial change in the intervention group, with a RR of 0.92 (95% CI: 0.86, 0.99; p = 0.04) and an OR of 0.86 (95% CI: 0.74, 0.99; p = 0.04); high heterogeneity was observed (I2 = 87%). In conclusion, both vitamin D supplementation and smoking cessation are associated with moderate BMI decline and an improvement of insulin sensitivity in people with T2DM.

Advances for pharmacological activities of Polygonum cuspidatum - A review.

CONTEXT: Polygonum cuspidatum Sieb. et Zucc (Polygonaceae), the root of which is included in the Chinese Pharmcopoeia under the name 'Huzhang', has a long history as a medicinal plant and vegetable. Polygonum cuspidatum has been used in traditional Chinese medicine for the treatment of inflammation, hyperlipemia, etc. OBJECTIVE: This article reviews the pharmacological action and the clinical applications of Polygonum cuspidatum and its extracts, whether in vivo or in vitro. We also summarized the main phytochemical constituents and pharmacokinetics of Polygonum cuspidatum and its extracts. METHODS: The data were retrieved from major medical databases, such as CNKI, PubMed, and SinoMed, from 2014 to 2022. Polygonum cuspidatum, pharmacology, toxicity, clinical application, and pharmacokinetics were used as keywords. RESULTS: The rhizomes, leaves, and flowers of Polygonum cuspidatum have different phytochemical constituents. The plant contains flavonoids, anthraquinones, and stilbenes. Polygonum cuspidatum and the extracts have anti-inflammatory, antioxidation, anticancer, heart protection, and other pharmacological effects. It is used in the clinics to treat dizziness, headaches, traumatic injuries, and water and fire burns. CONCLUSIONS: Polygonum cuspidatum has the potential to treat many diseases, such as arthritis, ulcerative colitis, asthma, and cardiac hypertrophy. It has a broad range of medicinal applications, but mainly focused on root medication; its aerial parts should receive more attention. Pharmacokinetics also need to be further investigated.

Antiplatelet effect of ginkgo diterpene lactone meglumine injection in acute ischemic stroke: A randomized, double-blind, placebo-controlled clinical trial.

This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, double-blind, placebo-controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease ≥5 or mRS scores decrease ≥2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA-MAR) and mean platelet volume (MPV) of the GDLI-aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14-day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 [95%CI, 1.03-50.68], p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.

Integrated metabolism, network pharmacology, and pharmacokinetics to explore the exposure differences of the pharmacodynamic material basis in vivo caused by different extraction methods for Saussurea involucrata.

ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata Kar.et Kir. (S.I.) has long been used as a precious national medicine and clinically proven to be an effective treatment for rheumatoid arthritis (RA) and cardiovascular diseases. In clinical practice, two extraction methods of S.I., including water decoction and alcohol extraction, are prescribed to treat the same conditions. Nevertheless, no study has been performed on the exposure differences of the pharmacodynamic material basis in vivo caused by different extraction methods. AIM OF THE STUDY: Based on the integrated strategy of metabolism, network pharmacology, and pharmacokinetics, we aimed to reveal exposure differences in pharmacodynamic substances caused by different extraction methods. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was employed to identify the chemical constituents of S.I. extracts and the metabolites in vivo after administration. Based on the analysis of prototype components in vivo, the major exposure active constituents, potential therapeutic targets and possible pharmacological mechanisms in RA treatment were investigated using network pharmacological analysis. Seven critical active components, including quercetin, hispidulin, apigenin, chlorogenic acid, arctigenin, syringin, and umbelliferone, were quantitatively compared between the alcohol, and aqueous extraction methods, which had been confirmed by the reference substance. RESULTS: The chemical comparison demonstrated that the types of chemicals in the two extracts were identical, mainly flavonoids, phenylpropanoids, coumarins, lignins, sesquiterpene lactones, and others, but the contents of the primary constituents in the aqueous extract were lower than those of the alcohol extract. A total of 30 prototype components and 174 metabolites were analyzed and identified in rat plasma, urine, fecal, and bile samples. Twenty-three prototype components were analyzed by network pharmacology, and seven critical active components were selected as representative markers for the pharmacokinetic study. Pharmacokinetic studies had shown that the Tmax values of apigenin, hispidulin, chlorogenic acid, arctigenin, and syringin after the oral administration of the alcohol extract were lower than those after the oral administration of the aqueous extract, and the above components in the alcohol extract could increase the absorption. Compared with the aqueous extract group, the Tmax and T1/2 of quercetin and umbelliferone were longer; it was suggested that alcohol extraction might have a slow-release and long-term effect on these two components. The relative bioavailability of apigenin, hispidulin, quercetin, chlorogenic acid, and umbelliferone in the alcohol extract group were higher than those in the aqueous extract group, which was consistent with the traditional clinical experience that alcohol extract could improve the efficacy of S.I. CONCLUSIONS: The major exposure active constituents in vivo were screened. The representative components that could be used in pharmacokinetics were determined by integrating network pharmacology and metabolism studies. The critical active compounds were quantitatively compared between the alcohol and aqueous extraction methods. This study clarified that flavonoids, coumarin, and phenylpropanoids might be the primary material basis that caused the exposure differences between aqueous and alcoholic extracts from S.I.. This research aimed to provide the basis of metabolism in vivo for further studying these pharmacodynamic differences.

The Protective Effect of Liquiritin in Hypoxia/Reoxygenation-Induced Disruption on Blood Brain Barrier.

Background: Stroke is the second leading cause of death in human life health, but current treatment strategies are limited to thrombolytic therapy, and because of the tight time window, many contraindications, and only a very small number of people can benefit from it, new therapeutic strategies are needed to solve this problem. As a physical barrier between the central nervous system and blood, the blood-brain barrier (BBB) maintains the homeostasis of the central nervous system. Maintaining the integrity of the BBB may emerge as a new therapeutic strategy. Liquiritin (LQ) is a flavonoid isolated from the medicinal plant Glycyrrhiza uralensis Fisch. ex DC. (Fabaceae), and this study aims to investigate the protective effects of LQ on brain microvascular endothelial cells (BMECs), to provide a new therapeutic strategy for stroke treatment, and also to provide research ideas for the development of traditional Chinese medicine (TCM). Methods: The protective effects of LQ on HBMECs under the treatment of hypoxia reoxygenation (H/R) were investigated from different aspects by establishing a model of H/R injury to mimic ischemia-reperfusion in vivo while administrating different concentrations of LQ, which includes: cell proliferation, migration, angiogenesis, mitochondrial membrane potential as well as apoptosis. Meanwhile, the mechanism of LQ to protect the integrity of BBB by antioxidation and inhibiting endoplasmic reticulum (ER) stress was also investigated. Finally, to search for possible targets of LQ, a proteomic analysis approach was employed. Results: LQ can promote cell proliferation, migration as well as angiogenesis and reduce mitochondrial membrane potential damage and apoptosis. Meanwhile, LQ can also reduce the expression of related adhesion molecules, and decrease the production of reactive oxygen species. In terms of mechanism study, we demonstrated that LQ could activate Keap1/Nrf2 antioxidant pathway, inhibit ER stress, and maintain the integrity of BBB. Through differential protein analysis, 5 disease associated proteins were found. Conclusions: Studies have shown that LQ can promote cell proliferation, migration as well as angiogenesis, and reduce cell apoptosis, which may be related to its inhibition of oxidative and ER stress, and then maintain the integrity of BBB. Given that five differential proteins were found by protein analysis, future studies will revolve around the five differential proteins.

The influence of maternal vitamin D supplementation on infant vitamin D status: A systematic review and meta-analyses.

BACKGROUND: Inconsistencies exist with regard to effect of maternal vitamin D supplementation on infant vitamin D status. The inconsistencies could be attributed to numerous factors, such as duration of intervention and dosage, among others. In this work, we conducted a systematic review and meta-analysis to determine the influence of maternal vitamin D supplementation on infant vitamin D status. METHODS: A comprehensive systematic search was performed in Scopus, EMBASE, Web of Science, and PubMed/MEDLINE, by investigators, from database inception until November 2019, without using any restrictions. Weighted mean difference (WMD) with the 95 % CI was used for assessing the effects of maternal vitamin D supplementation on 25(OH) D levels in infants. RESULTS: Overall results from 14 studies revealed a non-significant effect of maternal vitamin D administration on the level of 25(OH) D in breastfeeding infants (WMD: -0.464 ng/mL, 95 % CI: -6.68 to 5.75, p = 0.884, I2 = 98 %). Subgroup analyses demonstrated that vitamin D supplementation dosage ≥2000 IU/day (WMD: 9 ng/mL, 95 % CI: 8.19, 9.82, I2 = 99 %) and intervention duration ≥20 weeks (WMD: 16.20 ng/mL, 95 % CI: 14.89, 17.50, I2 = 99 %) significantly increased 25(OH) D. CONCLUSIONS: The main results indicate a non-significant increase in infant vitamin D following maternal vitamin D supplementation. Additionally, vitamin D supplementation dosage ≥2000 IU/day and intervention duration ≥20 weeks significantly increased infant 25(OH) D.

Cordycepin reduces weight through regulating gut microbiota in high-fat diet-induced obese rats.

BACKGROUND: An increasing number of studies have shown that obesity is the key etiological agent of cardiovascular diseases, nonalcoholic fatty liver disease, type 2 diabetes and several kinds of cancer and that gut microbiota change was one of the reasons suffering from obesity. At present, the gut microbiota has gained increased attention as a potential energy metabolism organ. Our recent study reported that cordycepin, a major bioactive component separated from Cordyceps militaris, prevented body weight gain in mice fed a high-fat diet directly acting to adipocytes, however, the effect of cordycepin regulating gut microbiota keeps unknown. METHODS: In this research, we synthesized cordycepin (3-deoxyadenosine) by chemical methods and verified that cordycepin reduces body weight gain and fat accumulation around the epididymis and the kidneys of rats fed a high-fat diet. Furthermore, we used high-throughput sequencing on a MiSeq Illumina platform to test the species of intestinal bacteria in high-fat-diet-induced obese rats. RESULTS: We found that cordycepin modifies the relative abundance of intestinal bacteria in high-fat-diet-induced obese rats. However, cordycepin did not alter the variety of bacteria in the intestine. Cordycepin treatment dramatically reversed the relative abundance of two dominant bacterial phyla (Bacteroidetes and Firmicutes) in the high-fat-diet-induced obese rats, resulting in abundance similar to that of the chow diet group. CONCLUSION: Our study suggests that cordycepin can reduce body weight and microbiome done by cordycepin seems be a result among its mechanisms of obesity reduction.

Transcriptional and functional analysis shows sodium houttuyfonate-mediated inhibition of autolysis in Staphylococcus aureus.

Sodium houttuyfonate (SH), an addition compound of sodium bisulfite and houttuynin, showed in vitro antibacterial activity against 21 Staphylococcus aureus (S. aureus) strains grown in planktonic cultures. Microarray results showed decreased levels of autolysin atl, sle1, cidA and lytN transcripts in the SH-treated strain as compared to the control strain, consistent with the induction of the autolytic repressors lrgAB and sarA and with the downregulation of the positive regulators agrA and RNAIII. Triton X-100-induced autolysis was significantly decreased by SH in S. aureus ATCC 25923, and quantitative bacteriolytic assays and zymographic analysis demonstrated SH-mediated reduction of extracellular murein hydrolase activity in these cells. Anti-biofilm assay showed that SH is poorly active against S. aureus grown in biofilm cultures, whereas SH diminished the amounts of extracellular DNA (eDNA) of S. aureus in a dose-dependent manner, which suggested that SH may impede biofilm formation by reducing the expression of cidA to inhibit autolysis and eDNA release in the early phase. Some of the microarray results were confirmed by real-time RT-PCR.

Microarray analysis of the chelerythrine-induced transcriptome of Mycobacterium tuberculosis.

Chelerythrine (a natural quaternary benzophenanthridine alkaloid) is an extract from the roots of Chelidonium majus with potential antimycobacterial activity. To reveal the possible mechanism of action of chelerythrine against Mycobacterium tuberculosis (M. tuberculosis), commercial oligonucleotide microarrays were used to analyze the genome-wide transcriptional changes triggered by treatment with subinhibitory concentrations of chelerythrine. Quantitative real-time RT-PCR was performed for selected genes to verify the microarray results. We interpreted our microarray data using Agilent software. Analysis of the microarray data revealed that a total of 759 genes were differentially regulated by chelerythrine. Of these, 372 genes were upregulated, and 387 genes were downregulated. Some of the important genes that were significantly regulated are related to different pathways (such as urease), methoxy-mycolic acid synthase, surface-exposed lipids, the heat shock response, and protein synthesis. This genome-wide transcriptomics approach produced the first insights into the response of M. tuberculosis to a chelerythrine challenge.

[Determination of gentiopicroside in different morphological types of cultivated Gentiana manshurica population].

OBJECTIVE: To study the correlation between morphological variation and gentiopicroside content in cultivated Gentiana manshurica roots and to investigate the feasibility of breeding new varieties of high effective constituent content. METHOD: Gentiopicroside was determined in 5 morphological types of cultivated G. manshurica roots by HPLC, which are normal (or wild) type, white-flowered type, thick-rooted type, broad-leaved type I and broad-leaved type II. RESULT: Among different types gentiopicroside content is the highest in the roots of thick-rooted type, the contents decrease as following order: normal type, broad-leaved type I white-flowered type and broad-leaved type II, and the gentiopicroside contents in the same type root system are a positive correlation with root ages, as 3-years-age roots > 2-years-age roots > 1-year-age varied with roots. CONCLUSION: The contents of effective constituent vary with the morphological variation in cultivated G. manshurica. It is feasible to breed a new variety with high effective constituent with the morphological character as a selecting index.