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Together, our results suggest that altered microbiota and functional changes are probably related to innate immune-mediated inflammatory injury and graft survival after SBT, suggesting that the monitoring and regulation of intestinal microbiota are necessary for SBT patients.
Together, our results suggest that altered microbiota and functional changes are probably related to innate immune-mediated inflammatory injury and graft survival after SBT, suggesting that the monitoring and regulation of intestinal microbiota are necessary for SBT patients.Ovarian cancer (OC) is the most common gynecological malignant tumor with the highest mortality rate. However, identification of effective immune therapeutic targets and biomarkers are beset by many challenges. CIBERSORT was used to calculate the abundance of 22 immune cell types in 379 OC samples, and indicated that three immune cell types were associated with poor prognoses. Further analysis revealed that 17 hub genes were associated with these three cell types. We screened differentially expressed immune-related prognostic gene associated with clinicopathological factors, which was CST4. We used clinical specimens to detect the expression of CST4, and determined that CST4 was both highly expressed in OC patients and associated with poor prognoses. Our findings indicated that infiltration of immune cells affected the survival of patients with OC, provided therapeutic targets represented by CST4, deepened our understanding of the immune microenvironment of OC, and enhanced the theoretical basis of immunotherapy.
The normal functioning of Kelch-like ECH-associated protein-1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) complex is necessary for the cellular protection against oxidative stress. We investigated the effect of chlorogenic acid (CGA), quercetin (Qt), coenzyme Q10 (Q10) and silymarin on the expression of Keap1/Nrf2 complex and its downstream target; heme oxygenase-1 (HO-1) as well as inflammation and apoptosis in an acute liver toxicity model induced by thioacetamide (TAA).
Wistar rats were divided into 13 groups Control, silymarin, CGA, Qt, Q10, TAA (single dose 50mg/kg, i.p.), TAA+silymarin (400mg/kg, p.o.), TAA+CGA (100 & 200mg/kg, p.o.), TAA+Qt (200 &300mg/kg, p.o.) and TAA+ Q10 (30&50mg/kg, p.o.) and treated for 8days.
The results showed improved liver functions and hepatic tissue integrity in all tested doses of TAA+silymarin, TAA+CGA, TAA+Qt and TAA+Q10 groups compared to the TAA group. Furthermore, these groups showed significantly lower ROS, malondialdehyde and nitric oxide levels but higher glutathione content and superoxide dismutase activity compared to the TAA group, p<0.05. In these groups, Keap1 expression was significantly decreased while Nrf2 expression and HO-1 activity were increased. In addition, the number of apoptotic cells and the expression level of TNF-α in the liver tissues were significantly decreased compared to the TAA group.
CGA, Qt, Q10 and silymarin protect against TAA-induced acute liver toxicity via antioxidant, anti-inflammatory, anti-apoptotic activities and regulating Keap1-Nrf2/HO-1 expression.
CGA, Qt, Q10 and silymarin protect against TAA-induced acute liver toxicity via antioxidant, anti-inflammatory, anti-apoptotic activities and regulating Keap1-Nrf2/HO-1 expression.Dental pulp stem cells (DPSCs) possess the ability of multi-lineage differentiation, and are excellent sources of tissue engineering and regenerative medicine. Oxygen concentration and inflammation are two critical environmental factors that affect the osteogenic differentiation of DPSCs. We aimed to study the role of the antimalarial drug artemisinin on the osteogenic differentiation of human DPSCs under the hypoxia and inflammation conditions. We demonstrated that hypoxia (5% O2) and inflammation (20 ng/mL TNF-α), alone or in combination, significantly diminished in vitro cell survival and increased apoptotic rates. Notably, hypoxia and TNF-α exerted accumulative effect in suppressing the osteogenic differentiation of DPSCs, as evidenced by reduced expression levels of osteogenesis-associated genes including ALP, RUNX2 and OCN in osteogenic condition, as well as reduced mineral nodules formation as indicated by alizarin red staining. Artemisinin at the dose of 40 μM markedly reversed the suppression in cell survival caused by hypoxia or inflammation, and reduced apoptotic rates and the expressions of pro-apoptotic proteins. Additionally, artemisinin restored osteogenic differentiation of DPSCs under the hypoxia or/and inflammation conditions. Moreover, the beneficial effect of artemisinin was dependent on upregulated expression of CA9 and CA9-mediated antioxidant responses, as CA9 knockdown abolished the protective role of artemisinin on DPSC osteogenesis. Furthermore, while hypoxia or/and inflammation significantly inactivated the Wnt/β-catenin signaling in DPSCs, additional exposure to artemisinin re-activated this pathway to promote osteogenic differentiation of DPSCs. Our results provide novel insight on the link between artemisinin and DPSC osteogenesis, and suggest promising artemisinin-based strategies for better dentin/pulp tissue engineering.
This study characterizes Gulf War Illness (GWI) among U.S. veterans who participated in the Gulf War Era Cohort and Biorepository (GWECB).
Mailed questionnaires were collected between 2014 and 2016. Self-reported GWI symptoms, symptom domain criteria, exclusionary diagnoses, and case status were examined based on the originally published Kansas and Centers for Disease Control (CDC) definitions in the GWECB cohort (n=849 deployed to Gulf and n=267 non-deployed). Associations among GWI and deployment status, demographic, and military service characteristics were examined using logistic regression.
Among deployed veterans in our sample, 39.9% met the Kansas criteria and 84.2% met the CDC criteria for GWI. Ricolinostat ic50 Relative to non-deployed veterans, deployed veterans had a higher odds of meeting four GWI case status-related measures including the Kansas symptom criteria (aOR=2.05, 95% CI=1.50, 2.80), Kansas GWI case status (aOR=1.42, 95% CI=1.05, 1.93), the CDC GWI case status (aOR=1.57, 95% CI=1.07, 2.29) and the C need to update GWI definitions to account for aging-related conditions and symptoms. This study provides a foundation for future efforts to establish a single GWI case definition and analyses that employ the biorepository.The Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) continues to be a major global public health issue, having claimed almost 33 million lives so far. According to the recent report of the World Health Organization (WHO) in 2019, about 38 million people are living with AIDS. Hence, finding a solution to overcome this life-threatening virus can save millions of lives. Scientists and medical doctors have prescribed HIV patients with specific drugs for many years. Methods such antiretroviral therapy (ART) or latency-reversing agents (LRAs) have been used for a while to treat HIV patients, however they have some side effects and drawbacks causing their application to be not quite successful. Instead, the application of gene therapy which refers to the utilization of the therapeutic delivery of nucleic acids into a patient's cells as a drug to treat disease has shown promising results to control HIV infection. Therefore, in this review, we will summarize recent advances in gene therapy approach against HIV.
In recent years, female infertility from Polycystic Ovary Syndrome (PCOS) has gained scientific interest. PCOS alters the metabolic and endocrine functioning in females. The elevation in androgens can damage the androgen receptors present on the kidney giving rise to renal disorders like Focal Segmental Glomerulosclerosis (FSGS). Transforming Growth Factor Beta (TGF-β) in the ovary is activated by activin for Follicle Stimulating Hormone (FSH) secretion and in the kidney by thrombospondin 1 (TSP1) for cell growth and apoptosis. Studies show that gamma-linolenic acid (GLA) effectively treats breast cancer, eczema, inflammatory conditions and PCOS.
The study aimed to find out the possibility of FSGS development in PCOS and to understand the effect of GLA on FSGS via the TGF-β pathway.
To carry out the study, the dehydroepiandrosterone (DHEA) induced PCOS model was used. Three groups namely vehicle control, DHEA, and DHEA+GLA, were used with six animals in each. TGF-β1, TGF-β2, and TSP1 genes were studied using real-time PCR.
The study showed an increase in the level of renal fibrosis biomarker, TSP1, in the DHEA group, which was further decreased by an anti-inflammatory agent, GLA. The TGF-β1 and TGF-β2 genes associated with the TGF-β pathway were seen to be increased in DHEA-induced PCOS rats which showed a possible relation between the two conditions.
The study shows a possible development of renal fibrosis in the DHEA-induced PCOS model. The GLA might act as a ligand to regulate TGF-β signaling in glomerulosclerosis in a DHEA-induced PCOS model.
The study shows a possible development of renal fibrosis in the DHEA-induced PCOS model. The GLA might act as a ligand to regulate TGF-β signaling in glomerulosclerosis in a DHEA-induced PCOS model.
Maresin 1 (MaR1) is a pro-resolving lipid mediator that has been reported to have strong regulatory effects on oxidative stress and inflammation. This study aimed to determine the effect of MaR1 on lipopolysaccharide (LPS)-induced sepsis-related cardiac injury and explore its possible mechanisms.
Mice were administered MaR1 or PBS and then treated with LPS or saline for 6h. Then, cardiac function, cardiac injury markers, cardiac macrophage differentiation, oxidative stress and myocardial cell apoptosis in each group were measured.
MaR1 treatment significantly decreased the serum levels of lactate dehydrogenase (LDH) and kinase isoenzyme (CK-MB) and improved cardiac function in LPS-induced mice. Treatment with MaR1 also inhibited LPS-induced M1 macrophage differentiation and reduced M1 macrophage-related cytokine secretion while promoting M2 macrophage differentiation and increasing M2 macrophage-related inflammatory mediator expression. In addition, MaR1 decreased serum malondialdehyde (MDA) levels and increased serum levels of superoxide dismutase (SOD) and glutathione (GSH), as well as cardiac expression of nuclear factor erythroid-2 related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1), in LPS-induced mice. Furthermore, fewer TUNEL-positive cells were observed in the LPS+MaR1 group than in the LPS group.
Our experimental results show that MaR1 alleviates cardiac injury and protects against cardiac dysfunction and may be beneficial in reducing sepsis-induced cardiac injury.
Our experimental results show that MaR1 alleviates cardiac injury and protects against cardiac dysfunction and may be beneficial in reducing sepsis-induced cardiac injury.
Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) shows high mortality. Hydrogen sulfide (H
S) is essential for regulating kidney function. This study explored the role and mechanism of H
S in I/R-induced AKI.
I/R-induced mouse model and hypoxia/reoxygenation (H/R)-induced HK2 cell model of AKI were established and treated with NaHS (H
S donor), MCC950 (NLRP3 inhibitor) or DL-Propargylglycine (PAG, CSE inhibitor). Serum creatinine (Cr) and blood urea nitrogen (BUN) were measured to evaluate kidney function. The pathological changes of kidney tissues were detected. H
S level and H
S synthetase activity in kidney tissues were detected. Pyroptosis was assessed by pyroptotic cell numbers and pyroptosis-related protein levels determination. HK-2 cell viability and apoptosis were measured. NLRP3 protein level was detected. The role of NLRP3/Caspase-1 was verified in vivo and in vitro after MCC950 or PAG intervention.
I/R-induced mice showed elevated levels of serum Cr and BUN, and obvious pathological changes, including severe tubular dilatation, tubular cell swelling, tubular epithelial cell abscission, tubular cell necrosis and inflammatory cell infiltration.
