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Despite mounting a robust antiviral CD8 T cell response to HIV infection, most infected individuals are unable to control HIV viral load without antiretroviral therapy (ART). Chimeric Ag receptor (CAR) T cell treatment is under intensive investigation as an alternative therapy for ART-free remission of chronic HIV infection. However, achieving durable remission of HIV will require a successful balance between CAR T cell effector function and persistence. CAR T cells with CD28 costimulatory domains have robust effector function but limited persistence in vivo, whereas CAR T cells with 4-1BB costimulatory domains present a more undifferentiated phenotype and greater in vivo persistence. We compared the in vitro phenotype and function of rhesus macaque and human CAR T cells that contained either the CD28 or 4-1BB costimulatory domain; both constructs also included CARs that are bispecific for gp120 of HIV or SIV and the CXCR5 moiety to promote in vivo homing of CAR/CXCR5 T cells to B cell follicles. Cells were transduced using a gammaretroviral vector and evaluated using flow cytometry. 4-1BB-CAR/CXCR5 T cells were phenotypically distinct from CD28-CAR/CXCR5 T cells and showed increased expression of CAR and CD95. Importantly, both CD28- and 4-1BB-CAR/CXCR5 T cells retained equal capacity to recognize and suppress SIV in vitro. These studies provide new insights into rhesus macaque and human 4-1BB- and CD28-bearing CAR T cells.

Neurodegeneration is a pathological process characterized by progressive neuronal impairment, dysfunction, and loss due to mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Many studies have shown that lithium protects against neurodegeneration. Herein, we summarize recent clinical and laboratory studies on the neuroprotective effects of lithium against neurodegeneration and its potential to modulate mitochondrial dysfunction, oxidative stress, inflammation, and apoptosis. Recent findings indicate that lithium regulates critical intracellular pathways such as phosphatidylinositol-3 (PI3)/protein kinase B (Akt)/glycogen synthase kinase-3 (GSK3β) and PI3/Akt/response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF). We queried PubMed, Web of Science, Scopus, Elsevier, and other related databases using search terms related to lithium and its neuroprotective effect in various neurodegenerative diseases and events from January 2000 to May 2022. We reviewed the major findings and mechanisms proposed for the effects of lithium. Lithium's neuroprotective potential against neural cell degeneration is mediated by inducing anti-inflammatory factors, antioxidant enzymes, and free radical scavengers to prevent mitochondrial dysfunction. Lithium effects are regulated by two essential pathways: PI3/Akt/GSK3β and PI3/Akt/CREB/BDNF. Lithium acts as a neuroprotective agent against neurodegeneration by preventing inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction using PI3/Akt/GSK3β and PI3/Akt/CREB/BDNF signaling pathways.

Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) is a respiratory disease that causes dysfunction in respiration. Since late 2019, this virus has infected and killed millions of people around the world and imposed many medical and therapeutic problems in the form of a pandemic. According to recent data, COVID-19 disease can increase the risk of stroke, which can be deadly or cause many neurological disorders after the disease. During the last two years, many efforts have been made to introduce new therapies for management of COVID-19-related complications, including stroke. To achieve this goal, several conventional drugs have been investigated for their possible therapeutic roles. Minocycline, a broad-spectrum, long-acting antibiotic with anti-inflammatory and antioxidant properties, is one such conventional drug that should be considered for treating COVID-19-related stroke, as indirect evidence indicates that it exerts neuroprotective effects, can modulate stroke occurrence, and can play an effective and strategic role in management of the molecular signals caused by stroke and its destructive consequences. The matrix metalloprotease (MMP) signaling pathway is one of the main signaling pathways involved in the occurrence and exacerbation of stroke; however, its role in COVID-19-induced stroke and the possible role of minocycline in the management of this signaling pathway in patients with COVID-19 is unclear and requires further investigation. Based on this concept, we hypothesize that minocycline might act via MMP signaling as a neuroprotective agent against COVID-19-induced neurological dysfunction, particularly stroke.