Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy.

BACKGROUND: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. METHODS: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. RESULTS: A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. CONCLUSIONS: Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Application of clinical value assessment of treatment protocols in guideline development: taking the WFAS Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine as an example. / 治疗方案临床价值评估在指南制定中的应用.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.

Effectiveness of Acupuncture for Prophylactic Treatment of Migraine: A Systematic Review and Bayesian Network Meta-Analysis.

It is aimed to evaluate the effectiveness and provide evidence-based medical support for acupuncture as a prophylactic treatment for migraines. Randomized controlled trials (RCTs) from inception to April 2022 are included in 14 databases. Pairwise meta-analysis is conducted using STATA software V14.0, while Windows Bayesian Inference Using Gibbs Sampling (WinBUGS V.1.4.3) is applied to generate Bayesian Network Meta-analysis (NMA) using Markov chain Monte Carlo algorithm. Forty RCTs are included, with 4405 participants. The effectiveness of six acupuncture techniques, three types of prophylactic drugs, and psychotherapy are compared and ranked. Acupuncture outperformed prophylactic drugs in terms of diminishing visual analog scale (VAS) score, migraine attack frequency, and days during the treatment and at the 12-week follow-up. At the 12-week follow-up, the effectiveness of various interventions is ranked as follows: manual acupuncture (MA) > electroacupuncture (EA) > calcium antagonists (CA) in reducing VAS score; MA > EA > CA in reducing migraine attack frequency; MA > EA > ß-receptor blocker and CA in reducing headache attack days. Acupuncture is a promising treatment for migraine prevention. The best option of acupuncture for improving various migraine outcomes has changed over time. However, the quality of included trials and NMA inconsistency limited the credibility of the conclusion.

Target RNA expression omics approach to reveal the liver detoxification effect induced by Chinese medicine prescription Niu Huang Jie Du against realgar overexposure to mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Niu Huang Jie Du prescription (NHJD) is a traditional Chinese medicine (TCM) widely used in patients suffering from excessive inner fire toxin (Huo Du Nei Sheng) syndrome, such as sore throat, gingival swelling, and pain, mouth and tongue sores, etc. This formula contains realgar (As4S4) which is one of the 28 toxic medicinal materials promulgated by the Chinese Ministry of Health. Many studies reported its toxicity on the liver and kidney, and the detoxification effect of NHJD. However, its detoxification mechanism is still unclear. AIM OF THE STUDY: To clarify the detoxification mechanism of NHJD to realgar, this study evaluated the detoxification effect of NHJD on realgar exposure in mice, and analyzed differences in mRNA expression profiles in liver tissues and associated functional predictions. MATERIAL AND METHODS: ICR mice were administered with NHJD, realgar, and CMC-Na as blank control for 12 weeks, respectively. Liver injury was evaluated by histopathologic examination and liver mRNA gene were sequenced by Illumina. Differentially expressed gene, functionally enrichment and protein association network analysis were conducted. RESULTS: 43 genes were screened out, among which 15 genes in the realgar group were decreased, but the extent of the decline has been restored in the NHJD group. The remaining 28 genes have exactly the opposite trends. Functional module analysis revealed that those detoxification function-related genes were primarily for positive regulation of glutathione metabolism, P450 on the metabolism of exogenous compounds, oxidative stress and immune-related, etc. CONCLUSIONS: The results indicated that realgar mainly causes liver damage by changing the common enzymes of drug metabolism, especially the expression of genes related to CYPs, GSTs family, oxidative stress, and complement immunity, while the TCM prescription NHJD has a regulatory effect on the abnormal expression of corresponding genes. Our results will provide some clues for the detoxification mechanism of arsenic-containing TCM prescriptions.

Selenium in Wheat from Farming to Food.

Selenium (Se) plays an important role in human health. Approximately 80% of the world's population does not consume enough Se recommended by the World Health Organization. Wheat is an important staple food and Se source for most people in the world. This review summarizes literature about Se from 1936 to 2020 to investigate Se in wheat farming soil, wheat, and its derived foods. Se fortification and the recommended Se level in wheat were also discussed. Results showed that Se contents in wheat farming soil, grain, and its derived foods around the world were 3.8-552 µg kg-1 (mean of 220.99 µg kg-1), 0-8270 µg kg-1 (mean of 347.30 µg kg-1), and 15-2372 µg kg-1 (mean of 211.86 µg kg-1), respectively. Adopting suitable agronomic measures could effectively realize Se fortification in wheat. The contents in grain, flour, and its derived foods could be improved from 93.94 to 1181.92 µg kg-1, from 73.06 to 1007.75 µg kg-1, and from 86.90 to 587.61 µg kg-1 on average after leaf Se fertilizer application in the field. There was a significant positive correlation between the Se content in farming soil and grain, and it was extremely the same between the foliar Se fertilizer concentration rate and the grain Se increased rate. The recommended Se fortification level in cultivation of wheat in China, India, and Spain was 18.53-23.96, 2.65-3.37, and 3.93-9.88 g hm-2, respectively. Milling processing and food type could greatly affect the Se content of wheat-derived food and should be considered seriously to meet people's Se requirement by wheat.

In Vitro Micropatterned Human Pluripotent Stem Cell Test (µP-hPST) for Morphometric-Based Teratogen Screening.

Exposure to teratogenic chemicals during pregnancy may cause severe birth defects. Due to high inter-species variation of drug responses as well as financial and ethical burdens, despite the widely use of in vivo animal tests, it's crucial to develop highly predictive human pluripotent stem cell (hPSC)-based in vitro assays to identify potential teratogens. Previously we have shown that the morphological disruption of mesoendoderm patterns formed by geometrically-confined cell differentiation and migration using hPSCs could potentially serve as a sensitive morphological marker in teratogen detection. Here, a micropatterned human pluripotent stem cell test (µP-hPST) assay was developed using 30 pharmaceutical compounds. A simplified morphometric readout was developed to quantify the mesoendoderm pattern changes and a two-step classification rule was generated to identify teratogens. The optimized µP-hPST could classify the 30 compounds with 97% accuracy, 100% specificity and 93% sensitivity. Compared with metabolic biomarker-based hPSC assay by Stemina, the µP-hPST could successfully identify misclassified drugs Bosentan, Diphenylhydantoin and Lovastatin, and show a higher accuracy and sensitivity. This scalable µP-hPST may serve as either an independent assay or a complement assay for existing assays to reduce animal use, accelerate early discovery-phase drug screening and help general chemical screening of human teratogens.

Butein and Its Role in Chronic Diseases.

Natural compounds isolated from various plant sources have been used for therapeutic purpose for centuries. These compounds have been routinely used for the management of various chronic ailments and have gained considerable attention because of their significant efficacy and comparatively low side effects. Butein, a chacolnoid compound that has been isolated from various medicinal plants has exhibited a wide range of beneficial pharmacological effects, such as anti-inflammatory, anticancer, antioxidant, and anti-angiogenic in diverse disease models. This article briefly summarizes the past published literature related to the therapeutic and protective effects of butein, as demonstrated in various models of human chronic diseases. Further analysis of its important cellular targets, toxicity, and pharmacokinetic profile may further significantly expand its therapeutic application.

Isolated diastolic hypertension associated risk factors among Chinese in Anhui Province, China.

OBJECTIVE: To explore potential risk factors of isolated diastolic hypertension (IDH) among young and middle-aged Chinese. METHODS: A community-based cross-sectional study was conducted among 338 subjects, aged 25 years and above, using random sampling technique. There were 68 cases of IDH, 46 cases of isolated systolic hypertension (ISH), 89 cases of systolic and diastolic hypertension (SDH), and 135 of subjects with normal blood pressure. Cases and controls were matched on sex by frequency matching. Demographic characteristics, blood pressure and other relevant information were collected. RESULTS: Compared with controls, patients with IDH and ISH had significant higher level of triglyceride, high density lipoprotein, blood glucose and body mass index (BMI) (p < 0.05); while patients with SDH had significantly higher level of total cholesterol, triglyceride, glucose and BMI (p < 0.05). Linear mixed effects model showed that drinking tea, family history of hypertension (FHH), higher blood glucose, triglyceride and low density lipoprotein were related with elevated diastolic blood pressure (DBP) (p < 0.01); HFH, blood glucose, creatinine and BMI have positive effect on systolic blood pressure (SBP) (p < 0.05). CONCLUSIONS: Drinking tea, FHH, high levels of triglyceride, high density lipoprotein, blood glucose and BMI are associated with IDH among young and middle-aged Chinese.