Vitamin K2 protects mice against non-alcoholic fatty liver disease induced by high-fat diet.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and there is a huge unmet need to find safer and more effective drugs. Vitamin K has been found to regulate lipid metabolism in the liver. However, the effects of vitamin K2 on NAFLD is unclear. This study aims to evaluate the preventive and therapeutic effects of vitamin K2 in the process of fatty liver formation and to explore molecular mechanisms the associated with lipid metabolism. A non-alcoholic fatty liver model was established by high-fat diet administration for three months. Vitamin K2 significantly reduced the body weight, abdominal circumference and body fat percentage of NAFLD mice. Vitamin K2 also showed histological benefits in reducing hepatic steatosis. NAFLD mice induced by high-fat diet showed increased HMGR while vitamin K2 intervention could reverse the pathological lterations. Adiponectin (APN) is an endogenous bioactive polypeptide or protein secreted by adipocytes. We detected APN, SOD, AlaDH and other indicators that may affect the state of high-fat diet mice, but the experimental results showed that the above indicators did not change significantly. It is worth noting that the effect of vitamin K2 supplementation on the lipid-lowering effect of uc OC in vivo needs to be further explored. This study first reported the protective effect of vitamin K2 on high-fat diet-induced NAFLD in mice. The protective effect of vitamin K2 may be related to the improvement of lipid metabolism disorder in NAFLD.

Akebia saponin D attenuates allergic airway inflammation through AMPK activation.

Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from Dipsacus asper Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200 µΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) (1 mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300 mg/kg) or AICAR (100 mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation.

Water-solubility croconic acid-bisindole dye with morpholine ring for tumor NIRF/PA imaging and photothermal therapy activated by lysosome pH-response.

A novel croconic acid-bisindole dye CR-630 with a morpholine ring showed good water-solubility and obvious lysosome-targeting. The protonation of the nitrogen atom in the indole and lysosome-targeting of morpholine ring let it exhibit stronger pH-responsive NIR/PA imaging and photothermal effect in the lysosome acidic microenvironment (pH 4.0-5.5) than in the tumor acidic microenvironment. In the animal study, compound CR-630 could NIRF/PA image in the tumor tissues in 1.5-2.0 h, effectively inhibit the growth of the tumor, and even ablate the tumor at the drug dose of 1 mg/kg. It also demonstrated good biosafety. This study gives a new idea to develop water-solubility organic dyes with lysosome targeting, stronger pH-responsive NIRF/PA imaging and PTT for breast cancer.

Optically activated MEK1/2 inhibitors (Opti-MEKi) as potential antimelanoma agents.

Mitogen-activated protein kinase kinases 1/2 (MEK1/2) play critical roles in the canonical RAS/RAF/MEK/ERK pathway. Highly selective and potent non-ATP-competitive allosteric MEK1/2 inhibitors have been developed, and three of them were clinically approved for the treatment of BRAFV600 -mutant melanoma. However, the accompanying side effects of the systemically administered MEK1/2 drugs largely constrain their tolerable doses and efficacy. In this study, a series of mirdametinib-based optically activatable MEK1/2 inhibitors (opti-MEKi) were designed and synthesized. A structural-based design led to the discovery of photocaged compounds with dramatically diminished efficacy in vitro, whose activities can be spatiotemporally induced by short durations of irradiation of ultraviolet (365 nm) light. We demonstrated the robust photoactivation of MEK1/2 inhibition and antimelanoma activity in cultured human cells, as well as in a xenograft zebrafish model. Taken together, the modular approach presented herein provides a method for the optical control of MEK1/2 inhibitor activity, and these data support the further development of optically activatable agents for light-mediated antimelanoma phototherapy.

Metabonomic and transcriptomic analyses of Tripterygium glycosides tablet-induced hepatotoxicity in rats.

We aimed to explore novel biomarkers involved in alterations of metabolism and gene expression related to the hepatotoxic effects of Tripterygium glycosides tablet (TGT) in rats. Rats were randomly divided into groups based on oral administration of TGTs for 6 weeks: control, low-dose (9.5 mg/kg), and high-dose (18.9 mg/kg). Serum samples and total liver RNA were subjected to metabonomic and transcriptomic analyses. Thirteen metabolites were significantly up-regulated by liver injury induced by Tripterygium glycosides. Five potential biomarkers were more sensitive than Alanine aminotransferase (ALT) for accurate and timely prediction of hepatic damage. The four metabolic pathways most obviously regulated by hepatotoxicity were D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, ether lipid metabolism, and tryptophan metabolism. Transcriptomics revealed significant differences in 1792 mRNAs and 400 long non-coding (lnc) RNAs. Dysregulated lncRNAs in the TGT-induced hepatotoxicity group were associated with genes involved in amino acid metabolism using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Up-regulated expression of Ehhadh, Gpt, and Got1, and down-regulated expression of dopa decarboxylase (Ddc), Cyp1a2, Ido2, Aldh1b1, and asparagine synthetase (Asns) was validated by quantitative real-time PCR. This multiomics study has elucidated the relationship between amino metabolism and liver injury, revealing potential biomarkers.

Clinicopathologic characteristics, outcomes, and prognostic factors of angioimmunoblastic T-cell lymphoma in China.

BACKGROUND: This study aimed to better characterize the clinicopathologic characteristics, outcomes, and prognostic factors of AITL in China. METHODS: We retrospectively analyzed 312 patients with AITL enrolled between January 2011 and December 2020 from five institutions in China. RESULTS: The median age was 65 years, with 92.6% advanced stage, 59.7% elevated LDH, 46.1% anemia, and 44.0% hypergammaglobulinemia. The majority of patients (84.9%) received anthracycline-based regimens with or without etoposide, and only 6.1% underwent autologous stem cell transplantation following first remission. The 5-year OS and PFS estimates were 43.4% and 25.0% with no significant improvement of survival between patients treated during 2011-2015 and 2016-2020, respectively. Both the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT), were predictive for OS. In multivariate analysis, age >70 years, elevated LDH, and albumin level <35 g/L were independent prognostic factors for OS. Combining these three factors, a novel prognostic model (the Chinese AITL score) was constructed, which stratified patients into low-, intermediate-, and high-risk groups, with 5-year OS rates of 69.0%, 41.5%, and 23.7%, respectively. This new model was successfully validated in an independent cohort. CONCLUSIONS: Patients with AITL were mainly treated with anthracycline-based regimens, and the outcomes were still unsatisfactory in China. Our novel prognostic model may improve our ability to identify patients at different risks for alternative therapies.

Heterojunction structured BiOCl-Bi2S3 nanosheets as mitochondria-targeted near-infrared photothermal and photodynamic therapy agent.

Mitochondria-targeted phototherapy, especially combined photothermal therapy (PTT) and photodynamic therapy (PDT), has been regarded as an attractive strategy for the treatment of tumor. In this study, a facile approach to prepare two-dimensional (2D) BiOCl-Bi2S3 nanostructures was developed, where Bi2S3 quantum dots were doped in/on the ultrathin BiOCl nanosheets, forming a p-n heterojunction. The BiOCl-Bi2S3 shows favorable photothermal conversion efficiency (32%) and synergistically reactive oxygen species (ROS) generating capability under near-infrared (NIR) irradiation. Moreover, the conjugation of synthetic targeting ligand to the surface of BiOCl-Bi2S3 endows the heterojunction effective tumor targeting ability and selective mitochondrial accumulation. The combined cancer targeting ability and synergistic PTT/PDT permit enhanced cooperative phototherapeutic efficiency of the 2D heterojunction. This study provides an attractive way for designing new class of heterostructure materials for potential applications in subcellular-targeted phototherapy.

Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy.

BACKGROUND: Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy. METHODS: Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis. RESULTS: The median follow-up time is 34 months (IQR: 11-64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis. CONCLUSION: The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.

COVID-19 pandemic: study on simple, easy, and practical relaxation techniques while wearing medical protective equipment.

BACKGROUND: No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment. METHODS: This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance. RESULTS: Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6). CONCLUSION: Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.

TCDO: A Community-Based Ontology for Integrative Representation and Analysis of Traditional Chinese Drugs and Their Properties.

Traditional Chinese drugs (TCDs) have been widely used in clinical practice in China and many other regions for thousands of years. Nowadays TCD's bioactive ingredients and mechanisms of action are being identified. However, the lack of standardized terminologies or ontologies for the description of TCDs has hindered the interoperability and deep analysis of TCD knowledge and data. By aligning with the Basic Formal Ontology (BFO), an ISO-approved top-level ontology, we constructed a community-driven TCD ontology (TCDO) with the aim of supporting standardized TCD representation and integrated analysis. TCDO provides logical and textual definitions of TCDs, TCD categories, and the properties of TCDs (i.e., nature, flavor, toxicity, and channel tropism). More than 400 popular TCD decoction pieces (TCD-DPs) and Chinese medicinal materials (CMMs) are systematically represented. The logical TCD representation in TCDO supports computer-assisted reasoning and queries using tools such as Description Logic (DL) and SPARQL queries. Our statistical analysis of the knowledge represented in TCDO revealed scientific insights about TCDs. A total of 36 TCDs with medium or high toxicity are most densely distributed, primarily in Aconitum genus, Lamiids clade, and Fabids clade. TCD toxicity is mostly associated with the hot nature and pungent or bitter flavors and has liver, kidney, and spleen channel tropism. The three pairs of TCD flavor-nature associations (i.e., bitter-cold, pungent-warm, and sweet-neutral) were identified. The significance of these findings is discussed. TCDO has also been used to support the development of a web-based traditional Chinese medicine semantic annotation system that provides comprehensive annotation for individual TCDs. As a novel formal TCD ontology, TCDO lays out a strong foundation for more advanced TCD studies in the future.

Metabolic profiling in early pregnancy and associated factors of folate supplementation: A cross-sectional study.

BACKGROUND: Pregnancy generally alters the balance of maternal metabolism, but the molecular profiles in early pregnancy and associated factors of folate supplementation in pregnant women remains incompletely understood. METHODS: Untargeted metabonomics based on high-performance liquid chromatography-high-resolution mass spectrometry integrated with multivariate metabolic pathway analysis were applied to characterize metabolite profiles and associated factors of folate supplements in early pregnancy. The metabolic baseline of early pregnancy was determined by metabolic analysis of 510 serum samples from 131 non-pregnant and 379 pregnant healthy Chinese women. The pathophysiology of adaptive reactions and metabolic challenges induced by folate supplementation in early pregnancy was further compared between pregnant women with (n = 168) and without (n = 184) folate supplements. RESULTS: Compared with non-pregnant participants, 106 metabolites, majority of which are related to amino acids and lysophosphatidylcholine/phosphatidylcholine, and 13 metabolic pathways were significantly changed in early pregnancy. The supplementation of folate in early pregnancy induced marked changes in N-acyl ethanolamine 22:0, N-acyl taurine 18:2, glycerophosphoserine 44:1 and 8,11,14-eicosatrienoate, proline, and aminoimidazole ribotide levels. CONCLUSIONS: During early pregnancy, the metabolism of amino acids significantly changes to meet the physiological requirements of pregnant women. Folate intake may change glucose and lipid metabolism. These findings provide a comprehensive landscape for understanding the basic characteristics and gestational metabolic networks of early pregnancy and folate supplementation. This study provides a basis for further research into the relationship between metabolic markers and pregnancy diseases. TRIAL REGISTRATION: This study protocol was registered on www.ClinicalTrials.gov, NCT03651934, on August 29, 2018 (prior to recruitment).

Efficacy of an Yinyanghuo (Herba Epimedii Brevicornus)-Xianmao (Rhizoma Curculiginis) drug pair in a rat model of polycystic ovary syndrome.

OBJECTIVE: To identify active compounds in an Yinyanghuo (Herba Epimedii Brevicornus) - Xianmao (Rhizoma Curculiginis) drug pair (ECD) and investigate its efficacy on polycystic ovary syndrome (PCOS), and its possible mechanism in a rat model of PCOS. METHODS: A network pharmacology approach involving a characteristic drug assessment, active compound and target prediction, PCOS gene collection as well as network analysis was employed. The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target. RESULTS: Six networks were constructed, an active compound-target network for the ECD (C-T network), a drug-target network (D-T network), a related genes network, a targets interaction network, a key genes interaction network, and a gene-pathway network. A total of 41 compounds and 261 targets were identified for the ECD, 232 PCOS-related genes, 31 cogenes, and 14 pathways. These pathways may be involved in the efficacy of ECD on PCOS. The proteins most involved in the signal pathways for all targets were AKT1, IL6, INSR, ESR, and GSK3B. The AKT1 target was selected for experimental verification. Based on the Western blot and real-time PCR results, the expression of AKT1 in the PCOS model varied after treatment with ECD. CONCLUSIONS: Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS. AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.

AMFormulaS: an intelligent retrieval system for traditional Chinese medicine formulas.

BACKGROUND: Formula is an important means of traditional Chinese medicine (TCM) to treat diseases and has great research significance. There are many formula databases, but accessing rich information efficiently is difficult due to the small-scale data and lack of intelligent search engine. METHODS: We selected 38,000 formulas from a semi-structured database, and then segmented text, extracted information, and standardized terms. After that, we constructed a structured formula database based on ontology and an intelligent retrieval engine by calculating the weight of decoction pieces of formulas. RESULTS: The intelligent retrieval system named AMFormulaS (means Ancient and Modern Formula system) was constructed based on the structured database, ontology, and intelligent retrieval engine, so the retrieval and statistical analysis of formulas and decoction pieces were realized. CONCLUSIONS: AMFormulaS is a large-scale intelligent retrieval system which includes a mass of formula data, efficient information extraction system and search engine. AMFormulaS could provide users with efficient retrieval and comprehensive data support. At the same time, the statistical analysis of the system can enlighten scientific research ideas and support patent review as well as new drug research and development.

Labeled-protein corona-coated Bi2S3 nanorods targeted to lysosomes for bioimaging and efficient photothermal cancer therapy.

One of the main diseases contributing to human death are malignant tumors. Phototherapy is a promising approach for cancer therapy, and functional nanoparticles with targeting ligands are commonly used to improve the therapeutic efficiency. However, recent studies have shown that nanoparticles in contact with a biological fluid can rapidly form a "protein corona" on their surface, which will remarkably decrease the targeting ability. Here, we describe the preparation of hybrid nanomaterials with Bi2S3 nanorods as the core, and fluorescein-isothiocyanate and folic acid-modified human serum albumin (HSA-FITC-FA) as the shell. By using fluorescent binding label (FITC) and imaging techniques, we discovered the image of the cell lysosomes, indicating that the photothermal therapy agent was predominantly targeted to and accumulated in lysosomes. Combined with photothermal therapy agent (Bi2S3 nanorods) and targeting ligand (FA), the obtained product shows enhanced photothermal therapy under near-infrared region laser irradiation. Additionally, SDS-PAGE shows that the modified HSA shell could remarkably reduce the reabsorption of protein corona from blood serum, minimized the adverse effect of protein corona on targetability. Taken together, the results indicate that our strategy has the potential for preparing efficient photothermal nanomaterials with image-guided subcellular organelle-targeting cancer cell ablation ability.

Curcumin inhibits the formation of atherosclerosis in ApoE-/- mice by suppressing cytomegalovirus activity in endothelial cells.

BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2 µM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.

Characterization of drug-related problems and associated factors in ambulatory patients in China.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to investigate the prevalence and the type of drug-related problems (DRPs) in ambulatory patients and identify factors that may be associated with risk of DRPs. METHODS: Consecutive patients were enrolled from pharmacist outpatient clinics between January 2018 and June 2019. The pharmacists performed a comprehensive assessment of the patient's drug therapy. The DRPs and recommendations were evaluated using the DOCUMENT classification system. RESULTS AND DISCUSSION: The study population consisted of 248 patients with a mean age of 72.55 ± 6.29. The patients had a mean of 7.55 ± 4.72 ongoing medications during patients' routine clinic visits. A total of 1188 DRPs were identified during the study period. An average of 4.79 DRPs per patient was detected. Sixty-two different traditional Chinese patent medicines (TCPMs) contributed to 102 DRPs. Drug selection (24.9%) was the most common DRP followed by under treated (24.2%) and monitoring needed (24.2%). The number of medications taken was the significant factor for DRPs. Pharmacists made 1092 recommendations to address the DRPs (an average 0.92 recommendations per DRP). A change in therapy was the most common recommendation (43.6%), followed by the category 'monitoring' (28.6%). The overall acceptance rate of clinical pharmacist recommendations was 88.7%. More than a half (51.6%) of all interventions were assigned a moderate level of clinical significance. WHAT IS NEW AND CONCLUSION: Drug-related problems were commonly observed among ambulatory Chinese patients. Clinical pharmacists had a valuable role to play in identifying and solving the DRPs.

Vitamin D supplementation rescues simvastatin induced myopathy in mice via improving mitochondrial cristae shape.

Statin induced myopathy (SIM) is a main deleterious effect leading to the poor treatment compliance, while the preventive or therapeutic treatments are absent. Mounting evidences demonstrated that vitamin D plays a vital role in muscle as a direct modulator. The deficiency of vitamin D was considered as a cause of muscle dysfunction, whereas the supplementation resulted in a remission. However, there is no causal proof that vitamin D supplementation rescues SIM. Here, using the mice model of simvastatin-induced myopathy, we investigated the role of vitamin D supplementation and the mechanisms associated with mitochondria. Results indicated that simvastatin administration (80 mg/kg) impaired skeletal muscle with the increased serum creatine kinase (CK) level and the declined grip strength, which were alleviated by vitamin D supplementation. Moreover, vitamin D supplementation rescued the energy metabolism dysfunction in simvastatin-treated mice gastrocnemius by reducing the abnormal aggregation of muscular glycogen and lactic acid. Mitochondrial homeostasis plays a key role in the process of energy metabolism. Thus, the mitochondrial dysfunction is a mortal damage for the highly energy-requiring tissue. In our study, the mitochondrial cristae observed under transmission electron microscope (TEM) were lytic in simvastatin-treated gastrocnemius. Interestingly, vitamin D supplementation improved the mitochondrial cristae shape by regulating the expression of mitofusin-1/2 (MFN1/2), optic atrophy 1 (OPA1) and dynamin-related protein 1 (Drp1). As expected, the mitochondrial dysfunction and oxidative stress was mitigated by vitamin D supplementation. In conclusion, these findings suggested that moderate vitamin D supplementation rescued simvastatin induced myopathy via improving the mitochondrial cristae shape and function.

Systems Pharmacology Uncovers Multiple Mechanisms of Erxian Decoction () for Treatment of Premature Ovarian Failure.

OBJECTIVE: To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction (, EXD) as a treatment for premature ovarian failure (POF) using a systems pharmacology approach. METHODS: The compounds present in EXD were obtained from three databases. The active ingredient was identified by analyzing the values of oral bioavailability (OB), drug-likeness (DL), and Lipinski's rule (LR). The active ingredients were further searched in research articles, drug targets in the DrugBank database, and the C-T and T-P networks, as well as by pathway analysis using the Cytoscape platform. RESULTS: A total of 728 compounds were identified in EXD. Of these, 59 were identified as active compounds that conformed to the criteria with OB ⩾30% and DL ⩾0.18. By further searches in the literature, 126 related targets were identified that could interact with the active compounds. Additionally, it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immune system, modulation of estrogen levels, and anti-oxidative activities, and that it may act in a synergistic or cooperative manner with other therapeutic agents. CONCLUSIONS: The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF. The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.

An ontological framework for the formalization, organization and usage of TCM-Knowledge.

BACKGROUND: The traditional Chinese Medicine Language System (TCMLS) is a large-scale terminology system, developed from 2002 on by the Institute of Information of Traditional Chinese Medicine (IITCM). Until now, more than 120,000 concepts, 300,000 terms and 1.27 million semantic relational links are included. Its top-level framework, called TCMLS-semantic network (SN), provides an important basis for the standardization and mapping of traditional Chinese Medicine (TCM) terminology systems. Though, many data produced and stored in TCMLS have poor quality for historical reasons or because of human factors. There is a large number of classification errors or inconsistent expressions of terms remained in the current TCMLS- SN, which hamper an efficient utilization of the data stored in TCMLS in practical applications. METHODS: We start with analyzing the technical specification based on TCMLS, considering some obvious classification errors and problems of ambiguity of semantic expressions in TCMLS-SN, followed with using a top-down approach for building a middle level ontology which is based on the framework General Formal Ontology (GFO), take into account the compatibility with TCM related concepts, turn out the results of a modification of the current TCMLS-SN, called GFO-TCM. RESULTS: Through comparison with TCMLS-SN, according to viewpoints of GFO, some semantic types and relations were reconstructed within GFO-TCM. We propose a middle level ontology for TCMLS which may support entailment and ensure coherence, we also draw out a mapping which possess a more reasonable framework with a unified semantic criterion, it is application scenarios oriented and can be further updated and extended. CONCLUSIONS: The goal is to construct a formal middle-level ontology that is compatible with both the traditional medical terminology system and modern medical terminology standards. it is intended to satisfy functional requirements which are relevant for natural language processing, information extraction, semantic retrieval, clinical decision support in the field of traditional Chinese medicine. It also provides a foundation and methodology for building a large-scale, unified semantic and extensible knowledge graph platform.