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Estrogen receptor α (ERα) promotes the growth and survival of ER-positive breast cancer (BC) cells. ER regulates ER expression target genes by directly binding to specific estrogen response elements, upon activation by estrogens. In this study, 106 proteins interacting with endogenous chromatin-bound ER in a BC cell line MCF7 were identified using the RIME method. The interactome data showed that the tripartite motif containing 28 (TRIM28) is the most significantly enriched ER-associated protein. This study provides evidence that TRIM28 expression improves ER transcriptional activity and promotes the BC cells proliferation, migration, and invasion of BC cells. The high expression of TRIM28 is associated with poor clinical outcomes in patients with ER-positive BC. Mechanistic experiments indicate that TRIM28 expression activates the AKT/GSK3ß pathway. To conclude, TRIM28 acts as a regulatory protein of ER and AKT signaling; therefore, it can be a target for the therapeutic interventions of BC.
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INTRODUCTION: The disruption of podocyte structure and function are the main pathological mechanism of membranous nephropathy (MN). Phospholipases A2, Group XII B (PLA2G12B) was reported involved in the regulation of MN by interfering with arachidonic acid (AA) metabolism, but there is a lack of sufficient evidence. In this study, we investigated the role and molecular mechanism of PLA2G12B in MN. METHODS: C57BL/6 mice were used to establish MN model to extract primary podocytes, then divided into control, model, si-phospholipases A2 receptor (PLA2R), PLA2G12B, PLA2G12B + si-PLA2R, PLA2G12B + nuclear factor kappa-B (NF-κB) inhibitor, PLA2G12B + NF-κB inhibitor + si-PLA2R groups. Hematoxylin-eosin staining and immunofluorescence were used to detect kidney histological arrangement, serum levels of cholesterol-related indices, and AA. Genes and proteins associated with metabolism and inflammatory factors were detected by quantitative real-time PCR and Western blot. RESULTS: The results revealed that AA metabolites were activated in the MN model mice, and the expression of PLA2G12B and NF-κB pathway levels were elevated. Besides, cellular experiments demonstrated that prostaglandin I2 (PGI2), thromboxane A2 (TXA2), leukotriene B4 (LTB4), and NF-κB pathway were significantly increased in the PLA2G12B group. Also, PLA2G12B promotes apoptosis and suppresses cell activity in podocytes, and these effects could be antagonized by NF-κB inhibitors. Furthermore, with the inference of si-PLA2R, the NF-κB inhibitors' effects were reversed. CONCLUSION: Promotional effects of PLA2G12B in primary MN are associated with the regulation of AA metabolism and NF-κB pathway.
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Glomerulonefritis Membranosa , FN-kappa B , Animales , Ratones , Ácido Araquidónico/metabolismo , Glomerulonefritis Membranosa/patología , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Fosfolipasas A2RESUMEN
BACKGROUND: Toxoplasma gondii infection endangers human health and affects animal husbandry. Serological detection is the main method used for epidemiological investigations and diagnosis of toxoplasmosis. The key to effective diagnosis of toxoplasmosis is the use of a standardized antigen and a specific and sensitive detection method. Peroxiredoxin is an antigenic protein and vaccine candidate antigen of T. gondii that has not yet been exploited for diagnostic application. METHODS: In this study, recombinant T. gondii peroxiredoxin protein (rTgPrx) was prepared and used in dot-immunogold-silver staining (Dot-IGSS) to detect IgG antibodies in serum from mice and pregnant women. The rTgPrx-Dot-IGSS method was established and optimized using mouse serum. Furthermore, serum samples from pregnant women were analyzed by rTgPrx-Dot-IGSS. RESULTS: Forty serum samples from mice infected with T. gondii and twenty negative serum samples were analyzed. The sensitivity and specificity of rTgPrx-Dot-IGSS were 97.5 and 100%, respectively, equivalent to those of a commercial ELISA kit for anti-Toxoplasma IgG antibody. Furthermore, 540 serum samples from pregnant women were screened with a commercial ELISA kit. Eighty-three positive and 60 negative serum samples were analyzed by rTgPrx-Dot-IGSS. The positive rate was 95.18%, comparable to that obtained with the commercial ELISA kit. CONCLUSIONS: The Dot-IGSS method with rTgPrx as an antigen might be useful for diagnosing T. gondii infection in individuals.
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Inmunohistoquímica/métodos , Peroxirredoxinas/inmunología , Complicaciones Parasitarias del Embarazo , Toxoplasmosis/diagnóstico , Animales , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Ratones , Peroxirredoxinas/genética , Embarazo , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Sensibilidad y Especificidad , Tinción con Nitrato de Plata , Toxoplasma/inmunología , Toxoplasma/patogenicidad , Toxoplasmosis/parasitologíaRESUMEN
Follicular helper T (Tfh) cells are dedicated to providing help to B cells and are strongly associated with antibody-mediated autoimmune disease. B cell lymphoma 6 (Bcl-6) is a key transcription factor of Tfh cells, and IL-21 is known to be a critical cytokine produced by Tfh cells. We silenced Bcl-6 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of Bcl-6 short hairpin RNAs (shRNAs) in experimental autoimmune myasthenia gravis (EAMG). Our data demonstrate that CD4(+)CXCR5(+)PD-1(+) Tfh cells, Bcl-6 and IL-21 were significantly increased in EAMG mice, compared with controls. In addition, we found that frequencies of Tfh cells were positively correlated with the levels of serum anti-AChR Ab. In-vivo transduction of lenti-siRNA-Bcl6 ameliorates the severity of ongoing EAMG with decreased Tfh cells, Bcl-6 and IL-21 expression, and leads to decreased anti-AChR antibody levels. Furthermore, we found that siRNA knockdown of Bcl-6 expression increases the expression of Th1(IFN-γ, T-bet) and Th2 markers (IL-4 and GATA3), but failed to alter the expression of Th17-related markers (RORγt, IL-17) and Treg markers (FoxP3). Our study suggests that Tfh cells contribute to the antibody production and could be one of the most important T cell subsets responsible for development and progression of EAMG or MG. Bcl-6 provides a promising therapeutic target for immunotherapy not only for MG, but also for other antibody-mediated autoimmune diseases.
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Proteínas de Unión al ADN/metabolismo , Terapia Genética , Miastenia Gravis Autoinmune Experimental/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Animales , Linfocitos B/inmunología , Linfocitos B/metabolismo , Proteínas de Unión al ADN/genética , Ratones , Ratones Endogámicos C57BL , Miastenia Gravis Autoinmune Experimental/genética , Miastenia Gravis Autoinmune Experimental/terapia , Proteínas Proto-Oncogénicas c-bcl-6 , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismoRESUMEN
Objectives: Skeletal muscles mitochondrial dysfunction is the main cause of sarcopenia. Both electroacupuncture (EA) and sulforaphane (SFN) have been shown to improve oxidative stress and inflammation levels to maintain mitochondrial function, but the effects and mechanisms of their combination on sarcopenia are unclear. This study aimed to investigate the regulatory effects of EA combined with SFN on sarcopenia. Materials and Methods: SAMP8 mice were used and intervened with EA or SFN, respectively, and Masson and HE staining were used to observe pathological changes in skeletal muscle tissue. Transmission electron microscopy was used to detect tissue mitochondrial changes. TUNEL staining was used to assess apoptosis. The biochemical and molecular content was tested by ELISA, western blot, and qRT-PCR. Results: The results showed that oxidative stress, apoptosis, and IL-6, TNF-α, Atrogin-1, and MuRF1 levels in skeletal muscles cells were suppressed and mitochondrial damage was repaired after EA or SFN intervention. In addition, we found that the above changes were associated with the activation of the AMPK/Sirt1/PGC-1α pathway in skeletal muscle tissues, and the promotion effect of combined EA and SFN intervention was more significant. Conclusion: In conclusion, this study found that EA combined with SFN mediated the repair of mitochondrial damage through activation of the AMPK/Sirt1/PGC-1α pathway, thereby alleviating skeletal muscles morphology and function in sarcopenia. This study combines EA with SFN, which not only broadens the use of electroacupuncture and SFN but also provides a scientific experimental basis for the treatment of sarcopenia.
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Background: Unusual site deep vein thrombosis (DVT) was defined as venous thromboembolism (VTE) occurring outside the conventional deep veins of the lower extremity or pulmonary arteries. However, the optimal anticoagulation therapy for unusual site DVT remained unclear. This study aims to evaluate the efficacy and safety of rivaroxaban in unusual site DVT. Methods: This retrospective cohort study enrolled consecutive patients at Nanjing Drum Tower Hospital between January 2011 and December 2021 who were diagnosed with unusual site DVT. Patients were divided into two groups based on their ultimate medication choice: the warfarin group and the rivaroxaban group. The demographic characteristics were recorded for all enrolled patients. Clinical outcomes included recurrent VTE, bleeding complications and major bleeding. Results: A total of 1,088 patients were divided into warfarin (n = 514) and rivaroxaban (n = 574) groups. After the stabilized inverse probability of treatment weighting, Hazard Ratios for warfarin vs. rivaroxaban of recurrent VTE, bleeding complications and major bleeding were 0.52(95% CI: 0.25-1.08), 0.30(95% CI: 0.14-0.60), and 0.33 (95% CI, 0.13-0.74), respectively. Risk of clinical outcomes in specified subgroups for age, gender, renal function, thrombosis sites and diagnosis were assessed. The interaction of gender and treatment on major bleeding was significant (P for interaction = 0.062). Otherwise, there was no significant interaction between the other subgroups and the treatment group in terms of clinical outcomes. Conclusion: Compared with warfarin, rivaroxaban exhibited comparable efficacy for the anticoagulant treatment of unusual site DVT, associated with a lower risk of bleeding complications and major bleeding.
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Previous studies have proved circFN1 is highly expressed in acute myeloid leukemia (AML) patients and AML cell lines. This study aims to investigate the impact of circFN1 on AML and its mechanism. Via real-time quantitative PCR to detect circFN1, miR-1294, ARHGEF10L expressions in clinical plasma samples and AML cell lines, AML cells were cultured in vitro and transfected with si-circFN1, pcDNA3.1-circFN1, and si-ARHGEF10L, respectively, or co-transfected pcDNA3.1-circFN1 + miR-1294 mimic and pcDNA3.1-circFN1 + si-ARHGEF10L. Using dual luciferase reporter experiment to detect the relationship between circFN1 and miR-1294, as well as miR-1294 and ARHGEF10L. CCK-8 was used to detect cell proliferation, Transwell to cell invasion, TUNEL staining and flow cytometry to detect cell apoptosis, RT-qPCR to circFN1 RNA, miR-1294, and ARHGEF10L expression levels in HL-60 cells, and western blot to ARHGEF10L protein expression level in HL-60 cells. We found highly expressed circFN1 and ARHGEF10L, as well as low-expressed miR-1294 in AML patients and AML cell lines. In contrast to si-NC group, si-circFN1 group could signally inhibit HL-60 cell proliferation and migration, but promote cell apoptosis; compared with mimic NC group, miR-1294 mimic group could visually inhibit HL-60 cell proliferation and migration, but promote cell apoptosis. miR-1294 was the target of circFN1, and ARHGEF10L was the target of miR-1294. Over-expressing miR-1294 or silencing ARHGEF10L could signally inhibit circFN1 promoting HL-60 cell proliferation and migration and repressing cell apoptosis. circFN1 promotes proliferation and invasion of AML cell and represses cell apoptosis via regulating miR-1294/ARHGEF10L axis, which provides new insight for molecular targeted-treatment for AML.
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Leucemia Mieloide Aguda , MicroARNs , Humanos , MicroARNs/metabolismo , Leucemia Mieloide Aguda/genética , Células HL-60 , Apoptosis/genética , Proliferación Celular/genética , Línea Celular Tumoral , Factores de Intercambio de Guanina Nucleótido Rho/genéticaRESUMEN
INTRODUCTION: Diabetic nephropathy (DN) is the most common clinical complication of diabetes mellitus. Moringa isothiocyanate-1 (MIC-1) is effective in the treatment of diabetes mellitus, but its mechanism of action in DN remains obscure. This research specifically probed the role of MIC-1 in modulating renal injury in DN. METHODS: Six db/m mice were assigned to control group and twelve db/db mice were randomly allocated to the db/db and db/db + MIC-1 groups. The body and kidney weights of the mice were monitored. Renal function indicators and oxidative stress-related markers were assessed by automatic biochemical analyzer and ELISA method. The pathological changes, apoptosis of renal tissues, extracellular regulated protein kinases (ERK) 1/2/ Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related markers, and the positive expressions of podocalyxin (Pod) and synaptopodin (Syn) were measured by H&E, PAS, and TUNEL staining, Western blot, and IHC assay. RESULTS: MIC-1 reduced the body and kidney weights, and increased the kidney organ index (calculated as 100*kidney weight/ body weight) in db/db mice. In addition, MIC-1 improved renal function, kidney tissue injury, and apoptosis of db/db mice. MIC1 noticeably repressed the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) and enhanced the contents of (glutathione) GSH, superoxide dismutase (SOD), and catalase (CAT) in db/db mice. At molecular level, db/db mice showed a decrease in p-ERK/ERK, Nrf2, SOD-1, heme oxygenase 1 (HO-1), and CAT and an increase in p- inhibitor kappa B alpha (IKBα) and p-Nuclear factor-kappa B (P65/P65), which were reversed when MIC-1 was administered. Furthermore, MIC-1 facilitated the positive expressions of Pod and Syn of the kidney tissues in db/db mice. CONCLUSION: MIC-1 reduces oxidative stress and renal injury by activating the ERK/Nrf2/HO-1 signaling and repressing the NFκB signaling in db/db mice. DOI: 10.52547/ijkd.7515.
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Diabetes Mellitus , Nefropatías Diabéticas , Moringa , Ratones , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/farmacología , Factor 2 Relacionado con NF-E2/uso terapéutico , Moringa/metabolismo , Riñón , Estrés Oxidativo , Glutatión , Isotiocianatos/farmacología , Isotiocianatos/metabolismo , Isotiocianatos/uso terapéuticoRESUMEN
Aim: To compare the differences in the effects of based on remote coached high intensity interval training and combined exercise training on the physical and mental health of university students. Method: Sixty university students were recruited from Shandong Normal University and randomly divided into HIIT group (n = 30) and AR group (n = 30), with the HIIT group using high-intensity interval training intervention and the AR group using combined exercise (aerobic combined with resistance) training intervention for 8 weeks. Mental health indicators, fitness indicators and body composition indicators were measured at the beginning and end of the intervention. Results: After 8 weeks, among the mental health indicators, the results of the Symptom Self-Rating Scale (SCL-90) test showed a significant improvement in the HIIT group in terms of total score, somatization, obsessive-compulsive, interpersonal sensitivity, depression, hostility, and psychoticism (p < 0.05); the AR group showed significant improvements in psychoticism (P < 0.05). There were no significant differences between the two groups. The results of the Pittsburgh Sleep Quality Index scale (PSQI) showed a significant difference in sleep efficiency in the HIIT group with an inverse improvement in scores; the AR group showed no significant improvement in each test item. The results of the between-group covariance showed significant differences in sleep efficiency and hypnotic drugs in the HIIT group (p < 0.05). Among the fitness indicators, the HIIT group showed significant improvements in maximum oxygen uptake, grip strength and flexibility (P < 0.05); the AR group showed significant improvements in back muscle strength and flexibility (P < 0.05). The results of the between-group covariance showed significant improvements in maximum oxygen uptake in the HIIT group (P < 0.01). Regarding body composition indicators, there was a significant improvement in Body weight, BMI, Body fat percentage and Waist-to-hip ratio in both the HIIT and AR groups (P < 0.01). There were no significant differences between the two groups. Conclusion: HIIT and combined exercise training based on remote coaching had some improvement on fitness level and body composition of university students, HIIT was more advantageous in improving aerobic endurance, and HIIT based on remote coaching may have better effect than combined exercise in mental health. Trial registration: Chinese Clinical Trial Register, ChiECRCT20220149. Registered on 16 May 2022.
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Previous studies had shown that the gut microbiota of polycystic ovary syndrome (PCOS) patients had significant differences from those of healthy individuals, which may play an important role in the pathogenesis of PCOS. Lifestyle intervention, such as nutritional intervention, could improve the metabolic profiles and PCOS-like phenotypes of PCOS patients. Meanwhile, nutritional intervention could rapidly alter and reshape the distribution of gut microbiota in individuals. Therefore, we sought to investigate the differences in gut microbiota in overweight and obese PCOS patients with or without nutritional intervention. Thirty-six overweight and obese PCOS patients were finally enrolled in the study. Eighteen individuals who refused nutritional intervention (RNI) were collected as the RNI group. Eighteen individuals who received the nutritional intervention were collected as the pre-NI group before the nutritional intervention. And they were also collected as the NI group after the nutritional intervention for 4-12 weeks. Significant decreases in BMI, FBG, TC, TG, APO A1, and APO B were observed when comparing the NI group with the pre-NI and RNI groups after the nutritional intervention for 4-12 weeks. Meanwhile, the differences in the phylum Firmicutes, Bacteroidetes, and the species Eubacterium rectale, Flavonifractor plautii, and Bacteroides vulgatus between the NI and the RNI groups were observed, which may be potentially linked to the improved inflammatory state and PCOS-like phenotypes of overweight and obese PCOS individuals.
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Microbioma Gastrointestinal , Síndrome del Ovario Poliquístico , Humanos , Femenino , Sobrepeso/complicaciones , Sobrepeso/terapia , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/terapia , Obesidad/complicaciones , Obesidad/terapia , MetabolomaRESUMEN
The exclusion, or otherwise, of small-scale farmers by cooperatives determines whether they can be well engaged in the grand strategy of agricultural modernization. By identifying the exclusion pattern of cooperatives and using the field research data on farmers in Fuchuan, Guangxi, this study finds that cooperatives tend to screen their members via both explicit and implicit exclusion and that small-scale farmers are more likely to be excluded. The theoretical analysis conducted in this study reveals that excluding small-scale farmers is a rational choice made by cooperatives to pursue efficiency in the context of organizational form variation. Furthermore, cooperatives' organizational form variation and their decisions to exclude small-scale farmers are endogenous, thereby suggesting that cooperatives in China may become unions of rural elites. During the exploration of using cooperatives as a carrier to involve small-scale farmers in agricultural modernization, the phenomenon of cooperatives' exclusion of small-scale farmers needs to be highly emphasized.
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Agricultura , Agricultores , China , Composición Familiar , Granjas , HumanosRESUMEN
We studied the case of a 36-year-old female patient who self-administered about 30 ml of diquat solution (200 g/L) during a suicide attempt. She developed nausea, vomiting, dizziness, and weakness in her limbs and was admitted to the emergency department of our hospital 4 h later. The patient developed progressive swelling and pain in both calves 12 h after admission. Based on symptoms, lower limb color Doppler ultrasound, and elevated levels of myoglobin and creatine kinase, the patient was diagnosed with rhabdomyolysis caused by diquat poisoning. The patient recovered and was discharged after treatment with hemoperfusion, continuous venovenous hemodialysis, acid suppression, liver protection, low-dose glucocorticoids, etc. Rhabdomyolysis caused by diquat poisoning has not been previously reported. We attempted to analyze the mechanism of this symptom through a literature review. We recommend the routine monitoring of creatine phosphokinase (CK) and myoglobin (MYO) in patients with diquat poisoning to avoid missed diagnosis. Further, the mechanism of this poisoning symptom was discussed through the literature review.
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Intoxicación , Rabdomiólisis , Adulto , Creatina Quinasa , Diquat , Femenino , Humanos , Mioglobina , Intoxicación/complicaciones , Intoxicación/terapia , Rabdomiólisis/inducido químicamente , Rabdomiólisis/diagnóstico , Rabdomiólisis/terapia , Intento de SuicidioRESUMEN
Due to the combined effect of biotic and abiotic constraints, rising population pressure, and inelastic demand in the crop and horticulture sector, Bangladesh has had to adopt heavily subsidized and intensified fertilizer policies to enhance crop productivity, achieve and sustain self-sufficiency in food production, and food security provision. Although the initiative has played a vital role in boosting production, it has also invigorated the unbalanced amount of fertilizer application practices raising questions about maintaining biodiversity and ecosystem services while feeding the nation's population. Further research in this area must thus be applied to monitor and improve this sector. This study attempts to understand the issue by investigating the factors influencing Boro rice farmers' adoption decisions of recommended fertilizer doses. The study employs an ordered probit model with a sample selection approach. The investigation is based on collected data from 405 randomly selected farmers using a face-to-face interview method. The farmers were classified into low, middle, high and non-adopter groups. The study revealed that farmers' age, land typology, soil water retention, knowledge, and availability of cow dung significantly influenced farmers' decision to apply fertilizers. However, farmers' carry an aversion to following recommendations for fertilizer application due to their ambiguity about the whole system, their current fertilizer application-seeking behavior, and the lack of understanding of the environmental benefits of adoption. These issues urge policy interventions to initiate village-based demonstration programs that synthesize better synergies between recommended dose adoption, yield amelioration, sustainable soil care, and economics.
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Fertilizantes , Oryza , Agricultura/métodos , Animales , Bovinos , Ecosistema , Agricultores , Femenino , Fertilizantes/análisis , Humanos , SueloRESUMEN
Objective: To investigate the effect of maternal estradiol (E2) elevation on long-term metabolic manifestations in the offspring. Study Design and Setting: This was a retrospective cohort study. Overall, 3690 children conceived by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) between July 2014 and December 2017 were recruited and divided into four groups categorized by maternal E2 quartiles (Q1, <2420; Q2, 2420-3839; Q3, 3839-5599; and Q4, ≥5599 pg/mL). The metabolic profiles were measured during childhood. Linear mixed models were used to evaluate the association between maternal E2 elevation and metabolic phenotypes of the offspring. Results: Lipoprotein cholesterol (LDL-C) was significantly higher in the highest quartile group than in the lowest quartile group during infancy (adjusted mean difference [95% confidence interval, CI]): 0.11 [0.02, 0.20], P = 0.005), but the difference disappeared in the later childhood phase. In children born after fresh embryo transfer, LDL-C showed an increasing trend with the increase in maternal E2 level (adjusted mean difference [95% CI]: Q2 vs Q1, -0.01 [-0.11, 0.08], Q3 vs Q1, 0.06 [-0.04, 0.15], Q4 vs Q1, 0.10 [0, 0.20]). Other metabolic variables were comparable across increasing quartiles of maternal E2 levels. Conclusion: This study demonstrates a temporary increase in LDL-C levels in infants with higher levels of maternal preconception E2 levels. However, the long-term safety of hyperestrogens after ovarian stimulation in the next generation is favorable. The mechanism underlying the transiently increased metabolic dysfunction risk in infants conceived by IVF/ICSI requires investigation in future studies.
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Background: The intestinal tract serves as a critical regulator for nutrient absorption and overall health. However, its involvement in anti-parasitic infection and immunity has been largely neglected, especially when a parasite is not transmitted orally. The present study investigated the colonic histopathology and functional reprogramming in mice with intraperitoneal infection of the larval Echinococcus granulosus (E. granulosus). Results: Compared with the control group, the E. granulosus-infected mice exhibited deteriorated secreted mucus, shortened length, decreased expression of tight junction proteins zonula occludens-1 (ZO-1), and occludin in the colon. Moreover, RNA sequencing was employed to characterize colonic gene expression after infection. In total, 3,019 differentially expressed genes (1,346 upregulated and 1,673 downregulated genes) were identified in the colon of infected mice. KEGG pathway and GO enrichment analysis revealed that differentially expressed genes involved in intestinal immune responses, infectious disease-associated pathways, metabolism, or focal adhesion were significantly enriched. Among these, 18 tight junction-relative genes, 44 immune response-associated genes, and 23 metabolic genes were annotated. Furthermore, mebendazole treatment could reverse the colonic histopathology induced by E. granulosus infection. Conclusions: Intraperitoneal infection with E. granulosus induced the pathological changes and functional reprogramming in the colon of mice, and mebendazole administration alleviated above alternations, highlighting the significance of the colon as a protective barrier against parasitic infection. The findings provide a novel perspective on host-parasite interplay and propose intestine as a possible target for treating parasitic diseases that are not transmitted orally.
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Escarabajos , Equinococosis , Echinococcus granulosus , Animales , Ratones , Mebendazol , Intestinos , Colon/metabolismoRESUMEN
Emerging data have revealed that CD95 can evoke non-apoptotic signals, thereby promoting pro-inflammatory functions that link to the severity of autoimmune disorders. Here, we reported that the expression of CD95 in CD4+ effector memory T (CD4+ TEM) cells was increased in myasthenia gravis (MG) patients. We also found increased expression of CD95 in CD4+ TEM cells from MG patients correlated positively with clinical severity scores (QMGs), serum IL-17 levels and plasma cells (PCs) frequencies. Conventional treatment, such as glucocorticoid, could down-regulate the expression of CD95 in CD4+ TEM cells, QMGs, serum IL-17 levels and PCs frequencies from MG patients. In vitro, low-dose of agonistic anti-CD95 mAb could promote Th17 cell development. This effect was reversed by CD95 siRNA. Moverover, CD95 stimulation induced the phosphorylation of p38 and Erk1/2 and Th17 cell differentiation, and p38 specific inhibitor SB203580 or Erk1/2 specific inhibitor PD98059 could induce opposite changes. However, SB203580 or PD98059 do not abrogate the increase of CCR6+IL-17A+ cells, ROR-γt and IL-17 expression induced by CD95 triggering relatively to each corresponding control. This suggests that p38 and Erk1/2 MAPK pathway plays a role in expression of CCR6+IL-17A+ cells, ROR-γt and IL-17, but not in their increase induced by CD95 triggering. Taken together, this study revealed that increased expression of CD95 in CD4+ TEM cells promotes Th17 response under the microenvironment of MG.
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Células T de Memoria , Miastenia Gravis , Células Th17 , Humanos , Interleucina-17/sangre , Células T de Memoria/inmunología , Miastenia Gravis/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Células Th17/inmunologíaRESUMEN
Background: We previously reported that the larval Echinococcus granulosus (E. granulosus) infection can expand the population of regulatory B cells in mice, thereby inhibiting the anti-infective immunity. However, the underlying mechanism is still largely unknown. This study further investigated the holistic transcriptomic profiles of total splenic B cells following the chronic infection of the parasite. Methods: The infection model of larval E. granulosus was established by intraperitoneal inoculation with 2000 protoscolexes. Magnetic-Activated Cell Separation (MACS) was used to isolate the total splenic B cells. RNA sequencing was performed to screen the differentially expressed genes (DEGs) after infection. The expression of selected DEGs was verified using qRT-PCR. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Co-expression network analysis were applied to predict these DEGs' underlying biological processes, pathways, and interactions respectively. Results: A total of 413 DEGs were identified in larval E. granulosus infected B cells, including 303 up- and 110 down-regulated genes. Notably, most DEGs related to inflammation and chemotaxis were significantly upregulated after infection. In line with these changes, significant expression upregulation of DEGs associated with fatty acid oxidation, lipid synthesis, lipolysis, lipid transport, and cholesterol biosynthesis, were observed in infected B cells. Co-expression network analysis showed an intimate interaction between these DEGs associated with immune and metabolism. Conclusions: The present study revealed that the larval E. granulosus infection induces metabolic reprogramming of B cells, which provides a novel clue to clarify the immunoregulatory mechanism of B cells in parasitic infection.
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In the title compound, [Co(H(2)O)(6)](C(9)H(7)O(4))(2)·2H(2)O, the Co(2+) cation lies on a twofold rotation axis and is coordinated by six water mol-ecules in a distorted octa-hedral geometry. In the 5-acetyl-2-hy-droxy-benzoate anion, the hy-droxy group links with the carboxyl-ate group via an intra-molecular O-Hâ¯O hydrogen bond and the acetyl group is twisted to the benzene ring at a dihedral angle of 16.99â (12)°. In the crystal structure, the cations, anions and water mol-ecules are linked by extensive O-Hâ¯O hydrogen bonding.
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High-performance extruded aluminum alloys with complex textures suffer significant dimension variation under environmental temperature fluctuations, dramatically decreasing the precision of navigation systems. This research mainly focuses on the effect of the texture of extruded pure aluminum on its dimensional stability after various annealing processes. The result reveals that a significant increment in the area fraction of recrystallized grains with <100> orientation and a decrement in the area fraction of grains with <111> orientation were found with increasing annealing temperature. Moreover, with the annealing temperature increasing from 150 °C to 400 °C, the residual plastic strain after twelve thermal cycles with a temperature range of 120 °C was changed from -1.6 × 10-5 to -4.5 × 10-5. The large amount of equiaxed grains with <100> orientation was formed in the microstructure of the extruded pure aluminum and the average grain size was decreased during thermal cycling. The area fraction of grain with <100> crystallographic orientation of the sample annealed at 400 °C after thermal cycling was 30.9% higher than annealed at 350 °C (23.7%) or at 150 °C (18.7%). It is attributed to the increase in the proportion of recrystallization grains with <100> direction as the annealing temperature increases, provided more nucleation sites for the formation of fine equiaxed grains with <100> orientation. The main orientation of the texture was rotated from parallel to <111> to parallel to <100> after thermal cycling. The change in the orientation of grains contributed to a change in interplanar spacing, which explains the change in the dimension along the extrusion direction during thermal cycling.
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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, which is characterized by ovulatory dysfunction, clinical and/or biochemical androgen excess, polycystic ovaries on ultrasound and genetic heterogeneity. It was well-accepted that many lncRNAs and mRNAs were associated with PCOS, however, remain unclear. Therefore, the purpose of our study was to examine different expression profiles of lncRNAs and mRNAs in ovarian granulosa cells (GCs) in PCOS and Controls, and identify the correlation between lncRNAs, mRNAs and clinical parameters. Sixty five PCOS patients and 65 Controls were enrolled in this study and adopted standard long agonist protocols or GnRH antagonist protocols. Then 6 GCs samples in each group were subjected to high-thoughput sequencing and the remaining samples were used for the further verification by quantitative real-time PCR (qRT-PCR). Gene Oncology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG) enrichment analysis were performed. We predicted the relationship between lncRNAs and mRNAs by Cytoscape software. According to the expression level of lncRNAs, mRNAs and the clinical parameters, we also explored their relationship and evaluate their predictive values for embryos quality and PCOS. We identified 1,049 differential expressed lncRNAs and 3,246 mRNAs (fold-change ≥2, p-value < 0.05). Seven lncRNAs (NONHSAT101926.2, NONHSAT136825.2, NONHSAT227177.1, NONHSAT010538.2, NONHSAT191377.1, NONHSAT230904.1, ENST00000607307) and 3 mRNAs (EREG, ENTPD6, YAP1) were validated consistent with sequence profile. Seven lncRNAs were related to hormone level and follicle counts, 3 mRNAs had connections with lipid metabolism. The area under curve (AUC) of 7 lncRNAs were valuable in distinguishing patients with PCOS from Controls. The AUC of NONHSAT230904.1 and NONHSAT227177.1 were 0.6807 and 0.6410, respectively, for distinguishing whether the rate of high-quality embryos exceeds 50%. Our study showed that the GCs lncRNAs and mRNAs were involved in the occurrence and development of PCOS, which contribute to clarify the pathogenesis mechanism of PCOS.