The Influence of CD40/CD40L, MMP2/MMP9 on Uterine Artery Blood Flow and Their Expression in Recurrent Miscarriage.

Objective: This study aims to investigate the expression levels of soluble CD40L (sCD40L), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in the serum of patients experiencing recurrent abortion and their impact on uterine artery blood flow. Methods: A cohort of 200 patients with recurrent abortion was selected for this investigation. The levels of sCD40L, MMP2, and MMP9 in serum were assessed using ELISA, while ultrasound was employed to measure the pulsatility index (PI) and resistance index (RI) in uterine artery blood flow. Pregnancy outcomes were observed, and the expression of CD40/CD40L and MMP2/MMP9 in villi tissues was compared between patients experiencing recurrent abortion failure and those with normal pregnancies. Results: In the successful pregnancy group of patients with recurrent spontaneous abortion (RSA), serum levels of sCD40L, MMP2, and MMP9 were significantly lower than those in the failed pregnancy group. Additionally, both RI and PI were notably reduced. The expression of each gene showed a correlation with RI and PI. Furthermore, the expression levels of CD40, CD40L, MMP2, and MMP9 in the pregnancy failure group were significantly higher than in the normal voluntary termination group. Conclusion: Serum levels of sCD40L, MMP2, and MMP9, along with non-invasive and easily accessible indicators such as PI and RI in uterine artery blood flow measured by ultrasound, emerge as potential predictive markers for the outcome of recurrent miscarriage pregnancies. Moreover, these indicators can serve as valuable evaluation markers in clinical practice, facilitating the monitoring of treatment effectiveness for recurrent miscarriage.

Precision cardiac targeting: empowering curcumin therapy through smart exosome-mediated drug delivery in myocardial infarction.

Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.

Mechanistic study of electroacupuncture preconditioning in alleviating myocardial ischemia-reperfusion injury in rats: involvement of mTOR/ROS signaling pathway to inhibit ferroptosis.

PURPOSE: The objective of this study was to investigate the mechanism of electroacupuncture pretreatment in reducing myocardial ischemia-reperfusion injury in rats. MATERIALS AND METHODS: The comparison of HR among the different groups did not yield statistically significant differences (p > 0.05). Additionally, the trend of HR change at different time points within each group was not statistically significant (p > 0.05). In contrast, the comparison of SBP among the different groups showed statistically significant differences (p < 0.05). Furthermore, the trend of SBP change at different time points within each group exhibited significant differences (p < 0.05). RESULTS: Compared to the Sham group, rats in the I/R group and EA control group showed a significant decrease in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and an increase in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). Compared to EA control group, rats in the EA group exhibited a significant increase in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and a decrease in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). Compared to the EA group, rats in the EA + RAP group showed a significant decrease in EF, FS, SOD, p-mTOR/mTOR, GPX4, and FTH1, and an increase in CK-MB, cTnI, LDH, iron, ROS, MDA, ACSL4, and NCOA4 (p < 0.05). CONCLUSIONS: Electroacupuncture preconditioning confers protective effects against myocardial ischemia-reperfusion injury in rats. Its mechanism may involve the activation of the mTOR/ROS signaling pathway by electroacupuncture to inhibit ferroptosis.

Advances in the study of vascular related protective effect of garlic (Allium sativum) extract and compounds.

Garlic (Allium sativum) is a functional food containing multiple bioactive compounds that find widespread applications in culinary and medicinal practices. It consists of multiple chemical components, including allicin and alliin. This article offers a comprehensive review of the protective effects of garlic extracts and their active constituents on the vascular system. In vitro and in vivo experiments have shown that garlic extracts and their active ingredients possess various bioactive properties. These substances demonstrate beneficial effects on blood vessels by demonstrating anti-inflammatory and antioxidant activities, inhibiting lipid accumulation and migration, preventing lipid peroxidation, promoting angiogenesis, reducing platelet aggregation, enhancing endothelial function, and inhibiting endothelial cell apoptosis. In clinical studies, garlic and its extracts have demonstrated their efficacy in managing vascular system diseases, including atherosclerosis, diabetes, and high cholesterol levels. In summary, these studies highlight the potential therapeutic roles and underlying mechanisms of garlic and its constituents in managing conditions like diabetes, atherosclerosis, ischemic diseases, and other vascular disorders.

L-carnitine alleviates synovitis in knee osteoarthritis by regulating lipid accumulation and mitochondrial function through the AMPK-ACC-CPT1 signaling pathway.

BACKGROUND: Knee osteoarthritis (KOA) is a disability-associated condition that is rapidly growing with the increase in obesity rates worldwide. There is a pressing need for precise management and timely intervention in the development of KOA. L-carnitine has been frequently recommended as a supplement to increase physical activity in obese individuals due to its role in fatty acid metabolism, immune disorders, and in maintaining the mitochondrial acetyl-CoA/CoA ratio. In this study, we aimed to investigate the anti-inflammatory effects of L-carnitine on KOA and delineate a potential molecular mechanism. METHODS: Lipopolysaccharide-stimulated primary rat fibroblast-like synoviocytes (FLS) were treated with an AMP-activated protein kinase (AMPK) inhibitor or siRNA and carnitine palmitoyltransferase 1 (CPT1) siRNA to examine the synovial protective effects of L-carnitine. An anterior cruciate ligament transection model of rats was treated with an AMPK agonist (metformin) and CPT1 inhibitor (etomoxir) to define the therapeutic effects of L-carnitine. RESULTS: L-carnitine displayed a protective effect against synovitis of KOA in vitro and in vivo experiments. Specifically, L-carnitine treatment can reduce synovitis by inhibiting AMPK-ACC-CPT1 pathway activation and showed an increase in fatty acid ß-oxidation, a lower lipid accumulation, and a noticeable improvement in mitochondrial function. CONCLUSIONS: Our data suggested that L-carnitine can mitigate synovitis in FLS and synovial tissue, and the underlying mechanism may be related to improving mitochondrial function and reducing lipid accumulation via the AMPK-ACC-CPT1 signaling pathway. Therefore, L-carnitine may be a potential treatment strategy for KOA.

Neuroprotective effects of PRG on Aß25-35-induced cytotoxicity through activation of the ERK1/2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Phylloporia ribis (Schumach:Fr.)Ryvarden is a genus of needle Phellinus medicinal fungi, parasitic on the living rhizomes of hawthorn and pear trees. As a traditional Chinese medicine, Phylloporia ribis was used in folklore for long-term illness, weakness and memory loss in old age. Previous studies have shown that polysaccharides from Phylloporia ribis (PRG) significantly promoted synaptic growth in PC12 cells in a dose-dependent manner, exhibiting "NGF"-like neurotrophic activity. Aß25-35 damage to PC12 cells produced neurotoxicity and decreased cell survival, and PRG reduced the apoptosis rate, suggesting that PRG has neuroprotective effects. The studies confirmed that PRG had the potential to be a neuroprotective agent, but its neuroprotective mechanism remained unclear. AIM OF THE STUDY: We aimed to elucidate the neuroprotective effects of PRG in an Aß25-35-induced Alzheimer's disease (AD) model. MATERIALS AND METHODS: Highly-differentiated PC12 cells were treated with Aß25-35 (AD model) and PRG, and were assessed for cellular apoptosis, inflammatory factors, oxidative stress, and kinase phosphorylation. RESULTS: The results showed that the PRG groups effectively inhibited the neurotoxicity, mainly manifested by inhibiting mitochondrial oxidative stress, attenuating neuroinflammatory responses, and improving mitochondrial energy metabolism, eventually resulting in higher cell survival. The expression of p-ERK, p-CREB and BDNF proteins was increased in the PRG groups compared to the model group, which confirmed that PRG reversed the inhibition of the ERK pathway. CONCLUSION: We provide evidence for neuroprotection conferred by PRG and its mechanism by inhibiting ERK1/2 hyper-phosphorylation, prevention of mitochondrial stress, and subsequent prevention of apoptosis. The study highlights PRG as a promising candidate with neuroprotective effects, the potential of which can be harnessed for identifying novel therapeutic targets.

ß-diversity in temperate grasslands is driven by stronger environmental filtering of plant species with large genomes.

Elucidating mechanisms underlying community assembly and biodiversity patterns is central to ecology and evolution. Genome size (GS) has long been hypothesized to potentially affect species' capacity to tolerate environmental stress and might therefore help drive community assembly. However, its role in driving ß-diversity (i.e., spatial variability in species composition) remains unclear. We measured GS for 161 plant species and community composition across 52 sites spanning a 3200-km transect in the temperate grasslands of China. By correlating the turnover of species composition with environmental dissimilarity, we found that resource filtering (i.e., environmental dissimilarity that includes precipitation, and soil nitrogen and phosphorus concentrations) affected ß-diversity patterns of large-GS species more than small-GS species. By contrast, geographical distance explained more variation of ß-diversity for small-GS than for large-GS species. In a 10-year experiment manipulating levels of water, nitrogen, and phosphorus, adding resources increased plant biomass in species with large GS, suggesting that large-GS species are more sensitive to the changes in resource availability. These findings highlight the role of GS in driving community assembly and predicting species responses to global change.

Higher blood selenium level is associated with lower risk of hyperhomocysteinemia in the elderly.

BACKGROUND AND AIMS: Earlier studies have reported inconsistent association between selenium (Se) and homocysteine (Hcy) levels, while no evidence could be found from Chinese population. To fill this gap, we investigated the association between blood Se and hyperhomocysteinemia (HHcy) of rural elderly population in China. METHODS: A cross-sectional study on 1823 participants aged 65 and older from four Chinese rural counties was carried out in this study. Whole blood Se and serum Hcy concentrations were measured in fasting blood samples. Analysis of covariance and restricted cubic spline models were used to examine the association between Se and Hcy levels. Logistic regression models were used to evaluate the risk of prevalent HHcy among four Se quartile groups after adjusting for covariates. RESULTS: For this sample, the mean blood Se concentration was 156.34 (74.65) µg/L and the mean serum Hcy concentration was 17.25 (8.42) µmol/L. A significant non-linear relationship was found between blood Se and serum Hcy, the association was inverse when blood Se was less than 97.404 µg/L and greater than 156.919 µg/L. Participants in the top three blood Se quartile groups had significantly lower risk of prevalent HHcy compared with the lowest quartile group. When defined as Hcy> 10 µmol/L, the odds ratios and 95% confidence interval of HHcy were 0.600 (0.390, 0.924), 0.616 (0.398, 0.951) and 0.479 (0.314, 0.732) for Q2, Q3, and Q4 Se quartile groups compared with the Q1 group, respectively. When defined as Hcy≥ 15 µmol/L, the odds ratios and 95% confidence interval of HHcy were 0.833 (0.633, 1.098) and 0.827 (0.626, 1.092), 0.647 (0.489, 0.857) for Q2, Q3, and Q4 Se quartile groups compared with Q1 group. CONCLUSIONS: Our findings suggest that higher blood Se level could be a protective factor for HHcy in the elderly.

Building Flexible Escherichia coli Modules for Bifunctionalizing n-Octanol: The Byproduct of Oleic Acid Biorefinery.

Artificial biorefinery of oleic acid into 1,10-decanedioic acid represents a revolutionizing route to the sustainable production of chemically difficult-to-make bifunctional chemicals. However, the carbon atom economy is extremely low (56%) due to the formation of unifunctional n-octanol. Here, we report a panel of recombinant Escherichia coli modules for diverse bifunctionalization, where the desired genetic parts are well distributed into different modules that can be flexibly combined in a plug-and-play manner. The designed ω-functionalizing modules could achieve ω-hydroxylation, consecutive ω-oxidation, or ω-amination of n-octanoic acid. By integrating these advanced modules with the reported oleic acid-cleaving modules, high-value C8 and C10 products, including ω-hydroxy acid, ω-amino acid, and α,ω-dicarboxylic acid, were produced with 100% carbon atom economy. These ω-functionalizing modules enabled the complete use of all of the carbon atoms from oleic acid (released from plant oil) for the green synthesis of structurally diverse bifunctional chemicals.

[Application and progress of data mining in study of compatibility law of traditional Chinese medicine].

Data mining is an important method to obtain the key information from a large amount of data, and it is widely applied in the research on the modernization of traditional Chinese medicine(TCM). The compatibility law of herbs is a key issue in the research of TCM prescriptions. This reflects the flexibility and effectiveness of TCM prescriptions, and it is also a crucial link to the development of TCM modernization. Therefore, it is the core purpose of the research on TCM prescriptions to find the compatibility law of herbs and clarify the scientific connotation. Data mining, as an effective method and an important approach, has formed a standardized system in the research of compatibility law of herbs, which can reveal the relationship between different Chinese herbs and summarize the internal rules in compatibility. Two hundred and twenty two effective papers were sorted out and categorized in this article. The results showed that data mining was mainly applied in finding the core Chinese herb pairs, summarizing the utility and attributes of TCM prescriptions, revealing the relationship between prescriptions, Chinese herbs and syndromes, finding the optimal dose of Chinese herbs, and producing the new prescriptions. The problems of data mining in research of herbs compatibility rules were summarized, and its development and trend in current researches were discussed in this article to provide useful references for the in-depth study of data mining in the compatibility law of Chinese herbs.

Interventional Efects of the Topical of "Sanse Powder" Essential Oils Nanoemulsion on Knee Osteoarthritis in Rats by Targeting the ERS/TXNIP/NLRP3 Signaling Axis.

Purpose: Our recent research is dedicated to finding effective drugs for the treatment of knee osteoarthritis (KOA) from traditional Chinese medicine and trying to make full use of modern science and technology to uncover the mechanisms and targets behind them. Synovial inflammation is one of the key pathological features of KOA, and a growing number of researchers realize that early intervention of synovial inflammation may be able to reverse disease progression. The close association of traditional natural products with modern nanotechnology may be important for improving the anti-synovitis efficacy. The purpose of our research was to explore the anti-synovitis mechanism of NEs-SP-EO that might be associated with the ERS/TXNIP/NLRP3 signalling axis. Methods: Chemical composition of "Sanse Powder" essential oil (SP-EO) and NEs-SP-EO were analyzed by GC-MS. NEs-SP-EO were prepared and characterized by nanoparticle tracking analysis, polydispersity index (PDI), zeta potential (ZP), ultraviolet-visible spectroscopy, and transmission electronic microscopy. The CCK8 assay for cell viability of NEs-SP-EO was performed on fibroblast-like synovial cells (FLSs) and the inflammatory environment was stimulated by LPS to explore the therapeutic mechanisms in vitro. Experiments of NEs-SP-EO in vivo were performed in male SD rats. Results: The GC-MS results showed that 30 compounds were present in SP-EO and 11 components of NEs-SP-EO were identified. The results also showed that the formulation of NEs-SP-EO exhibited suitable particle size, negative charge, and stable system. In vitro and vivo testing, NEs-SP-EO produced anti-synovitis efficacy by reduced the induction of the ERS/TXNIP/NLRP3 signaling axis as well as regulating the overproduction of IL-1ß, IL-18. Conclusion: We have developed a new type of essential oil nanoemulsion from "Sanse Powder" and demonstrated that it can managing synovitis of KOA. Besides, we have initially explored the anti-inflammatory mechanism that may be related to the ERS/TXNIP/NLRP3 signaling axis.

RBC-derived nanosystem with enhanced ferroptosis triggered by oxygen-boosted phototherapy for synergized tumor treatment.

Photodynamic and ferroptosis therapies for cancer treatment are restricted by the scarcity of oxygen and Fe in cancer cells, and the complicated structure of delivery systems. Herein, a red blood cell-derived vehicle (RDV) inherently enriched with hemoglobin co-delivers a photosensitizer, Ce6, and a ferroptosis promoter, sorafenib (SRF) into cancer cells for boosting oxygen and providing iron, which leads to enhanced PDT and stronger ferroptosis therapy. Damage to the RDV membrane under local irradation leads to SRF release at the tumor site for tumor-targeted therapy. The lipid membrane of the RDV could also improve the drug delivery efficiency in vitro and in vivo. The novel nanosystem exhibited enhanced tumor killing efficacy and improved safety compared with traditional PDT and ferroptosis therapy.

Application of an extreme learning machine network with particle swarm optimization in syndrome classification of primary liver cancer.

OBJECTIVE: By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes. METHODS: From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used "TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information" as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models. RESULTS: The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%. CONCLUSION: Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system.

Objectives: Integrins, the coordinator of extracellular and intracellular signaling, are often found to be aberrant in tumors and can reshape the tumor microenvironment. Although previous studies showed that integrin beta 2 (ITGB2) is important for host defense, its expression profile and role in tumors, especially in cancer associated fibroblasts (CAFs) are still unknown. Methods: Immunofluorescence stain and fluorescence activated cell sorting were used to analyze the ITGB2 expression profile in oral squamous cell carcinoma (OSCC). RT-PCR and western blot were used to compare ITGB2 expression in normal fibroblasts (NFs) and cancer associated fibroblasts (CAFs). Clinical data and function-based experiments were used to investigate the promoting tumor growth ability of ITGB2 expressing CAFs. Enhanced glycolysis activity was identified by using bioinformatics analyses and GC/MS assays. MCT1 knockdown OSCC cell lines were constructed to explore the pro-proliferative mechanisms of ITGB2 expressing CAFs in multiple in vitro and in vivo assays. Results: We found that CAFs exhibited significantly higher ITGB2 expression than the matched NFs. In addition, higher ITGB2 expression in CAFs was correlated with higher TNM stages and more Ki67+ tumor cells, indicating its ability to promote OSCC proliferation. Further, co-culture assay demonstrated that ITGB2-mediated lactate release in CAFs promoted OSCC cell proliferation. Mechanically, ITGB2 regulated PI3K/AKT/mTOR pathways to enhance glycolysis activity in CAFs. Accordingly, lactate derived from ITGB2-expressing CAFs was absorbed and metabolized in OSCC to generate NADH, which was then oxidized in the mitochondrial oxidative phosphorylation system (OXPHOS) to produce ATP. Notably, inhibiting the OXPHOS system with metformin delayed the proliferative capacity of OSCC cells cultured in the ITGB2-expressing CAFs medium. Conclusions: Our study uncovered the ITGB2high pro-tumoral CAFs that activated the PI3K/AKT/mTOR axis to promote tumor proliferation in OSCC by NADH oxidation in the mitochondrial oxidative phosphorylation system.

Chrysin Attenuates the NLRP3 Inflammasome Cascade to Reduce Synovitis and Pain in KOA Rats.

PURPOSE: Our recent reports have revealed that inhibiting NLRP3 activation reduces synovial inflammation and fibrosis in knee osteoarthritis (KOA). Synovial inflammation is involved the entire process of KOA and promotes the progression of KOA. Natural flavonoid Chrysin from Scutellariae Radix, a traditional Chinese medicine, exhibits multifarious biological activities and potentially has protective activity against osteoarthritis. However, the mechanism of Chrysin in the treatment of synovial inflammation remains elusive. The purpose of our research was to explore the anti-inflammatory effects of Chrysin on KOA, which was induced by monoiodoacetic acid (MIA) in rats by targeting the NLRP3 inflammasome in the hopes of identifying an effective drug to treat KOA. METHODS: The MIA-induced KOA model was used to evaluate the cold pain threshold and paw withdrawal threshold (PWT) of joints after MIA (40 mg/mL) injection into the knee joints. Microscopically, we used LPS (5 ug/mL) and ATP (4 mmol/L) to stimulate fibroblast-like synovial cells (FLSs) to explore the underlying mechanisms and effects of Chrysin. Two staining methods, H&E and Sirius Red, were applied to assess histopathological changes in synovial membranes. Cellular signal transduction was determined by qRT-PCR and WB. Cytokine expression (inflammatory cytokines and pain-related cytokines) was detected by ELISA. The degree of chronic inflammatory pain was evaluated by c-Fos immunofluorescence. RESULTS: The results showed that Chrysin not only attenuated synovial inflammation but also reduced the secretion of pain-related factors and increased the PWT and cold pain threshold in rats. Chrysin also inhibited NLRP3 inflammasome activation and increased IL-1ß levels to alleviate the synovitis. CONCLUSION: Chrysin can relieve knee synovial inflammation and improve pain behavior in KOA rats, which may be related to the ability of Chrysin to inhibit NLRP3 inflammasome activation. Therefore, Chrysin may be developed as a new drug for the treatment of KOA.

Network Pharmacology Approach to Uncover the Mechanism Governing the Effect of Radix Achyranthis Bidentatae on Osteoarthritis.

BACKGROUND: This study used a network pharmacology approach to elucidate the molecular mechanism governing the effect of Radix Achyranthis Bidentatae (RAB) on osteoarthritis (OA). METHODS: Based on oral bioavailability and drug-likeness, the main active components of RAB were screened via the Traditional Chinese Medicine Systems Pharmacology platform. The GeneCard, OMIM, PharmGkb, Therapeutic Targets database, and DrugBank database were used to establish a database of osteoarthritis targets. The interactive active network map of "ingredient-target" was constructed with Cytoscape software (Version 3.7.1). The protein-protein interaction network was constructed with the STRING database, and the related protein interaction relationship was analysed. GO biological function analysis and KEGG enrichment analysis for core targets were performed. Finally, docking of the active components with the core target was carried out. RESULTS: Sixteen active components of RAB were obtained, and 63 potential targets for OA were identified. Network analysis results indicate that these targets are primarily involved in regulating biological processes, such as cell metabolism, apoptosis, and cell proliferation. Pathways involved in the treatment of osteoarthritis include virus-related signalling pathways, apoptosis signalling pathways, IL-17 signalling pathways, and PI3K/AKT signalling pathways. CONCLUSION: RAB has the characteristics of being multi-system, multi-component and multi-target. Possible mechanisms of action for RAB include regulating the immune and inflammatory responses, reducing chondrocyte apoptosis, and protecting the joint synovial membrane and cartilage to control disease development. The active ingredients in RAB, such as sterols and flavonoids, exhibit strong potential as candidate drugs for the treatment of osteoarthritis.

Electroacupuncture preconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated by the mTORC1-ULK1-FUNDC1 pathway.

Myocardial ischemia/reperfusion (I/R) is an important complication of reperfusion therapy for myocardial infarction, and trimetazidine is used successfully for treatment of ischemic cardiomyopathy by regulating mitochondrial function. Moreover, electroacupuncture (EA) preconditioning was demonstrated to be cardioprotective in both in vivo rodent models and in patients undergoing heart valve replacement surgery. However, the mechanisms have not been well elucidated. Mitophagy, mediated by the mTORC1-ULK1-FUNDC1 (mTOR complex 1-unc-51-like autophagy-activating kinase 1-FUN14 domain-containing 1) pathway, can regulate mitochondrial mass and cell survival effectively to restrain the development of myocardial ischemia/reperfusion injury (MIRI). In this study, we hypothesized that EA preconditioning ameliorated MIRI via mitophagy. To test this, rapamycin, an mTOR inhibitor, was used. The results showed that EA preconditioning could reduce the infarct size and risk size, and decrease the ventricular arrhythmia score and serum creatine kinase-myocardial band isoenzyme (CK-MB), lactate dehydrogenase (LDH), and cardiac troponin T (cTnT) in MIRI rats. Moreover, it also attenuated MIRI-induced apoptosis and mitophagy accompanied by elevated mTORC1 level and decreased ULK1 and FUNDC1 levels. However, these effects of EA preconditioning were blocked by rapamycin, which aggravated MIRI, reduced adenosine triphosphate (ATP) production, and antagonized infarct size reduction. In conclusion, our results indicated that EA preconditioning protected the myocardium against I/R injury by inhibiting mitophagy mediated by the mTORC1-ULK1-FUNDC1 pathway.

Amino acids signatures of distance-related surgical margins of oral squamous cell carcinoma.

BACKGROUND: Histological assessment of resected margins has some drawbacks. We therefore aimed to identify a panel of metabolic markers for evaluating the surgical margins of oral squamous cell carcinoma during surgery. METHODS: A total of 28 case of OSCC samples were enrolled in the study. Gas chromatography-mass spectrometry based untargeted metabolic analysis was employed to acquire the metabolic perturbation of the distance-related surgical margins in the development group. The acquired MS data were then subjected to univariate and multivariate analysis by MetaboAnalyst. Ultra-high performance liquid chromatography-tandem mass spectrometerbased targeted metabolomics for quantitative analysis of the validation group was performed to verify the results of the development group. Another 60 OSCC patients with dysplastic surgical margins were used to further validate the results of the development group by immunohistochemical examination of key enzyme expression, and correlate them with clinicopathological parameters and clinical outcomes. FINDINGS: We finally identified 4 amino acids as negative margin markers, and 6 amino acids as dysplastic margin markers. IHC analysis showed that asparagine synthetase positive expression in dysplastic surgical margins and its higher expression was correlated with tumor recurrence and local relapse-free survival. INTERPRETATIONS: We developed a panel of metabolic molecular markers to supplement the evaluation of negative and dysplastic margins. FUND: This study was supported by Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012); Center of Nanjing Clinical Medicine Tumor (Since 2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

[Progress of Acupuncture and Moxibustion Research on the Signal Transduction Pathways Involved in Cell Apoptosis in Myocardial Ischemia Reperfusion Injury].

Myocardial cell apoptosis is very common in the clinic, and is caused by myocardial ischemia reperfusion injury (MIRI). There are different degrees of cell apoptosis in MIRI. However, initiation of the signal transduction mechanism of myocardial cell apoptosis is unclear. The present research confirmed that acupuncture and moxibustion are effective interventions for cell apoptosis in MIRI through three approaches:the death receptor pathway, mitochondrial pathway and endoplasmic reticulum pathway. In this paper, the authors summarize the mechanism characteristics of acupuncture and moxibustion in MIRI cell apoptosis, and discuss the signal transduction pathways involved in the effects of acupuncture and moxibustion in MIRI cell apoptosis, in order to provide new ideas and evidence for the clinical application of acupuncture and moxibustion to prevent cell apoptosis in MIRI.

[Grain-Moxibustion may Protect Myocardium by Reducing Oxidative Stress in Doxorubicin-induced Cardiomyopathy Rats].

OBJECTIVE: To observe the effectiveness of grain-moxibustion in resisting oxidative stress in doxorubicin (DOX)-induced cardiomyopathy rats. METHODS: Sixty Sprague-Dawley (SD) rats were randomly divided into blank control group (blank group), cardiomyopathy model (model) group and grain-moxibustion (moxibustion) group, with 20 rats in each one. The cardiomyopathy model was established by intraperitoneal injection of DOX (0.5 mg/100 g), once a week for 4 weeks. Grain-moxibustion was applied to "Guanyuan" (CV 4) and "Juque" (CV 14) for 5 cones, once daily for 4 weeks except the Sundays. The rats' heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular pressure maximum rising rate (+dp/dtmax), left ventricular pressure maximum decline rate (-dp/dtmax), left ventricular pressure change time (t-dp/dtmax) were detected to evaluate the cardiac function by using a physiological signal acquisition-analysis system. The pathological changes of the myocardium were observed by optical microscopy after H.E. staining. The activity of serum lactate dehydrogenase(LDH), creatine kinase(CK) and myocardial superoxide dismutase (SOD), and myocardial malondialdehyde (MDA) and serum cardiac troponin Ⅰ(cTnⅠ) contents were assayed by enzyme-linked immuno sorbent assay kit (ELISA). RESULTS: Following modeling, the HR, LVSP, +dp/dtmax, -dp/dtmax, and myocardial SOD activity were significantly down-regulated (P<0.05, P<0.01), while the LVDP, t-dp/dtmax, serum LDH and CK activity and cTnⅠ content, as well as myocardial MDA content were considerably increased in comparison with the blank group (P<0.05, P<0.01). After moxibustion intervention, the decreased HR, LVSP, +dp/dtmax, -dp/dtmax, and myocardial SOD activity levels and the increased LVDP, t-dp/dtmax, serum LDH and CK activity and cTnⅠ content, as well as myocardial MDA content were remarkably suppressed in comparison with the model group (P<0.05, P<0.01). CONCLUSIONS: Grain-moxibustion can significantly improve the left ventricular function, increase heart rate in cardiomyopathy rats, which may be associated with its effects in reducing myocardial oxidative stress damage by down-regulating the content of MDA and up-regulating SOD activity in the heart.