A review of the advances, insights, and prospects of gene therapy for Alzheimer's disease: A novel target for therapeutic medicine.

Neurodegenerative diseases such as Alzheimer's disease (AD) are still an important issue for scientists because it is difficult to cure with the available molecular medications and conventional treatments. Due to the complex nature of the brain structures and heterogeneous morphological and physiological properties of neuronal cells, interventions for cerebral-related disorders using surgical approaches, and classical and ongoing treatments remain hard for physicians. Furthermore, the development of newly designed medications attempts to target AD are not successful in improving AD, because abnormalities of tau protein, aggregation of amyloid ß (Aß) peptide, inflammatory responses, etc lead to advanced neurodegeneration processes that conventional treatments cannot stop them. In recent years, novel diagnostic strategies and therapeutic approaches have been developed to identify and cure early pathological events of AD. Accordingly, many gene-based therapies have been developed and introduce the therapeutic potential to prevent and cure AD. On the other hand, genetic investigations and postmortem assessments have detected a large number of factors associated with AD pathology. Also, genetically diverse animal models of AD help us to detect and prioritize novel resilience mechanisms. Hence, gene therapy can be considered an effective and powerful tool to identify and treat human diseases. Ultimately, gene study and gene-based therapy with a critical role in the detection and cure of various human disorders will have a fundamental role in our lives forever. This scientific review paper discusses the present status of different therapeutic strategies, particularly gene-based therapy in treating AD, along with its challenges.

Developing nanosize carrier systems for Amphotericin-B: A review on the biomedical application of nanoparticles for the treatment of leishmaniasis and fungal infections.

New formulations of Amphotericin-B (Am-B), the most popular therapeutic drug for many human infections such as parasitic and fungal pathogens, are safe, economical, and effective in the world. Several newly designed carrier systems for Am-B can also be considered orally with sufficient gastrointestinal permeability and good solubility. However, the clinical application of several new formulations of Am-B with organ cytotoxicity, low bioavailability, high costs, and technical problems have caused some issues. Therefore, more attention and scientific design are required to progress safe and effective drug delivery systems. Currently, the application of nano-based technology and nanomaterials in the advancement of drug delivery systems exhibits promising outcomes to cure many human systemic infections. Designing novel drug delivery systems including solid lipid nanostructured materials, lipo-polymersomes, drug conjugates and microneedles, liposomes, polymer and protein-based nanostructured materials, dendrimers, emulsions, mixed micelles, polymeric micelles, cyclodextrins, nanocapsules, and nanocochleate for Am-B has many advantages to reducing several related issues. The unique properties of nanostructured particles such as proper morphology, small size, surface coatings, and, electrical charge, permit scientists to design new nanocomposite materials against microorganisms for application in various human diseases. These features have made these nanoparticles an ideal candidate for drug delivery systems in clinical approaches to cure a number of human disorders and currently, several therapeutic nanostructured material formulations are under different stages of clinical tests. Hence, this scientific paper mainly discussed the advances in new formulations of Am-B for the treatment of human systemic infections and related clinical tests.

Tumor-educated platelets.

Beyond traditional roles in homeostasis and coagulation, growing evidence suggests that platelets also reflect malignant transformation in cancer. Platelets are present in the tumor microenvironment where they interact with cancer cells. This interaction results in direct and indirect "education" as evident by platelet alterations in adhesion molecules, glycoproteins, nucleic acids, proteins and various receptors. Subsequently, these tumor-educated platelets (TEPs) circulate throughout the body and play pivotal roles in promotion of tumor growth and dissemination. Accordingly, platelet status can be considered a unique blood-based biomarker that can potentially predict prognosis and therapeutic success. Recently, liquid biopsies including TEPs have received much attention as safe, minimally invasive and sensitive alternatives for patient management. Herein, we provide an overview of TEPs and explore their benefits and limitations in cancer.

Liquid biopsy in colorectal cancer.

Liquid biopsy refers to a set of pathological samples retrieved from non-solid sources, such as blood, cerebrospinal fluid, urine, and saliva through non-invasive or minimally invasive approaches. In the recent decades, an increasing number of studies have focused on clinical applications and improving technological investigation of liquid biopsy biosources for diagnostic goals particularly in cancer. Materials extracted from these sources and used for medical evaluations include cells like circulating tumor cells (CTCs), tumor-educated platelets (TEPs), cell-free nucleic acids released by cells, such as circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), cell-free RNA (cfRNA), and exosomes. Playing significant roles in the pathogenesis of human malignancies, analysis of these sources can provide easier access to genetic and transcriptomic information of the cancer tissue even better than the conventional tissue biopsy. Notably, they can represent the inter- and intra-tumoral heterogeneity and accordingly, liquid biopsies demonstrate strengths for improving diagnosis in early detection and screening, monitoring and follow-up after therapies, and personalization of therapeutical strategies in various types of human malignancies. In this review, we aim to discuss the roles, functions, and analysis approaches of liquid biopsy sources and their clinical implications in human malignancies with a focus on colorectal cancer.

Modifying CAR-T cells with anti-checkpoints in cancer immunotherapy: A focus on anti PD-1/PD-L1 antibodies.

Chimeric antigen receptor-modified T (CAR-T) are genetically engineered cells to express tumor-specific antigens revolutionizing the treatment of hematologic malignancies. The hostile tumor microenvironment (TME) remains a challenge for CAR-T cell therapy in solid tumors. As a solution, combinational therapy with immune checkpoint inhibitors (ICIs) is shown to improve the safety and efficacy of CAR-T cell therapy. To avoid side effects related to the application of ICIs in combinational therapy, engineering CARs to express tumor-specific antigens may help improvement of clinical outcomes. Those CARs expressing single chain variable fragments (scFvs) or nanobodies against immune checkpoint stimulatory or inhibitory molecules, such as the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis are being extensively studied in various clinical trials. In this review, we discuss the significance of anti-PD-(L)1 scFv-expressing CAR-T cells in the treatment of human cancers, describing current challenges and potential strategies to overcome such predicaments in the area of cancer immunotherapy.

microRNA-184 in the landscape of human malignancies: a review to roles and clinical significance.

MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) with a short length of 19-22 nucleotides. miRNAs are posttranscriptional regulators of gene expression involved in various biological processes like cell growth, apoptosis, and angiogenesis. miR-184 is a well-studied miRNA, for which most studies report its downregulation in cancer cells and tissues and experiments support its role as a tumor suppressor inhibiting malignant biological behaviors of cancer cells in vitro and in vivo. To exert its functions, miR-184 affects some signaling pathways involved in tumorigenesis like Wnt and ß-catenin, and AKT/mTORC1 pathway, oncogenic factors (e.g., c-Myc) or apoptotic proteins, such as Bcl-2. Interestingly, clinical investigations have shown miR-184 with good performance as a prognostic/diagnostic biomarker for various cancers. Additionally, exogenous miR-184 in cell and xenograft animal studies suggest it as a therapeutic anticancer target. In this review, we outline the studies that evaluated the roles of miR-184 in tumorigenesis as well as its clinical significance.

Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.

Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.

The Mechanisms of Long Non-coding RNA-XIST in Ischemic Stroke: Insights into Functional Roles and Therapeutic Potential.

Ischemic stroke, which occurs due to the occlusion of cerebral arteries, is a common type of stroke. Recent research has highlighted the important role of long non-coding RNAs (lncRNAs) in the development of cerebrovascular diseases, specifically ischemic stroke. Understanding the functional roles of lncRNAs in ischemic stroke is crucial, given their potential contribution to the disease pathology. One noteworthy lncRNA is X-inactive specific transcript (XIST), which exhibits downregulation during the early stages of ischemic stroke and subsequent upregulation in later stages. XIST exert its influence on the development of ischemic stroke through interactions with multiple miRNAs and transcription factors. These interactions play a significant role in the pathogenesis of the condition. In this review, we have provided a comprehensive summary of the functional roles of XIST in ischemic stroke. By investigating the involvement of XIST in the disease process, we aim to enhance our understanding of the mechanisms underlying ischemic stroke and potentially identify novel therapeutic targets.

Circular RNAs-mediated angiogenesis in human cancers

Circular RNAs (circRNAs) as small non-coding RNAs with cell, tissue, or organ-specific expression accomplish a broad array of functions in physiological and pathological processes such as cancer development. Angiogenesis, a complicated multistep process driving a formation of new blood vessels, speeds up tumor progression by supplying nutrients as well as energy. Abnormal expression of circRNAs reported to affect tumor development through impressing angiogenesis. Such impacts are introduced as constant with different tumorigenic features known as “hallmarks of cancer”. In addition, deregulated circRNAs show possibilities to prognosis and diagnosis both in the prophecy of prognosis in malignancies and also their prejudice from healthy individuals. In the present review article, we have evaluated the angiogenic impacts and anti-angiogenic managements of circRNAs in human cancers (AU)

The role of microRNAs in the pathophysiology of human central nervous system: A focus on neurodegenerative diseases.

microRNAs (miRNAs) are suggested to play substantial roles in regulating the development and various physiologic functions of the central nervous system (CNS). These include neurogenesis, cell fate and differentiation, morphogenesis, formation of dendrites, and targeting non-neural mRNAs. Notably, deregulation of an increasing number of miRNAs is associated with several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and CNS tumors. They are particularly known to affect the amyloid ß (Aß) cleavage and accumulation, tau protein homeostasis, and expression of alpha-synuclein (α-syn), Parkin, PINK1, and brain-derived neurotrophic factor (BDNF) that play pivotal roles in the pathogenesis of neurodegenerative diseases. These include miR-16, miR-17-5p, miR-20a, miR-106a, miR-106b, miR-15a, miR-15b, miR-103, miR-107, miR-298, miR-328, miR-195, miR-485, and miR-29. In CNS tumors, several miRNAs, including miR-31, miR-16, and miR-21 have been identified to modulate tumorigenesis through impacting tumor invasion and apoptosis. In this review article, we have a look at the recent advances on our knowledge about the role of miRNAs in human brain development and functions, neurodegenerative diseases, and their clinical potentials.

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view.

Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened. In addition, reproductive health is closely related to overall health and comorbidity in aging men. In this review, we will outline the role of autophagy as a new player in aging male reproductive dysfunction and prostate cancer. We first provide an overview of the mechanisms of autophagy and its role in regulating male reproductive cells. We then focus on the link between autophagy and aging-related diseases. This is followed by a discussion of therapeutic strategies targeting autophagy before we end with limitations of current studies and suggestions for future developments in the field.

The role of microRNA-185 in the pathogenesis of human diseases: A focus on cancer.

MicroRNAs (miRNAs) are a widely-studied class of non-coding RNAs characterized by their short length (18-25 nucleotides). The precise functions of miRNAs are not well-elucidated; however, an increasing number of studies suggest their involvement in various physiologic processes and deregulation in pathologic conditions. miRNA-185 (miR-185) is among the mostly-studied miRNAs in human diseases, which is found to play putative roles in conditions like metabolic disorders, asthma, frailty, schizophrenia, and hepatitis. Notably, many cancer studies report the downregulation of miR-185 in cell lines, tumor tissues, and plasma specimens of patients, while it demonstrates a suppressing role on the malignant properties of cancer cells in vitro and in vivo. Accordingly, miR-185 can be considered a tumor suppressor miRNA in human malignancies, while a few studies also report inconsistent findings. Being suggested as a prognostic/diagnostic biomarker, mi-185 is also found to offer clinical potentials, particularly for early diagnosis and prediction of the prognosis of cancer patients. In this review, we have outlined the studies that have evaluated the functions and clinical significance of miR-185 in different human diseases with a particular focus on cancer.

microRNA-382 as a tumor suppressor? Roles in tumorigenesis and clinical significance.

MicroRNAs (miRNAs) are small single-stranded RNAs belonging to a class of non-coding RNAs with an average length of 18-22 nucleotides. Although not able to encode any protein, miRNAs are vastly studied and found to play role in various human physiologic as well as pathological conditions. A huge number of miRNAs have been identified in human cells whose expression is straightly regulated with crucial biological functions, while this number is constantly increasing. miRNAs are particularly studied in cancers, where they either can act with oncogenic function (oncomiRs) or tumor-suppressors role (referred as tumor-suppressor/oncorepressor miRNAs). miR-382 is a well-studied miRNA, which is revealed to play regulatory roles in physiological processes like osteogenic differentiation, hematopoietic stem cell differentiation and normal hematopoiesis, and liver progenitor cell differentiation. Notably, miR-382 deregulation is reported in pathologic conditions, such as renal fibrosis, muscular dystrophies, Rett syndrome, epidural fibrosis, atrial fibrillation, amelogenesis imperfecta, oxidative stress, human immunodeficiency virus (HIV) replication, and various types of cancers. The majority of oncogenesis studies have claimed miR-382 downregulation in cancers and suppressor impact on malignant phenotype of cancer cells in vitro and in vivo, while a few studies suggest opposite findings. Given the putative role of this miRNA in regulation of oncogenesis, assessment of miR-382 expression is suggested in a several clinical investigations as a prognostic/diagnostic biomarker for cancer patients. In this review, we have an overview to recent studies evaluated the role of miR-382 in oncogenesis as well as its clinical potential.

Potential roles of lncRNA-XIST/miRNAs/mRNAs in human cancer cells

Long non-coding RNAs (lncRNAs) are non-coding RNAs that contain more than 200 nucleotides but do not code for proteins. In tumorigenesis, lncRNAs can have both oncogenic and tumor-suppressive properties. X inactive-specific transcript (XIST) is a known lncRNA that has been implicated in X chromosome silencing in female cells. Dysregulation of XIST is associated with an increased risk of various cancers. Therefore, XIST can be a beneficial prognostic biomarker for human malignancies. In this review, we attempt to summarize the emerging roles of XIST in human cancers (AU)

Extracellular vesicle-based drug delivery in cancer immunotherapy.

Extracellular vesicles (EVs) are a group of nanoscale membrane-bound organelles including exosomes, microvesicles (MVs), membrane particles, and apoptotic bodies, which are released from almost all eukaryotic cells. Owing to their ingredients, EVs can be employed as biomarkers for human diseases. Interestingly, EVs show favorable features as candidates for targeted drug delivery and thus, they are suggested as ideal drug carriers as well as good vaccines for various human diseases including cancer. Among various drugs loaded in EVs for targeted drug delivery, immune checkpoint inhibitors (ICIs), including antibodies against programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), have attracted an increasing attention for cancer researchers and clinicians. Animal and clinical studies have shown combination of EVs and immunotherapy antibodies to improve the efficacy and reduce possible side effects in systemic administration of ICIs. In this review, we discuss the EVs and their significance in drug delivery with a focus on cancer immunotherapy agents.

An interplay between non-coding RNAs and gut microbiota in human health.

Humans have a complicated symbiotic relationship with their gut microbiome, which is postulated to impact host health and disease broadly. Epigenetic alterations allow host cells to regulate gene expression without altering the DNA sequence. The gut microbiome, offering environmental hints, can influence responses to stimuli by host cells with modifications on their epigenome and gene expression. Recent increasing data suggest that regulatory non-coding RNAs (miRNAs, circular RNAs, and long lncRNA) may affect host-microbe interactions. These RNAs have been suggested as potential host response biomarkers in microbiome-associated disorders, including diabetes and cancer. This article reviews the current understanding of the interplay between gut microbiota and non-coding RNA, including lncRNA, miRNA, and circular RNA. This can lead to a profound understanding of human disease and influence therapy. Furthermore, microbiome engineering as a mainstream strategy for improving human health has been discussed and confirms the hypothesis about a direct cross-talk between microbiome composition and non-coding RNA.

Emerging roles of the long non-coding RNA NEAT1 in gynecologic cancers.

Gynecologic cancers are a worldwide problem among women. Recently, molecular targeted therapy opened up an avenue for cancer diagnosis and treatment. Long non-coding RNAs (lncRNAs) are RNA molecules (> 200 nt) that are not translated into protein, and interact with DNA, RNA, and proteins. LncRNAs were found to play pivotal roles in cancer tumorigenesis and progression. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a lncRNA that mediates cell proliferation, migration, and EMT in gynecologic cancers by targeting several miRNAs/mRNA axes. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of breast, ovarian, cervical, and endometrial cancers. In this narrative review, we summarized various NEAT1-related signaling pathways that are critical in gynecologic cancers. Long non-coding RNA (lncRNA) by targeting various signaling pathways involved in its target genes can regulate the occurrence of gynecologic cancers.

The impact of particulate matters on apoptosis in various organs: Mechanistic and therapeutic perspectives.

Ecological air contamination is the non-homogenous suspension of insoluble particles into gas or/and liquid fluids known as particulate matter (PM). It has been discovered that exposure to PM can cause serious cellular defects, followed by tissue damage known as cellular stress. Apoptosis is a homeostatic and regulated phenomenon associated with distinguished physiological actions inclusive of organ and tissue generation, aging, and development. Moreover, it has been proposed that the deregulation of apoptotic performs an active role in the occurrence of many disorders, such as autoimmune disease, neurodegenerative, and malignant, in the human population. Recent studies have shown that PMs mainly modulate multiple signaling pathways involved in apoptosis, including MAPK, PI3K/Akt, JAK/STAT, NFκB, Endoplasmic Stress, and ATM/P53, leading to apoptosis dysregulation and apoptosis-related pathological conditions. Here, the recently published data concerning the effect of PM on the apoptosis of various organs, with a particular focus on the importance of apoptosis as a component in PM-induced toxicity and human disease development, is carefully discussed. Moreover, the review also highlighted the various therapeutic approaches, including small molecules, miRNA replacement therapy, vitamins, and PDRN, for treating diseases caused by PM toxicity. Notably, researchers have considered medicinal herbs a potential treatment for PM-induced toxicity due to their fewer side effects. So, in the final section, we analyzed the performance of some natural products for inhibition and intervention of apoptosis arising from PM-induced toxicity.

The mitochondrial calcium signaling, regulation, and cellular functions: A novel target for therapeutic medicine in neurological disorders.

Mitochondrial calcium (Ca2+ ) dynamics play critical roles in regulating vital physiological conditions in the brain. Importantly, Mitochondria-associated endoplasmic reticulum (ER) membranes serve different cellular functions including Ca2+ signaling, bioenergetics, phospholipid biosynthesis, cholesterol esterification, programmed cell death, and communication between the two organelles. Several Ca2+ -transport systems specialize at the mitochondria, ER, and their contact sites that provide tight control of mitochondrial Ca2+ signaling at the molecular level. The biological function of Ca2+ channels and transporters as well as the role of mitochondrial Ca2+ signaling in cellular homeostasis can open new perspectives for investigation and molecular intervention. Emerging evidence suggests that abnormalities in ER/mitochondrial brain functions and dysregulation of Ca2+ homeostasis are neuropathological hallmarks of neurological disorders like Alzheimer's disease, but little evidence is available to demonstrate their relationship to disease pathogenesis and therapeutic approaches. In recent years, the detection of the molecular mechanism regulating cellular Ca2+ homeostasis and also mitochondrial functions have expanded the number of targeted treatments. The main experimental data identify beneficial effects, whereas some scientific trials did not meet the expectations. Together with an overview of the important function of mitochondria, this review paper introduced the possible tested therapeutic approaches that target mitochondria in the context of neurodegenerative diseases. Since these treatments in neurological disorders have shown different degrees of progress, it is essential to perform a detailed assessment of the significance of mitochondrial deterioration in neurodegenerative diseases and of a pharmacological treatment at this stage.

Advances in dendritic cell vaccination therapy of cancer.

Traditionally, vaccines have helped eradication of several infectious diseases and also saved millions of lives in the human history. Those prophylactic vaccines have acted through inducing immune responses against a live attenuated, killed organism or antigenic subunits to protect the recipient against a real infection caused by the pathogenic microorganism. Nevertheless, development of anticancer vaccines as valuable targets in human health has faced challenges and requires further optimizations. Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) that play essential roles in tumor immunotherapies through induction of CD8+ T cell immunity. Accordingly, various strategies have been tested to employ DCs as therapeutic vaccines for exploiting their activity against tumor cells. Application of whole tumor cells or purified/recombinant antigen peptides are the most common approaches for pulsing DCs, which then are injected back into the patients. Although some hopeful results are reported for a number of DC vaccines tested in animal and clinical trials of cancer patients, such approaches are still inefficient and require optimization. Failure of DC vaccination is postulated due to immunosuppressive tumor microenvironment (TME), overexpression of checkpoint proteins, suboptimal avidity of tumor-associated antigen (TAA)-specific T lymphocytes, and lack of appropriate adjuvants. In this review, we have an overview of the current experiments and trials evaluated the anticancer efficacy of DC vaccination as well as focusing on strategies to improve their potential including combination therapy with immune checkpoint inhibitors (ICIs).