Modulatory Effects of Phytochemicals on Gut-Brain Axis: Therapeutic Implication.

This article explores the potential therapeutic implications of phytochemicals on the gut-brain axis (GBA), which serves as a communication network between the central nervous system and the enteric nervous system. Phytochemicals, which are compounds derived from plants, have been shown to interact with the gut microbiota, immune system, and neurotransmitter systems, thereby influencing brain function. Phytochemicals such as polyphenols, carotenoids, flavonoids, and terpenoids have been identified as having potential therapeutic implications for various neurological disorders. The GBA plays a critical role in the development and progression of various neurological disorders, including Parkinson's disease, multiple sclerosis, depression, anxiety, and autism spectrum disorders. Dysbiosis, or an imbalance in gut microbiota composition, has been associated with a range of neurological disorders, suggesting that modulating the gut microbiota may have potential therapeutic implications for these conditions. Although these findings are promising, further research is needed to elucidate the optimal use of phytochemicals in neurological disorder treatment, as well as their potential interactions with other medications. The literature review search was conducted using predefined search terms such as phytochemicals, gut-brain axis, neurodegenerative, and Parkinson in PubMed, Embase, and the Cochrane library.

Recent Advances in Immune Regulation by Targeting Dendritic Cells using Small Interfering RNAs.

Gene silencing through RNA interference (RNAi) technology has provided forceful therapeutic modalities to specific knockdown of the genes' expression related to diseases. Small interfering RNAs (siRNAs) can start a process that specifically degrades and silences the expression of cognate mRNAs. These RNA interference processes could effectively adjust many biological processes, including immune responses. Dendritic cells (DCs) are specialist antigen-presenting cells with potent functions in regulating innate and adaptive immunity. SiRNAs performed vital roles in coordinating immune processes mediated by DCs. This review describes the findings that shed light on the significance of siRNAs in DC immune regulation and highlight their potential applications for improving DC-based immunotherapies.

Gene-edited cells: novel allogeneic gene/cell therapy for epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of rare genetic skin fragility disorders, which are hereditary. These disorders are associated with mutations in at least 16 genes that encode components of the epidermal adhesion complex. Currently, there are no effective treatments for this disorder. All current treatment approaches focus on topical treatments to prevent complications and infections. In recent years, significant progress has been achieved in the treatment of the severe genetic skin blistering condition known as EB through preclinical and clinical advancements. Promising developments have emerged in the areas of protein and cell therapies, such as allogeneic stem cell transplantation; in addition, RNA-based therapies and gene therapy approaches have also become a reality. Stem cells obtained from embryonic or adult tissues, including the skin, are undifferentiated cells with the ability to generate, maintain, and replace fully developed cells and tissues. Recent advancements in preclinical and clinical research have significantly enhanced stem cell therapy, presenting a promising treatment option for various diseases that are not effectively addressed by current medical treatments. Different types of stem cells such as primarily hematopoietic and mesenchymal, obtained from the patient or from a donor, have been utilized to treat severe forms of diseases, each with some beneficial effects. In addition, extensive research has shown that gene transfer methods targeting allogeneic and autologous epidermal stem cells to replace or correct the defective gene are promising. These methods can regenerate and restore the adhesion of primary keratinocytes in EB patients. The long-term treatment of skin lesions in a small number of patients has shown promising results through the transplantation of skin grafts produced from gene-corrected autologous epidermal stem cells. This article attempts to summarize the current situation, potential development prospects, and some of the challenges related to the cell therapy approach for EB treatment.

Exosomal long non-coding RNAs in glioblastoma.

Glioblastoma multiforme (GBM) is the most prevalent primary tumor found in the central nervous system, accounting for 70% of all adult brain tumors. The median overall survival rate is one year post-diagnosis with treatment, and only four months without treatment. Current GBM diagnostic methods, such as magnetic resonance imaging (MRI), surgery, and brain biopsies, have limitations. These include difficulty distinguishing between tumor recurrence and post-surgical necrotic regions, and operative risks associated with obtaining histological samples through direct surgery or biopsies. Consequently, there is a need for rapid, inexpensive, and minimally invasive techniques for early diagnosis and improved subsequent treatment. Research has shown that tumor-derived exosomes containing various long non-coding RNAs (lncRNAs) play critical regulatory roles in immunomodulation, cancer metastasis, cancer development, and drug resistance in GBM. They regulate genes that enhance cancer growth and progression and alter the expression of several key signaling pathways. Due to the specificity and sensitivity of exosomal lncRNAs, they have the potential to be used as biomarkers for early diagnosis and prognosis, as well as to monitor a patient's response to chemotherapy for GBM. In this review, we discuss the role of exosomal lncRNAs in the pathogenesis of GBM and their potential clinical applications for early diagnosis.

An Investigation into Cell-Free DNA in Different Common Cancers.

Diagnosis is the most important step in different diseases, especially in cancers and blood malignancies. There are different methods in order to better diagnose of cancer, but many of them are invasive and also, some of them are not useful for immediate diagnosis. Cell-free DNA (cfDNA) or liquid biopsy easily accessible in peripheral blood is one of the non-invasive prognostic biomarkers in various areas of cancer management. In fact, amounts of cfDNA in serum or plasma can be used for diagnosis. In this review, we have considered some cancers such as hepatocellular carcinoma, lung cancer, breast cancer, and hematologic malignancies to compare the various methods of cfDNA diagnosis.

Recent advances and applications of peptide-agent conjugates for targeting tumor cells.

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.

The Regulation, Functions, and Signaling of miR-153 in Neurological Disorders, and Its Potential as a Biomarker and Therapeutic Target.

Treatment of neurological disorders has always been one of the challenges facing scientists due to poor prognosis and symptom overlap, as well as the progress of the disease process. Neurological disorders such as Huntington's, Parkinson's, Alzheimer's diseases, and Amyotrophic Lateral Sclerosis are very debilitating. Therefore, finding a biomarker is essential for early diagnosis and treatment goals. Recent studies have focused more on molecular factors and gene manipulation to find effective diagnostic and therapeutic biomarkers. Among these factors, microRNAs (miRNAs/ miRs) have attracted much attention. On the other hand, a growing correlation between miRNAs and neurological disorders has caused scientists to consider it as a diagnostic and therapeutic target. In this line, the miR-153 is one of the most important and highly conserved miRNAs in mice and humans, whose expression level is not only altered in neurological disorders but also improves neurogenesis. MiR-153 can regulate multiple biological processes by targeting various factors. Furthermore, the miR-153 expression also can be regulated by important regulators, such as long non-coding RNAs (e.g., KCNQ1OT1) and some compounds (e.g., Tanshinone IIA) altering the expression of miR-153. Given the growing interest in miR-153 as a biomarker and therapeutic target for neurological diseases as well as the lack of comprehensive investigation of miR-153 function in these disorders, it is necessary to identify the downstream and upstream targets and also it's potential as a therapeutic biomarker target. In this review, we will discuss the critical role of miR-153 in neurological disorders for novel diagnostic and prognostic purposes and its role in multi-drug resistance.

The role of miR-153 and related upstream/downstream pathways in cancers: from a potential biomarker to treatment of tumor resistance and a therapeutic target.

MicroRNAs (miRNAs/miRs) are small non-coding RNAs that have a multifunction and play essential roles in gene regulation. Their dysregulation is associated with several human cancers. MiR-153 has a critical role in many biological processes, such as suppressing tumor growth (mostly), responses to treatment, and drug resistance. However, miR-153 in some cancers shows a different role as an oncogene, such as prostate. The miR-153 expression can be regulated by several regulators, such as lncRNAs and circular RNAs. By discovering the target factors for miR-153, it may be possible to approach early diagnosis, reversing drug resistance, and treatment of cancers. This will help choose the precise treatment for the patient and not incur additional costs in treatment. Thus, we attempt to summarize the current situation and potential development prospects about the role of miR-153 in cancers. The miR-153 paly an important role in cancers and can be used for diagnosis and prognosis.

microRNA in inflammatory bowel disease at a glance.

Inflammatory bowel disease (IBD) as a chronic inflammation in colon and small intestine has two subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Genome studies have shown that UC and CD are related to microRNAs (miRNAs) expression in addition to environmental factors. This article reviews important researches that have recently been done on miRNAs roles in CD and UC disease. First, miRNA is introduced and its biogenesis and function are discussed. Afterward, roles of miRNAs in inflammatory processes involved in IBD are showed. Finally, this review proposes some circulating and tissue-specific miRNAs, which are useful for CD and UC fast diagnosis and grade prediction. As a conclusion, miRNAs are efficient diagnostic molecules especially in IBD subtypes discrimination and can be used by microarray and real time PCR methods for disease detection and classification.

MiRNA-7 Replacement Effect on Proliferation and Tarceva-Sensitivity in U373-MG Cell Line.

BACKGROUND: Deregulation of the EGFR signaling pathway activity has been shown to can be effective in resistance to EGFR-TKIs, such as Tarceva (erlotinib), in glioblastoma cells. In addition, reports have shown that the reduction of miRNA-7 expression levels is associated with an increase in the expression of EGFR. Here, we evaluated the effect of miRNA-7 on EGFR expression and sensitivity of the U373-MG glioblastoma to erlotinib. METHODS: The effect of miRNA-7 on EGFR expression was examined using RT-qPCR and western blotting. Trypan blue and MTT assays were performed to explore the effect of treatments on cell growth and survival, respectively. The combination index analysis was used to evaluate the interaction between drugs. Apoptosis was measured by ELISA cell death assay. RESULTS: We showed that miRNA-7 markedly inhibited the expression of EGFR and decreased the growth of glioblastoma cells, relative to blank control and negative control miRNA (p < 0.05). Introduction of miRNA-7 synergistically increased the sensitivity of the U373-MG cells to erlotinib. Results of apoptosis assay demonstrated that miRNA-7 can trigger apoptosis and enhance the erlotinib-mediated apoptosis. CONCLUSIONS: Our results show that miRNA-7 plays a critical role in the growth, survival and sensitivity of the U373-MG cells to erlotinib by targeting EGFR. Thus, miRNA-7 replacement therapy can become an effective therapeutic procedure in glioblastoma.

MiRNA-7 enhances erlotinib sensitivity of glioblastoma cells by blocking the IRS-1 and IRS-2 expression.

OBJECTIVES: Down-regulation of miRNA-7 is correlated with over-expression of IRS-1 and IRS-2 proteins, the upstream regulators of IGF-1R/Akt pathway, in glioblastoma cells. In this study, the effect of miRNA-7 on expression of IRS-1 and IRS-2 and sensitivity of the U373-MG glioblastoma cells to erlotinib was explored. METHODS: After miRNA-7 transfection, the expression of IRS-1 and IRS-2 mRNAs was measured by RT-qPCR. Trypan blue assay was used to assess the effect of miRNA-7 on cell proliferation. The effects of miRNA-7 and erlotinib, alone and in combination, on cell survival and apoptosis were measured using MTT assay and ELISA cell death assay, respectively. KEY FINDINGS: Our data showed that miRNA-7 markedly inhibited the expression of IRS-1 and IRS-2 in a time-dependent manner, inhibited the proliferation of glioblastoma cells and enhanced apoptosis (P < 0.05, relative to control). Pretreatment with miRNA-7 synergistically inhibited the cell survival rate and decreased the IC50 of erlotinib. Furthermore, miRNA-7 significantly augmented the apoptotic effect of erlotinib. CONCLUSIONS: Our data propose that inhibition of IRS-1 and IRS-2 by miRNA-7 can effectively induce apoptosis and sensitize glioblastoma cell to EGFR-TKIs. Therefore, miRNA-7 may be a potential therapeutic target in patients with glioblastoma.