Elevated circulating dipeptidyl peptidase-4 (DPP4) is a biomarker for liver disease, but its involvement in gluconeogenesis and metabolic associated fatty liver disease progression remains unclear. Here, we identified that DPP4 in hepatocytes but not TEK receptor tyrosine kinase–positive endothelial cells regulates the local bioactivity of incretin hormones and gluconeogenesis. However, the complete absence of DPP4 ( Dpp4 ^–/– ) in aged mice with metabolic syndrome accelerates liver fibrosis without altering dyslipidemia and steatosis. Analysis of transcripts from the livers of Dpp4 ^–/– mice displayed enrichment for inflammasome, p53, and senescence programs compared with littermate controls. High-fat, high-cholesterol feeding decreased Dpp4 expression in F4/80 ⁺ cells, with only minor changes in immune signaling. Moreover, in a lean mouse model of severe nonalcoholic fatty liver disease, phosphatidylethanolamine N -methyltransferase mice, we observed a 4-fold increase in circulating DPP4, in contrast with previous findings connecting DPP4 release and obesity. Last, we evaluated DPP4 levels in patients with hepatitis C infection with dysglycemia (Homeostatic Model Assessment of Insulin Resistance > 2) who underwent direct antiviral treatment (with/without ribavirin). DPP4 protein levels decreased with viral clearance; DPP4 activity levels were reduced at long-term follow-up in ribavirin-treated patients; but metabolic factors did not improve. These data suggest elevations in DPP4 during hepatitis C infection are not primarily regulated by metabolic disturbances.

HIV causes intense polyclonal activation of B cells, resulting in increased numbers of spontaneously antibody-secreting cells in the circulation and hypergammaglobulinemia. It is accompanied by significant perturbations in various B cell subsets, such as increased frequencies of immature/transitional B cells, activated memory B cells, atypical memory B cells, short-lived plasmablasts and regulatory B cells, as well as by decreased frequencies of resting memory and resting naïve B cells. Furthermore, both memory and antigen-inexperienced naïve B cells show exhausted and immune-senescent phenotypes. HIV also drives the expansion and functional impairment of CD4⁺ T follicular helper cells, which provide help to B cells, crucial for the generation of germinal center reactions and production of long-lived plasma and memory B cells. By suppressing viral replication, anti-retroviral therapy reverses the virus-induced perturbations and functional defects, albeit inadequately. Due to HIV’s lingering impact on B cells, immune senescence and residual chronic inflammation, people with HIV (PWH), especially immune non-responders, are immunocompromised and mount suboptimal antibody responses to vaccination for SARS-CoV-2. Here, we review how functionally and phenotypically distinct B cell subsets are induced in response to a vaccine and an infection and how HIV infection and anti-retroviral therapy (ART) impact them. We also review the role played by HIV-induced defects and perturbations in B cells in the induction of humoral immune responses to currently used anti-SARS-CoV-2 vaccines in PWH on ART. We also outline different strategies that could potentially enhance the vaccine-induced antibody responses in PWH. The review will provide guidance and impetus for further research to improve the immunogenicity of these vaccines in this human population.

Injectable hydrogels are increasingly being developed for biomedical applications due to their ability to be delivered in a minimally invasive manner. One potential use for such materials is in cell delivery for cardiac regeneration. While the materials’ properties are often characterized, how these properties (and in particular gelation) are affected by the addition of the therapeutic agent(s) they are designed to deliver is often overlooked. The aim of this study was to examine the interactive effects between collagen-based hydrogels and different additives (cells and microspheres). The results demonstrated that the incorporation of either cells or microspheres to a collagen hydrogel decreased its gelation time and increased its viscosity. Increased concentrations of the EDC/NHS cross-linker resulted in greater loss of cell viability. However, it was found that this cell loss could be minimized by delivering cells with the cross-linker scavenger glycine. A better understanding of how materials and cells (and other additives) respond to each other will help towards the goal of improving scaffolds being developed for regenerative therapy.

Cannabis-based medicines (CBMs) could help reduce systemic inflammation in people with HIV (PWH). In a prospective, randomized pilot study we enrolled participants from August 2021–April 2022 with HIV, aged ≥18 and on antiretroviral therapy and randomly assigned them to cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks with the primary objective being to assess safety and tolerability. Here we report on timeliness to study initiation, enrolment, compliance and retention rates. The target sample size was not reached. Two hundred and five individuals were approached, and 10 consented and were randomized; the rest refused (reasons: cannabis-related stigma/discomfort; too many study visits/insufficient time; unwillingness to undergo a “washout period” for three weeks) or were not eligible. The age of those randomized was 58 years (IQR 55–62); 80% were male. Only three met all criteria (30% enrolment compliance); seven were enrolled with minor protocol deviations. Compliance was excellent (100%). Eight (80%) participants completed the study; two (20%) were withdrawn for safety reasons (transaminitis and aggravation of pre-existing anemia). Time to study initiation and recruitment were the most challenging aspects. Ongoing work is required to reduce stigma related to CBMs. Future studies should find a balance between the requirements for safety monitoring and frequency of study visits.

Background: The Canadian HIV Cure Enterprise (CanCURE) is a pan-Canadian research collaboratory, investigating approaches for achieving sustainable HIV remission. In preparation for the next research cycle, CanCURE researchers and the Community Advisory Board (CAB) co-designed a web-based survey to identify HIV research priorities from the perspective of people with HIV (PWH) in Canada. The current study examined gender-based differences in these priorities. Methods: From August to December 2024, we recruited PWH across Canada through community organizations and community members. We collected data using REDCap electronic data capture tools hosted at The Research Institute of the McGill University Health Centre. The survey included 36 demographic questions, 16 questions related to general knowledge about HIV and HIV cure-related concepts, and 21 questions ranking research priorities. Knowledge questions were multiple choice, while priorities could be ranked on a scale. We summarized participant characteristics via descriptive statistics, and the research priorities were further stratified according to gender. Results: Of 109 participants, 48.6% self-identified as men, 46.8% as women, and 4.6% as two-spirit, non-binary, agender, or other. The median age was 53 years old. Approximately one-third of participants had lived with HIV for ≤14 years, one-third for 15–24 years, and one-third for ≥25 years. Overall, the median knowledge score of respondents was 79%. Among the 78 participants with prior HIV research experience, three times as many men (61.1%) as women (19.0%) participated in interventional studies involving medication or medical procedures. Men ranked preventing HIV transmission to partners as a priority, studying where the virus hides as the second, and avoiding high comorbidity risks as the third. In contrast, women ranked not having to take pills daily as a priority and avoiding higher risks for comorbidities as the second priority. Both genders equally valued expanding community involvement in HIV cure research. However, men focused more on integrating social and behavioural research, while women emphasized the need for diverse ethnic representation in research. Conclusions: Although both men and women share some common priorities regarding HIV cure research, there are notable gender differences in their specific concerns. Furthermore, a significant gender gap in participation in interventional studies, essential for advancing HIV cure research, highlights the importance of aligning research priorities with concerns of both genders.