Online mindfulness-based stress reduction improves anxiety and depression status and quality of life in caregivers of patients with severe mental disorders. / ç½‘ç»œæ­£å¿µå‡åŽ‹ç–—æ³•å¯æ”¹å–„ä¸¥é‡ç²¾ç¥žéšœç¢æ‚£è€ ç §æ–™è€ ç„¦è™‘æŠ‘éƒçŠ¶æ€åŠå ¶ç”Ÿæ´»è´¨é‡.

OBJECTIVES: To explore the effects of online mindfulness-based stress reduction (MBSR) on the anxiety and depression status, and quality of life in the caregivers of patients with severe mental disorders. METHODS: Ninety-three caregivers for patients with schizophrenia or bipolar disorder, who were hospitalized in Yunnan Provincial Mental Hospital in March 2021, were enrolled and randomly divided into control group (n=47) and MBSR intervention group (n=46). Both groups received basic health education and rehabilitation skill training, while the intervention group received additional online MBSR for 8 weeks. The anxiety and depression status, and the quality of life of the caregivers were evaluated by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 36-item Short Form Health Survey (SF-36) before and 8 weeks after intervention, respectively. RESULTS: Thirteen caregivers dropped out of the study, and 80 subjects (40 in each group) were included in the final analysis. At the baseline, there were no significant differences in SAS, SDS and SF-36 scores between two groups (all P>0.05). Compared with the baseline, SAS and SDS scores in the intervention group significantly decreased after 8 weeks of intervention (both P<0.01) and were significantly lower than those in the control group (both P<0.01). There were no significant changes in the control group (all P>0.05). Except the physiological function dimension, the total score and the scores of each dimension of SF-36 in the intervention group were significantly increased after 8-week intervention (all P<0.05), and were significantly higher than those in the control group (all P<0.01). There were no significant changes in the control group before and after intervention (all P>0.05). CONCLUSIONS: Online MBSR can reduce the anxiety and depression levels, improve the quality of life in the caregivers of patients with severe mental disorders.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Integrating pharmacological evaluation and computational identification for deciphering the action mechanism of Yunpi-Huoxue-Sanjie formula alleviates diabetic cardiomyopathy.

Background: Yunpi-Huoxue-Sanjie (YP-SJ) formula is a Chinese herbal formula with unique advantages for the treatment of diabetic cardiovascular complications, such as Diabetic cardiomyopathy (DCM). However, potential targets and molecular mechanisms remain unclear. Therefore, our research was designed to evaluate rat myocardial morphology, fat metabolism and oxidative stress to verify myocardial protective effect of YP-SJ formula in vivo. And then to explore and validate its probable mechanism through network pharmacology and experiments in vitro and in vivo. Methods: In this study, DCM rats were randomly divided into five groups: control group, model group, and three YP-SJ formula groups (low-dose, middle-dose, and high-dose groups). Experimental rats were treated with 6 g/kg/d, 12 g/kg/d and 24 g/kg/d YP-SJ formula by gavage for 10 weeks, respectively. Cardiac function of rats was measured by high-resolution small-animal imaging system. The cells were divided into control group, high glucose group, high glucose + control serum group, high glucose + dosed serum group, high glucose + NC-siRNA group, high glucose + siRNA-FoxO1 group. The extent of autophagy was measured by flow cytometry, immunofluorescence, and western blotting. Results: It was found that YP-SJ formula could effectively improve cardiac systolic function in DCM rats. We identified 46 major candidate YP-SJ formula targets that are closely related to the progression of DCM. Enrichment analysis revealed key targets of YP-SJ formula related to environmental information processing, organic systems, and the metabolic occurrence of reactive oxygen species. Meanwhile, we verified that YP-SJ formula can increase the expression of forkhead box protein O1 (FoxO1), autophagy-related protein 7 (Atg7), Beclin 1, and light chain 3 (LC3), and decrease the expression of phosphorylated FoxO1 in vitro and in vivo. The results showed that YP-SJ formula could activate the FoxO1 signaling pathway associated with DCM rats. Further experiments showed that YP-SJ formula could improve cardiac function by regulating autophagy. Conclusion: YP-SJ formula treats DCM by modulating targets that play a key role in autophagy, improving myocardial function through a multi-component, multi-level, multi-target, multi-pathway, and multi-mechanism approach.

Computational identification of Shenshao Ningxin Yin as an effective treatment for novel coronavirus infection (COVID-19) with myocarditis.

BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the 2019 coronavirus disease (COVID-19), which has killed more than 4.5 million people. SARS-CoV-2 causes severe respiratory distress syndrome by targeting the lungs and also induces myocardial damage. Shenshao Ningxin Yin (SNY) has been used for more than 700 years to treat influenza. Previous randomized controlled trials (RCTs) have demonstrated that SNY can improve the clinical symptoms of viral myocarditis, reverse arrhythmia, and reduce the level of myocardial damage markers. METHODS: This work uses a rational computational strategy to identify existing drug molecules that target host pathways for the treatment of COVID-19 with myocarditis. Disease and drug targets were input into the STRING database to construct proteinɃprotein interaction networks. The Metascape database was used for GO and KEGG enrichment analysis. RESULTS: SNY signaling modulated the pathways of coronavirus disease, including COVID-19, Ras signaling, viral myocarditis, and TNF signaling pathways. Tumor necrosis factor (TNF), cellular tumor antigen p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), and the signal transducer and activator of transcription 3 (STAT3) were the pivotal targets of SNY. The components of SNY bound well with the pivotal targets, indicating there were potential biological activities. CONCLUSION: Our findings reveal the pharmacological role and molecular mechanism of SNY for the treatment of COVID-19 with myocarditis. We also, for the first time, demonstrate that SNY displays multi-component, multi-target, and multi-pathway characteristics with a complex mechanism of action.

Magnesium implantation or supplementation ameliorates bone disorder in CFTR-mutant mice through an ATF4-dependent Wnt/ß-catenin signaling.

Magnesium metal and its alloys are being developed as effective orthopedic implants; however, the mechanisms underlying the actions of magnesium on bones remain unclear. Cystic fibrosis, the most common genetic disease in Caucasians caused by the mutation of CFTR, has shown bone disorder as a key clinical manifestation, which currently lacks effective therapeutic options. Here we report that implantation of magnesium-containing implant stimulates bone formation and improves bone fracture healing in CFTR-mutant mice. Wnt/ß-catenin signaling in the bone is enhanced by the magnesium implant, and inhibition of Wnt/ß-catenin by iCRT14 blocks the magnesium implant to improve fracture healing in CFTR-mutant mice. We further demonstrate that magnesium ion enters osteocytes, increases intracellular cAMP level and activates ATF4, a key transcription factor known to regulate Wnt/ß-catenin signaling. In vivo knockdown of ATF4 abolishes the magnesium implant-activated ß-catenin in bones and reverses the improved-fracture healing in CFTR-mutant mice. In addition, oral supplementation of magnesium activates ATF4 and ß-catenin as well as enhances bone volume and density in CFTR-mutant mice. Together, these results show that magnesium implantation or supplementation may serve as a potential anabolic therapy for cystic fibrosis-related bone disease. Activation of ATF4-dependent Wnt/ß-catenin signaling in osteocytes is identified as a previously undefined mechanism underlying the beneficial effect of magnesium on bone formation.

Exploration of the anti-insomnia mechanism of Ganoderma by central-peripheral multi-level interaction network analysis.

BACKGROUND: Ganoderma (Lingzhi in Chinese) has shown good clinical outcomes in the treatment of insomnia, restlessness, and palpitation. However, the mechanism by which Ganoderma ameliorates insomnia is unclear. We explored the mechanism of the anti-insomnia effect of Ganoderma using systems pharmacology from the perspective of central-peripheral multi-level interaction network analysis. METHODS: The active components and central active components of Ganoderma were obtained from the TCMIP and TCMSP databases, then screened to determine their pharmacokinetic properties. The potential target genes of these components were identified using the Swiss Target Prediction and TCMSP databases. The results were matched with the insomnia target genes obtained from the GeneCards, OMIM, DisGeNET, and TCMIP databases. Overlapping targets were subjected to multi-level interaction network analysis and enrichment analysis using the STRING, Metascape, and BioGPS databases. The networks analysed were protein-protein interaction (PPI), drug-component-target gene, component-target gene-organ, and target gene-extended disease; we also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: In total, 34 sedative-hypnotic components (including 5 central active components) were identified, corresponding to 51 target genes. Multi-level interaction network analysis and enrichment analysis demonstrated that Ganoderma exerted an anti-insomnia effect via multiple central-peripheral mechanisms simultaneously, mainly by regulating cell apoptosis/survival and cytokine expression through core target genes such as TNF, CASP3, JUN, and HSP90αA1; it also affected immune regulation and apoptosis. Therefore, Ganoderma has potential as an adjuvant therapy for insomnia-related complications. CONCLUSION: Ganoderma exerts an anti-insomnia effect via complex central-peripheral multi-level interaction networks.

Involvement of kisspeptin in androgen-induced hypothalamic endoplasmic reticulum stress and its rescuing effect in PCOS rats.

Endoplasmic reticulum (ER) stress, with adaptive unfolded protein response (UPR), is a key link between obesity, insulin resistance and type 2 diabetes, all of which are often present in the most common endocrine-metabolic disorder in women of reproductive age, polycystic ovary syndrome (PCOS), which is characterized with hyperandrogenism. However, the link between excess androgen and endoplasmic reticulum (ER) stress/insulin resistance in patients with polycystic ovary syndrome (PCOS) is unknown. An unexpected role of kisspeptin was reported in the regulation of UPR pathways and its involvement in the androgen-induced ER stress in hypothalamic neuronal cells. To evaluate the relationship of kisspeptin and ER stress, we detected kisspeptin and other factors in blood plasm of PCOS patients, rat models and hypothalamic neuronal cells. We detected higher testosterone and lower kisspeptin levels in the plasma of PCOS than that in non-PCOS women. We established a PCOS rat model by dihydrotestosterone (DHT) chronic exposure, and observed significantly downregulated kisspeptin expression and activated UPR pathways in PCOS rat hypothalamus compared to that in controls. Inhibition or knockdown of kisspeptin completely mimicked the enhancing effect of DHT on UPR pathways in a hypothalamic neuronal cell line, GT1-7. Kp10, the most potent peptide of kisspeptin, effectively reversed or suppressed the activated UPR pathways induced by DHT or thapsigargin, an ER stress activator, in GT1-7 cells, as well as in the hypothalamus in PCOS rats. Similarly, kisspeptin attenuated thapsigargin-induced Ca2+ response and the DHT- induced insulin resistance in GT1-7 cells. Collectively, the present study has revealed an unexpected protective role of kisspeptin against ER stress and insulin resistance in the hypothalamus and has provided a new treatment strategy targeting hypothalamic ER stress and insulin resistance with kisspeptin as a potential therapeutic agent.

Magnesium and vitamin C supplementation attenuates steroid-associated osteonecrosis in a rat model.

Magnesium (Mg)-based biometal attracts clinical applications due to its biodegradability and beneficial biological effects on tissue regeneration, especially in orthopaedics, yet the underlying anabolic mechanisms in relevant clinical disorders are lacking. The present study investigated the effect of magnesium (Mg) and vitamin C (VC) supplementation for preventing steroid-associated osteonecrosis (SAON) in a rat experimental model. In SAON rats, 50 mg/kg Mg, or 100 mg/kg VC, or combination, or water control was orally supplemented daily for 2 or 6 weeks respectively. Osteonecrosis was evaluated by histology. Serum Mg, VC, and bone turnover markers were measured. Microfil-perfused samples prepared for angiography and trabecular architecture were evaluated by micro-CT. Primary bone marrow cells were isolated from each group to evaluate their potentials in osteoblastogenesis and osteoclastogenesis. The mechanisms were tested in vitro. Histological evaluation showed SAON lesions in steroid treated groups. Mg and VC supplementation synergistically reduced the apoptosis of osteocytes and osteoclast number, and increased osteoblast surface. VC supplementation significantly increased the bone formation marker PINP, and the combination significantly decreased the bone resorption marker CTX. TNFα expression and oxidative injury were decreased in bone marrow in Mg/VC/combination group. Mg significantly increased the blood perfusion in proximal tibia and decreased the leakage particles in distal tibia 2 weeks after SAON induction. VC significantly elevated the osteoblast differentiation potential of marrow cells and improved the trabecular architecture. The combination supplementation significantly inhibited osteoclast differentiation potential of marrow cells. In vitro study showed promoting osteoblast differentiation effect of VC, and anti-inflammation and promoting angiogenesis effect of Mg with underlying mechanisms. Mg and VC supplementation could synergistically alleviate SAON in rats, indicating great translational potentials of metallic minerals for preventing SAON.

[Multi-index optimization of extraction process of Fengyin Decoction based on BAS-GA-BP neural network combined with entropy weight method].

To optimize the ethanol extraction technology parameters of Fengyin Decoction by orthogonal experiment combined with beetle antennae search(BAS)-genetic algorithm(GA)-back propagation neural network(BPNN). Based on single factor investigation, the extraction temperature, ethanol volume, extraction time, and ethanol concentration were used as orthogonal experiment factors, and entropy weight method was used to calculate the comprehensive scores of aloe-emodin, glycyrrhizic acid ammonium salt, rhein, emodin, chrysophanol, physcion, cinnamaldehyde, 6-gingerol, extraction ratio and fingerprint similarity. BAS-BPNN model was established, and then, GA was used to predict the optimal extraction process. The results showed that BAS-BPNN was optimized to obtain the optimal ethanol extraction process of Fengyin Decoction as follows: extraction temperature of 87 ℃, adding 9 times of 75 % ethanol, and extracting for 47 minutes, with a comprehensive score of 1.052 9. Meanwhile, the optimal process parameters obtained by orthogonal design were as follows: the extraction temperature of 80 ℃, adding 10 times of 75% ethanol, extracting for 30 minutes, with a comprehensive score of 1.003 7. The comprehensive score of the process obtained from the BAS-BPNN model was slightly better than that from the orthogonal test, indicating that the optimized process from BAS-BPNN model was more ideal, so it was finally determined as the best extraction process for Fengyin Decoction. The process of Fengyin Decoction obtained from BAS-GA-BPNN has high extraction efficiency and good stability, which provides reference for the subsequent development and quality control.

[Investigation of iodine content in drinking-water of Gansu Province in 2017].

OBJECTIVE: To investigate the water iodine content and distribution of drinking-water in Gansu Province, and provide scientific evidence for the implementation of strategies for prevention and treatment of iodine-related diseases. METHODS: The multilevel sampling method was adopted, take the township as sampling unit at the first level, and the administrative village with the median water iodine ≥10 µg/L as the second level sampling unit, different water supply modes(centralized, partial concentration and decentralized water supply) were sampled and the water iodine were detected by recommended iodine deficiency disease test method. RESULTS: A total of 8976 drinking water samples were detected from 1388 towns of 14 cities. the detection range was 0. 0-84. 6 µg/L, the median water iodine was 2. 3 µg/L, and 8301 samples were<10 µg/L, 663 samples were 10～<50 µg/L, 12 samples were ≥50 µg/L, with a ratio of total at 92. 5%, 7. 4% and 0. 1%, respectively. Water iodine content varies between three different water supply method(χ~2=8. 923, P<0. 05), decentralized water iodine was lower than partial concentration water supply(Z=-2. 891, P<0. 01). 71 townships of median water iodine were ≥10 µg/L(5. 1%), the water iodine median range was 10. 1～64. 3 µg/L, 76. 1% of townships were 10-<20 µg/L, 11. 3% were 20-<30 µg/L, 5. 6% were 30-<40 µg/L, 7. 0% were ≥40 µg/L(χ~2=13. 302, P<0. 05). Water samples of 895 administrative villages were detected, the median water iodine was 10. 8 µg/L, 466 administrative villages with a median water iodine ≥10 µg/L, the water iodine range was 10. 0～113. 1 µg/L, the median water iodine was 10. 8 µg/L, Administrative villages of 10-<50 µg/L, 50～<100 µg/L and ≥100 µg/L accounted for 96. 6%, 2. 4% and 1. 0%, respectively. CONCLUSION: Iodine deficiency areas were exist universally in Gansu Province, but there is high iodine point-like distribution areas in the administrative villages. While pay close attention to prevention of Iodine deficiency, the iodine nutrition status monitor in different iodine areas and the iodine supplementation strategy adjusting should be concerned too.

[Analysis on the metabolites of mesaconitine in the rat urine by liquid chromatography and electrospray ionization mass spectrometry].

The mesaconitine and its major metabolites in the rat urine were identified by liquid chromatography and electrospray ionization tandem mass spectrometry. The rat urine was collected for consecutive 24 hours from the rat following intragastric infusion of mesaconitine, subsequently which were enriched and purified using solid phase extraction. The metabolites of mesaconitine in the rat urine were analyzed by the liquid chromatography and electrospray ionization tandem mass spectrometry. It is shown that the parent drug mesaconitine and its metabolites were found in the rat urine, such as hypo-mesaconitine glucuronic acid conjugate, 10-hydroxy-mesaconitine, 1-O-demethyl mesaconitine, deoxy-mesaconitine and hypo-mesaconitine. Among the five of metabolites, the hypo-mesaconitine glucuronic acid conjugate (m/z 766) was first discovered as the aconitine in rats phase II metabolites, which revealed a new way of mesaconitine metabolism in rats.