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Neurobiological fits of cue-reactivity within alcohol-use disorders: A voxel-wise meta-analysis associated with fMRI reports.
Moreover, when DR5 was silenced by small interfering RNA, the proportion of apoptotic cells induced by 5'-epiequisetin remarkably declined. In addition, 5'-epiequisetin downregulated the expression of survivin which plays a key role in the process of survival and apoptosis. 5'-Epiequisetin also impacted beta-catenin and cadherins, which were associated with cell migration. In addition, 5'-Epiequisetin significantly inhibited the progression of prostate cancer in mice, accompanied by regulating the protein expression of DR5, caspase 8, survivin, and cadherins in vivo. Taken together, these findings indicated that 5'-epiequisetin showed an anti-prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both in vitro and in vivo, suggesting a promising lead compound for the pharmacotherapy of prostate cancer.Background Although various effective compounds for the second- and third-line treatment of advanced or recurrent cervical cancer improved the overall survival, the optimal regimen remains controversial. Previous studies revealed that apatinib had extensive anti-tumor activities. However, almost all studies on apatinib in recurrent cervical cancer are non-randomized controlled trials with small sample sizes, different first-line treatments, and uncontrolled statistical analysis, which may result in a lack of effective metrics to evaluate the efficacy and safety of apatinib. Here, this meta-analysis aims to evaluate the efficacy and safety of apatinib in patients with advanced or recurrent cervical cancer. Methods PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for relevant studies. Outcomes including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for further analysis. Results Seven studies involving 243 patients were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 22.9% and 68.6%, respectively. With regard to survival analysis, the pooled PFS and OS were 5.19 months and 10.63 months, respectively. The most common treatment-related adverse events of apatinib were hand-foot syndrome (all grade 39.6%, ≥grade III 7.5%), hypertension (all grade 34.5%, ≥grade III 9.2%), and fatigue (all grade 28.0%, ≥grade III 5.1%). Conclusions In summary, this meta-analysis demonstrated that apatinib has promising efficacy and safety for patients with advanced or recurrent cervical cancer. Systematic Review Registration https//inplasy.com/inplasy-2022-7-0049/, identifier INPLASY202270049.Cadmium (Cd) is a toxic heavy metal extensively used in industrial and agricultural production. Among the main mechanisms of Cd-induced liver damage is oxidative stress. Quercetin (QE) is a natural antioxidant. Herein, the protective effect of QE on Cd-induced hepatocyte injury was investigated. BRL-3A cells were treated with 12.5 μmol/L CdCl2 and/or 5 μmol/L QE for 24 h. The cells and medium supernatant were collected, and the ALT, AST, and LDH contents of the medium supernatant were detected. The activities or contents of SOD, CAT, GSH, and MDA in cells were determined. Intracellular ROS levels were examined by flow cytometry. Apoptosis rate and mitochondrial-membrane potential (ΔΨm) were detected by Hoechst 33,258 and JC-1 methods, respectively. The mRNA and protein expression levels of Nrf2, NQO1, Keap1, CytC, caspase-9, caspase-3, Bax, and Bcl-2 were determined by real-time PCR (RT-PCR) and Western blot methods. Results showed that Cd exposure injured BRL-3A cells, the activity of antioxidant enzymes decreased and the cell ROS level increased, whereas the ΔΨm decreased, and the expression of apoptotic genes increased. Cd inhibited the Nrf2-Keap1 pathway, decreased Nrf2 and NQO1, or increased Keap1 mRNA and protein expression. Through the combined action of Cd and QE, QE activated the Nrf2-Keap1 pathway. Consequently, antioxidant-enzyme activity decreased, cellular ROS level decreased, ΔΨm increased, Cd-induced BRL-3A cell damage was alleviated, and cell apoptosis was inhibited. After the combined action of QE and Cd, Nrf2 and NQO1 mRNA and protein expression increased, Keap1 mRNA and protein expression decreased. Therefore, QE exerted an antioxidant effect by activating the Nrf2-Keap1 pathway in BRL-3A cells.Objectives Curcuma longa (CL) and Boswellia serrata (BS) extracts are used to relieve osteoarthritis symptoms. The aim of this in vitro study was to investigate their mechanisms of action at therapeutic plasmatic concentrations on primary human osteoarthritic (OA) chondrocytes. Methods BS (10-50 μg/ml) and CL (0.4-2 μg/ml corresponding to 1-5 µM of curcumin) were evaluated separately or in combination on primary chondrocytes isolated from 17 OA patients and cultured in alginate beads. Ten patients were used for RNA-sequencing analysis. Proteomic confirmation was performed either by immunoassays in the culture supernatant or by flow cytometry for cell surface markers after 72 h of treatment. Results Significant gene expression modifications were already observed after 6 h of treatment at the highest dose of CL (2 μg/ml) while BS was significantly effective only after 24 h of treatment irrespective of the concentration tested. The most over-expressed genes by CL were anti-oxidative, detoxifying, and cytoprotective genes involved in the Nrf2 pathway. Down-regulated genes were principally pro-inflammatory cytokines and chemokines. Inversely, BS anti-oxidant/detoxifying activities were related to the activation of Nrf1 and PPARα pathways. BS anti-inflammatory effects were associated with the increase in GDF15, decrease in cholesterol cell intake and fatty acid metabolism-involved genes, and down-regulation of Toll-like receptors (TLRs) activation. Similar to CL, BS down-regulated ADAMTS1, 5, and MMP3, 13 genes expression. The combination of both CL and BS was significantly more effective than CL or BS alone on many genes such as IL-6, CCL2, ADAMTS1, and 5. Conclusion BS and CL have anti-oxidative, anti-inflammatory, and anti-catabolic activities, suggesting a protective effect of these extracts on cartilage. Even if they share some mechanism of action, the two extracts act mainly on distinct pathways, and with different time courses, justifying their association to treat osteoarthritis.Purpose Immune checkpoint and antiangiogenic inhibitors have a potentially synergistic antitumor effect. We aimed to assess the efficacy and safety of immunotherapy in combination with antiangiogenesis therapy with or without chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods PubMed, Embase, the Cochrane library, Google Scholar, Ovid, Scopus, and Web of Science were searched for eligible trials. ClinicalTrials.gov and meeting abstracts were also searched for qualified clinical studies. TGF-beta cancer The inclusion criteria were as follows prospective studies (including single-arm studies) that evaluated efficacy and/or toxicity of immunotherapy combined with antiangiogenic agents (A + I) with or without chemotherapy (A + I + chemo) in patients with advanced or metastatic NSCLC; and primary outcome of each study reported at least one of these endpoints progression-free survival (PFS), overall survival, objective response rate (ORR), disease control rate (DCR), or adverse events (AEs). Results . 16.2% vs. 9.7% for hypertension, and 1.9% vs. 1.2% vs. 2.8% for rash, respectively. No new safety signals were identified in this pooled analysis. Conclusion Immunotherapy combined with antiangiogenic agents with or without chemotherapy showed encouraging antitumor activity and an acceptable toxicity profile in treatment-naïve or pretreated patients with advanced NSCLC. Doublet treatment with immunotherapy and antiangiogenic agents might be a new option for patients with advanced NSCLC, especially those who are treatment-naive or cannot tolerate chemotherapy.Introduction Medication-related osteonecrosis of the jaw (MRONJ) is an oral complication in cancer patients being treated with either antiresorptives, mainly denosumab and bisphosphonates, or antiangiogenic drugs. Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for the treatment of patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC). TKI-induced osteonecrosis of the jaw has been reported in recent years, but these cases almost occur in combination with bisphosphonates, and the data on MRONJ associated to osimertinib is scarce. Case report We reported a case of MRONJ associated only with osimertinib. A 69-year-old female patient with NSCLC developed MRONJ after 4 years of treatment with osimertinib. Six months ago, she felt persistent pain and swelling in the right maxilla. After 3 months of pain, her dentist extracted one tooth in the right maxilla under local anesthesia. We examined her gingiva and found fistula and pus spillage. A digital volume tomography scan revealed sequestrum. The patient underwent surgical debridement of the necrotic bone under general anesthesia and administered intravenous antibiotics at the hospital. Histopathological analysis of the bone biopsy revealed a diagnosis of MRONJ. Conclusion This report provides evidence that osimertinib monotherapy can cause MRNOJ, and has a contribution to explore the formation mechanism of MRONJ. For those patients who take osimertinib, routine oral examinations and monitoring should be performed before and during treatment, as well as prompt closure of wounds and antibiotic treatment to avoid infection after invasive oral surgery such as tooth extraction.Light is a natural agent consisting of a range of visible and invisible electromagnetic spectrum travels in waves. Near-infrared (NIR) light refers to wavelengths from 800 to 2,500 nm. It is an invisible spectrum to naked eyes and can penetrate through soft and hard tissues into deep structures of the human body at specific wavelengths. NIR light may carry different energy levels depending on the intensity of emitted light and therapeutic spectrum (wavelength). Stimulation with NIR light can activate intracellular cascades of biochemical reactions with local short- and long-term positive effects. These properties of NIR light are employed in photobiomodulation (PBM) therapy, have been linked to treating several brain pathologies, and are attracting more scientific attention in biomedicine. Transcranial brain stimulations with NIR light PBM in recent animal and human studies revealed a positive impact of treatment on the progression and improvement of neurodegenerative processes, management of brain energy mets.Background At present, a number of systematic reviews (SRs) on Xuebijing injection (a patent in China) in the treatment of acute pancreatitis (AP) or severe acute pancreatitis (SAP) have been published. However, the quality of evidence is uneven and has not been comprehensively evaluated. Aim We evaluated the efficacy of Xuebijing injection for AP/SAP through an overview of SR, and to provide a scientific basis for its effectiveness and safety. Methods We searched Cochrane Library, Embase, PubMed, SinoMed, CNKI, Wanfang, and VIP comprehensively. The retrieval period from inception to 30 November 2021, and the two reviewers independently complete the literature retrieval, data extraction and evaluation. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) were used to evaluate the methodological quality and reporting quality of the SRs, respectively. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool was used to evaluate the quality grading of outcomes and the risk of bias in SRs was evaluated by ROBIS Tool.
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