P-selectin glycoprotein ligand-1 and cardiovascular diseases: from a general perspective to an HIV infection context

Globally, cardiovascular diseases (CVDs) are a leading cause of death as they are responsible for the loss of at least 17 million lives annually. It has been established that the pathogenesis of CVDs is strongly associated both with inflammation as well as with inflammatory markers (proteins, cytokines, amongst others). In this perspective, the role of one of these proinflammatory proteins, referred to as P-selectin glycoprotein ligand (PSGL)-1, is of particular interest. Indeed, contemporary evidence points to the fact that P-selectin glycoprotein ligand (PSGL)-1 plays a critical role in the development of CVDs via its interactions with P-selectin, L-selectin, and/or E-selectin. However, due to the dearth of published contemporary research concerning PSGL-1 expression in people living with HIV (PLWH), it remains challenging to comprehensively investigate this area of study, although potential clues exist in the literature which may serve as potential directions for future investigations. Hence, in the first part of this article, a scoping review of the literature regarding the role of PSGL-1 in the development of CVDs is provided. Then, in the second part, observations concerning PSGL-1 expression in PLWH receiving ART are presented and interpreted. Through this work, we hope that increased attention will be directed towards the screening of PSGL-1 expression, which we believe may serve as a reliable biomarker to predict the presence and evolution of CVDs in PLWH

HIV-associated neurocognitive disorder: key implications of the microbiota-gut-brain axis

HIV-associated neurocognitive disorder (HAND) is now recognized to be relatively common in people living with HIV (PLWH), and remains a common cause of cognitive impairment. Unfortunately, the fundamental pathogenic processes underlying this specific outcome of HIV infection have not as yet been fully elucidated. With increased interest in research related to the microbiota-gut-brain axis, the gut-brain axis has been shown to play critical roles in regulating central nervous system disorders such as Alzheimer’s disease and Parkinson’s disease. PLWH are characterized by a particular affliction, referred to as gut-associated dysbiosis syndrome, which provokes an alteration in microbial composition and diversity, and of their associated metabolite composition within the gut. Interestingly, the gut microbiota has also been recognized as a key element, which both positively and negatively influences human brain health, including the functioning and development of the central nervous system (CNS). In this review, based on published evidence, we critically discuss the relevant interactions between the microbiota-gut-brain axis and the pathogenesis of HAND in the context of HIV infection. It is likely that HAND manifestation in PLWH mainly results from (i) gut-associated dysbiosis syndrome and a leaky gut on the one hand and (ii) inflammation on the other hand. In other words, the preceding features of HIV infection negatively alter the composition of the gut microbiota (microbes and their associated metabolites) and promote proinflammatory immune responses which singularly or in tandem damage neurons and/or induce inadequate neuronal signaling. Thus, HAND is fairly prevalent in PLWH. This work aims to demonstrate that in the quest to prevent and possibly treat HAND, the gut microbiota may ultimately represent a therapeutically targetable “host factor.

Mechanisms underlying the development of type 1 diabetes in ART-treated people living with HIV: an enigmatic puzzle

The immunopathogenesis of HIV infection remains poorly understood. Despite the widespread use of effective modern antiretroviral therapy (ART), people living with HIV (PLWH) are known to develop several comorbidities, including type 1 diabetes (T1DM). However, the etiology and critical mechanisms accounting for the onset of T1DM in the preceding context remain unknown. This article proposes to address this topic in order to provide further understanding and future research directions

The Optimal Timing of Antiretroviral Therapy Initiation in HIV-Infected Patients with Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Trial

The optimal timing of antiretroviral therapy (ART) initiation in human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (HIV/CM) is controversial. We designed a clinical trial to inves-tigate the optimal timing for ART initiation in HIV/CM patients. This will be a multicenter, prospective, and randomized clinical trial. Each enrolled patient will be randomized into either the early ART arm or the deferred ART arm. We will compare the mortality and incident rates of immune reconstitution inflammatory syndrome between the two arms. We hope to elucidate the optimal timing for ART initiation in HIV/CM patients

The diverse roles of miRNAs in HIV pathogenesis: Current understanding and future perspectives

Despite noteworthy progress made in the management and treatment of HIV/AIDS-related disease, including the introduction of the now almost ubiquitous HAART, there remains much to understand with respect to HIV infection. Although some roles that miRNAs play in some diseases have become more obvious of late, the roles of miRNAs in the context of HIV pathogenesis have not, as yet, been elucidated, and require further investigations. miRNAs can either be beneficial or harmful to the host, depending upon the genes they target. Some miRNAs target the 3′ UTR of viral mRNAs to accomplish restriction of viral infection. However, upon HIV-1 infection, there are several dysregulated host miRNAs which target their respective host factors to either facilitate or abrogate viral infection. In this review, we discuss the miRNAs which play roles in various aspects of viral pathogenesis. We describe in detail the various mechanisms thereby miRNAs either directly or indirectly regulate HIV-1 infection. Moreover, the predictive roles of miRNAs in various aspects of the HIV viral life cycle are also discussed. Contemporary antiretroviral therapeutic drugs have received much attention recently, due to their success in the treatment of HIV/AIDS; therefore, miRNA involvement in various aspects of antiretroviral therapeutics are also elaborated upon herein. The therapeutic potential of miRNAs are discussed, and we also propose herein that the therapeutic potential of one specific miRNA, miR-34a, warrants further exploration, as this miRNA is known to target three host proteins to promote HIV-1 pathogenesis. Finally, future perspectives and some controversy around the expression of miRNAs by HIV-1 are also discussed

Fullerenol inhibits tendinopathy by alleviating inflammation

Tendinopathy is a common disease in orthopaedics, seriously affecting tendon functions. However, the effects of non-surgical treatment on tendinopathy are not satisfactory and surgical treatments possibly impair the function of tendons. Biomaterial fullerenol has been proved to show good anti-inflammatory effects on various inflammatory diseases. For in vitro experiments, primary rat tendon cells (TCs) were treated by interleukin-1 beta (IL-1β) combined with aqueous fullerenol (5, 1, 0.3 μg/mL). Then inflammatory factors, tendon-related markers, migration and signaling pathways were detected. For in vivo experiments, rat tendinopathy model was constructed by local injection of collagenase into Achilles tendons of rats and fullerenol (0.5, 1 mg/mL) was locally injected 7 days after collagenase injection. Inflammatory factors and tendon-related markers were also investigated. Fullerenol with good water-solubility showed excellent biocompatibility with TCs. Fullerenol could increase expression of tendon-related factors (Collagen I and tenascin C) and decrease expression of inflammatory factors (matrix metalloproteinases-3, MMP-3, and MMP-13) and reactive oxygen species (ROS) level. Simultaneously, fullerenol slowed the migration of TCs and inhibited activation of Mitogen-activated protein kinase (MAPK) signaling pathway. Fullerenol also attenuated tendinopathy in vivo, including reduction of fiber disorders, decrease of inflammatory factors and increase of tendon markers. In summary, fullerenol is a promising biomaterial that can be used to treat tendinopathy

Dehydroleucodine exerts an antiproliferative effect on human Burkitt’s lymphoma Daudi cells via SLC7A11-mediated ferroptosis

BackgroundBurkitt’s lymphoma (BL) is a rare, highly aggressive B-cell non-Hodgkin’s lymphoma known for rapid proliferation. While most patients respond well to intensive chemotherapy, those who are older, have comorbidities, or develop therapy resistance show limited outcomes.PurposeThis study aims to evaluate the in vitro anti-tumor activity of dehydroleucodine (DhL), a novel plant-derived chemotherapeutic agent, against BL cells and to elucidate the molecular mechanisms underlying its effects.MethodsA screening of 42 plant-derived small molecules identified DhL as a potent inhibitor of BL growth. We evaluated DhL’s effects on cell cycle progression, apoptosis, and ferroptosis pathways using cell viability assays, flow cytometry, transcriptomic analysis, and validation experiments.ResultsDhL demonstrated robust and specific anti-proliferative effects against BL Daudi cells. Mechanistic investigations revealed that DhL exerts its effects through cell cycle modulation, induction of apoptosis, and ferroptosis. Transcriptomic analysis identified SLC7A11 as a critical regulator of DhL-mediated ferroptosis, which was further validated experimentally.ConclusionDhL shows strong potential as a novel chemotherapeutic agent for BL treatment by targeting SLC7A11-mediated ferroptosis. Further investigation is warranted to confirm its efficacy and clinical utility in diverse BL patient populations

Accelerating attribute-focused cell culture process development through the deployment of an automatic assay preparation platform

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