Evodiamine suppresses endometriosis development induced by early EBV exposure through inhibition of ERß.

Introduction: Endometriosis (EMS) is characterized as a prevalent gynecological inflammatory disorder marked by the existence of endometrial tissues situated beyond the uterus. This condition leads to persistent pelvic pain and may contribute to infertility. In this investigation, we explored the potential mechanism underlying the development of endometriosis (EMS) triggered by transient exposure to either latent membrane protein 1 (LMP1) or Epstein-Barr virus (EBV) in a mouse model. Additionally, we examined the potential inhibitory effect of evodiamine (EDM) on EMS. Methods: Immortalized human endometrial stromal cells (HESC) or epithelial cells (HEEC) were transiently exposed to either EBV or LMP1. The presence of evodiamine (EDM) was assessed for its impact on estrogen receptor ß (ERß) expression, as well as on cell metabolism parameters such as redox balance, mitochondrial function, inflammation, and proliferation. Additionally, a mixture of LMP1-treated HESC and HEEC was administered intraperitoneally to generate an EMS mouse model. Different dosages of EDM were employed for treatment to evaluate its potential suppressive effect on EMS development. Results: Transient exposure to either EBV or LMP1 triggers persistent ERß expression through epigenetic modifications, subsequently modulating related cell metabolism for EMS development. Furthermore, 4.0 µM of EDM can efficiently reverse this effect in in vitro cell culture studies. Additionally, 20 mg/kg body weight of EDM treatment can partly suppress EMS development in the in vivo EMS mouse model. Conclusion: Transient EBV/LMP1 exposure triggers permanent ERß expression, favoring later EMS development, EDM inhibits EMS development through ERß suppression. This presents a novel mechanism for the development of endometriosis (EMS) in adulthood stemming from early Epstein-Barr virus (EBV) exposure during childhood. Moreover, evodiamine (EDM) stands out as a prospective candidate for treating EMS.

A Bimetallic Electro-Sensitizer Improves ROS Therapy by Relieving Autophagy-Induced ROS Tolerance and Immune Suppression.

Reactive oxygen species (ROS)-dependent monotherapy usually demonstrates poor therapeutic outcomes, due to the accompanied activation of protective autophagy in tumor cells, which results in ROS tolerance and immune suppression. In this study, a bimetallic electro-sensitizer, Pt-Ir NPs is constructed, loaded with the autophagy inhibitor chloroquine (Pt-Ir-CQ NPs), to enhance the effectiveness of electrotherapy by inhibiting autophagy and activating anti-tumor immune responses. This novel electrotherapy platform demonstrates unique advantages, particularly in the treatment of hypoxic and immunosuppressive tumors. First, the electro-sensitizer catalyzes water molecules into ROS under electric field, achieving tumor ablation through electrotoxicity. Second, the incorporated CQ inhibits the protective autophagy induced by electrotherapy, restoring the sensitivity of tumor cells to ROS and thereby enhancing the anti-tumor effects of electrotherapy. Third, Pt-Ir-CQ NPs enhance the functionality of antigen-presenting cells and immunogenic cells through inhibiting autophagy, synergistically activating the anti-tumor immune responses along with the immunogenic cell death (ICD) effect induced by electrotherapy. This study provides a novel approach for the effective ablation and long-term inhibition of solid tumors through flexible modulation by an exogenous electric field.

Carrier-Free Photodynamic Bioregulators Inhibiting Lactic Acid Efflux Combined with Immune Checkpoint Blockade for Triple-Negative Breast Cancer Immunotherapy.

Abnormal tumor metabolism creates a complex tumor immune microenvironment that plays a dominant role in the metastasis of triple-negative breast cancer (TNBC). TNBC is insensitive to immune checkpoint blockade (ICB) therapy because of insufficient cytotoxic T lymphocyte (CTL) infiltration and a hyper-lactic acid-suppressive immune microenvironment caused by abnormal glycolysis. Herein, we propose an amplified strategy based on lactic acid regulation to reprogram the immunosuppressive tumor microenvironment (ITM) and combine it with ICB therapy to achieve enhanced antitumor immunotherapy effects. Specifically, we constructed CASN, a carrier-free photodynamic bioregulator, through the self-assembly of the photosensitizer Chlorin e6 and monocarboxylate transporter 1 (MCT1) inhibitor AZD3965. CASN exhibited a uniform structure, good stability, and drug accumulation at the tumor site. CASN-mediated photodynamic therapy following laser irradiation inhibited primary tumor growth and induced immunogenic cell death. Furthermore, CASN reduced lactic acid-mediated regulatory T cell generation and M2 tumor-associated macrophage polarization by blocking MCT1-mediated lactic acid efflux to attenuate immune suppression, inducing the recruitment and activation of CTLs. Ultimately, CASN-mediated immunopotentiation combined with ICB therapy considerably strengthened tumor immunotherapy and effectively inhibited tumor growth and metastasis of TNBC. This synergistic amplification strategy overcomes the limitations of an acidic ITM and presents a potential clinical treatment option for metastatic tumors.

Camrelizumab-induced anaphylactic reaction: a case report and literature review.

Camrelizumab is an immune checkpoint inhibitor clinically used to treat various types of tumours. In this study, the authors provided the first report of a case of an anaphylactic reaction induced by camrelizumab in the treatment of a patient with squamous cell carcinoma of the floor of the mouth. The patient, a 58-year-old man, was diagnosed with advanced squamous cell carcinoma of the floor of the mouth, with cancer infiltration and multiple metastases. He underwent treatment for nine cycles, in which cycles 1-5 he received camrelizumab, albumin-bound paclitaxel, and cisplatin (200 mg of camrelizumab each time, every 3 weeks), with no adverse reactions; in cycle 6, he received albumin-bound paclitaxel and cisplatin, with no adverse reactions; and in cycles 7-9, he received camrelizumab and albumin-bound paclitaxel. However, 30 min after 8th administration of camrelizumab (cycle 9), he suddenly developed sweating, a pale complexion, clamminess and cyanosis of the limbs (percutaneous arterial oxygen saturation [SpO2] = 82%, blood pressure [BP] = 79/49 mmHg, heart rate [HR] = 83 beats/min [bpm] and respiratory rate [RR) = 12 bpm). The patient underwent intravenous infusion of methylprednisolone (80 mg) combined with dopamine to boost the BP; he regained consciousness 20 min later, and many parts of his skin appeared smooth, with no desquamation and accompanied by itching erythema, especially on the upper limbs. Approximately 2 h after treatment, the patient's skin erythema subsided (vital sign monitoring results: SpO2 = 100%, BP = 122/84 mmHg, HR = 91 bpm and RR = 17 bpm); the patient did not complain about his obvious discomfort. Despite the rarity of acute anaphylactic reactions among immune-related adverse reactions, great importance should be given to anaphylactic reactions of camrelizumab due to its extensive clinical application.

Immune micro-environment analysis and drug screening for ovarian endometriosis.

BACKGROUND: Patients of ovary endometriosis have an abnormal immune micro-environment, leading to endometrial tissue that from retrograde menstruation evade immune surveillance and subsequently develop into ectopic lesions. OBJECTIVE: This study aims to elucidate the crucial immune cells and molecular pathways that are associated with an aberrant immune micro-environment of endometriosis. METHOD: In this study, we identified differentially expressed genes between ovarian ectopic endometrial tissue (OVE) and eutopic endometrial tissue from patients with endometriosis (PE) and non-endometriosis patients (CON) by analyzing the mRNA sequencing data. Additionally, we used WGCNA(Weighted Gene Co-expression Network Analysis) to screen for key genes related to immune cell infiltration and compared the sub-types of infiltrating immune cells using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcript). Subsequently, we conducted a single-cell analysis on the identified key genes. Furthermore, we analyzed potential drugs suitable for ovarian endometriosis treatment using pRRophertic. RESULTS: Seven key genes associated with immune cell infiltration were screened out. The expression of these genes in OVE was significantly lower than that in PE and CON. These key genes were mainly enriched in the NK cell-mediated cytotoxicity pathway, especially for CD16 + CD56dim NK. Moreover, NK cells infiltration in ovarian endometriosis was significantly reduced compared with PE and CON, while M2 macrophage shown the opposite. Results of the single-cell analysis showed that the expression of the seven key genes in NK cells and monocyte-macrophages in OVE was significantly lower than that in PE or CON. Additionally, we identified potential drugs suitable for ovarian endometriosis treatment. CONCLUSION: The decreased infiltration of NK cells and increased infiltration of M2 macrophages contribute to the evasion of immune surveillance against endometrial tissue, promoting the progression of OVE. Therefore, potential strategies for the treatment of OVE include increasing NK cell activation and decreasing M2 macrophage polarization.

Electrically activated polymetallic nanocrystals for long-term tumor suppression via oxygen-independent ROS generation and electro-immunotherapy.

The low oxidation level and immunosuppressive microenvironment within hypoxic tumor tissue are critical factors contributing to the inefficacy of various anti-tumor strategies. Herein, we have designed a novel intravenous injection nanoplatform to conduct electro-immunotherapy, based on phospholipid-modified PtPd nanocrystals loaded with the immunoregulator IPI549 (LP@Pt-Pd@IPI549 nanoparticles, LPPI). LPPI responds to reactive oxygen species (ROS), triggering a cascade of therapeutic effects that overcome hypoxia-related resistance and effectively eradicate hypoxic tumors. Firstly, under electric field exposure, LPPI relied on water rather than oxygen to generate abundant ROS under hypoxic conditions for tumor electrodynamic therapy (EDT). Moreover, the generated ROS further induced the disintegration of the outer phospholipid membrane of LPPI, leading to the release of the immunoregulator and inhibition of myeloid-derived suppressor cells (MDSCs), triggering cascade immune responses. Additionally, the immunomodulatory effects of IPI549, in synergy with the immunogenic cell death (ICD) induced by EDT, reversed the immunosuppressive microenvironment contributing to tumor resistance. In summary, EDT transiently killed tumor cells while simultaneously generating antigen release, instigating an adaptive immune response for electro-immunotherapy, resulting in a potent and long-lasting tumor inhibition effect.

[Network Meta-analysis of Chinese patent medicine in treatment of heart failure with preserved ejection fraction].

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

Xylanase Supplement Enhances the Growth Performance of Broiler by Modulating Serum Metabolism, Intestinal Health, Short-Chain Fatty Acid Composition, and Microbiota.

This study aimed to investigate the effects of different levels of xylanase supplementation in a wheat-based diet on growth performance, short-chain fatty acids, intestinal health, microbial composition, and serum metabolism. A total of 1200 male chicks were randomly assigned to four wheat-based diet treatments: Group C (adding 0 mg/kg of xylanase), Group L (adding 50 mg/kg of xylanase), Group M (adding 100 mg/kg of xylanase), and Group H (adding 150 mg/kg of xylanase). The experiment lasted for 56 days. The results indicated that Group H broilers experienced a decreased feed-to-gain ratio throughout the study period. Additionally, dietary supplementation with xylanase led to an increase in the physical barrier, as indicated by increased VH and VH/CD in the gut (p < 0.05). Furthermore, levels of D-lactic acid and endotoxin were reduced. Xylanase supplementation also increased the abundance of Muc-2, ZO-1, and Occludin (p < 0.05). Moreover, xylanase supplementation enhanced the activity of sucrase and maltase in the duodenum (p < 0.05), which may be attributable to the upregulation of the abundance of SI and MGA (p < 0.05). Furthermore, xylanase addition promoted propionic acid produced by specific bacteria, such as Phascolarctobacterium, and influenced the microbial composition to some extent, promoting intestinal health. Additionally, 150 mg/kg of xylanase supplementation increased the amino acid, peptide, and carbohydrate content and upregulated the metabolism of amino acids related to histidine, cysteine, methionine, and other pathways (p < 0.05). These findings suggest adequate xylanase supplementation can enhance nutritional digestibility and absorption, improve growth performance, stimulate endogenous enzyme activity, optimize intestinal morphology and barrier function, and positively influence acid-producing bacteria and amino acid metabolic pathways.

Identification of circulating miRNA as early diagnostic molecular markers in malignant glioblastoma base on decision tree joint scoring algorithm.

PURPOSE: The lack of clinical markers prevents early diagnosis of glioblastoma (GBM). Many studies have found that circulating microRNAs (miRNAs) can be used as early diagnostic markers of malignant tumours. Therefore, the identification of novel circulating miRNA biomolecular markers could be beneficial to clinicians in the early diagnosis of GBM. METHODS: We developed a decision tree joint scoring algorithm (DTSA), systematically integrating significance analysis of microarray (SAM), Pearson hierarchical clustering, T test, Decision tree and Entropy weight score algorithm, to screen out circulating miRNA molecular markers with high sensitivity and accuracy for early diagnosis of GBM. RESULTS: DTSA was developed and applied for GBM datasets and three circulating miRNA molecular markers were identified, namely, hsa-miR-2278, hsa-miR-555 and hsa-miR-892b. We have found that hsa-miR-2278 and hsa-miR-892b regulate the GBM pathway through target genes, promoting the development of GBM and affecting the survival of patients. DTSA has better classification effect in all data sets than other classification algorithms, and identified miRNAs are better than existing markers of GBM. CONCLUSION: These results suggest that DTSA can effectively identify circulating miRNA, thus contributing to the early diagnosis and personalised treatment of GBM.

Selenomethionine Attenuated H2O2-Induced Oxidative Stress and Apoptosis by Nrf2 in Chicken Liver Cells.

Earlier studies have shown that selenomethionine (SM) supplements in broiler breeders had higher deposition in eggs, further reduced the mortality of chicken embryos, and exerted a stronger antioxidant ability in offspring than sodium selenite (SS). Since previous studies also confirmed that Se deposition in eggs was positively correlated with maternal supplementation, this study aimed to directly investigate the antioxidant activities and underlying mechanisms of SS and SM on the chicken hepatocellular carcinoma cell line (LMH). The cytotoxicity results showed that the safe concentration of SM was up to 1000 ng/mL, while SS was 100 ng/mL. In Se treatments, both SS and SM significantly elevated mRNA stability and the protein synthesis rate of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), two Se-containing antioxidant enzymes. Furthermore, SM exerted protective effects in the H2O2-induced oxidant stress model by reducing free radicals (including ROS, MDA, and NO) and elevating the activities of antioxidative enzymes, which performed better than SS. Furthermore, the results showed that cotreatment with SM significantly induced apoptosis induced by H2O2 on elevating the content of Bcl-2 and decreasing caspase-3. Moreover, investigations of the mechanism revealed that SM might exert antioxidant effects on H2O2-induced LMHs by activating the Nrf2 pathway and enhancing the activities of major antioxidant selenoenzymes downstream. These findings provide evidence for the effectiveness of SM on ameliorating H2O2-induced oxidative impairment and suggest SM has the potential to be used in the prevention or adjuvant treatment of oxidative-related impairment in poultry feeds.

Acupuncture and moxibustion for endometriosis: A systematic review and analysis.

OBJECTIVES: This study aimed to examine the effect of acupuncture on symptoms and health-related quality of life in patients with endometriosis. METHODS: Nine biomedical databases were searched to April 2022 to identify randomized controlled trials of acupuncture and/or moxibustion used alone or as adjunct to guideline-recommended pharmacotherapy for the treatment of endometriosis. One reviewer extracted data and another verified the data. A random effects model was used to calculate mean differences. RESULTS: Fifteen trials involving 1018 patients met the inclusion criteria, but diversity in comparisons and outcome measures prevented meta-analysis. Compared to sham acupuncture, manual acupuncture was more effective at reducing dysmenorrhea VAS pain score (mean difference [MD] - 2.40, 95 % CI [- 2.80, - 2.00]; moderate certainty evidence), pelvic pain VAS score (MD - 2.65, 95 % CI [- 3.40, - 1.90]; high certainty evidence) and dyspareunia VAS scores (MD - 2.88, [- 3.83, - 1.93]), lessened the size of ovarian cyst (MD - 3.88, 95 % CI [- 7.06, - 0.70]), and improved quality of life. Compared to conventional therapy, manual acupuncture plus conventional therapy and warm needle alone resulted in greater improvements in quality of life than conventional therapy. Among the six studies that reported safety, fewer adverse events were reported in participants who received acupuncture or moxibustion. CONCLUSIONS: Low to moderate certainty evidence from single studies showed that manual acupuncture may improve pain-related symptoms and quality of life; however, there is insufficient evidence on the overall effectiveness of acupuncture and moxibustion for endometriosis.

Changes of Bioactive Components and Antioxidant Capacity of Pear Ferment in Simulated Gastrointestinal Digestion In Vitro.

Fruit ferment is rich in polyphenols, organic acids, enzymes, and other bioactive components, which contribute to their antioxidant ability. In this study, we investigated the effect of the simulated gastric and intestinal digestion in vitro on the total phenolic content (TPC), total flavonoid content (TFC), phenolic components content, organic acid content, protease activity, superoxide dismutase (SOD) activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (DPPH-RSA), hydroxyl (·OH) radical scavenging activity (·OH-RSA), and total reducing capacity in 'Xuehua' pear (Pyrus bretschneideri Rehd) ferment. The result showed that the TPC, TFC, protease activity, and phenolic components such as arbutin, protocatechuic acid, malic acid, and acetic acid showed a rising trend during the simulated gastric digestion in 'Xuehua' pear ferment, and these components might contribute to the increasing of ·OH-RSA and total reducing capacity. The SOD activity and epicatechin content showed an increasing trend at first and then a decreasing trend, which was likely associated with DPPH-RSA. During in vitro-simulated intestinal digestion, the majority of evaluated items reduced, except for protease activity, quercetin, and tartaric acid. The reason for the decreasing of bio-accessibility resulted from the inhibition of the digestive environment, and the transformation between substances, such as the conversion of hyperoside to quercetin. The correlation analysis indicated that the antioxidant capacity of 'Xuehua' pear ferment was mainly affected by its bioactive compounds and enzymes activity as well as the food matrices and digestive environment. The comparison between the digestive group with and without enzymes suggested that the simulated gastrointestinal digestion could boost the release and delay the degradation of phenolic components, flavonoids, and organic acid, protect protease and SOD activity, and stabilize DPPH-RSA, ·OH-RSA, and total reducing capacity in 'Xuehua' pear ferment; thus, the 'Xuehua' pear ferment could be considered as an easily digestible food.

Integrated proteomic and phosphoproteomic analysis for characterization of colorectal cancer.

Proteins and translationally modified proteins like phosphoproteins have essential regulatory roles in tumorigenesis. This study attempts to elucidate the dysregulated proteins driving colorectal cancer (CRC). To explore the differential proteins, we performed iTRAQ labeling proteomics and TMT labeling phosphoproteomics analysis of CRC tissues and adjacent non-cancerous tissues. The functions of quantified proteins were analyzed using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Subcellular localization analysis. Depending on the results, we identified 330 differential proteins and 82 phosphoproteins in CRC. GO and KEGG analyses demonstrated that protein changes were primarily associated with regulating biological and metabolic processes through binding to other molecules. Co-expression relationships between proteomic and phosphoproteomic analysis revealed that TMC5, SMC4, SLBP, VSIG2, and NDRG2 were significantly dysregulated differential proteins. Additionally, based on the predicted co-expression proteins, we identified that the stem-loop binding protein (SLBP) was up-regulated in CRC cells and promoted the proliferation and migration of CRC. This study reports an integrated proteomic and phosphoproteomic analysis of CRC to discern the functional impact of protein alterations and provides a candidate diagnostic biomarker or therapeutic target for CRC. SIGNIFICANCE: Combining one or more high-throughput omics technologies with bioinformatics to analyze biological samples and explore the links between biomolecules and their functions can provide more comprehensive and multi-level insights for disease mechanism research. Proteomics, phosphoproteomics, metabolomics and their combined analysis play an important role in the auxiliary diagnosis, the discovery of biomarkers and novel therapeutic targets for colorectal cancer. In this integrated proteomic and phosphoproteomic analysis, we identified proteins and phosphoproteins in colorectal cancer tissue and analyzed potential mechanisms contributing to progression in colorectal cancer. The results of this study provide a foundation to focus future experiments on the contribution of altered protein and phosphorylation patterns to prevention and treatment of colorectal cancer.

Tumor microenvironment-regulating nanomedicine design to fight multi-drug resistant tumors.

The tumor microenvironment (TME) is a very cunning system that enables tumor cells to escape death post-traditional antitumor treatments through the comprehensive effect of different factors, thereby leading to drug resistance. Deep insights into TME characteristics and tumor resistance encourage the construction of nanomedicines that can remodel the TME against drug resistance. Tremendous interest in combining TME-regulation measurement with traditional tumor treatment to fight multidrug-resistant tumors has been inspired by the increasing understanding of the role of TME reconstruction in improving the antitumor efficiency of drug-resistant tumor therapy. This review focuses on the underlying relationships between specific TME characteristics (such as hypoxia, acidity, immunity, microorganisms, and metabolism) and drug resistance in tumor treatments. The exciting antitumor activities strengthened by TME regulation are also discussed in-depth, providing solutions from the perspective of nanomedicine design. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Integrated Tissue and Blood miRNA Expression Profiles Identify Novel Biomarkers for Accurate Non-Invasive Diagnosis of Breast Cancer: Preliminary Results and Future Clinical Implications.

We aimed to identify miRNAs that were closely related to breast cancer (BRCA). By integrating several methods including significance analysis of microarrays, fold change, Pearson's correlation analysis, t test, and receiver operating characteristic analysis, we developed a decision-tree-based scoring algorithm, called Optimized Scoring Mechanism for Primary Synergy MicroRNAs (O-PSM). Five synergy miRNAs (hsa-miR-139-5p, hsa-miR-331-3p, hsa-miR-342-5p, hsa-miR-486-5p, and hsa-miR-654-3p) were identified using O-PSM, which were used to distinguish normal samples from pathological ones, and showed good results in blood data and in multiple sets of tissue data. These five miRNAs showed accurate categorization efficiency in BRCA typing and staging and had better categorization efficiency than experimentally verified miRNAs. In the Protein-Protein Interaction (PPI) network, the target genes of hsa-miR-342-5p have the most regulatory relationships, which regulate carcinogenesis proliferation and metastasis by regulating Glycosaminoglycan biosynthesis and the Rap1 signaling pathway. Moreover, hsa-miR-342-5p showed potential clinical application in survival analysis. We also used O-PSM to generate an R package uploaded on github (SuFei-lab/OPSM accessed on 22 October 2021). We believe that miRNAs included in O-PSM could have clinical implications for diagnosis, prognostic stratification and treatment of BRCA, proposing potential significant biomarkers that could be utilized to design personalized treatment plans in BRCA patients in the future.

Prioritizing key synergistic circulating microRNAs for the early diagnosis of biliary tract cancer.

Biliary tract cancer (BTC) is a highly aggressive malignant tumor. Serum microRNAs (ser-miRNAs) serve as noninvasive biomarkers to identify high risk individuals, thereby facilitating the design of precision therapies. The study is to prioritize key synergistic ser-miRNAs for the diagnosis of early BTC. Sampling technology, significant analysis of microarrays, Pearson Correlation Coefficients, t-test, decision tree, and entropy weight were integrated to develop a global optimization algorithm of decision forest. The source code is available at https://github.com/SuFei-lab/GOADF.git. Four key synergistic ser-miRNAs were prioritized and the synergistic classification performance was better than the single miRNA' s. In the internal feature evaluation dataset, the area under the receiver operating characteristic curve (AUC) for each single miRNA was 0.8413 (hsa-let-7c-5p), 0.7143 (hsa-miR-16-5p), 0.8571 (hsa-miR-17-5p), and 0.9365 (hsa-miR-26a-5p), respectively, whereas the synergistic AUC value increased to 1.0000. In the internal test dataset, the single AUC was 0.6500, 0.5125, 0.6750, and 0.7500, whereas the synergistic AUC increased to 0.8375. In the independent test dataset, the single AUC was 0.7280, 0.8313, 0.8957, and 0.8303, and the synergistic AUC was 0.9110 for discriminating between BTC patients and healthy controls. The AUC for discriminating BTC from pancreatic cancer was 0.9000. Hsa-miR-26a-5p was a predictor of prognosis, patients with high expression had shorter survival than those with low expression. In conclusion, hsa-let-7c-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-26a-5p may act as key synergistic biomarkers and provide important molecular mechanisms that contribute to pathogenesis of BTC.

Efficacy and Safety of Qili Qiangxin Capsule on Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis of 35 Randomized Controlled Trials.

Objective: Qili Qiangxin Capsule (QQC), a Chinese patent medicine, is clinically effective in treating dilated cardiomyopathy (DCM). However, the meta-analysis of QCC combined with conventional western medicine (CWM) on DCM remains unexplored. This study aimed to systematically evaluate the efficacy and safety of QCC in the treatment of DCM. Methods: Searched the studies of the combination of QQC and CWM in the treatment of DCM, from databases like PubMed, Cochrane Library, Web of Science, Wan Fang Databases, Chinese Biomedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, prior to 15 January 2022. Two reviewers respectively regulated research selection, data extraction, and risk of bias assessment. Review Manager Software 5.4 was used for meta-analysis. Furthermore, GRADE pro3.6.1 software was selected to grade the current evidence in our findings. This meta-analysis has been registered in PROSPERO (CRD42022297906). Results: There were 35 studies pertaining to 3,334 patients included. The meta-analysis showed compared with CWM alone, the combination therapy had significant advantages in improving the clinical efficiency rate (RR = 1.24, 95% CI: 1.19 to 1.29, p < 0.00001), 6 min walking distance (6MWD) (MD = 41.93, 95%CI: 39.82 to 44.04, p < 0.00001), superior in ameliorating the left ventricular ejection fraction (LVEF) (MD = 5.73, 95%CI: 4.70 to 6.77, p < 0.00001), left ventricular end-diastolic dimension (LVEDD) (MD = -4.09, 95%CI: -4.91 to -3.27), p < 0.00001), left ventricular end-systolic diameter (LVESD) (MD = -4.73, 95%CI: -5.63 to -3.84), p < 0.00001) and BNP (MD = -101.09, 95%CI: -132.99 to -69.18), p < 0.00001), and also superior in reducing hypersensitive-C-Reactive Protein (hs-CRP) (MD = -3.78, 95%CI: -4.35 to -3.21), p < 0.00001), Interleukin- 6 (IL-6) (MD = -25.92, 95%CI: -31.35 to -20.50), p < 0.00001), tumor necrosis factor-α (TNF-α) (MD = -5.04, 95%CI: -6.13 to -3.95), p < 0.00001), high mobility group protein B1 (HMGB1) (MD = -4.34, 95%CI: -5.22 to -3.46), p < 0.00001), and adverse reactions (ARs) (RR = 0.70, 95%CI: 0.51-0.97), p = 0.03). The GRADE evidence quality rating presented with moderate or low quality of evidence for the available data. Conclusion: Compared with the control group, QQC combined with CWM may be effective in treating DCM. However, the conclusion of this study must be interpreted carefully due to the inferior quality and ambiguity of bias in the included trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier [CRD42022297906].

Paper-based detection of Epstein-Barr virus using asymmetric polymerase chain reaction and gold silicon particles.

A new paper-based lateral flow nucleic acid (LFNA) test platform was established in this study using asymmetric polymerase chain ceaction (A-PCR) for signal amplification. This new method allowed a visual detection of Epstein-Barr virus (EBV) nucleic acids with high specificity and low cost. In addition, as part of our strategy we employed a sandwich system of capture probe (CP)/gold nanoparticles (AuNPS) and silicon dioxide (SiO2) (AuNPS@SiO2) nanospheres/target DNA/avidin complexes as the sensing platform. Biotin-labeled target DNA was obtained by A-PCR and later introduced in the LF device. The CP/target DNA/AuNPS@SiO2 complexes were captured on the test zone by the specific reaction between biotin and avidin, and the remaining CP/AuNPS@SiO2 particles were captured on the quality control zone by the hybridization between CP and a quality control probe. Au@SiO2 accumulation in the test and quality control zones of the device enabled a visual detection of the specific target sequences. The method detection limit was 50 nM of the target DNA, which was lower than that of the LFNA biosensor (LFNAB) without PCR amplification and Au@SiO2 particles. In conclusion, the novel paper-based platform described here is a low cost, efficient and fast visual detection method that offers high sensitivity and other benefits compared to alternative methods in use.

Exocellular polysaccharides extracted from mangrove fungus Paecilomyces Lilacinuson present anti-HSV-1 activity in mice.

This study examined the anti-HSV-1 activity of EPS extracts isolated from mangrove fungus Paecilomyces Lilacinuson after intraperitoneal administration in mice. Mice were experimentally infected with HSV-1 intracranially and treated intraperitoneally with three different doses of EPS extract (6 g/Kg, 8 g/Kg, and 10 g/Kg) for 7 days. One group of 15 mice was infected with HSV-1 but did not receive any treatment, while another group of 15 mice was mock-infected to remain a control group. Animals were observed twice a day for 14 days after virus infection, searching for clinical signs of weight loss, piloerection, isolation, or retardation movement. Compared with the mock-infected group, mortality was significantly increased (p < 0.05) in the virus-infected group and the groups that received 6 g/Kg and 8 g/Kg EPS extract. Interestingly, no significant differences in mortality were found between the 10 g/Kg EPS extract and the mock-infected group. Mortality in the 10 g/Kg EPS extract group was substantially improved compared with virus-infected(p < 0.05). Additionally, EPS extracts inhibited HSV-1 replication in the mice brain in a dose-dependent manner. Furthermore, the extracts decreased NF-κB protein and mRNA expression and the production of TNF-α in HSV-1-infected mice brain tissue. These effects were also dose-dependent. Our findings suggest that the EPS extract may be a potential candidate for developing an antiviral drug against HSV-1.