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Cotton is of great economic value because of its fiber that is used in natural textile commodities and its seeds that contain an edible oil with a high content of unsaturated fatty acids and biodiesel applications. Here, we reported that GhKASI_A05 was associated with the cottonseed oil content (SOC) in a natural population via candidate gene association analysis. An 11-bp Indel located in the GhKASI_A05 promoter was found to contribute to SOC and differential expression in upland cotton inbred accessions. Interaction analysis showed that GhWRI1, an AP2/EREBP family transcription factor, that reportedly functions in plant seed oil and fatty acids (FAs) accumulation, directly bound to AW-box cis-elements in two haplotypes of the GhKASI_A05 promoter and activated the expression of GhKASI_A05 at different levels. The seed-specific overexpression of GhKASI_A05 resulted in increased seed size, weight, and protein content, and C16:0 and C18:1 contents but reduced SOC. Our results provide new insights into the biological function of GhKASI in SOC and effective strategies for cotton breeding in the future.
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During surveys conducted in 2020, severe symptoms associated with death and decline were observed on >30-year-old Metasequoia glyptostroboides (Chinese redwood) trees in the shelter-forests along Yangtze River in Jingzhou city, Hubei province, China. A previous study showed that Phytophthora acerina was one of the causal agents of the decline of the Chinese redwood. In this study, a total of 147 fungal isolates were obtained from the diseased roots and xylem of trunks of declining M. glyptostroboides trees. Through morphology and multi-locus phylogenetic analysis, these isolates were identified as eight species belonging to the genera Fusarium and Neocosmospora including F. fujikuroi, F. irregulare, F. odoratissimum, F. reticulatumï¼ N. falciformis, N. keratoplastica, N. solani, and N. tonkinensis. Single inoculation and co-inoculation with P. acerina assays of these Fusarium and Neocosmospora species were then performed to test pathogenicity on three-year-old seedlings of M. glyptostroboides. Lesions (i.e., on seedling stems) caused by species of the genera Neocosmopora and Fusarium were smaller than those caused by P. acerina. Co-inoculation of F. fujikuroi and P. acerina, as well as the co-inoculation of F. reticulatum and P. acerina caused larger lesions than inoculations with P. acerina alone. All these species of Fusarium and Neocosmospora were shown to have the potential to be pathogenic to M. glyptostroboides. This study provided evidence that the decline of M. glyptostroboides in Jingzhou is a disease complex.
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Background: Previous research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits. Methods: This study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development. Results: Based on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8+ T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. Actinobacteria remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps. Conclusions: Our findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.
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Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Microbioma Gastrointestinal/imunologia , Pólipos/imunologia , Pólipos/microbiologia , Predisposição Genética para DoençaRESUMO
BACKGROUND: Substantial evidence supports that glaucoma and dementia share pathological mechanisms and pathogenic risk factors. However, the association between glaucoma, cognitive decline and dementia has yet to be elucidated. OBJECTIVE: This study was aimed to assess whether glaucoma increase the risk of dementia or cognitive impairment. METHODS: PubMed, Cochrane Library, Web of Science, and EMBASE databases for cohort or case-control studies were searched from inception to March 10, 2024. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to the risk of bias. Heterogeneity was rigorously evaluated using the I2 test, while publication bias was assessed by visual inspection of the funnel plot and by Egger' s regression asymmetry test. Subgroup analyses were applied to determine the sources of heterogeneity. RESULTS: Twenty-seven studies covering 9,061,675 individuals were included. Pooled analyses indicated that glaucoma increased the risk of all-cause dementia, Alzheimer's disease, vascular dementia, and cognitive impairment. Subgroup analysis showed that the prevalence of dementia was 2.90 (95% CI: 1.45-5.77) in age ≥ 65 years and 2.07 (95% CI: 1.18-3.62) in age<65 years; the incidence rates in female glaucoma patients was 1.46 (95% CI: 1.06-2.00), respectively, which was no statistical significance in male patients. Among glaucoma types, POAG was more likely to develop dementia and cognitive impairment. There were also differences in regional distribution, with the highest prevalence in the Asia region, while glaucoma was not associated with dementia in Europe and North America regions. CONCLUSION: Glaucoma increased the risk of subsequent cognitive impairment and dementia. The type of glaucoma, gender, age, and region composition of the study population may significantly affect the relationship between glaucoma and dementia.
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Disfunção Cognitiva , Demência , Glaucoma , Humanos , Demência/epidemiologia , Disfunção Cognitiva/epidemiologia , Glaucoma/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analysis (BPRF) to investigate the relationship of whole grain consumption on type 2 diabetes (T2D), colorectal cancer (CRC), stroke, and ischemic heart disease (IHD). METHODS: We conducted a literature search in the Medline and Web of Science up to June 12, 2023, to identify related cohort studies and systematic reviews. The mean RR (relative risk) curve and uncertainty intervals (UIs), BPRF function, risk-outcome score (ROS), and the theoretical minimum risk exposure level (TMREL) were estimated to evaluate the level of four risk-outcome pairs. RESULTS: In total, 27 prospective cohorts were included in our analysis. Consuming whole grain at the range of TMREL (118.5-148.1 g per day) was associated with lower risks: T2D (declined by 37.3%, 95% UI: 5.8 to 59.5), CRC (declined by 17.3%, 6.5 to 27.7), stroke (declined by 21.8%, 7.3 to 35.1), and IHD (declined by 36.9%, 7.1 to 58.0). For all outcomes except stroke, we observed a non-linear, monotonic decrease as whole grain consumption increased; For stroke, it followed a J-shaped curve (the greatest decline in the risk of stroke at consuming 100 g whole grain for a day). The relationships between whole grain consumption and four diseases are all two-star pairs (ROS: 0.087, 0.068, 0.062, 0.095 for T2D, CRC, stroke, and IHD, respectively). CONCLUSION: Consuming 100 g of whole grains per day offers broad protective benefits. However, exceeding this threshold may diminish the protective effects against stroke. Our findings endorse replacing refined grains with whole grains as the main source of daily carbohydrates. REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: We have registered our research in PROSPERO, and the identifier of our meta-analyses is CRD42023447345.
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Doenças Cardiovasculares , Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Grãos Integrais , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Colorretais/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Dieta/métodos , Dieta/estatística & dados numéricos , Estudos Prospectivos , Fatores de RiscoRESUMO
The carbonization of lignocellulosic biomass with ionic liquids (ILs) are considered as an advantageous approach for the preparation of carbonaceous materials. The commonly used imidazolium and pyridinium based ILs have drawbacks such as toxicity, resistance to biodegradation, high cost and viscosity. These issues can be mitigated by diluting ILs with water, although excessive water content above 1 wt% can reduce the solubility of biomass. This research aims to investigate the potential of pretreating wastepaper with a "fully green" ILs, amino acid-based IL with high water content, followed by pyrolysis without IL, in enhancing the properties of biochar. For this purpose, the paper was treated with an aqueous solution of IL cysteine nitrate ([Cys][NO3]), and the IL was not involved in the pyrolysis process to prevent the formation of secondary gaseous pollutants. The findings revealed that the hemicellulose and mineral filler in the paper were eliminated during pretreatment, leading to higher carbon content but lower oxygen content. As a result, the biochar exhibited micropores of 0.42 cm3g-1 and a specific surface area of 1011.21 m2 g-1. The biochar demonstrated high adsorption capacities for Cd2+, enrofloxacin, bisphenol A, ciprofloxacin, and tetracycline, with values of 45.20 mg g-1, 49.82 mg g-1, 49.90 mg g-1, 49.88 mg g-1, and 49.65 mg g-1, respectively. The proposed mechanism for the adsorption of enrofloxacin by the biochar primarily involves physical adsorption such as pore filling and electrostatic interactions, along with chemical adsorption facilitated by graphitic nitrogen.
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Aminoácidos , Carvão Vegetal , Líquidos Iônicos , Líquidos Iônicos/química , Carvão Vegetal/química , Adsorção , Aminoácidos/químicaRESUMO
Optimizing photosynthesis is considered an important strategy for improving crop yields to ensure food security. To evaluate the potential of using photosynthesis-related parameters in crop breeding programs, we measured chlorophyll fluorescence along with growth-related and morphological traits of 23 barley inbred lines across different developmental stages in field conditions. The photosynthesis-related parameters were highly variable, changing with light intensity and developmental progression of plants. Yet, the variation in photosystem II quantum yield observed among the inbred lines in the field largely reflected the variation in CO2 assimilation properties in controlled climate chamber conditions, confirming that the chlorophyll fluorescence-based technique can provide proxy parameters of photosynthesis to explore genetic variation under field conditions. Heritability (H2) of the photosynthesis-related parameters in the field ranged from 0.16 for the quantum yield of non-photochemical quenching to 0.78 for the fraction of open photosystem II center. Two parameters, the maximum photosystem II efficiency in the light-adapted state (H2=0.58) and the total non-photochemical quenching (H2=0.53), showed significant positive and negative correlations, respectively, with yield-related traits (dry weight per plant and net straw weight) in the barley inbred lines. These results indicate the possibility of improving crop yield through optimizing photosynthetic light use efficiency by conventional breeding programs.
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Variação Genética , Hordeum , Fotossíntese , Hordeum/genética , Hordeum/crescimento & desenvolvimento , Hordeum/fisiologia , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/genética , Clorofila/metabolismoRESUMO
The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.
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Benzofenonas , Ferroptose , Osteoartrite , Osteonectina , Humanos , Benzofenonas/metabolismo , Benzofenonas/toxicidade , Biologia Computacional , Estudos Transversais , Ferroptose/efeitos dos fármacos , Inquéritos Nutricionais , Osteoartrite/induzido quimicamente , Osteonectina/antagonistas & inibidores , Osteonectina/genética , Osteonectina/metabolismo , ProteômicaRESUMO
Myofibrillogenesis regulator-1 (MR-1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR-1 on the development and metastasis of non-small cell lung cancer (NSCLC). MR-1 is upregulated in NSCLC and positively associated with poor prognosis. The overexpression of MR-1 promotes the metastasis of NSCLC cells by stabilizing the expression of Notch3-ICD (NICD3) in the cytoplasm through enrichment analysis, in vitro and in vivo experimental researches. And Notch3 signaling can upregulate many genes related to metastasis. The stabilizing effect of MR-1 on NICD3 is achieved through the mono-ubiquitin lysosomal pathway and the specific E3 ubiquitin ligase is Itchy homolog (ITCH). There is a certain interaction between MR-1 and NICD3. Elevated MR-1 can affect the level of ITCH phosphorylation, reduce its E3 enzyme activity, and thus lead to reduce the ubiquitination and degradation of NICD3. Interference with the interaction between MR-1 and NICD3 can increase the degradation of NICD3 and impair the metastatic ability of NSCLC cells, which is a previously overlooked treatment option in NSCLC. In summary, interference with the interaction between MR-1 and NICD3 in the progression of lung cancer may be a promising therapeutic target.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Neoplasias Pulmonares/genética , Lisossomos/metabolismo , Desenvolvimento Muscular , Ubiquitina , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Hylurgus ligniperda, a major international forestry quarantine pest, was recently found to have invaded and posed a serious threat to the Pinus forests of the Jiaodong Peninsula in China. Continuous monitoring and vigilance of the early population is imperative, and rapid molecular detection technology is urgently needed. We focused on developing a single-gene-based species-specific PCR (SS-PCR) method. RESULTS: We sequenced and assembled the mitochondrial genome of H. ligniperda to identify suitable target genes. We identified three closely related species for detecting the specificity of SS-PCR through phylogenetic analysis based on 13 protein-coding genes (PCGs). Subsequently, we analyzed the evolution of 13 PCGs and selected four mitochondrial genes to represent slow-evolving gene (COI) and faster-evolving genes (e.g. ND2, ND4, and ND5), respectively. We developed four species-specific primers targeting COI, ND2, ND4, and ND5 to rapidly identify H. ligniperda. The results showed that the four species-specific primers exhibited excellent specificity and sensitivity in the PCR assays, with consistent performance across a broader range of species. This method demonstrates the ability to identify beetles promptly, even during their larval stage. The entire detection process can be completed within 2-3 h. CONCLUSIONS: This method is suitable for large-scale species detection in laboratory settings. Moreover, the selection of target genes in the SS-PCR method is not affected by the evolutionary rate. SS-PCR can be widely implemented at port and forestry workstations, significantly enhancing early management strategies and quarantine measures against H. ligniperda. This approach will help prevent the spread of the pest and effectively preserve the resources of Chinese pine forests.
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Besouros , Genoma Mitocondrial , Pinus , Gorgulhos , Animais , Filogenia , China , Primers do DNA , Pinus/genéticaRESUMO
The function of Biliverdin Reductase A (BLVRA) in hepatocellular carcinoma (HCC) cells proliferation, invasion and migration remains unclear. Therefore, this research intends to explore the effect of BLVRA on HCC cells growth and metastasis. BLVRA expression was analyzed in public dataset and examined by using western blot. The malignant function of BLVRA in HCC cell lines and its effect on Wnt/ß-catenin pathway were measured. Analysis from GEPIA website showed that BLVRA expression was significantly increased in HCC tissues, and high expression of BLVRA resulted in worse prognosis of HCC patients. Results from western blot showed that BLVRA expression was obviously increased in HCC cell lines. Moreover, HepG2 and Hep3B cells in si-BLVRA-1 or si-BLVRA-2 group displayed an obvious reduction in its proliferation, cell cycle, invasion and migration compared to those in the si-control group. Additionally, si-BLVRA-1 or si-BLVRA-2 transfection significantly reduced the protein levels of Vimentin, Snail1 and Snail2, as well as decreased Bcl-2 expression and increased Bax and cleaved-caspase 3 expression. Furthermore, si-BLVRA treatment inhibited the protein levels of c-MYC, ß-catenin, and Cyclin D1. After IWP-4 (Wnt/ß-catenin inhibitor) treatment, the proliferation ability of HCC cells was significantly reduced. BLVRA expression was significantly increased in HCC tissues and cell lines, and knocked down of BLVRA could suppress the proliferation, invasion and migration in HCC cell lines, as well as induce cell apoptosis. Moreover, si-BLVRA transfection blocked the activation of Wnt/ß-catenin pathway.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , beta Catenina/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Via de Sinalização WntRESUMO
Agrilus mali stands as a significant wood-boring pest prevalent in Northeast Asia. Identifying this pest beetle is often hindered by insufficient efficient, rapid, on-site discrimination methods beyond examining adult morphological features. As a result, an urgent need arises for developing and implementing a rapid and accurate molecular technique to distinguish and manage the beetle. This study presents a straightforward, swift, highly specific, and sensitive method built upon recombinase polymerase amplification combined with a lateral flow dipstick (RPA-LFD). This method demonstrates the capability to promptly identify the beetle, even during its larval stage. RPA primers and probes were designed using the internal transcribed spacer 1 region. Through probe optimization, false-positive signals were successfully eliminated, with an accompanying discussion on the underlying causes of such signals. The RPA-LFD assays exhibited remarkable specificity and sensitivity, requiring as little as 10-3 ng of purified DNA. Furthermore, the extraction of crude DNA was achieved through immersion in sterile distilled water, thus streamlining the assay process. Achievable at temperatures ranging from 30 to 50 °C, the RPA-LFD assay can be executed manually without specialized equipment. By merging the RPA-LFD assay with DNA coarse extraction, A. mali can be detected within just 30 min. This current study effectively demonstrates the immense potential of RPA-LFD in quarantine and pest management. Additionally, it presents a universal technique for the rapid on-site diagnosis of insects, showcasing the wide applicability of this method.
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Besouros , Recombinases , Animais , Técnicas de Amplificação de Ácido Nucleico/métodos , Madeira , Besouros/genética , Mali , China , Sensibilidade e Especificidade , DNARESUMO
The Lentinula edodes stipe (LES), a by-product of L. edodes fruiting body processing, is rich in dietary fiber, protein, and polysaccharides, which can be served as the functional ingredient in dairy products. In this study, stirred yogurts fortified with 1%, 2%, and 3% LES were prepared, and the effects of LES on the changes in color, pH, titratable acidity (TA), viable lactic acid bacteria (LAB) cells, syneresis, viscosity, texture, and antioxidant activity of the flavored yogurt were monitored at the beginning and the end of storage. The LES decreased the lightness, increased the red-green color values and yellow-blue color values, decreased the pH values, and increased the contents of TA, the viable LAB cells, and the antioxidant activity of yogurt samples in a dose-dependent manner. The addition of LES showed double-edged effects on the texture of yogurt, which significantly reduced firmness and viscosity but decreased the syneresis. Compared with plain yogurt, the 2% LES-fortified yogurt exhibited similar index values of texture parameters and higher scores of the appearance, fermented odor, taste quality, and overall acceptance, suggesting that this might be the optimal dose for industrial production. After cold storage for 28 days, pH values of all yogurt samples further decreased with increasing of TA. Interestingly, syneresis of LES-fortified yogurt decreased and the viable LAB cells and antioxidant activity of 3% LES-fortified yogurt slightly decreased. Therefore, LES is beneficial to improve physicochemical, sensory, and antioxidant properties of yogurt, which has the potential to be used in functional dairy products.
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Objective: Osteoarthritis (OA) and asthma are two common chronic diseases with increasing incidence and prevalence, whereas there has been rare evidence to suggest the relationship between OA and asthma. This study aimed to analyze the causal relationship between OA and asthma. Methods: Existing studies of the relationship between asthma and OA published till July 18, 2023, were identified from PubMed and Web of Science databases for meta-analysis. Subsequently, the causal relationship of all and site-specific OA with asthma was explored through a bidirectional two-sample Mendelian randomization (MR) analysis. Results: A total of four eligible studies were included in the meta-analysis. In these studies, 80,550 participants were recruited, of whom 13,781 patients had OA. The asthma group had a significantly higher prevalence of OA than the control group (odds ratio (OR) = 2.08; 95% confidence intervals (CI): 1.42-3.03). However, MR analysis did not support a causal relationship between asthma and all OA and site-specific OA: knee and hip OA (OR = 1.03; 95% CI: 0.98-1.09), knee OA (OR = 1.02; 95% CI:0.96-1.08), and hip OA (OR = 1.04; 95% CI: 0.97-1.12). No causal relationship between OA and asthma was found through reverse MR analysis. Conclusions: This meta-analysis suggests that patients with asthma are likely to have a greater prevalence of OA. However, the result of MR analysis reveals that asthma does not have a causal relationship to all OA or site-specific OA.
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Icariin (ICA), a flavonoid phytoestrogen, was isolated from traditional Chinese medicine Yin Yang Huo (Epimedium brevicornu Maxim.). Previous studies reporting the cardioprotective effects of ICA are available; however, little is known about the impact of ICA on cardioprotection under conditions of reduced estrogen levels. This study aimed to provide detailed information regarding the antihypertrophic effects of ICA in ovariectomized female mice. Female mice were subjected to ovariectomy (OVX) and transverse aortic constriction and then orally treated with ICA at doses of 30, 60 or 120 mg/kg/day for 4 weeks. Morphological assessments, echocardiographic parameters, histological analyses, and immunofluorescence were performed to evaluate cardiac hypertrophy. Cardiomyocytes from mice or rats were stimulated using phenylephrine, and cell surface and hypertrophy markers were tested using immunofluorescence and qPCR. Western blotting, qPCR, and luciferase reporter gene assays were used to assess the expression of proteins and mRNA and further investigate the proteins related to the G-protein coupled estrogen receptor (GPER1) and CaMKII/HDAC4/MEF2C signaling pathways in vivo and in vitro. ICA blocks cardiac hypertrophy induced by pressure overload in OVX mice. Additionally, we demonstrated that ICA activated GPER1 and inhibited the nuclear export or promoted the nuclear import of histone deacetylase 4 (HDAC4) through regulation of phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and further improved the repression of myocyte enhancer factor-2C (MEF2C). ICA ameliorated cardiac hypertrophy in OVX mice by activating GPER1 and inhibiting the CaMKII/HDAC4/MEF2 signaling pathway.
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BACKGROUND: Artesunate (ART) has been reported to have an antifibrotic effect in various organs. The underlying mechanism has not been systematically elucidated. We aimed to clarify the effect of ART on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in an experimentally infected rodent model and the potential underlying mechanisms. METHODS: The effect of ART on hepatic stellate cells (HSCs) was assessed using CCK-8 and Annexin V-FITC/PI staining assays. The experimental model of liver fibrosis was established in the Mongolian gerbil model infected with S. japonicum cercariae and then treated with 20 mg/kg or 40 mg/kg ART. The hydroxyproline (Hyp) content, malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in liver tissue were measured and histopathological changes of liver tissues were observed. Whole-transcriptome RNA sequencing (RNA-seq) of the liver tissues was performed. Differentially expressed genes (DEGs) were identified using bioinformatic analysis and verified by quantitative PCR (qPCR) and western blot assay. RESULTS: ART significantly inhibited the proliferation and induce the apoptosis of HSCs in a dose-dependent manner. In vivo, Hyp content decreased significantly in the ART-H group compared to the model (MOD) group and GPX activity was significantly higher in the ART-H group than in the MOD group. Besides, ART treatment significantly reduced collagen production (p <0.05). A total of 158 DEGs and 44 differentially expressed miRNAs related to ART-induced anti-schistosomiasis liver fibrosis were identified. The qPCR and western blot results of selected DEGs were consistent with the sequencing results. These DEGs were implicated in key pathways such as immune and inflammatory response, integrin-mediated signaling and toll-like receptor signaling pathways. CONCLUSION: ART is effective against liver fibrosis using Mongolian gerbil model induced by S. japonicum infection. We identified host candidate regulators of schistosomiasis-induced liver fibrosis in response to ART through transcriptomics approach.
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Non-alcoholic fatty liver disease (NAFLD) is a progressive metabolic disease characterized by hepatic steatosis, inflammation, and fibrosis that seriously endangers global public health. Epidemiological studies have shown that the incidence of non-alcoholic fatty liver disease in postmenopausal women has significantly increased. Studies have shown that estrogen deficiency is the main reason for this situation, and supplementing estrogen has become a new direction for preventing the occurrence of postmenopausal fatty liver. However, although classical estrogen replacement therapy can reduce the incidence of postmenopausal NAFLD, it has the risk of increasing stroke and cardiovascular diseases, so it is not suitable for the treatment of postmenopausal NAFLD. More and more recent studies have provided evidence that phytoestrogens are a promising method for the treatment of postmenopausal NAFLD. However, the mechanism of phytoestrogens in preventing and treating postmenopausal NAFLD is still unclear. This paper summarizes the clinical and basic research evidence of phytoestrogens and reviews the potential therapeutic effects of phytoestrogens in postmenopausal NAFLD from six angles: enhancing lipid metabolism in liver and adipose tissue, enhancing glucose metabolism, reducing oxidative stress, reducing the inflammatory response, regulating intestinal flora, and blocking liver fibrosis (Graphical Abstract).
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Copper is an essential trace element that acts as a cofactor in various enzyme active sites in the human body. It participates in numerous life activities, including lipid metabolism, energy metabolism, and neurotransmitter synthesis. The proposal of "Cuproptosis" has made copper metabolism-related pathways a research hotspot in the field of tumor therapy, which has attracted great attention. This review discusses the biological processes of copper uptake, transport, and storage in human cells. It highlights the mechanisms by which copper metabolism affects hepatocellular carcinogenesis and metastasis, including autophagy, apoptosis, vascular invasion, cuproptosis, and ferroptosis. Additionally, it summarizes the current clinical applications of copper metabolism-related drugs in antitumor therapy.
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[This corrects the article DOI: 10.3389/fimmu.2023.1118449.].