Comparison of three digestion methods for microplastic extraction from aquaculture feeds.

Microplastics (MPs) are ubiquitous pollutants found in aquaculture animals that may threaten human health through the food chain. However, there is a lack of effective methods for extracting MPs from aquaculture feeds containing complex components such as organic matter and fish bones. Therefore, in the present study, the extraction efficiency of three digestion methods using 30 % H2O2, Fenton reagent, and 30 % H2O2 + HNO3 for different particle sizes and types of MPs in aquaculture feeds was investigated and compared. The total digestion efficiency of the aquaculture feeds by 30 % H2O2 was 97.3 ± 0.1 %, while the recovery efficiency of MPs was 91.3 ± 1.1 % -103.1 ± 0.9 %. However, there was a large deviation in the extraction efficiency of MPs from aquaculture feeds by the Fenton reagent and 30 % H2O2 + HNO3. Notably, the surface morphology, particle size distribution, and oxidation degree of MPs hardly changed after 30 % H2O2 digestion. More importantly, the changes in the spectral features and carbonyl index of MPs after 30 % H2O2 digestion were smaller than those of the Fenton reagent and 30 % H2O2 + HNO3, which did not affect the identification of MPs. Overall, 30 % H2O2 was more efficient in extracting MPs from aquaculture feeds, and no significant effect on the characteristics of MPs was observed. This work provides novel insights into the effect of chemical pretreatment on the extraction of MPs in aquaculture feeds and provides an optimal protocol for the detection of MPs in aquaculture feeds.

Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.

Breast cancer is the most prevalent cancer worldwide and its incidence increases with age, posing a significant threat to women's health globally. Due to the clinical heterogeneity of breast cancer, the majority of patients develop drug resistance and metastasis following treatment. Ferroptosis, a form of programmed cell death dependent on iron, is characterized by the accumulation of lipid peroxides, elevated levels of iron ions and lipid peroxidation. The underlying mechanisms and signalling pathways associated with ferroptosis are intricate and interconnected, involving various proteins and enzymes such as the cystine/glutamate antiporter, glutathione peroxidase 4, ferroptosis inhibitor 1 and dihydroorotate dehydrogenase. Consequently, emerging research suggests that ferroptosis may offer a novel target for breast cancer treatment; however, the mechanisms of ferroptosis in breast cancer urgently require resolution. Additionally, certain natural compounds have been reported to induce ferroptosis, thereby interfering with breast cancer. Therefore, this review not only discusses the molecular mechanisms of multiple signalling pathways that mediate ferroptosis in breast cancer (including metastasis, invasion and proliferation) but also elaborates on the mechanisms by which natural compounds induce ferroptosis in breast cancer. Furthermore, this review summarizes potential compound types that may serve as ferroptosis inducers in future tumour cells, providing lead compounds for the development of ferroptosis-inducing agents. Last, this review proposes the potential synergy of combining natural compounds with traditional breast cancer drugs in the treatment of breast cancer, thereby suggesting future directions and offering new insights.

Efficacy and safety of iguratimod in the treatment of rheumatic and autoimmune diseases: a meta-analysis and systematic review of 84 randomized controlled trials.

Objective: To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Methods: Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software. Results: A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren's syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], p = 0.003), ACR50 (RR 1.80 [1.43, 2.26], p < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], p = 0.001), DAS28 (WMD -1.11 [-1.69, -0.52], p = 0.0002), reduce ESR (WMD -11.05 [-14.58, -7.51], p < 0.00001), CRP (SMD -1.52 [-2.02, -1.02], p < 0.00001), RF (SMD -1.65 [-2.48, -0.82], p < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], p < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], p < 0.00001), BASFI score (WMD -1.07 [-1.39, -0.75], p < 0.00001), VAS (WMD -2.01 [-2.83, -1.19], p < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD -1.71 [-2.44, -0.98], p < 0.00001; IGU only group: WMD -2.10 [-2.40, -1.81], p < 0.00001) and ESSDAI score (IGU + other therapy group: WMD -1.62 [-2.30, -0.94], p < 0.00001; IGU only group: WMD -1.51 [-1.65, -1.37], p < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer's test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], p < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], p = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], p = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function. Conclusion: Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia. Systematic Review Registration: (CRD42021289489).

[Photodegradation of Plastic Blends in Seawater and Its Risk to the Marine Environment].

The production and use of plastic blends have been gradually increasing owing to their versatility and low cost. However, the photodegradation of plastic blends in seawater and the potential risk to the marine environment are still not well understood. In this study, plastic blends including polypropylene/thermoplastic starch blends(PP/TPS) and polylactic acid/poly(butylene adipate-co-terephthalate)/thermoplastic starch blends(PLA/PBAT/TPS) were investigated. The corresponding neat polymers, namely polypropylene(PP) and polylactic acid(PLA), were set as control groups. We investigated the formation of MPs and the changes in the physicochemical properties of plastic blends after photodegradation in seawater. The size distribution of MPs indicated that PP/TPS and PLA/PBAT/TPS were more likely to produce small-sized particles after photodegradation than PP and PLA owing to their poorer mechanical properties and lower resistance to UV irradiation. Noticeable surface morphology alterations, including cracks and wrinkles, were observed for plastic blends following photodegradation, whereas PP and PLA were relatively resistant. After photodegradation, the ATR-FTIR spectrum of PP/TPS and PLA/PBAT/TPS showed a significant decrease in the characteristic bands of thermoplastic starch(TPS), indicating the degradation of their starch fractions. The C 1s spectra demonstrated that aged plastic blends contained fewer -OH groups than the pristine MPs did, further confirming the photodegradation of TPS. These results indicate that PP/TPS and PLA/PBAT/TPS had a higher degree of photodegradation than PP and PLA and thereby generated more small-sized MPs. In summary, plastic blends may pose a higher risk to the marine environment than neat polymers, and caution should be taken in the production and use of plastic blends.

Updating the therapeutic role of ginsenosides in breast cancer: a bibliometrics study to an in-depth review.

Breast cancer is currently the most common malignancy and has a high mortality rate. Ginsenosides, the primary bioactive constituents of ginseng, have been shown to be highly effective against breast cancer both in vitro and in vivo. This study aims to comprehensively understand the mechanisms underlying the antineoplastic effects of ginsenosides on breast cancer. Through meticulous bibliometric analysis and an exhaustive review of pertinent research, we explore and summarize the mechanism of action of ginsenosides in treating breast cancer, including inducing apoptosis, autophagy, inhibiting epithelial-mesenchymal transition and metastasis, and regulating miRNA and lncRNA. This scholarly endeavor not only provides novel prospects for the application of ginsenosides in the treatment of breast cancer but also suggests future research directions for researchers.

Research progress in the molecular mechanism of ferroptosis in Parkinson's disease and regulation by natural plant products.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder of the central nervous system after Alzheimer's disease. The current understanding of PD focuses mainly on the loss of dopamine neurons in the substantia nigra region of the midbrain, which is attributed to factors such as oxidative stress, alpha-synuclein aggregation, neuroinflammation, and mitochondrial dysfunction. These factors together contribute to the PD phenotype. Recent studies on PD pathology have introduced a new form of cell death known as ferroptosis. Pathological changes closely linked with ferroptosis have been seen in the brain tissues of PD patients, including alterations in iron metabolism, lipid peroxidation, and increased levels of reactive oxygen species. Preclinical research has demonstrated the neuroprotective qualities of certain iron chelators, antioxidants, Fer-1, and conditioners in Parkinson's disease. Natural plant products have shown significant potential in balancing ferroptosis-related factors and adjusting their expression levels. Therefore, it is vital to understand the mechanisms by which natural plant products inhibit ferroptosis and relieve PD symptoms. This review provides a comprehensive look at ferroptosis, its role in PD pathology, and the mechanisms underlying the therapeutic effects of natural plant products focused on ferroptosis. The insights from this review can serve as useful references for future research on novel ferroptosis inhibitors and lead compounds for PD treatment.

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.

Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review.

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its complex pathogenesis and limitations of clinical treatment strategies, it poses a serious medical challenge and medical burden worldwide. The pathogenesis of AD is not clear, and its potential biological mechanisms include aggregation of soluble amyloid to form insoluble amyloid plaques, abnormal phosphorylation of tau protein and formation of intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress and metal ion disorders. Among them, ferroptosis is a newly discovered programmed cell death induced by iron-dependent lipid peroxidation and reactive oxygen species. Recent studies have shown that ferroptosis is closely related to AD, but the mechanism remains unclear. It may be induced by iron metabolism, amino acid metabolism and lipid metabolism affecting the accumulation of iron ions. Some iron chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine and its derivatives, antioxidants (vitamin E, lipoic acid, selenium), chloroiodohydroxyquine and its derivatives Fer-1, tet, etc. have been shown in animal studies to be effective in AD and exert neuroprotective effects. This review summarizes the mechanism of ferroptosis in AD and the regulation of natural plant products on ferroptosis in AD, in order to provide reference information for future research on the development of ferroptosis inhibitors.

The mechanism of intestinal microbiota regulating immunity and inflammation in ischemic stroke and the role of natural botanical active ingredients in regulating intestinal microbiota: A review.

Intestinal microbiota is a unique ecosystem, known as the "second genome" of human beings. With the widespread application of next generation sequencing (NGS), especially 16 S rRNA and shotgun sequencing, numerous studies have shown that dysregulation of intestinal microbiota is associated with many central nervous system diseases. Ischemic stroke (IS) is a cerebrovascular disease with high morbidity and mortality. Brain damage in IS affects intestinal function, and intestinal dysfunction further aggravates brain damage, forming a vicious circle of mutual interference in pathology. The microbiota-gut-brain axis study based on the intestinal microbiota has opened up broader ideas for exploring its pathogenesis and risk factors, and also provided more possibilities for the selection of therapeutic targets for this type of drug. This review discussed the application of NGS technology in the study of intestinal microbiota and the research progress of microbiota-gut-brain axis in recent years, and systematically sorts out the literature on the relationship between ischemic stroke and intestinal microbiota. It starts with the characteristics of microbiota-gut-brain axis' bidirectional regulation, respectively discusses the high risk factors of IS under intestinal microbiota imbalance and the physiological and pathological changes of intestinal microbiota after IS, and summarizes the related targets, in order to provide reliable reference for the treatment of IS from intestinal microbiota. In addition, natural botanical active ingredients have achieved good results in the treatment of IS based on regulating the homeostasis of gut microbiota, providing new evidence for studying the potential targets and therapies of IS based on the microbiota-gut-brain axis.

A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury.

Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have shown that nerve cells die of ischemia several hours after ischemic stroke, which activates the innate immune response in the brain, promotes the production of neurotoxic substances such as inflammatory cytokines, chemokines, reactive oxygen species and - nitrogen oxide, and mediates the destruction of blood-brain barrier and the occurrence of a series of inflammatory cascade reactions. Meanwhile, the expression of adhesion molecules in cerebral vascular endothelial cells increased, and immune inflammatory cells such as polymorphonuclear neutrophils, lymphocytes and mononuclear macrophages passed through vascular endothelial cells and entered the brain tissue. These cells recognize antigens exposed by the central nervous system in the brain, activate adaptive immune responses, and further mediate secondary neuronal damage, aggravating neurological deficits. In order to reduce the above-mentioned damage, the body induces peripheral immunosuppressive responses through negative feedback, which increases the incidence of post-stroke infection. This process is accompanied by changes in the immune status of the ischemic brain tissue in local and systemic systems. A growing number of studies implicate noncoding RNAs (ncRNAs) as novel epigenetic regulatory elements in the dysfunction of various cell subsets in the neurovascular unit after cerebral infarction/ischemia-reperfusion injury. In particular, recent studies have revealed advances in ncRNA biology that greatly expand the understanding of epigenetic regulation of immune responses and inflammation after cerebral infarction/ischemia-reperfusion injury. Identification of aberrant expression patterns and associated biological effects of ncRNAs in patients revealed their potential as novel biomarkers and therapeutic targets for cerebral infarction/ischemia-reperfusion injury. Therefore, this review systematically presents recent studies on the involvement of ncRNAs in cerebral infarction/ischemia-reperfusion injury and neuroimmune inflammatory cascades, and elucidates the functions and mechanisms of cerebral infarction/ischemia-reperfusion-related ncRNAs, providing new opportunities for the discovery of disease biomarkers and targeted therapy. Furthermore, this review introduces clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possible transformative tool for studying lncRNAs. In the future, ncRNA is expected to be used as a target for diagnosing cerebral infarction/ischemia-reperfusion injury, judging its prognosis and treatment, thereby significantly improving the prognosis of patients.

The mechanism of ferroptosis regulating oxidative stress in ischemic stroke and the regulation mechanism of natural pharmacological active components.

Cerebrovascular diseases, such as ischemic stroke, pose serious medical challenges worldwide due to their high morbidity and mortality and limitations in clinical treatment strategies. Studies have shown that reactive oxygen species (ROS)-mediated inflammation, excitotoxicity, and programmed cell death of each neurovascular unit during post-stroke hypoxia and reperfusion play an important role in the pathological cascade. Ferroptosis, a programmed cell death characterized by iron-regulated accumulation of lipid peroxidation, is caused by abnormal metabolism of lipids, glutathione (GSH), and iron, and can accelerate acute central nervous system injury. Recent studies have gradually uncovered the pathological process of ferroptosis in the neurovascular unit of acute stroke. Some drugs such as iron chelators, ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) can protect nerves after neurovascular unit injury in acute stroke by inhibiting ferroptosis. In addition, combined with our previous studies on ferroptosis mediated by natural compounds in ischemic stroke, this review summarized the progress in the regulation mechanism of natural chemical components and herbal chemical components on ferroptosis in recent years, in order to provide reference information for future research on ferroptosis and lead compounds for the development of ferroptosis inhibitors.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD. Methods: The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis. Results: The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients. Conclusion: Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.

DNA Methylation of Imprinted Genes KCNQ1, KCNQ1OT1, and PHLDA2 in Peripheral Blood Is Associated with the Risk of Breast Cancer.

Methylation alterations of imprinted genes lead to loss of imprinting (LOI). Although studies have explored the mechanism of LOI in breast cancer (BC) development, the association between imprinted gene methylation in peripheral blood and BC risk is largely unknown. We utilized HumanMethylation450 data from TCGA and GEO (n = 1461) to identify the CpG sites of imprinted genes associated with BC risk. Furthermore, we conducted an independent case-control study (n = 1048) to validate DNA methylation of these CpG sites in peripheral blood and BC susceptibility. cg26709929, cg08446215, cg25306939, and cg16057921, which are located at KCNQ1, KCNQ1OT1, and PHLDA2, were discovered to be associated with BC risk. Subsequently, the association between cg26709929, cg26057921, and cg25306939 methylation and BC risk was validated in our inhouse dataset. All 22 CpG sites in the KCNQ1OT1 region were associated with BC risk. Individuals with a hypermethylated KCNQ1OT1 region (>0.474) had a lower BC risk (OR: 0.553, 95% CI: 0.397−0.769). Additionally, the methylation of the KCNQ1OT1 region was not significantly different among B cells, monocytes, and T cells, which was also observed at CpG sites in PHLDA2. In summary, the methylation of KCNQ1, KCNQ1OT1, and PHLDA2 was associated with BC risk, and KCNQ1OT1 methylation could be a potential biomarker for BC risk assessment.

The efficacy and safety of Xihuang Pill/capsule in adjuvant treatment of breast cancer: A systematic review and meta-analysis of 26 randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang Pill is a traditional Chinese medicine prescription for the treatment of breast cancer. There are many randomized controlled trials (RCTs) of Xihuang Pill in the treatment of breast cancer that have been published. Hence, a comprehensive systematic review and meta-analysis is needed. AIM: To evaluate the safety of Xihuang pill/capsule and its effect on the improvement of tumor progression, quality of life, immunity and prognosis in adjuvant treatment of breast cancer. METHODS: Chinese and English databases such as Sinomed, PubMed, Embase were searched to collect the RCTs of Xihuang pill/capsule in adjuvant treatment of breast cancer. Then the researchers extracted data from the RCTs that met the inclusion criteria, and used Cochrane standard risk bias to assess the quality of the data, and used Rev Man 5.3 statistical software for statistical analysis. RESULTS: A total of 26 RCTs with 2272 participants were included. The primary outcomes showed that Xihuang pill combined with chemotherapy and with endocrine therapy may suppress of tumor progression {Chemotherapy: risk ratio (RR) = 0.59, 95%Confidence interval (CI) [0.48,0.73], P < 0.00001; Endocrine therapy: RR = 0.56, 95%CI [0.33,0.96], P = 0.04}. Xihuang pill combined with chemotherapy, with endocrine therapy and with radiotherapy may improve the quality of life (chemotherapy: RR = 1.73, 95%CI[1.11, 2.70], P = 0.02; Endocrine therapy: RR = 1.18, 95%CI [1.01,1.38], P = 0.03; radiotherapy:RR = 1.51, 95%CI [1.01,2.27], P = 0.05). Xihuang pill combined with TCM + chemotherapy may decrease the inefficiency rate for clinical symptom improvement (RR = 0.50, 95%CI [0.28, 0.88], P = 0.02). Xihuang pill combined with chemotherapy may increase the Karnofsky Performance Scale (KPS) {Weighted Mean Difference (WMD) = 15.40, 95%CI [8.18, 22.62], P < 0.0001}. For adverse events, Xihuang pill combined with chemotherapy may alleviate adverse digestive events and leukopenia; Xihuang pill combined with endocrine therapy will not increase adverse events; Xihuang pill combined with non-antitumor therapy may reduce the incidence of leukopenia and red blood cell or hemoglobin reduction. CONCLUSION: The addition of Xihuang pill/capsule to breast cancer in conventional anti-tumor therapy may inhibit tumor progression, improve patient quality of life, reduce toxic reactions, regulate immunity, and reduce tumor markers. However, due to the overall low quality of RCTs, the research results need more high-quality RCTs to further test the conclusions.

Uncovering the Neuroprotective Effect of Hedysarum multijugum Maxim-Chuanxiong Rhizoma Compound on Cerebral Infarction through Quantitative Proteomics.

Objective: To uncover the neuroprotective effect of Hedysarum multijugum Maxim-Chuanxiong Rhizoma compound (Huangqi-Chuanxiong Compound (HCC)) on cerebral infarction (CI) through quantitative proteomics. Method: CI model was established by the modified Zea Longa intracavitary suture blocking method. After modeling, the rats were given intragastric administration for 7 days, once a day. After the 7-day intervention, the neurological function score was performed, the brain tissue was pathologically observed, and the total serum protein was extracted. Then, these proteins were analyzed by LC-MS/MS to identify the differentially expressed proteins (DEPs) in the HCC/CI group and CI/sham operation group. Finally, bioinformatics analysis was used to analyze DEPs, including gene ontology (GO) analysis, pathway analysis, and protein interaction analysis. ELISA and Western blotting were used to verify the proteomics results. Result: The neurological function scores of the HCC group were lower than those of the CI group. HE staining showed that the pathological results of the HCC group were improved. A total of 1340 proteins were identified by LC-MS/MS, of which 1138 proteins contain quantitative information. There are 122 DEPs in the CI/sham operation group and 25 DEPs in the HCC/CI group with fold change >1.3 or <0.77 and FDR<0.05. The 12 upregulated proteins in HCC/CI group include Protein Actn2, Kelch-like protein 41, Alpha-1, 4 glucan phosphorylase, Protein Lrtm2, Dystrophin, Galectin-1, and C4b-binding protein beta chain. The 13 downregulated proteins include Alpha-2 antiplasmin, Arachidonate 15-lipoxygenase, Carbonic anhydrase 2, Complement factor I, angiotensinogen, catalase, Protein LOC103691744, and Anionic trypsin-1. The bioinformatics analysis showed that HCC may treat CI through regulating cell-substrate adhesion and regulation, reactive oxygen species metabolic process, angiotensin response (cellular response to angiotensin), positive regulation of the occurrence of nerves and neurons (positive regulation of neurogenesis), inflammatory response, response to hypoxia (response to hypoxia, response to decreased oxygen levels), and cellular calcium homeostasis (cellular calcium ion homeostasis). The results of ELISA and Western blot also showed that, compared with model group, the angiotensinogen and catalase in HCC group were decreased (P < 0.05), which is consistent with the findings of proteomics. Conclusion: The therapeutic mechanism of HCC in the treatment of CI may involve fibrinolysis, cell-matrix adhesion, inflammation, hypoxia, and oxidative stress.

Exploring the Mechanism of Edaravone for Oxidative Stress in Rats with Cerebral Infarction Based on Quantitative Proteomics Technology.

OBJECTIVE: To explore the mechanism of edaravone in the treatment of oxidative stress in rats with cerebral infarction based on quantitative proteomics technology. METHOD: The modified Zea Longa intracavitary suture blocking method was utilized to make rat CI model. After modeling, the rat was intragastrically given edaravone for 7 days, once a day. After the 7-day intervention, the total proteins of serum were extracted. After proteomics analysis, the differentially expressed proteins are analyzed by bioinformatics. Then chemoinformatics methods were used to explore the biomolecular network of edaravone intervention in CI. RESULT: The neurological scores and pathological changes of rats were improved after the intervention of edaravone. Proteomics analysis showed that in the model/sham operation group, 90 proteins in comparison group were upregulated, and 26 proteins were downregulated. In the edaravone/model group, 21 proteins were upregulated, and 41 proteins were downregulated. Bioinformatics analysis and chemoinformatics analysis also show that edaravone is related to platelet activation and aggregation, oxidative stress, intercellular adhesion, glycolysis and gluconeogenesis, iron metabolism, hypoxia, inflammatory chemokines, their mediated signal transduction, and so on. CONCLUSION: The therapeutic mechanism of edaravone in the treatment of CI may involve platelet activation and aggregation, oxidative stress, intercellular adhesion, glycolysis and gluconeogenesis, iron metabolism, hypoxia, and so on. This study revealed the serum protein profile of edaravone in the treatment of cerebral infarction rats through serum TMT proteomics and discovered the relevant mechanism of edaravone regulating iron metabolism in cerebral infarction, which provides new ideas for the study of edaravone intervention in cerebral infarction and also provides reference information for future research on the mechanism of edaravone intervention in iron metabolism-related diseases.

The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review.

Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms of IS. In particular, the early proinflammatory response resulting from the overactivation of resident microglia and the infiltration of circulating monocytes and macrophages in the brain after cerebral ischemia leads to secondary brain injury. Microglia are innate immune cells in the brain that constantly monitor the brain microenvironment under normal conditions. Once ischemia occurs, microglia are activated to produce dual effects of neurotoxicity and neuroprotection, and the balance of the two effects determines the fate of damaged neurons. The activation of microglia is defined as the classical activation (M1 type) or alternative activation (M2 type). M1 type microglia secrete pro-inflammatory cytokines and neurotoxic mediators to exacerbate neuronal damage, while M2 type microglia promote a repairing anti-inflammatory response. Fine regulation of M1/M2 microglial activation to minimize damage and maximize protection has important therapeutic value. This review focuses on the interaction between M1/M2 microglia and other immune cells involved in the regulation of IS phenotypic characteristics, and the mechanism of natural plant components regulating microglia after IS, providing novel candidate drugs for regulating microglial balance and IS drug development.

Exploring the Mechanism of Baicalin Intervention in Breast Cancer Based on MicroRNA Microarrays and Bioinformatics Strategies.

OBJECTIVE: To explore the mechanism of baicalin intervention in breast cancer based on microRNA microarrays. METHODS: The inhibitory rate of baicalin intervention in MCF-7 breast cancer cells was determined by MTT. Then, the miRNA microarrays were used to validate the key microRNAs. After that, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate microRNA, hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-miR-7t. Finally, the potential targets of these key microRNAs are predicted by miRWalk, and DAVID was utilized for gene ontology (GO) enrichment analysis and pathway enrichment analysis. RESULTS: Baicalin may inhibit the proliferation of MCF-7 cells in a dose-dependent and time-dependent manner. The concentration of baicalin 150 µmol/L was determined for the subsequent miRNA chip research. A total of 92 upregulated microRNAs and 35 downregulated microRNAs were obtained. The upregulated miRNAs include hsa-miR-6799-5p, hsa-miR-6126, hsa-miR-4792, hsa-miR-6848-5p, hsa-miR-3197, hsa-miR-6779-5p, and hsa-miR -654-5p. The downregulated miRNAs include hsa-miR-3911, hsa-miR-504-5p, hsa-miR-30a-3p, hsa-miR-193b-3p, and hsa-miR-181b-5p. Then, differentially expressed miRNA was verified by qRT-PCR. The results showed that the expression of hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-let-7c was upregulated (P < 0.05), which was consistent with the results of the miRNA microarray. The enrichment analysis showed that baicalin might regulate the DNA-templated proliferation, DNA-templated transcription, p53 signaling pathway, etc., of MCF-7 breast cancer cells through miRNA. CONCLUSION: Baicalin inhibits the proliferation of breast cancer cells. It may achieve antitumor effects through regulating microRNAs so as to affect the DNA replication (such as cellular response to DNA damage stimulus and DNA binding), RNA transcription (such as regulation of transcription, DNA-templated, transcription from RNA polymerase II promoter, and transcription factor binding), protein synthesis (such as mRNA binding, Golgi apparatus, and protein complex), endocytosis, pathways in cancer, p53 signaling pathway, and so on.

Systems Biology and Chemoinformatics-Based Strategies to Explore the Biological Mechanism of Fugui Wenyang Decoction in Treating Vascular Dementia Rats.

OBJECTIVE: To explore the biological mechanism of Fugui Wenyang Decoction (FGWYD) in treating vascular dementia (VD) rats based on systems pharmacology, proteomics, and a multidirectional pharmacology integration strategy. METHODS: Chemoinformatics was utilized to construct and analyze the FGWYD-VD protein-protein interaction (PPI) network. Then, the total protein in the brain tissue of the infarcted side of the rat was extracted for protein identification, pattern identification, and protein quantitative analysis. The differentially expressed proteins are analyzed by bioinformatics. Finally, the important proteins in the oxidative stress-related biological process proteins and indicators were detected through experimental pharmacology to verify the findings of systems biology and chemoinformatics. RESULTS: There were a total of 73 FGWYD components with 245 FGWYD and 145 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate the inflammation module, oxidative stress, the synaptic plasticity regulation module, and the neuronal apoptosis section module. Compared with the sham operation group, there were 23 upregulated proteins and 17 downregulated proteins in the model group (P < 0.05). Compared with the model group, there were 16 upregulated proteins and 10 downregulated proteins in the FGWYD group (P < 0.05). Bioinformatics analysis shows that those proteins were closely related to processes such as inflammation, oxidative stress, neuronal apoptosis, neuronal growth and differentiation, signaling pathways, and transcriptional regulation. Multidirectional pharmacology further verified the neuroprotective mechanism of the Nrf2/HO-1 pathway in FGWYD treatment of VD. CONCLUSION: The mechanism of FGWYD in the treatment of VD may be related to inflammation, oxidative stress, angiogenesis, and neuronal apoptosis.

Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury's Biological Network Based on Systematic Pharmacology.

Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained. Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC's potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC's targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR. Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05). Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.