TRPV3 regulates Breast Cancer Cell Proliferation and Apoptosis by EGFR/AKT pathway.

Breast cancer (BC) is one of the most common cancer types worldwide and the first cause of cancer-related deaths in women. Transient receptor potential vanillin 3 (TRPV3) has been preliminarily discovered to play an important role in various cancers, including BC. Here, we explored the effect of TRPV3 on breast cancer cells and its potential mechanism. TRPV3 level was measured in BC tissue and adjacent noncancerous breast tissue using real-time RT-PCR and Western blot. Wound healing was used to detect cell migration. MTT and EDU were detected cell proliferation. TUNEL and Caspase-3 activity were used to detect cell apoptosis. We found that TRPV3 expression significantly increased in both human BC tissues and breast cells line. TRPV3 siRNA (TRPV3 inhibition) dramatically suppressed cell migration and proliferation, promoted the apoptosis, and decreased [Ca2+]i; whereas Carvacrol (TRPV3 agonist) has opposite effect in MCF-7 cells. We validated EGFR (Epidermal growth factor receptor) is a direct target protein of TRPV3. Mechanism studies have shown that Carvacrol increased phosphorylation levels of EGFR and AKT, and were decreased by suppression of TRPV3. Moreover, Erlotinib (EGFR inhibitor) and LY294002 (PI3K inhibitor) diminished Carvacrol induced cell migration and proliferation, promoted cell apoptosis, and increased [Ca2+]i in Carvacrol group. Our results collectively suggest that TRPV3 siRNA inhibits migration and proliferation, and promoted apoptosis in breast cancer cells by EGFR/AKT pathway. These findings indicate that TRPV3 may represent a novel therapeutic strategy for breast cancer.

Undescribed matrine-type alkaloids from Sophora alopecuroides with anti-inflammatory activity.

A phytochemical investigation on the alkaloid fractions of Sophora alopecuroides L. led to the production of 11 undescribed matrine-type alkaloids, sophaloseedlines I-S (1-11), 12 known analogs (12-23), and an unexpected artificial matrine-derived Al(III) complex (24). The corresponding structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and six instances (1-4, 18, and 24), verified by X-ray crystallography. The biological activities screening demonstrated that none of the isolates exhibited cytotoxicity against four human cancer cell lines (HepG2, A549, THP-1, and MCF-7) and respiratory syncytial virus (RSV) at 50 µM, while moderate anti-inflammatory activity with IC50 value from 15.6 to 47.8 µM was observed. The key structure-activity relationships of those matrine-type alkaloids for anti-inflammatory effects have been summarized. In addition, the most potent 7-epi-sophoramine (19) and aluminum sophaloseedline T (24) could effectively inhibit the release of pro-inflammatory factors (TNF-α, IL-6, and IL-1ß), as well as the expression of iNOS and COX-2 proteins.

A novel lncRNA-mediated epigenetic regulatory mechanism in periodontitis.

Periodontitis is a highly prevalent chronic inflammatory disease with an exaggerated host immune response, resulting in periodontal tissue destruction and potential tooth loss. The long non-coding RNA, LncR-ANRIL, located on human chromosome 9p21, is recognized as a genetic risk factor for various conditions, including atherosclerosis, periodontitis, diabetes, and cancer. LncR-APDC is an ortholog of ANRIL located on mouse genome chr4. This study aims to comprehend the regulatory role of lncR-APDC in periodontitis progression. Our experimental findings, obtained from lncR-APDC gene knockout (KO) mice with induced experimental periodontitis (EP), revealed exacerbated bone loss and disrupted pro-inflammatory cytokine regulation. Downregulation of osteogenic differentiation occurred in bone marrow stem cells harvested from lncR-APDC-KO mice. Furthermore, single-cell RNA sequencing of periodontitis gingival tissue revealed alterations in the proportion and function of immune cells, including T and B cells, macrophages, and neutrophils, due to lncR-APDC silencing. Our findings also unveiled a previously unidentified epithelial cell subset that is distinctively presenting in the lncR-APDC-KO group. This epithelial subset, characterized by the positive expression of Krt8 and Krt18, engages in interactions with immune cells through a variety of ligand-receptor pairs. The expression of Tff2, now recognized for its role in chronic inflammatory conditions, exhibited a notable increase across various tissue and cell types in lncR-APDC deficient mice. Additionally, our investigation revealed the potential for a direct binding interaction between lncR-APDC and Tff2. Intra-gingival administration of AAV9-lncR-APDC was shown to have therapeutic effects in the EP model. In conclusion, our results suggest that lncR-APDC plays a critical role in the progression of periodontal disease and holds therapeutic potential for periodontitis. Furthermore, the presence of the distinctive epithelial subpopulation and significantly elevated Tff2 levels in the lncR-APDC-silenced EP model offer new perspectives on the epigenetic regulation of periodontitis pathogenesis.

A Progressively Disassembled DNA Repair Inhibitors Nanosystem for the Treatment of BRCA Wild-Type Triple-Negative Breast Cancer.

Background: Olaparib, a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor has demonstrated promising efficacy in patients with triple-negative breast cancer (TNBC) carrying breast cancer gene (BRCA) mutations. However, its impact on BRCA wild-type (BRCAwt) TNBC is limited. Hence, it is crucial to sensitize BRCAwt TNBC cells to olaparib for effective clinical practice. Novobiocin, a DNA polymerase theta (POLθ) inhibitor, exhibits sensitivity towards BRCA-mutated cancer cells that have acquired resistance to PARP inhibitors. Although both of these DNA repair inhibitors demonstrate therapeutic efficacy in BRCA-mutated cancers, their nanomedicine formulations' antitumor effects on wild-type cancer remain unclear. Furthermore, ensuring effective drug accumulation and release at the cancer site is essential for the clinical application of olaparib. Materials and Methods: Herein, we designed a progressively disassembled nanosystem of DNA repair inhibitors as a novel strategy to enhance the effectiveness of olaparib in BRCAwt TNBC. The nanosystem enabled synergistic delivery of two DNA repair inhibitors olaparib and novobiocin, within an ultrathin silica framework interconnected by disulfide bonds. Results: The designed nanosystem demonstrated remarkable capabilities, including long-term molecular storage and specific drug release triggered by the tumor microenvironment. Furthermore, the nanosystem exhibited potent inhibitory effects on cell viability, enhanced accumulation of DNA damage, and promotion of apoptosis in BRCAwt TNBC cells. Additionally, the nanosystem effectively accumulated within BRCAwt TNBC, leading to significant growth inhibition and displaying vascular regulatory abilities as assessed by magnetic resonance imaging (MRI). Conclusion: Our results provided the inaugural evidence showcasing the potential of a progressively disassembled nanosystem of DNA repair inhibitors, as a promising strategy for the treatment of BRCA wild-type triple-negative breast cancer.

LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Therapeutic options for advanced HCC are limited, which is due to a lack of full understanding of pathogenesis. Cellular senescence is a state of cell cycle arrest, which plays important roles in the pathogenesis of HCC. Mechanisms underlying hepatocellular senescence are not fully understood. LncRNA NEAT1 acts as an oncogene and contributes to the development of HCC. Whether NEAT1 modulates hepatocellular senescence in HCC is unknown. METHODS: The role of NEAT1 and KIF11 in cellular senescence and tumor growth in HCC was assessed both in vitro and in vivo. RNA pulldown, mass spectrometry, Chromatin immunoprecipitation (ChIP), luciferase reporter assays, RNA FISH and immunofluorescence (IF) staining were used to explore the detailed molecular mechanism of NEAT1 and KIF11 in cellular senescence of HCC. RESULTS: We found that NEAT1 was upregulated in tumor tissues and hepatoma cells, which negatively correlated with a senescence biomarker CDKN2A encoding p16INK4a and p14ARF proteins. NEAT1 was reduced in senescent hepatoma cells induced by doxorubicin (DOXO) or serum starvation. Furthermore, NEAT1 deficiency caused senescence in cultured hepatoma cells, and protected against the progression of HCC in a mouse model. During senescence, NEAT1 translocated into cytosol and interacted with a motor protein KIF11, resulting in KIF11 protein degradation and subsequent increased expression of CDKN2A in cultured hepatoma cells. Furthermore, KIF11 knockdown caused senescence in cultured hepatoma cells. Genetic deletion of Kif11 in hepatocytes inhibited the development of HCC in a mouse model. CONCLUSIONS: Conclusively, NEAT1 overexpression reduces senescence and promotes tumor progression in HCC tissues and hepatoma cells, whereas NEAT1 deficiency causes senescence and inhibits tumor progression in HCC. This is associated with KIF11-dependent repression of CDKN2A. These findings lay the foundation to develop potential therapies for HCC by inhibiting NEAT1 and KIF11 or inducing senescence.

Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy.

BACKGROUND: Novel compounds and more efficient treatment options are urgently needed for the treatment of non-small cell lung cancer (NSCLC). The decoction of Sophora flavescens has been used to treat NSCLC in the clinic, and matrine-type alkaloids are generally considered to be the key pharmacodynamic material basis. But the previous study showed that common matrine-type alkaloids exhibit significant cytotoxicity only when at concentrations close to the millimolar (mM) level. The key antitumor alkaloids in S. flavescens seem to have not yet been revealed. PURPOSE: The aim of this study was to screen water-soluble matrine alkaloid with novel skeleton and enhanced activity from S. flavescens, and to reveal the pharmacological mechanism of its therapeutic effect on NSCLC. METHODS: Alkaloid was obtained from S. flavescens by chromatographic separation methods. The structure of alkaloid was determined by spectroscopic methods, and single-crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro with cellular models was evaluated by MTT assay, western blotting, cell migration and invasion assay, plate colony-formation assay, tube formation assay, immunohistochemistry assay, hematoxylin and eosin staining. The antitumor efficacy in vivo was test in NSCLC xenograft models. RESULTS: A novel water-soluble matrine-derived alkaloid incorporating 6/8/6/6 tetracyclic ring system, named sophflarine A (SFA), was isolated from the roots of S. flavescens. SFA had significantly enhanced cytotoxicity compared with the common matrine-type alkaloids, having an IC50 value of 11.3 µM in A549 and 11.5 µM in H820 cells at 48 h. Mechanistically, SFA promoted NSCLC cell death by inducing pyroptosis via activating the NLRP3/caspase-1/GSDMD signaling pathway, and inhibited cancer cell proliferation by increasing the ROS production to activate autophagy via blocking the PI3K/AKT/mTOR signaling pathway. Additionally, SFA also inhibited NSCLC cell migration and invasion by suppressing EMT pathway, and inhibited cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. In concordance with the above results, SFA treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model. CONCLUSION: This study revealed a potential therapeutic mechanism of a novel matrine-derived alkaloid, which not only described a rational explanation for the clinical utilization of S. flavescens, but also provided a potential candidate compound for NSCLC treatment.

A Nicotiana benthamiana receptor-like kinase regulates Phytophthora resistance by coupling with BAK1 to enhance elicitin-triggered immunity.

Cell-surface-localized leucine-rich-repeat receptor-like kinases (LRR-RLKs) are crucial for plant immunity. Most LRR-RLKs that act as receptors directly recognize ligands via a large extracellular domain (ECD), whereas LRR-RLK that serve as regulators are relatively small and contain fewer LRRs. Here, we identified LRR-RLK regulators using high-throughput tobacco rattle virus (TRV)-based gene silencing in the model plant Nicotiana benthamiana. We used the cell-death phenotype caused by INF1, an oomycete elicitin that induces pattern-triggered immunity, as an indicator. By screening 33 small LRR-RLKs (≤6 LRRs) of unknown function, we identified ELICITIN INSENSITIVE RLK 1 (NbEIR1) as a positive regulator of INF1-induced immunity and oomycete resistance. Nicotiana benthamiana mutants of eir1 generated by CRISPR/Cas9-editing showed significantly compromised immune responses to INF1 and were more vulnerable to the oomycete pathogen Phytophthora capsici. NbEIR1 associates with BRI1-ASSOCIATED RECEPTOR KINASE 1 (NbBAK1) and a downstream component, BRASSINOSTEROID-SIGNALING KINASE 1 (NbBSK1). NbBSK1 also contributes to INF1-induced defense and P. capsici resistance. Upon INF1 treatment, NbEIR1 was released from NbBAK1 and NbBSK1 in vivo. Moreover, the silencing of NbBSK1 compromised the association of NbEIR1 with NbBAK1. We also showed that NbEIR1 regulates flg22-induced immunity and associates with its receptor, FLAGELLIN SENSING 2 (NbFLS2). Collectively, our results suggest that NbEIR1 is a novel regulatory element for BAK1-dependent immunity. NbBSK1-NbEIR1 association is required for maintaining the NbEIR1/NbBAK1 complex in the resting state.

Surgical Pharmacy for Optimizing Medication Therapy Management Services within Enhanced Recovery after Surgery (ERAS®) Programs.

Drug-related problems (DRPs) are common among surgical patients, especially older patients with polypharmacy and underlying diseases. DRPs can potentially lead to morbidity, mortality, and increased treatment costs. The enhanced recovery after surgery (ERAS) system has shown great advantages in managing surgical patients. Medication therapy management for surgical patients (established as "surgical pharmacy" by Guangdong Province Pharmaceutical Association (GDPA)) is an important part of the ERAS system. Improper medication therapy management can lead to serious consequences and even death. In order to reduce DRPs further, and promote the rapid recovery of surgical patients, the need for pharmacists in the ERAS program is even more pressing. However, the medication therapy management services of surgical pharmacy and how surgical pharmacists should participate in ERAS programs are still unclear worldwide. Therefore, this article reviews the main perioperative medical management strategies and precautions from several aspects, including antimicrobial agents, antithrombotic agents, pain medication, nutritional therapy, blood glucose monitoring, blood pressure treatment, fluid management, treatment of nausea and vomiting, and management of postoperative delirium. Additionally, the way surgical pharmacists participate in perioperative medication management, and the relevant medication pathways are explored for optimizing medication therapy management services within the ERAS programs. This study will greatly assist surgical pharmacists' work, contributing to surgeons accepting that pharmacists have an important role in the multidisciplinary team, benefitting medical workers in treating, counseling, and advocating for their patients, and further improving the effectiveness, safety and economy of medication therapy for patients and promoting patient recovery.

Undescribed phloroglucinol derivatives with antiviral activities from Dryopteris atrata (Wall. Ex Kunze) Ching.

Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton-a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C-C bond. Dryatraol D features a rare spiro [benzofuran-2',5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 µM and 5.5 µM, respectively. Dryatraols F-H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 µM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle.

An F-box protein attenuates fungal xylanase-triggered immunity by destabilizing LRR-RLP NbEIX2 in a SOBIR1-dependent manner.

Receptor-like proteins (RLPs) lacking the cytoplasmic kinase domain play crucial roles in plant growth, development and immunity. However, what remains largely elusive is whether RLP protein levels are fine-tuned by E3 ubiquitin ligases, which are employed by receptor-like kinases for signaling attenuation. Nicotiana benthamiana NbEIX2 is a leucine-rich repeat RLP (LRR-RLP) that mediates fungal xylanase-triggered immunity. Here we show that NbEIX2 associates with an F-box protein NbPFB1, which promotes NbEIX2 degradation likely by forming an SCF E3 ubiquitin ligase complex, and negatively regulates NbEIX2-mediated immune responses. NbEIX2 undergoes ubiquitination and proteasomal degradation in planta. Interestingly, NbEIX2 without its cytoplasmic tail is still associated with and destabilized by NbPFB1. In addition, NbPFB1 also associates with and destabilizes NbSOBIR1, a co-receptor of LRR-RLPs, and fails to promote NbEIX2 degradation in the sobir1 mutant. Our findings reveal a distinct model of NbEIX2 degradation, in which an F-box protein destabilizes NbEIX2 indirectly in a SOBIR1-dependent manner.

Bio-Pd(0) diverting electron from CoQ-long chain to FDH/Hase-short chain during sulfamethoxazole degradation.

Microbial electron output capacity is critical for organic contaminants biodegradation. Herein, original C. freundii JH could oxidate formate in anaerobic respiration, but lack the ability to degrade sulfamethoxazole (SMX). While the incorporation of Pd(0) could effectively improve the electron output via improving the combination between flavins and c-type cytochromes (c-Cyts), increasing the activities of key enzymes (formate dehydrogenase, hydrogenase, F0F1-ATPases), etc. More importantly, the presence of Pd(0) caused the NADH dehydrogenase (complex I) nearly in idle, and triggered the decrease of NADH/NAD+ ratio and increase of H+-efflux transmembrane gradient, eventually resulting in the electrons diverting from CoQ-involved long respiratory chain (decreasing from 91.67% to 36.25%) to FDH/Hases-based hydrogen-producing short chain (increasing from 22.44% to 84.88%), which further intensified the electron output. Above changes effectively launched and guaranteed the high-level SMX degradation by palladized C. freundii JH, alleviating the ecotoxicity of SMX in aquatic and terrestrial environments. These conclusions provided the new view to regulate the microbial electron output behaviors.

Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade.

BACKGROUND: Mutations in BRCA1 or BRCA2 (BRCA1/2) cause homologous recombination deficiency (HRD). Ovarian cancer (OvCa) patients harbouring HRD beyond BRCA1/2 mutation result in a state referred to as "BRCAness". OvCa with BRCAness could benefit from PARP inhibitors. This study aims to identify a signature to detect the BRCAness population at the transcriptome level. METHODS: We used a rank-based algorithm to develop a qualitative BRCAness signature for OvCa. Upregulation of CXCL1 with downregulation of SV2A and upregulation of LY9 with downregulation of CHRNB3 were constructed as the BRCAness signature (2 gene pairs, 2-GPS) for OvCa. RESULTS: OvCa samples that were classified as BRCAness by 2-GPS showed improved overall survival, progression-free survival and exhibited increased multi-omics alterations in homologous recombination genes and enhanced sensitivity to immune checkpoint blockade. BRCAness cells were sensitive to PARP inhibitors. By biological experiments, we validated SKOV3 cells and patients with HRD exhibited higher expression of CXCL1 than SV2A and higher expression of LY9 than CHRNB3 at mRNA level. Both SKOV3 and A2780 with HRD were sensitive to mitomycin C, cisplatin and olaparib. CONCLUSIONS: In conclusion, 2-GPS could robustly predict BRCAness OvCa at the individual level and extend the population who may benefit from PARP inhibitors.

A G-type lectin receptor-like kinase regulates the perception of oomycete apoplastic expansin-like proteins.

Phytophthora capsici is one of the most harmful pathogens in agriculture, which threatens the safe production of multiple crops and causes serious economic losses worldwide. Here, we identified a P. capsici expansin-like protein, PcEXLX1, by liquid chromatography-tandem mass spectrometry from Nicotiana benthamiana apoplastic fluid infected with P. capsici. Clustered regularly interspaced short palindromic repeats/crispr associated protein 9 (CRISPR/Cas9)-mediated PcEXLX1 knockout mutants exhibited significantly enhanced virulence, while the overexpression of PcEXLX1 impaired the virulence. Prokaryotically expressed PcEXLX1 activated multiple plant immune responses, which were BRI1-associated kinase 1 (BAK1)- and suppressor of BIR1-1 (SOBIR1)-dependent. Furthermore, overexpression of PcEXLX1 homologs in N. benthamiana could also increase plant resistance to P. capsici. A G-type lectin receptor-like kinase from N. benthamiana, expansin-regulating kinase 1 (ERK1), was shown to regulate the perception of PcEXLX1 and positively mediate the plant resistance to P. capsici. These results reveal that the expansin-like protein, PcEXLX1, is a novel apoplastic effector with plant immunity-inducing activity of oomycetes, perception of which is regulated by the receptor-like kinase, ERK1.

Gastrointestinal Microbiota Changes in Patients With Gastric Precancerous Lesions.

Background: Gastric microbiota may be involved in gastric cancer. The relationship between gastrointestinal microbes and the risk of gastric cancer is unclear. This study aimed to explore the gastric and intestinal bacteria associated with gastritis and gastric precancerous lesions. We conducted a case-control study by performing 16S rRNA gene analysis of gastric biopsies, juices, and stool samples from 148 cases with gastritis or gastric precancerous lesions from Anhui and neighboring provinces, China. And we validated our findings in public datasets. Results: Analysis of microbial sequences revealed decreased bacterial alpha diversity in gastric bacteria during the progression of gastritis. Helicobacter pylori was the main contributor to the decreased microbial composition and diversity in the gastric mucosa and had little influence on the microbiota of gastric juice and feces. The gastric mucosal genera Gemella, Veillonella, Streptococcus, Actinobacillus, and Hemophilus had the higher degree of centrality across the progression of gastric precancerous lesions. And Acinetobacter may contribute to the occurrence of intraepithelial neoplasia. In addition, the microbial model of H. pylori-positive gastric biopsies and feces showed value in the prediction of gastric precancerous lesions. Conclusions: This study identified associations between gastric precancerous lesions and gastric microbiota, as well as the changes in intestinal microbiota, and explored their values in the prediction of gastric precancerous lesions.

miR-145-5p Modulates Gefitinib Resistance by Targeting NRAS and MEST in Non-Small Cell Lung Cancer.

OBJECTIVE: microRNAs may play essential roles in the development and drug resistance of non-small cell lung cancer (NSCLC). However, their functions and mechanisms are not fully understood. Our goal was to define the role of miR-145-5p in the gefitinib resistance of NSCLC. MATERIALS AND METHODS: An A549 gefitinib-resistant cell line and xenograft nude mice were used in this study. The expression of miR-145-5p and its targets, NRAS and MEST, were detected and measured by qPCR, Western blot, RNA-FISH, or immunofluorescence analysis. RESULTS: miR-145-5p was downregulated in gefitinib-resistant A549 cells (A549/Gef R). Overexpression of miR-145-5p enhanced the sensitivity to gefitinib and inhibited cell proliferation and invasion in A549/Gef R. miR-145-5p was also significantly reduced in LUAD and LUSC clinical samples and closely associated with a favorable prognosis, according to the UALCAN and TCGA databases. Moreover, NRAS and MEST were found to be downstream target genes of miR-145-5p and to function as oncogenes in NSCLC samples, and gefitinib resistance could be improved following the interference of these two molecules. CONCLUSION: miR-145-5p improves the sensitivity of acquired gefitinib-resistant cells to gefitinib via inhibiting NRAS and MEST expression. The miR 145-5p-NRAS/MEST axis in NSCLC provides insights for the development of a NRAS/MEST targeting therapeutic approach to overcome gefitinib resistance in NSCLC patients.

Clinical Evidence of Tai Chi Exercise Prescriptions: A Systematic Review.

OBJECTIVES: This systematic review aims to summarize the existing literature on Tai Chi randomized controlled trials (RCTs) and recommend Tai Chi exercise prescriptions for different diseases and populations. METHODS: A systematic search for Tai Chi RCTs was conducted in five electronic databases (PubMed, Cochrane Library, EMBASE, EBSCO, and Web of Science) from their inception to December 2019. SPSS 20.0 software and Microsoft Excel 2019 were used to analyze the data, and the risk of bias tool in the RevMan 5.3.5 software was used to evaluate the methodological quality of RCTs. RESULTS: A total of 139 articles were identified, including diseased populations (95, 68.3%) and healthy populations (44, 31.7%). The diseased populations included the following 10 disease types: musculoskeletal system or connective tissue diseases (34.7%), circulatory system diseases (23.2%), mental and behavioral disorders (12.6%), nervous system diseases (11.6%), respiratory system diseases (6.3%), endocrine, nutritional or metabolic diseases (5.3%), neoplasms (3.2%), injury, poisoning and certain other consequences of external causes (1.1%), genitourinary system diseases (1.1%), and diseases of the eye and adnexa (1.1%). Tai Chi exercise prescription was generally classified as moderate intensity. The most commonly applied Tai Chi style was Yang style (92, 66.2%), and the most frequently specified Tai Chi form was simplified 24-form Tai Chi (43, 30.9%). 12 weeks and 24 weeks, 2-3 times a week, and 60 min each time was the most commonly used cycle, frequency, and time of exercise in Tai Chi exercise prescriptions. CONCLUSIONS: We recommend the more commonly used Tai Chi exercise prescriptions for different diseases and populations based on clinical evidence of Tai Chi. Further clinical research on Tai Chi should be combined with principles of exercise prescription to conduct large-sample epidemiological studies and long-term prospective follow-up studies to provide more substantive clinical evidence for Tai Chi exercise prescriptions.

Accelerating H2 Evolution by Anodic Semi-dehydrogenation of Tetrahydroisoquinolines in Water over Co3 O4 Nanoribbon Arrays Decorated Nickel Foam.

Coupling the H2 evolution reaction in water with thermodynamically favorable organic oxidation reactions is highly desirable, because it can enhance the energy conversion efficiency compared with electrocatalytic water splitting, and produce value-added chemicals instead of O2 in the anodic reaction. Herein, Co3 O4 nanoribbon arrays in situ grown on nickel foam (Co3 O4 @NF) was employed as an effective electrocatalyst for the selective oxidation of tetrahydroisoquinolines (THIQs). Various value-added semi-dehydrogenation products including dihydroisoquinolines with electro-deficient or -rich groups could be obtained with moderate yields and faradaic efficiencies. Benefitting from the rich surface active sites of Co3 O4 @NF, a two-electrode (Co3 O4 @NF||Pt) electrolytic system drove a benchmark current density of 10 mA cm-2 at a cell voltage as low as 1.446 V in 1.0 M KOH aqueous solution containing 0.02 M THIQ, which was reduced by 174 mV in comparison with that of overall water splitting.

MicroRNA-369 attenuates hypoxia-induced cardiomyocyte apoptosis and inflammation via targeting TRPV3.

Hypoxia-induced apoptosis and inflammation play an important role in cardiovascular diseases including myocardial infarction (MI). miR-369 has been suggested to be a key regulator of cardiac fibrosis. However, the role of miR-369 in regulating hypoxia-induced heart injury remains unknown. Our data indicated that miR-369 expression was significantly down-regulated and TRPV3 was significantly up-regulated in myocardial tissue after MI in rats and in hypoxic-treated neonatal rat cardiomyocytes (NRCMs). In addition, we observed that hypoxia significantly promoted apoptosis and the inflammatory response, accompanied by increased caspase-3 activity and the secretion of the cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. miR-369 overexpression significantly suppressed cell apoptosis and inflammatory factor production triggered by hypoxia, whereas miR-369 inhibition had an opposite effect. Importantly, we identified TRPV3 as a direct target of miR-369-3p. TRPV3 inhibition with small interfering RNA (siRNA) significantly inhibited hypoxia-induced inflammation and apoptosis, which can reverse the injury effects of miR-369 inhibitors. Our findings indicated that miR-369 reduced hypoxia-induced apoptosis and inflammation by targeting TRPV3.

MicroRNA-369 attenuates hypoxia-induced cardiomyocyte apoptosis and inflammation via targeting TRPV3

Hypoxia-induced apoptosis and inflammation play an important role in cardiovascular diseases including myocardial infarction (MI). miR-369 has been suggested to be a key regulator of cardiac fibrosis. However, the role of miR-369 in regulating hypoxia-induced heart injury remains unknown. Our data indicated that miR-369 expression was significantly down-regulated and TRPV3 was significantly up-regulated in myocardial tissue after MI in rats and in hypoxic-treated neonatal rat cardiomyocytes (NRCMs). In addition, we observed that hypoxia significantly promoted apoptosis and the inflammatory response, accompanied by increased caspase-3 activity and the secretion of the cytokines interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. miR-369 overexpression significantly suppressed cell apoptosis and inflammatory factor production triggered by hypoxia, whereas miR-369 inhibition had an opposite effect. Importantly, we identified TRPV3 as a direct target of miR-369-3p. TRPV3 inhibition with small interfering RNA (siRNA) significantly inhibited hypoxia-induced inflammation and apoptosis, which can reverse the injury effects of miR-369 inhibitors. Our findings indicated that miR-369 reduced hypoxia-induced apoptosis and inflammation by targeting TRPV3.

Elevated DHODH expression promotes cell proliferation via stabilizing ß-catenin in esophageal squamous cell carcinoma.

As a key enzyme in de novo pyrimidine biosynthesis, the expression level of dihydroorotate dehydrogenase (DHODH) has been reported to be elevated in various types of malignant tumors and its tumor-promoting effect was considered to relate to its pyrimidine synthesis function. Here, we revealed one intriguing potential mechanism that DHODH modulated ß-catenin signaling in esophageal squamous cell carcinoma (ESCC). We demonstrated that DHODH directly bound to the NH2 terminal of ß-catenin, thereby, interrupting the interaction of GSK3ß with ß-catenin and leading to the abrogation of ß-catenin degradation and accumulation of ß-catenin in the nucleus, which in turn, resulted in the activation of ß-catenin downstream genes, including CCND1, E2F3, Nanog, and OCT4. We further demonstrated that the regulation of ß-catenin by DHODH was independent of DHODH catalyzing activity. Univariate and multivariate analyses suggested that DHODH expression might be an independent prognostic factor for ESCC patients. Collectively, our study highlights the pivotal role of DHODH mediated ß-catenin signaling and indicates that DHODH may act as a multi-functional switcher from catalyzing pyrimidine metabolism to regulating tumor-related signaling pathways in ESCC.