Background HIV self-testing (HIVST) offers an opportunity to increase HIV testing among people not reached by facility-based services. However, the promotion of HIVST is limited due to insufficient community engagement. We built a Social Entrepreneurship Model (SET) to promote HIVST linkage to care among Chinese MSM in Guangzhou. Method SET model includes a few key steps: Each participant first completed an online survey, and paid a $23 USD (refundable) deposit to get a HIVST kit and a syphilis self-testing (SST) kit. After the testing, the results were sent to the platform by the participants and interpreted by CDC staff. Meanwhile, the deposit was returned to each participant. Finally, the CBO contacted the participants to provide counseling services, confirmation testing and linkage to care. Result During April–June of 2015, a total of 198 MSM completed a preliminary survey and purchased self-testing kits. Among them, the majority were aged under 34 (84.4%) and met partners online (93.1%). In addition, 68.9% of participants ever tested for HIV, and 19.5% had ever performed HIVST. Overall, feedback was received from 192 (97.0%) participants. Among these, 14 people did not use kits, and the HIV and syphilis prevalence among these users were of 4.5% (8/178) and 3.7% (6/178), respectively. All of the screened HIV-positive cases sought further confirmation testing and were linked to care. Conclusion Using an online SET model to promote HIV and syphilis among Chinese MSM is acceptable and feasible, and this model adds a new testing platform to the current testing service system.
It has been confirmed that the systemic inflammation response index (SIRI) based on peripheral blood neutrophil, monocyte and lymphocyte counts can be used for the prognostication of patients with various malignant tumors. However, the prognostic value of SIRI in cervical cancer patients has not yet been reported. This study found that a higher SIRI was related to lymphovascular invasion and was also significantly associated with FIGO stage, radiotherapy, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) but not related to other clinical and pathological parameters. According to the Kaplan-Meier survival analysis, a high SIRI was associated with the poor prognosis of cervical cancer patients in the primary and validation groups. SIRI, NLR, PLR, and MLR can all be used to determine the prognosis of patients with operable cervical cancer. Moreover, it was confirmed that only SIRI was an independent prognostic factor for patients with operable cervical cancer. The same result was obtained in the propensity score matching (PSM) analysis. In the ROC curve analysis, SIRI was more accurate in predicting the prognosis of cervical cancer patients. Then, a nomogram was established based on SIRI, FIGO stage and lymphovascular invasion, which could determine the prognosis of cervical cancer patients more accurately than FIGO stage. The validation cohort showed the same results. In addition, the changes in SIRI relative to the baseline value at 4-8 weeks after surgery were closely related to the survival of cervical cancer patients. Compared with those with unchanged SIRI (absolute value of variation <25%), cervical cancer patients with an increase in SIRI > 75% had worse OS (P < 0.001), while patients with a decrease in SIRI > 75% had a better prognosis (P < 0.001). SIRI can serve as a new independent prognostic index and a potential marker for therapeutic response monitoring in patients with curable cervical cancer. Compared with the traditional FIGO staging system, the nomogram integrating SIRI can predict the survival of cervical cancer patients more objectively and reliably after radical surgery.
A significant proportion of prostate cancer patients treated with curative intent go on to develop advanced disease. At a fundamental biological level, very little is known about what makes the disease aggressive and metastatic. Observational pathology reports and experimental data suggest that epithelial-mesenchymal transition is involved in prostate cancer invasiveness. Here, we investigated vimentin expression of prostate cancer cells, and explored the potential mechanism of vimentin promoting prostate cancer cells invasion. Vimentin expression was not detected in well differentiated tumors or in moderately differentiated tumors, but the majority of poorly differentiated cancers (5/11 with negative bone scan, 11/14 bone with positive scan) and bone metastases (8/8) had high vimentin expression in tumor cells. Downregulation of vimentin expression in PC-3 cells by transfection with antisense-vimentin led to a significant decrease in tumor cells motility and invasive activity. Furthermore, the expression of E-cadherin was inversely associated with expression of vimentin. Our results suggest that vimentin affects prostate cancer cells motility and invasiveness.
Acute pancreatitis (AP) is a serious condition associated with intestinal barrier disruption or inflammation of the pancreatic tissue. Specific microRNAs are involved in the pathogenesis of AP, during which IL-17-producing CD4+ T helper (Th17) cells accumulate in the pancreas. In this study, significantly increased levels of miR-155 were detected in clinical samples from patients with AP, and overexpression of miR-155 correlated with severe AP (SAP). To identify the effect of miR-155 on T cell differentiation, we isolated CD4+ T lymphocytes and in vitro experiments showed that inhibition of miR-155 significantly reversed the stress-induced increase in the Th17/Treg ratio. The results also showed that miR-155 increased the Th17-mediated inflammatory response by targeting SOCS1. The interaction between miR-155 and the 3′-UTR of SOCS1 was confirmed by a dual luciferase reporter assay and RT-PCR. Experimental AP of varying severity was induced in BALB/c mice by caerulein hyperstimulation and miR-155 expression was found to increase with disease progression. Inhibition of miR-155 expression significantly improved the pathology of the pancreas. We also observed downregulation of expression of inflammatory factors, IL-17, SOCS1 and phosphorylated STAT1 after miR-155 inhibition. In summary, miR-155 regulates the Th17/Treg ratio by targeting SOCS1, most probably via direct binding to its 3′-UTR region, indicating that this microRNA may be a potential biomarker and/or therapeutic target for AP.
Obesity impaired physical but not mental health, and the impairments varied between genders. Public health agencies and government should emphasize the impairments of obesity on physical health.
Background MicroRNAs (miRs) are involved in lymphoma progression by regulating tumor cell interaction with microenvironment. MiR155 is overexpressed in diffuse large B-cell lymphoma (DLBCL) and its biological effect on tumor microenvironment needs to be futher investigated. Methods MiR155 was detected by quantitative real-time PCR in patients with newly diagnosed DLBCL. The mechanism of action of miR155 on lymphoma progression and tumor microenvironment was examined in vitro in B-lymphoma cell lines and in vivo in a murine xenograft model. Results Serum miR155 was significantly elevated, correlated with tumor miR155 expression, and indicated poor disease outcome in DLBCL. MiR155 overexpression was associated with decreased peripheral blood CD8+T cells and inhibition of T-cell receptor signaling. Of note, EBV-positive patients showed higher serum miR155 than EBV-negative patients. In co-culture systems of B-lymphoma cells with immune cells, miR155 induced Fas-mediated apoptosis of CD8+T cells, which could be targeted by anti-PD-1 and anti-PD-L1 antibodies. Moreover, miR155 enhanced lymphoma cell PD-L1 expression, recruited CD8+T cells by PD-1/PD-L1 interaction and inhibited CD8+T cell function via dephosphorylating AKT and ERK. MiR155-induced AKT/ERK inactivation was more obvious in CD8+T cells co-cultured with EBV-infected B-lymphoma cells. In vivo in a murine xenograft model established with subcutaneous injection of A20 cells, PD-L1 blockade particularly retarded miR155-overexpressing tumor growth, consistent with maintenance of CD8+T cells and their function. Conclusions As a oncogenic biomarker of B-cell lymphoma, serum miR155 was related to lymphoma progression through modulating PD-1/PD-L1-mediated interaction with CD8+T cells of tumor microenvironment, indicating the sensitivity of B-cell lymphoma to PD-L1 blockade. Also CD8+T cells could be a therapeutic mediator of immune checkpoint inhibitors in treating EBV-associated lymphoid malignancies. Electronic supplementary material The online version of this article (10.1186/s12943-019-0977-3) contains supplementary material, which is available to authorized users.
Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz–enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90β. At the molecular level, inactivation of HSP90 can mimic vibsanin B’s effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90β and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.
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