Hypertension is a major risk factor for heart attack, produce atherosclerosis (hardening of the arteries), congestive heart failure, stroke, kidney infection, blindness, end-stage renal infection, and cardiovascular diseases. Many mechanisms are involved in causing hypertension, i.e., via calcium channels, alpha and beta receptors, and the renin-angiotensin system (RAS). RAS has an important role in blood pressure control and is also involved in the metabolism of glucose, homeostasis, and balance of electrolytes in the body. The components of RAS that are involved in the regulation of blood pressure are angiotensinogen, Ang I (angiotensin I), Ang II (angiotensin II), ACE (angiotensin-converting enzyme), and ACE 2 (angiotensin-converting enzyme 2). These components provide for relevant therapeutic targets for the treatment of hypertension, and various drugs are commercially available that target individual components of RAS. Angiotensin receptor blockers (ARBs) and ACE inhibitors are the most popular among these drugs. ACE is chosen in this review as it makes an important target for blood pressure control because it converts Ang I into Ang II and also acts on the vasodilator, bradykinin, to degrade it into inactive peptides. This review highlights various aspects of blood pressure regulation in the body with a focus on ACE, drugs targeting the components involved in regulation, their associated side effects, and a need to shift to alternative therapy for putative hypertension treatment in the form of bioactive peptides from food.

CAR-T cell therapy is not without some clinical adverse effects, namely cytokine storms, due to a massive release of cytokines when CAR-T cells multiply in the body. Our goal was to develop exosomes expressing CD19 CAR to treat CD19-positive B-cell malignancies, instead of using whole CD19 CAR-T cells, thereby reducing the clinical risk of uncontrolled cytokine storms. Exosomes are extracellular nanovesicles (30–150 nm), composed of lipids, proteins, and nucleic acids, that carry the fingerprint of their parent cells. Exosomes are a preferred delivery system in nano-immunotherapy. Here, HEK293T parent cells were transduced with CD19 CAR plasmids and cellular CD19 CAR expression was confirmed. Exosomes (Exo-CD19 CAR) were isolated from the conditioned medium of non-transduced (WT) and CD19 CAR plasmid transduced HEK293T cells. Consequently, CD19 B-lineage leukemia cell lines were co-cultured with Exo-CD19 CAR and cell death was measured. Our data show that Exo-CD19 CAR treatment induced cytotoxicity and elevated pro-apoptotic genes in CD19-positive leukemia B-cells without inducing cell death in CD19-negative cells. Overall, the novel CD19 CAR exosomes target the CD19 surface antigens of leukemic B-cells and can induce contact-dependent cytotoxicity.

Vitamin D receptor (VDR) deficient status has been shown to be associated with the activation of renin angiotensin system (RAS). We hypothesized that lack of VDR would enhance p53 expression in podocytes through down regulation of SIRT1; the former would enhance the transcription of angiotensinogen (Agt) and angiotensinogen II type 1 receptor (AT1R) leading to the activation of RAS. Renal tissues of VDR mutant (M) mice displayed increased expression of p53, Agt, renin, and AT1R. In vitro studies, VDR knockout podocytes not only displayed up regulation p53 but also displayed enhanced expression of Agt, renin and AT1R. VDR deficient podocytes also displayed an increase in mRNA expression for p53, Agt, renin, and AT1R. Interestingly, renal tissues of VDR-M as well as VDR heterozygous (h) mice displayed attenuated expression of deacetylase SIRT1. Renal tissues of VDR-M mice showed acetylation of p53 at lysine (K) 382 residues inferring that enhanced p53 expression in renal tissues could be the result of ongoing acetylation, a consequence of SIRT1 deficient state. Notably, podocytes lacking SIRT1 not only showed acetylation of p53 at lysine (K) 382 residues but also displayed enhanced p53 expression. Either silencing of SIRT1/VDR or treatment with high glucose enhanced podocyte PPAR-y expression, whereas, immunoprecipitation (IP) of their lysates with anti-retinoid X receptor (RXR) antibody revealed presence of PPAR-y. It appears that either the deficit of SIRT1 has de-repressed expression of PPAR-y or enhanced podocyte expression of PPAR-y (in the absence of VDR) has contributed to the down regulation of SIRT1.

The developments of antibodies for cancer therapeutics have made remarkable success in recent years. There are multiple factors contributing to the success of the biological molecule including origin of the antibody, isotype, affinity, avidity and mechanism of action. With better understanding of mechanism of cancer progression and immune manipulation, recombinant formats of antibodies are used to develop therapeutic modalities for manipulating the immune cells of patients by targeting specific molecules to control the disease. These molecules have been successful in minimizing the side effects instead caused by small molecules or systemic chemotherapy but because of the developing therapeutic resistance against these antibodies, combination therapy is thought to be the best bet for patient care. Here, in this review, we have discussed different aspects of antibodies in cancer therapy affecting their efficacy and mechanism of resistance with some relevant examples of the most studied molecules approved by the US FDA.

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties.