Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential

Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, further aggravate the damage of brain tissue. Paradoxically, there are still no effective methods to prevent CI/RI, since the detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, which are characterized by mitochondrial oxidative stress, Ca2+ overload, iron dyshomeostasis, mitochondrial DNA (mtDNA) defects and mitochondrial quality control (MQC) disruption, are closely relevant to the pathological process of CI/RI. There is increasing evidence that mitochondrial dysfunctions play vital roles in the regulation of programmed cell deaths (PCDs) such as ferroptosis and PANoptosis, a newly proposed conception of cell deaths characterized by a unique form of innate immune inflammatory cell death that regulated by multifaceted PANoptosome complexes. In the present review, we highlight the mechanisms underlying mitochondrial dysfunctions and how this key event contributes to inflammatory response as well as cell death modes during CI/RI. Neuroprotective agents targeting mitochondrial dysfunctions may serve as a promising treatment strategy to alleviate serious secondary brain injuries. A comprehensive insight into mitochondrial dysfunctions-mediated PCDs can help provide more effective strategies to guide therapies of CI/RI in IS

Combined effects of tenofovir and interferon α1b on viral load and levels of peripheral regulatory T cells in chronic hepatitis B subjects

Purpose: To study the combined effects of tenofovir and interferon α1b on viral load and peripheral blood regulatory T cell concentrations of chronic hepatitis B (CHB) subjects. Methods: Patients with chronic hepatitis B (86 cases) were randomly assigned to two groups: control group and study group. In control subjects, tenofovir was given orally (300 mg/kg bwt/day). In addition to tenofovir, the study group received interferon α1b injection intramuscularly at a dose of 50 μg/kg thrice a week. Liver function, serum hepatitis B viral (HBV) load, and serum levels of peripheral blood regulatory T-lymphocytes were determined. Clinical effectiveness and adverse reactions in both groups were also assessed. Results: After treatment, total effectiveness was higher in the study group (86.04 %) than in control patients (62.79 %) (p < 0.05). Serum aspartate transaminase (AST), alanine aminotransferase (ALT) and total bilirubin (TBIL) significantly decreased in the study group, relative to control, but HBV DNAnegative, HbeAg-negative and HbsAg-negative cells were markedly higher in patients in the study group (p < 0.05). Moreover, there were higher CD4+ T and CD8+ T counts, and CD4+ T/CD8+ T ratio in study subjects than in control subjects (p < 0.05). Conclusion: The combination of tenofovir with interferon α1b effectively improves liver functions in patients with CHB, reduces viral load, and exerts anti-HBV effect by regulating the levels of peripheral blood T-lymphocytes

Beneficial effects and safety of traditional Chinese medicine for chronic inflammatory demyelinating polyradiculoneuropathy: A case report and literature review

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy. First-line treatments for CIDP include corticosteroids, intravenous immunoglobulin, and plasma exchange. However, the application is always limited by high costs, effectiveness, and adverse events. This study investigated a new potentially effective and safe therapeutic treatment to alleviate CIDP symptoms and improve the quality of life. In the present case, a 47-year-old rural woman presented with weakness and numbness of progressive extremities. She was diagnosed with CIDP based on abnormal cerebrospinal fluid and electromyography. The patient was treated with intravenous dexamethasone for 1 week and with Huangqi-Guizhi-Wuwu and Bu-Yang-Huan-Wu decoctions for 90 days. Surprisingly, after the treatment, the weakness and numbness were eliminated, and the quality of life improved. The varying INCAT, MRC, and BI scores also reflected the treatment effects. After 8 months of discharge, the symptoms did not relapse during the follow-up. We also searched “traditional Chinese medicine (TCM)” and “CIDP” in PubMed, EMBASE, the Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure Databases, Wanfang Data, and the Chongqing Chinese Science and Technology Periodical Database. Finally, only ten studies were included in the literature review. Three studies were randomized controlled trials, and seven were case reports or case series. There were 419 CIDP patients, but all study sites were in China. Nine TCM formulas involving 44 herbs were reported, with Huang Qi (Astragalus membranaceus) being the most important herb. In conclusion, the case and literature demonstrated that TCM treatment might be a more effective, low-cost, and safe option for treating CIDP. Although these preliminary findings are promising, a larger sample size and higher-quality randomized clinical trials are urgently required to confirm our findings

Exploring the Pharmacological Mechanism of Danzhi Xiaoyao Powder on ER-Positive Breast Cancer by a Network Pharmacology Approach

Background. Breast cancer is the most common malignancy among women worldwide, but the long-term endocrine therapy is frequently associated with adverse side effects. Danzhi Xiaoyao powder (DXP) is a herbal formula that has an effect on breast cancer, especially ER-positive breast cancer. However, the active compounds, potential targets, and pharmacological and molecular mechanism of its action against cancer remain unclear. Methods. A network pharmacology approach comprising drug-likeness evaluation, oral bioavailability prediction, Caco-2 permeability prediction, multiple compound target prediction, multiple known target collection, breast cancer genes collection, and network analysis has been used in this study. Results. Four networks are set up—namely, ER-positive breast cancer network, compound-compound target network of DXP, DXP-ER-positive breast cancer network, and compound-known target-ER-positive breast cancer network. Some ER-positive breast cancer and DXP related targets, clusters, biological processes, and pathways, and several potential anticancer compounds are found. Conclusion. This network analysis successfully predicted, illuminated, and confirmed the molecular synergy of DXP for ER-positive breast cancer, got potential anticancer active compounds, and found the potential ER-positive breast cancer associated targets, cluster, biological processes, and pathways. This work also provides clues to the researcher who explores ethnopharmacological or/and herbal medicine’s or even multidrugs’ various synergies

Effectiveness of Omega-3 fatty acid for polycystic ovary syndrome: a systematic review and meta-analysis

Abstract Objective To assess the effectiveness and safety of omega-3 fatty acid for patients with PCOS. Methods In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of omega-3 fatty acid versus placebo or western medicine in women with PCOS. The study’s registration number is CRD42017065859. The primary outcomes included the change of homeostatic model assessment (HOMA) of insulin resistance, total cholesterol (TC), triglyceride (TG) and adiponectin. Result Nine trials involving 591 patients were included. Comparing with the control group, omega-3 fatty acid may improve HOMA index (WMD -0.80; 95% CI -0.89, − 0.71; P<0. 00001), decrease TC and TG level [TC: (WMD -9.43; 95% CI -11.90, − 6.95; P<0. 00001); TG: (WMD -29.21; 95% CI -48.08, − 10.34; P = 0. 002)], and increase adiponectin level (WMD 1.34; 95% CI 0.51, 2.17; P = 0. 002). Conclusion Based on current evidence, omega-3 fatty acid may be recommended for the treatment of PCOS with insulin resistance as well as high TC (especially LDL-C) and TG

Exploring the Oxidative Stress Mechanism of Buyang Huanwu Decoction in Intervention of Vascular Dementia Based on Systems Biology Strategy

Objective. To explore the oxidative stress mechanism of modified Buyang Huanwu decoction (MBHD) in intervention of vascular dementia (VD) based on systems biology strategy. Methods. In this study, through the reverse virtual target prediction technology and transcriptomics integration strategy, the active ingredients and potential targets of MBHD treatment of VD were analyzed, and the drug-disease protein-protein interaction (PPI) network was constructed. Then, bioinformatics analysis methods are used for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis, and finally find the core biological process. After that, in animal models, low-throughput technology is used to detect gene expression and protein expression of key molecular targets in oxidative stress-mediated inflammation and apoptosis signaling pathways to verify the mechanism of MBHD treatment of VD rats. Finally, the potential interaction relationship between MBHD and VD-related molecules is further explored through molecular docking technology. Results. There are a total of 54 MBHD components, 252 potential targets, and 360 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate neuronal apoptosis, nitric oxide synthesis and metabolism, platelet activation, NF-κB signaling pathway-mediated inflammation, oxidative stress, angiogenesis, etc. Among them, SIRT1, NF-κB, BAX, BCL-2, CASP3, and APP may be important targets for MBHD to treat VD. Low-throughput technology (qRT-PCR/WB/immunohistochemical technology) detects oxidative stress-mediated inflammation and apoptosis-related signaling pathway molecules. The molecular docking results showed that 64474-51-7, cycloartenol, ferulic acid, formononetin, kaempferol, liquiritigenin, senkyunone, wallichilide, xanthinin, and other molecules can directly interact with NF-κB p65, BAX, BCL-2, and CASP3. Conclusion. The active compounds of MBHD interact with multiple targets and multiple pathways in a synergistic manner, and have important therapeutic effects on VD mainly by balancing oxidative stress/anti-inflammatory and antiapoptotic, enhancing metabolism, and enhancing the immune system

Adaptive Learning Based Tracking Control of Marine Vessels with Prescribed Performance

A novel adaptive tracking controller of fully actuated marine vessels is proposed with completely unknown dynamics and external disturbances. The model of dominant dynamic behaviors and unknown disturbances of the vessel are learned by a neural network in real time. The controller is designed and it unifies backstepping and adaptive neural network techniques with predefined tracking performance constraints on the tracking convergence rate and the transient and steady-state tracking error. The stability of the proposed adaptive tracking controller of the vessel is proven with a uniformly bounded tracking error. The proposed adaptive tracking controller is shown to be effective in the tracking control of marine vessels by simulations

A Survey on Multimodal Knowledge Graphs: Construction, Completion and Applications

As an essential part of artificial intelligence, a knowledge graph describes the real-world entities, concepts and their various semantic relationships in a structured way and has been gradually popularized in a variety practical scenarios. The majority of existing knowledge graphs mainly concentrate on organizing and managing textual knowledge in a structured representation, while paying little attention to the multimodal resources (e.g., pictures and videos), which can serve as the foundation for the machine perception of a real-world data scenario. To this end, in this survey, we comprehensively review the related advances of multimodal knowledge graphs, covering multimodal knowledge graph construction, completion and typical applications. For construction, we outline the methods of named entity recognition, relation extraction and event extraction. For completion, we discuss the multimodal knowledge graph representation learning and entity linking. Finally, the mainstream applications of multimodal knowledge graphs in miscellaneous domains are summarized

Efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis: A systematic review and meta-analysis

Objective: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis Methods: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. Results: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)− 6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. Conclusion: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation