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Niemann–Pick disease (NPD) is another type of metabolic disorder that is classified as lysosomal storage diseases (LSDs). The main cause of the disease is mutation in the SMPD1 (type A and B) or NPC1 or NPC2 (type C) genes, which lead to the accumulation of lipid substrates in the lysosomes of the liver, brain, spleen, lung, and bone marrow cells. This is followed by multiple cell damage, dysfunction of lysosomes, and finally dysfunction of body organs. So far, about 346, 575, and 30 mutations have been reported in SMPD1, NPC1, and NPC2 genes, respectively. Depending on the type of mutation and the clinical symptoms of the disease, the treatment will be different. The general aim of the current study is to review the clinical and molecular characteristics of patients with NPD and study various treatment methods for this disease with a focus on gene therapy approaches. Significance statement: This work concerns an overview of Niemann–Pick disease (types A, B, and C) of clinical, molecular, and therapeutic features (focus on therapy approaches especially gene therapy). [ABSTRACT FROM AUTHOR]

One of the most important inherited metabolic disorders is GM1 gangliosidosis, which is a progressive neurological disorder. The main cause of this disease is a genetic defect in the enzyme β‐galactosidase due to a mutation in the glb1 gene. Lack of this enzyme in cells (especially neurons) leads to the accumulation of ganglioside substrate in nerve tissues, followed by three clinical forms of GM1 disease (neonatal, juvenile, and adult variants). Genetically, many mutations occur in the exons of the glb1 gene, such as exons 2, 6, 15, and 16, so the most common ones reported in scientific studies include missense/nonsense mutations. Therefore, many studies have examined the genotype‐phenotype relationships of this disease and subsequently using gene therapy techniques have been able to reduce the complications of the disease and alleviate the signs and symptoms of the disease. In this regard, the present article reviews the general features of GM1 gangliosidosis and its mutations, as well as gene therapy studies and animal and human models of the disease. Significance statement: This work concerns an overview of the molecular mechanisms of GM1 gangliosidosis and the gene therapies performed in cell, animal, and human models of this disease. [ABSTRACT FROM AUTHOR]

Background: FCSK‐congenital disorder of glycosylation (FCSK‐CDG) is a recently discovered rare autosomal recessive genetic disorder with defective fucosylation due to mutations in the fucokinase encoding gene, FCSK. Despite the essential role of fucokinase in the fucose salvage pathway and severe multisystem manifestations of FCSK‐CDG patients, it is not elucidated which cells or which types of fucosylation are affected by its deficiency. Methods: In this study, CRISPR/Cas9 was employed to construct an FCSK‐CDG cell model and explore the molecular mechanisms of the disease by lectin flow cytometry and real‐time PCR analyses. Results: Comparison of cellular fucosylation by lectin flow cytometry in the created CRISPR/Cas9 FCSK knockout and the same unedited cell lines showed no significant change in the amount of cell surface fucosylated glycans, which is consistent with the only documented previous study on different cell types. It suggests a probable effect of this disease on secretory glycoproteins. Investigating O‐fucosylation by analysis of the NOTCH3 gene expression as a potential target revealed a significant decrease in the FCSK knockout cells compared with the same unedited ones, proving the effect of fucokinase deficiency on EGF‐like repeats O‐fucosylation. Conclusion: This study expands insight into the FCSK‐CDG molecular mechanism; to the best of our knowledge, it is the first research conducted to reveal a gene whose expression level alters due to this disease. [ABSTRACT FROM AUTHOR]

Aging causes numerous age-related diseases, leading the human species to death. Nevertheless, rejuvenating strategies based on cell epigenetic modifications are a possible approach to counteract disease progression while getting old. Cell reprogramming of adult somatic cells toward pluripotency ought to be a promising tool for age-related diseases. However, researchers do not have control over this process as cells lose their fate, and cause potential cancerous cells or unexpected cell phenotypes. Direct and partial reprogramming were introduced in recent years with distinctive applications. Although direct reprogramming makes cells lose their identity, it has various applications in regeneration medicine. Temporary and regulated in vivo overexpression of Yamanaka factors has been shown in several experimental contexts to be achievable and is used to rejuvenate mice models. This regeneration can be accomplished by altering the epigenetic adult cell signature to the signature of a younger cell. The greatest advantage of partial reprogramming is that this method does not allow cells to lose their identity when they are resetting their epigenetic clock. It is a regimen of short-term Oct3/4, Sox2, Klf4, and c-Myc expression in vivo that prevents full reprogramming to the pluripotent state and avoids both tumorigenesis and the presence of unwanted undifferentiated cells. We know that many neurological age-related diseases, such as Alzheimer's disease, stroke, dementia, and Parkinson's disease, are the main cause of death in the last decades of life. Therefore, scientists have a special tendency regarding neuroregeneration methods to increase human life expectancy. [ABSTRACT FROM AUTHOR]

Background: Cancer, being a complex disease, presents a major challenge for the scientific and medical communities. Peptide therapeutics have played a significant role in different medical practices, including cancer treatment. Method: This review provides an overview of the current situation and potential development prospects of anticancer peptides (ACPs), with a particular focus on peptide vaccines and peptide-drug conjugates for cancer treatment. Results: ACPs can be used directly as cytotoxic agents (molecularly targeted peptides) or can act as carriers (guiding missile) of chemotherapeutic agents and radionuclides by specifically targeting cancer cells. More than 60 natural and synthetic cationic peptides are approved in the USA and other major markets for the treatment of cancer and other diseases. Compared to traditional cancer treatments, peptides exhibit anticancer activity with high specificity and the ability to rapidly kill target cancer cells. ACP's target and kill cancer cells via different mechanisms, including membrane disruption, pore formation, induction of apoptosis, necrosis, autophagy, and regulation of the immune system. Modified peptides have been developed as carriers for drugs, vaccines, and peptide–drug conjugates, which have been evaluated in various phases of clinical trials for the treatment of different types of solid and leukemia cancer. Conclusions: This review highlights the potential of ACPs as a promising therapeutic option for cancer treatment, particularly through the use of peptide vaccines and peptide–drug conjugates. Despite the limitations of peptides, such as poor metabolic stability and low bioavailability, modified peptides show promise in addressing these challenges. Various mechanism of action of anticancer peptides. Modes of action against cancer cells including: inducing apoptosis by cytochrome c release, direct cell membrane lysis (necrosis), inhibiting angiogenesis, inducing autophagy-mediated cell death and immune cell regulation. [ABSTRACT FROM AUTHOR]

Infertility is a global health problem affecting about 15% of all couples, of which 50% are due to male infertility. Although the etiology of infertility is known in most infertile men, idiopathic male infertility remains a challenge. Therefore, there is a need for novel diagnostic methods to detect the underlying mechanisms and develop appropriate therapies. Recent studies have focused on the role of non-coding RNAs (ncRNAs) in male infertility. Circular RNAs (CircRNAs), a type of ncRNAs, are found to play a key role in the development of some pathological conditions, including cardiovascular diseases, diabetes, cancers, autoimmune diseases, etc. Several studies have reported the presence of CircRNAs and their target genes in the human reproductive system. In addition, their expression in testicular tissues, sperm cells, and seminal fluid has been identified. Abnormal expression of CircRNAs has been associated with azoospermia and asthenozoospermia in infertile men. The present narrative review provides a brief description of the role of CircRNAs in spermatogenic cells, male infertility, and reproductive cancers. In addition, some CircRNAs have been identified as potential biomarkers for disease detection and treatment. [ABSTRACT FROM AUTHOR]

A woman who is infertile is defined as a woman who is unable to conceive after having unprotected sex for more than one year. 20-25% of couples worldwide suffer from infertility each year (60 to 80 million couples). In vitro fertilization (IVF) plays a significant role in the treatment of various types of infertility, including fallopian tube defects, endometriosis, immunity, and male causes. IVF is a complex procedure that can be used to aid fertility or prevent genetic problems in the fetus. The objective of this review is to investigate factors that affect IVF failure and success rates. Need for this review is predicated on the different results obtained from previous studies, the high prevalence of infertility, and the lack of a similar study in this field. Articles were regarded as suitable if they evaluated the association between any factor and IVF outcome. A comprehensive search of databases was completed from their inception until March 2021. Our search resulted in 1278 articles. After assessing the titles and abstracts, we selected 70 articles for further reading. Our review shows that the effectiveness of IVF treatment depends on many factors. These include the physical environment, genetics, psychological factors, serum levels of certain hormones, sperm characteristics, as well as the age and body mass index of couples. Based on the results of our study, nutrient supplementation maybe beneficial for the enhancement of semen quality. For better IVF outcome, it is better for obese women to balance their body mass index (BMI) before IVF procedure initiation. [ABSTRACT FROM AUTHOR]

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease that diabetes mellitus is one of its major risk factors. MiR-126 as an endothelial cells specific miRNA plays a main role in angiogenesis. The objective of this study was to find a promising treatment by increasing therapeutic potential of adipose tissue mesenchymal stem cells (AT-MSCs) with microRNA-126 in diabetic mouse model with critical limb ischemia. AT-MSCs were isolated from male C57BL/6 mouse and characterized. The cells were infected with miR-126 recombinant lentiviral vectors. Diabetes mellitus type 1 was induced and CLI was created in the animals. Animals were divided in different groups to receive PBS, MSCs, miR-126, and MSCmiR-126 and after the experiment, behavioural tests, cell survival, real-time PCR, and histopathological analysis were assessed. The results of function scores, VEGF-A level, and histopathology data demonstrated that the miR-126 treated group was better than PBS and MSCs groups. The expression of PIK3R2 and SPRED1 were decreased in miR-126 group compared to the control group. Our results showed that MSCsmiR-126 can live longer than MSCs in the gastrocnemius muscle. We conclude that mice treated with MSCsmiR-126 in functional tests showed better results and also the expression of VEGF-A and Microvessel density in them were higher than other groups. This study suggested that AT-MSCs overexpressing miR-126 could be an efficient therapeutic approach for angiogenesis in CLI with diabetes by downregulating SPRED1 and PIK3R2 and increasing secretion of angiogenic cytokines which can prolong the MSC survival. • AT-MSCs overexpressing miR-126 promote angiogenesis by downregulating SPRED1 and PIK3R2. • MiR-126 modification prolongs the MSC survival. • AT-MSCs overexpressing miR-126 can indicate as an efficient therapeutic method for treatment of limb ischemia. [ABSTRACT FROM AUTHOR]