Chimeric Antigen Receptor T-cell Therapy in Cancer: A Critical Review.

Targeted cancer therapy acts on targeted molecules, is less toxic to normal cells, and acts more specifically on cancer cells. The two primary strategies for preventing malignancy growth are the blocking of T-cell repression signals or forwarding of T-cell to tumor target with both T and tumor-specific antibodies. The CAR comprises three domains, the extracellular antigen recognition domain and the intracellular T-cell signaling domain, which participate in activating T-cells. The two most common adverse effects of CAR T-cell treatment are cytokine release syndrome (CRS) and cell-associated neurotoxicity syndrome (CANS). The adaptability of intracellular signaling domains inside CARs allows the cell to counterbalance the downregulation of costimulatory molecules produced by tumor cells, either indirectly or directly. The major disadvantage of CAR-T cell therapy is off-target toxicity. Treatment with CARs expressing CD3, CD123, Lewis Y, CLL-1, CD44v6, FLT3, and folate receptors showed promising results in preclinical models of acute myeloid leukemia (AML). A recent study has revealed that B7-H3 CART cells exhibit significant anticancer efficacy in a variety of solid tumor preclinical models, including PDAC, ovarian cancer, neuroblastoma, and various pediatric malignancies. The notion of SUPRA CAR, with its unique capacity to alter targets without the need to re-engineer, is a recent innovation in CAR. Given the importance of NK cells in tumor development and metastatic defence, NK cell-based immunotherapies, including adoptive transfer of NK cells, have garnered a lot of interest. With the advancement of improved cellular manufacturing methods, novel cellular engineering strategies, precision genome editing technologies, and combination therapy approaches, we firmly believe that CAR-T cells will soon become an off-the-shelf, cost-effective, and potentially curative therapy for oncogenesis.

Emphasizing roles of BDNF promoters and inducers in Alzheimer's disease for improving impaired cognition and memory.

Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophic factor adding to neurons' development and endurance. The amount of BDNF present in the brain determines susceptibility to various neurodegenerative diseases. In Alzheimer's disease (AD), often it is seen that low levels of BDNF are present, which primarily contributes to cognition deficit by regulating long-term potentiation (LTP) and synaptic plasticity. Molecular mechanisms underlying the synthesis, storage and release of BDNF are widely studied. New molecules are found, which contribute to the signal transduction pathway. Two important receptors of BDNF are TrkB and p75NTR. When BDNF binds to the TrkB receptor, it activates three main signalling pathways-phospholipase C, MAPK/ERK, PI3/AKT. BDNF holds an imperative part in LTP and dendritic development, which are essential for memory formation. BDNF supports synaptic integrity by influencing LTP and LTD. This action is conducted by modulating the glutamate receptors; AMPA and NMDA. This review paper discusses the aforesaid points along with inducers of BDNF. Drugs and herbals promote neuroprotection by increasing the hippocampus' BDNF level in various disease-induced animal models for neurodegeneration. Advancement in finding pertinent molecules contributing to the BDNF signalling pathway has been discussed, along with the areas that require further research and study.

Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2.

PURPOSE OF REVIEW: The rapid spread of virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned out to be a global emergency. Symptoms of this viral infection, coronavirus disease 2019 (COVID-19), include mild infections of the upper respiratory tract, viral pneumonia, respiratory failure, multiple organ failure and death. Till date, no drugs have been discovered to treat COVID-19 patients, and therefore, a considerable amount of interest has been shown in repurposing the existing drugs. RECENT FINDINGS: Out of these drugs, chloroquine (CQ) and hydroxychloroquine (HCQ) have demonstrated positive results indicating a potential antiviral role against SARS-CoV-2. Its mechanism of action (MOA) includes the interference in the endocytic pathway, blockade of sialic acid receptors, restriction of pH mediated spike (S) protein cleavage at the angiotensin-converting enzyme 2 (ACE2) binding site and prevention of cytokine storm. Unfortunately, its adverse effects like gastrointestinal complications, retinopathy and QT interval prolongation are evident in treated COVID-19 patients. Yet, multiple clinical trials have been employed in several countries to evaluate its ability in turning into a needed drug in this pandemic. SUMMARY: This review attempts to summarize the MOA of CQ/HCQ and its side effects. The existing literature hints that till date, the role of CQ/HCQ in COVID-19 may be sceptical, and further studies are warranted for obtaining a therapeutic option that could be effectively used across the world to rise out from this pandemic.