ABSTRACT
Humanin (HN) is a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA. HN exhibits protective effects in several cell types, including leukocytes, germ cells, neurons, tissues against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein. HN is an essential cytoprotective peptide in the human body that regulates mitochondrial functions under stress conditions. The present review aims to evaluate HN peptide's antiapoptotic activities as a potential therapeutic target in the treatment of cancer, diabetes mellitus, male infertility, bone-related diseases, cardiac diseases, and brain diseases. Based on in vitro and in vivo studies, HN significantly suppressed the apoptosis during the treatment of bone osteoporosis, cardiovascular diseases, diabetes mellitus, and neurodegenerative diseases. According to accumulated data, it is concluded that HN exerts the proapoptotic activity of TNF-α in cancer, which makes HN as a novel therapeutic agent in the treatment of cancer and suggested that along with HN, the development of another mitochondrial-derived peptide could be a viable therapeutic option against different oxidative stress and apoptosis-related diseases.
Subject(s)
Apoptosis/physiology , Cytoprotection/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/therapeutic use , Mitochondria/metabolism , Amino Acid Sequence , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/therapeutic use , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Humans , Intracellular Signaling Peptides and Proteins/genetics , Mitochondria/genetics , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolismABSTRACT
Cancer is one of the most leading causes of death and a major public health problem, universally. According to accumulated data, annually, approximately 8.5 million people died because of the lethality of cancer. Recently, a novel RNA domain-containing endonuclease-based genome engineering technology, namely the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9) have been proved as a powerful technique in the treatment of cancer cells due to its multifunctional properties including high specificity, accuracy, time reducing and cost-effective strategies with minimum off-target effects. The present review investigates the overview of recent studies on the newly developed genome-editing strategy, CRISPR/Cas9, as an excellent pre-clinical therapeutic option in the reduction and identification of new tumor target genes in the solid tumors. Based on accumulated data, we revealed that CRISPR/Cas9 significantly inhibited the robust tumor cell growth (breast, lung, liver, colorectal, and prostate) by targeting the oncogenes, tumor-suppressive genes, genes associated to therapies by inhibitors, genes associated to chemotherapies drug resistance, and suggested that CRISPR/Cas9 could be a potential therapeutic target in inhibiting the tumor cell growth by suppressing the cell-proliferation, metastasis, invasion and inducing the apoptosis during the treatment of malignancies in the near future. The present review also discussed the current challenges and barriers, and proposed future recommendations for a better understanding.
Subject(s)
CRISPR-Cas Systems , Gene Editing , Genetic Therapy , Genome, Human , Neoplasms/therapy , Humans , Neoplasms/genetics , Neoplasms/pathologyABSTRACT
In December 2019, a novel virus, namely COVID-19 caused by SARS-CoV-2, developed from Wuhan, (Hubei territory of China) used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Data revealed that the newly emerged SARS-CoV-2 affected more than 24,854,140 people with 838,924 deaths worldwide. Until now, no licensed immunization or drugs are present for the medication of SARS-CoV-2. The present review aims to investigate the latest developments and discuss the candidate antibodies in different vaccine categories to develop a reliable and efficient vaccine against SARS-CoV-2 in a short time duration. Besides, the review focus on the present challenges and future directions, structure, and mechanism of SARS-CoV-2 for a better understanding. Based on data, we revealed that most of the vaccines are focus on targeting the spike protein (S) of COVID-19 to neutralized viral infection and develop long-lasting immunity. Up to phase-1 clinical trials, some vaccines showed the specific antigen-receptor T-cell response, elicit the humoral and immune response, displayed tight binding with human-leukocytes-antigen (HLA), and recognized specific antibodies to provoke long-lasting immunity against SARS-CoV-2.
