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关键词： African contexts   gender transformative   operationalise gender   transformative approaches  

摘要： Africa is the second largest and second most populous continent in the world. Governed by 54 recognised sovereign states, its people celebrate multiple traditions and speak countless dialects and languages apart from those inherited by varied colonial legacies. Despite historical and ongoing debts, it has one of the fastest growing global economies and vast natural resources.1 Its full potential, however, is not realized due in part to the lack of progress and regression on gender equality and sexual and reproductive health and rights.2.

关键词： liver fibrosis   IL-17A   inflammation   inverse agonist   ROR gamma t  

摘要： Liver fibrosis is a global health problem. IL-17A has proven profibrogenic properties in liver disease making it an interesting therapeutic target. IL-17A is regulated by ROR gamma t and produced by Th17 CD4(+) and gamma delta-T cells. We hypothesized that blocking IL-17A production will limit fibrosis progression by reducing recruitment of inflammatory cells. Herein, we tested the therapeutic potential of 2 novel ROR gamma t inverse agonists (2,3 derivatives of 4,5,6,7-tetrahydro-benzothiophene) in a mouse model of CCl4-induced liver injury. C57BL/6 mice received 2 weekly injections of CCl4 for 4 weeks. As of week 3, mice were treated with the 2 novel inverse agonists (TF-S10 and TF-S14) and GSK805 as a positive control. Mice treated with the inverse agonists showed reduced immune cells infiltrate around the portal and central veins. TF-S14 significantly reduced AST levels (P < 0.05), and all inhibitors led to an improvement in relative liver weight (liver index). Flow cytometry analysis demonstrated that all inhibitors reduced the numbers of intrahepatic lymphocytes (CD4(+), CD8(+), and gamma delta-T cells, P < 0.05), and myeloid (CD11b(+)) cells (P = 0.04), most significantly eosinophils (P < 0.05). Furthermore, IL-17A production by CD4(+) and gamma delta-T cells was diminished (P < 0.05 and P < 0. 01, respectively). Finally, livers from inhibitors-treated mice showed decreased markers of hepatic stellate cell activation (desmin and alpha-smooth muscle actin [alpha-SMA]) and significantly reduced expression of the profibrogenic genes (Col1a1, Acta, Loxl2, and Tgf beta) (P < 0.001). This was accompanied by diminished collagen deposition as measured by Picrosirius Red staining (P < 0.001). In conclusion, our results suggest that inhibition of the IL-17A pathway could be a promising therapeutic strategy for liver fibrosis.

关键词： post-traumatic osteomyelitis   chlorogenic acid   regulatory T cells   interleukin-2   T lymphocytes  

摘要： Background: Chlorogenic acid (CGA) exerts immunomodulatory effects by regulating the proportion of regulatory T cells (Tregs), and T-cell dysregulation is a known feature of post-traumatic osteomyelitis (PTO). This study explored the mechanism of CGA in the treatment of PTO from the perspective of T-cell immunity. Methods: Lymphocytes isolated from rat spleens were stimulated with interleukin (IL)-2. A PTO model was established by injecting Staphylococcus aureus into the tibial marrow cavity of New Zealand white rabbits. PTO rabbits were treated with either CGA by gavage or lentiviral IL-2 injection. The Treg proportion was evaluated by flow cytometry. The expression of forkhead box protein 3 (Foxp3), cytotoxic T lymphocyte antigen-4 (Ctla-4), and IL-2 was quantified by quantitative real-time polymerase chain reaction. The concentrations of tumor necrosis factor-ca (TNF-ca), IL-10, and IL-2 were measured using enzyme-linked immunosorbent assays. Micro-computed tomography and hematoxylin and eosin staining were performed to characterize bone destruction. The proliferation of CD4+ T/CD8+ T cells was evaluated by flow cytometry. Results: IL-2 stimulation elevated the proportion of Tregs in rat splenic lymphocytes, upregulated Foxp3, Ctla-4, and IL-10 expression, and decreased TNF-ca expression (p G 0.05). PTO rabbits exhibited significant bone destruction and inflammatory cell infiltration in bone tissue. In the peripheral blood of PTO rabbits, the Treg proportion was elevated, with increased expressions of Foxp3, Ctla-4, IL-10, and IL-2, reduced TNF-ca expression, and increased proliferation of CD4+ T/CD8+ T cells. These changes were significantly reversed by CGA administration (p G 0.001). However, the reversal effects of CGA were offset by exogenous IL-2 (p G 0.001). Conclusion: CGA alleviates PTO by inhibiting IL-2-mediated upregulation of Tregs.

关键词： CD200   CD200R   Central Nervous System   Experimental Autoimmune Encephalomyelitis   Interferon beta  

摘要： Background: Interferon-(3 (IFN-(3), a glycoprotein released during viral infections, plays a crucial role in modulating T cells involved in multiple sclerosis (MS). CD200 is an immunomodulatory molecule expressed in many cell types, including neurons. It reduces the progression of MS and experimental autoimmune encephalomyelitis (EAE) by interacting with CD200R, mainly expressed on myeloid lineage cells. This interaction prevents brain damage and slows the progression of the disease. Objective: This study investigated changes in the expression of CD200 and CD200R genes in the brains of mice induced with EAE. Methods: Female C57B/L6 mice were divided into three distinct groups: 1) EAE-induced and treated with IFN-(3, 2) EAE-induced and treated with phosphate-buffered saline (PBS), and 3) a healthy control group. Two weeks after treatment, the mice were euthanized, and whole-brain tissues were used for mRNA extraction. After cDNA synthesis, the expression of CD200 and CD200R genes was evaluated using Taqman Real-Time PCR. Leukocyte infiltration and demyelination were assessed using Hematoxylin and Eosin staining (H&E) as well as Luxol fast blue (LFB). Results: IFN-(3 treatment significantly reduced disease progression and demyelination. Furthermore, mice treated with IFN-(3 showed improved weight gain. The findings also indicated no notable change in CD200 gene expression across the groups examined. However the expression of CD200R decreased in the IFN-(3-treated group, but significantly increased in the untreated group. Conclusion: Ourfindings suggestthatIFN-(3 treatment may decrease CD200R expression by reducing inflammation. Additionally, the elevated expression in the untreated group may explain why EAE is self-limiting.

关键词： LAR   IL-6   Severe acute pancreatitis   Clinical diagnosis   Prognostic analysis   Efficacy  

摘要： To analyze the clinical value of lactate dehydrogenase to albumin ratio (LAR) and interleukin-6 (IL-6) in the early diagnosis and prognostic assessment of severe acute pancreatitis (SAP). A retrospective study was conducted on 98 cases of acute pancreatitis patients. These patients were divided into two groups based on the severity of their condition: non-SAP group (n = 68) and SAP group (n = 30). Spearman correlation analysis was utilized to investigate the correlation of LAR and IL-6 with the bedside index for severity in acute pancreatitis (BISAP). Patients in the SAP group exhibited significantly higher LAR values and IL-6 levels compared to those in the non-SAP group (P < 0.05). The APR and IL-6 of SAP patients were significantly positively correlated with BISAP scores (R = 0.758, P < 0.001) (R = 0.660, P < 0.001). The diagnostic AUC of LAR and IL-6 for SAP were 0.742 (P < 0.001) and 0.749 (P < 0.001), respectively. The Logistic regression analysis demonstrated that LAR and IL-6 were independent risk factors for SAP (P < 0.05). The levels of LAR and IL-6 in the death subgroup were significantly higher than those in the survival subgroup (P < 0.05). The diagnostic AUC of LAR and IL-6 for poor prognosis of SAP were 0.971 (P < 0.001) and 0.713 (P = 0.055), respectively. LAR was an independent risk factor for poor prognosis in SAP patients (P < 0.05). Patients with SAP may exhibit abnormally elevated levels of LAR and IL-6. LAR and IL-6 are closely associated with the severity of the patient's condition, which can be applied in the diagnosis of SAP.

关键词： Anti-HLA antibody   DSA   PBSCT   Engraftment   MFI  

摘要： Anti-human leukocyte antigen (HLA) antibodies, particularly donor-specific HLA antibodies (DSA), negatively impact engraftment in hematopoietic cell transplantation. Past studies have proposed various interventions to reduce DSA, but these were primarily from single centers and not from large-scale registry data. Therefore, we conducted a retrospective analysis of nationwide registry data to examine the effects of anti-HLA antibodies on engraftment. Evaluable patients were classified into an anti-HLA antibody-negative group (n = 3657), an anti-HLA antibody-positive group (without high DSA) (n = 137), and a high-DSA (MFI > 5000) group (n = 8). Patient characteristics differed significantly between the anti-HLA antibody-negative and anti-HLA antibody-positive groups, and the number of patients with DSA was lower than expected. Statistical analyses revealed that the anti-HLA antibody-positive group had better neutrophil engraftment than the anti-HLA antibody-negative group (94.0% vs 84.2%, p < 0.001) but worse platelet engraftment (60.3% vs 64.9%, p = 0.047). In the high DSA group, two patients received a DSA-depleting intervention. Only one patient with an MFI of 5832 (without intervention) developed primary graft failure, while the remaining seven achieved engraftment. In this study, the effect of anti-HLA antibodies remained inconclusive, and the possibility of neutrophil engraftment with high-DSA levels was confirmed.

关键词： Registries   biological DMARD   Real-world evidence