FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma.

BACKGROUND: Stomach adenocarcinoma (STAD) is one of the main reasons for cancer-related deaths worldwide. This investigation aimed to define the connection between STAD and Cuproptosis-related genes (CRGs). Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper. AIM: To explore the identification of potential biomarkers for STAD disease based on cuproptosis. METHODS: A predictive model using Gene Ontology (GO), Least Absolute Shrinkage and Selection Operator (LASSO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis analyzed gene interconnections, focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD. Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed. The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic, Kaplan-Meier curves, and COX regression analysis. Validation was conducted with datasets GSE26942, GSE54129, and GSE66229. Expression of copper-related differentially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas. RESULTS: Three significant genes (FDX1, LIAS, MTF1) were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups. These genes were down-regulated in both risk categories. GO and KEGG analyses highlighted their involvement mainly in the electron transport chain. After validating their differential expression, FDX1 emerged as the most accurate diagnostic marker for gastric cancer. Additionally, the RCircos package localized FDX1 on chromosome 11. CONCLUSION: Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.

Hydroxysafflor yellow A inhibits the hyperactivation of rat platelets by regulating the miR-9a-5p/SRC axis.

Pathological platelet activation plays a vital role in the prevalence of cardiovascular diseases. Hydroxysafflor yellow A (HSYA) has been shown to have significant anti-platelet aggregation and anti-activation effects, but its mechanism of action is unclear. Our study showed that HSYA inhibited the expression of platelet surface glycoproteins IIß/III α (GPIIß/III α) and thromboxane A2 (TXA2) during platelet activation and reduced platelet Ca2+ accumulation. HSYA significantly reduced the number of platelets and inhibited adrenaline-induced platelet hyperaggregation in rats. Transcriptomic analysis of platelets suggested that HSYA significantly suppressed SRC and MAPK3 (ERK1/2) gene expression. YEEI peptide, an SRC activator, could significantly reverse the inhibition of HSYA on the phosphorylation of SRC/PLCγ2/PKCδ/MEK/ERK1/2 pathway proteins and reverse the effect of HSYA on platelet activation-related markers GPIIß/IIIα protein, TXA2 and cAMP. The SRC genes were further predicted by transcriptome analysis of HSYA-regulated miRNAs combined with bioinformatics techniques. The results suggested that HSYA could significantly upregulate the expression level of the miR-9a-5p gene and further confirmed that miR-9a-5p had a targeted regulatory relationship with SRC by dual-luciferase activity reporter and cell transfection experiments. The inhibitory effect of HSYA on the SRC/PLCγ2/PKCδ/MEK/ERK1/2 pathway was significantly reversed after platelets were transfected with the miR-9a inhibitor, while SRC siRNA attenuated the effect of the miR-9a inhibitor. SRC siRNA was able to attenuate the effect of the miR-9a inhibitor. In conclusion, this study suggests that HSYA can inhibit the activation of the SRC/PLCγ2/PKC δ/MEK/ERK1/2 axis by upregulating platelet miR-9a-5p, thereby reducing the activation of platelets and inhibiting platelet aggregation.

Efficacy of L-Carnitine for Dilated Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: L-carnitine mediates the utilization of fatty acids and glucose in the myocardium. The potential of L-carnitine in managing dilated cardiomyopathy (DCM) in patients has been extensively reported, with additional benefits. OBJECTIVE: This meta-analysis purposed to explore the clinical efficacy of L-carnitine therapy on DCM patients. METHODS: We searched publications up to May 2020 from several databases including PubMed, Embase, Cochrane Library, Chinese Biomedical (CBM) database, Chinese Science and Technology Periodicals database (VIP), Chinese National Knowledge Infrastructure (CNKI) database, and Wanfang database. Subsequently, publications that met the inclusion criteria were systematically evaluated by two independent reviewers. RESULTS: A total of 23 RCTs conducted in China with 1455 DCM patients were included in this study. In the meta-analysis, L-carnitine therapy was associated with a considerable improvement in the overall efficacy (RR = 1.28, 95% CI (1.21-1.36), P < 0.0001), left ventricular ejection fraction (LVEF) (MD = 6.16%, 95% CI (4.50, 7.83), P < 0.0001), and cardiac output (CO) (MD = 0.88 L/min, 95% CI (0.51, 1.25), P < 0.0001) as compared to the control group. Moreover, L-carnitine therapy significantly decreased left ventricular end-diastolic dimension (LVEDD) (MD = -2.53, 95% CI (-3.95, -1.12), P = 0.0005), brain natriuretic peptide (BNP) (SMD = -1.71 ng/L, 95% CI (-3.02, -0.40), P = 0.01), and the transforming growth factor-beta (TGF-ß1) (MD = -56.78 ng/L, 95% CI (-66.02, -47.53), P < 0.0001). CONCLUSIONS: L-carnitine potentially enhanced the therapeutic efficiency in DCM patients. Following weaknesses in the evidence due to low methodological quality and high clinical heterogeneity in the included studies, well-designed trials are recommended.

Hypofibrinogenemia induced by high-dose tigecycline-case report and review of literature.

RATIONALE: Extensive off-label use may affect the safety profile of tigecycline. Tigecycline-associated hypofibrinogenemia is potentially life threatening, although the frequency of life-threatening reactions is unknown and their incidence is easily overlooked. We report a case of 2 instances of treatment with high-dose tigecycline, each of which presented with hypofibrinogenemia. PATIENT CONCERNS: An 86-year-old male patient was treated twice with high-dose tigecycline and presented with hypofibrinogenemia both times. The decrease in fibrinogen occurred within 3 to 7 days of tigecycline treatment. Other coagulation parameters had slightly prolonged values. DIAGNOSES: Coagulopathy and hypofibrinogenemia. INTERVENTIONS: We discontinued the tigecycline. OUTCOMES: The fibrinogen level normalized within 5 days after the withdrawal of tigecycline. Following 80 days of hospitalization, the patient was transferred to the rehabilitation hospital for further treatment. LESSONS: We suggest routine strict monitoring of coagulation parameters, particularly fibrinogen. Attention should be paid to below-normal fibrinogen levels due to increased bleeding risk and severity of reaction at fibrinogen levels below 1 g/L.

Molecular mechanisms of the action of Arctigenin in cancer.

Since antediluvian times, the scientific community has realized that natural compounds exhibit enormous potential for the treatment of terrible diseases, such as cancer. Despite a variety of effective bioactive molecules, effective therapies still need to be developed to treat cancer. Hence, it is necessary to study the interactions of natural molecules with their cellular targets. Arctigenin (ATG), a natural lignan compound extracted from Arctium lappa, inhibits the growth of various cancer cells, such as those of the stomach, lungs, liver, and colon, as well as leukocytes, and regulates numerous intracellular activities, such as antioxidative, anti-inflammatory, and anticancer activities. The intention of this paper is to summarize and generally analyse the molecular pathways that are involved in the anticancer effects of ATG. In addition, the interactions of ATG with other drugs are also highlighted in this paper.

The effectiveness of acupuncture for chronic pain with depression: A systematic review protocol.

BACKGROUND: Chronic pain is a major public health problem and 30% to 45% of sufferers experience severe depression. Acupuncture is often used to treat both depression and a range of pain disorders. We aim to conduct a systematic review of randomized controlled trials (RCTs) to evaluate the efficacy of acupuncture for patients experiencing chronic pain with depression. METHODS: To identify relevant RCTs, the following databases will be searched electronically from their inception to July 1, 2017: PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, the Allied and Complementary Medicine Database, the Cumulative Index to Nursing and Allied Health Literature, Chinese medical databases, and others. Manual retrieval will also be conducted. RCTs that evaluated acupuncture as the sole or adjunct treatment for patients with chronic pain and depression will be included. The primary outcomes will be based on a visual analog pain measurement scale and the Hamilton Depression Scale. The secondary outcomes will include scores on a numerical rating scale, verbal rating scale, and the Hospital Anxiety and Depression Scale. The study selection, data extraction, and study quality evaluation will be performed independently by 2 researchers. If the data permit, meta-analysis will be performed using RevMan V5.3 statistical software. If the data are not appropriate for meta-analysis, descriptive analysis or subgroup analysis will be conducted. The methodological quality of the included trials will be assessed using the Cochrane risk-of-bias criteria and the Standards for Reporting Interventions in Controlled Trials of Acupuncture checklist. RESULTS: This study will provide a high-quality synthesis of current evidence of acupuncture for chronic pain with depression from several scales including visual analog pain measurement scale, the Hamilton Depression Scale, a numerical rating scale, verbal rating scale and the Hospital Anxiety and Depression Scale. CONCLUSION: The conclusion of our study will provide updated evidence to judge whether acupuncture is an effective intervention for patients suffered from chronic pain with depression.