Non-alcoholic fatty liver disease and steatohepatitis: State of the art on effective therapeutics based on the gold standard method for diagnosis

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Platinum Nanoparticles in Biomedicine: Preparation, Anti-Cancer Activity, and Drug Delivery Vehicles

Cancer is the main cause of morbidity and mortality worldwide, excluding infectious disease. Because of their lack of specificity in chemotherapy agents are used for cancer treatment, these agents have severe systemic side effects, and gradually lose their therapeutic effects because most cancers become multidrug resistant. Platinum nanoparticles (PtNPs) are relatively new agents that are being tested in cancer therapy. This review covers the various methods for the preparation and physicochemical characterization of PtNPs. PtNPs have been shown to possess some intrinsic anticancer activity, probably due to their antioxidant action, which slows tumor growth. Targeting ligands can be attached to functionalized metal PtNPs to improve their tumor targeting ability. PtNPs-based therapeutic systems can enable the controlled release of drugs, to improve the efficiency and reduce the side effects of cancer therapy. Pt-based materials play a key role in clinical research. Thus, the diagnostic and medical industries are exploring the possibility of using PtNPs as a next-generation anticancer therapeutic agent. Although, biologically prepared nanomaterials exhibit high efficacy with low concentrations, several factors still need to be considered for clinical use of PtNPs such as the source of raw materials, stability, solubility, the method of production, biodistribution, accumulation, controlled release, cell-specific targeting, and toxicological issues to human beings. The development of PtNPs as an anticancer agent is one of the most valuable approaches for cancer treatment. The future of PtNPs in biomedical applications holds great promise, especially in the area of disease diagnosis, early detection, cellular and deep tissue imaging, drug/gene delivery, as well as multifunctional therapeutics

Decoy technology as a promising therapeutic tool for atherosclerosis

Cardiovascular diseases (CVDs) have been classified into several types of disease, of which atherosclerosis is the most prevalent. Atherosclerosis is characterized as an inflammatory chronic disease which is caused by the formation of lesions in the arterial wall. Subsequently, lesion progression and disruption ultimately lead to heart disease and stroke. The development of atherosclerosis is the underlying cause of approximately 50% of all deaths in westernized societies. Countless studies have aimed to improve therapeutic approaches for atherosclerosis treatment; however, it remains high on the global list of challenges toward healthy and long lives. Some patients with familial hypercholesterolemia could not get intended LDL‐C goals even with high doses of traditional therapies such as statins, with many of them being unable to tolerate statins because of the harsh side effects. Furthermore, even in patients achieving target LDL‐C levels, the residual risk of traditional therapies is still significant thus highlighting the necessity of ongoing research for more effective therapeutic approaches with minimal side effects. Decoy‐based drug candidates represent an opportunity to inhibit regulatory pathways that promote atherosclerosis. In this review, the potential roles of decoys in the treatment of atherosclerosis were described based on the in vitro and in vivo findings

Harnessing the Therapeutic Potential of Decoys in Non-Atherosclerotic Cardiovascular Diseases: State of the Art

Cardiovascular disease (CVD) is the main cause of global death, highlighting the fact that conventional therapeutic approaches for the treatment of CVD patients are insufficient, and there is a need to develop new therapeutic approaches. In recent years, decoy technology, decoy oligodeoxynucleotides (ODN), and decoy peptides show promising results for the future treatment of CVDs. Decoy ODN inhibits transcription by binding to the transcriptional factor, while decoy peptide neutralizes receptors by binding to the ligands. This review focused on studies that have investigated the effects of decoy ODN and decoy peptides on non-atherosclerotic CVD

Decoy Technology as a Promising Therapeutic Tool for Atherosclerosis

Cardiovascular diseases (CVDs) have been classified into several types of disease, of which atherosclerosis is the most prevalent. Atherosclerosis is characterized as an inflammatory chronic disease which is caused by the formation of lesions in the arterial wall. Subsequently, lesion progression and disruption ultimately lead to heart disease and stroke. The development of atherosclerosis is the underlying cause of approximately 50% of all deaths in westernized societies. Countless studies have aimed to improve therapeutic approaches for atherosclerosis treatment; however, it remains high on the global list of challenges toward healthy and long lives. Some patients with familial hypercholesterolemia could not get intended LDL-C goals even with high doses of traditional therapies such as statins, with many of them being unable to tolerate statins because of the harsh side effects. Furthermore, even in patients achieving target LDL-C levels, the residual risk of traditional therapies is still significant thus highlighting the necessity of ongoing research for more effective therapeutic approaches with minimal side effects. Decoy-based drug candidates represent an opportunity to inhibit regulatory pathways that promote atherosclerosis. In this review, the potential roles of decoys in the treatment of atherosclerosis were described based on the in vitro and in vivo findings

TGF-β and WNT signaling pathways in cardiac fibrosis: non-coding RNAs come into focus

Abstract:Cardiac fibrosis describes the inappropriate proliferation of cardiac fibroblasts (CFs), leading to accumulation of extracellular matrix (ECM) proteins in the cardiac muscle, which is found in many pathophysiological heart conditions. A range of molecular components and cellular pathways, have been implicated in its pathogenesis. In this review, we focus on the TGF-β and WNT signaling pathways, and their mutual interaction, which have emerged as important factors involved in cardiac pathophysiology. The molecular and cellular processes involved in the initiation and progression of cardiac fibrosis are summarized. We focus on TGF-β and WNT signaling in cardiac fibrosis, ECM production, and myofibroblast transformation. Non-coding RNAs (ncRNAs) are one of the main players in the regulation of multiple pathways and cellular processes. MicroRNAs, long non-coding RNAs, and circular long non-coding RNAs can all interact with the TGF-β/WNT signaling axis to affect cardiac fibrosis. A better understanding of these processes may lead to new approaches for diagnosis and treatment of many cardiac conditions

Angiogenesis-related non-coding RNAs and gastrointestinal cancer

Abstract: Gastrointestinal (GI) cancers are among the main reasons for cancer death globally. The deadliest types of GI cancer include colon, stomach, and liver cancers. Multiple lines of evidence have shown that angiogenesis has a key role in the growth and metastasis of all GI tumors. Abnormal angiogenesis also has a critical role in many non-malignant diseases. Therefore, angiogenesis is considered to be an important target for improved cancer treatment. Despite much research, the mechanisms governing angiogenesis are not completely understood. Recently, it has been shown that angiogenesis-related non-coding RNAs (ncRNAs) could affect the development of angiogenesis in cancer cells and tumors. The broad family of ncRNAs, which include long non-coding RNAs, microRNAs, and circular RNAs, are related to the development, promotion, and metastasis of GI cancers, especially in angiogenesis. This review discusses the role of ncRNAs in mediating angiogenesis in various types of GI cancers and looks forward to the introduction of mimetics and antagonists as possible therapeutic agents

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis

Abstract:Malignant gliomas are the most common and deadly type of central nervous system tumors. Despite some advances in treatment, the mean survival time remains only about 1.25years. Even after surgery, radiotherapy and chemotherapy, gliomas still have a poor prognosis. Exosomes are the most common type of extracellular vesicles with a size range of 30 to 100nm, and can act as carriers of proteins, RNAs, and other bioactive molecules. Exosomes play a key role in tumorigenesis and resistance to chemotherapy or radiation. Recent evidence has shown that exosomal microRNAs (miRNAs) can be detected in the extracellular microenvironment, and can also be transferred from cell to cell via exosome secretion and uptake. Therefore, many recent studies have focused on exosomal miRNAs as important cellular regulators in various physiological and pathological conditions. A variety of exosomal miRNAs have been implicated in the initiation and progression of gliomas, by activating and/or inhibiting different signaling pathways. Exosomal miRNAs could be used as therapeutic agents to modulate different biological processes in gliomas. Exosomal miRNAs derived from mesenchymal stem cells could also be used for glioma treatment. The present review summarizes the exosomal miRNAs that have been implicated in the pathogenesis, diagnosis and treatment of gliomas. Moreover, exosomal proteins could also be involved in glioma pathogenesis. Exosomal miRNAs and proteins could also serve as non-invasive biomarkers for prognosis and disease monitoring

In silico and in vitro analysis of microRNAs with therapeutic potential in atherosclerosis

Atherosclerosis is a chronic inflammatory disease in which aberrant lipid metabolism plays a key role. MicroRNAs (miRNAs), micro-coordinators of gene expression, have been recently proposed as novel clinical biomarkers and potential therapeutic tools for a broad spectrum of diseases. This study aimed to identify miRNAs with therapeutic potential in atherosclerosis. Bioinformatic databases, including experimentally validated and computational prediction tools as well as a novel combination method, were used to identify miRNAs that are able to simultaneously inhibit key genes related to the pathogenesis of atherosclerosis. Further validation of genes and miRNAs was conducted using the STRING online tool, KEGG pathway analysis and DIANA-miRPath. The inhibitory effects of the identified miRNAs in HepG2 and Huh7 cells were verified by real-time PCR. The MTT assay was utilized to evaluate cell cytotoxicity effects of miRNAs. Atherosclerotic drug-targeted genes were selected as key genes. Strong interactions between genes were confirmed using STRING. These genes were shown to be integral to critical pathological processes involved in atherosclerosis. A novel combined method of validated and predicted tools for the identification of effective miRNAs was defined as the combination score (C-Score). Bioinformatic analysis showed that hsa-miR-124-3p and hsa-miR-16-5p possessed the best C-Score (0.68 and 0.62, respectively). KEGG and DIANA-miRPath analysis showed that selected genes and identified miRNAs were involved in atherosclerosis-related pathways. Compared with the controls in both HepG2 and Huh7 cell lines, miR-124 significantly reduced the expression of CETP, PCSK9, MTTP, and APOB, and miR-16 significantly reduced the expression of APOCIII, CETP, HMGCR, PCSK9, MTTP, and APOB, respectively. The cytotoxicity assay showed that miR-124 reduced cell viability, especially after 72 h; however, miR-16 did not show any significant cytotoxicity in either cell line. Our findings indicate that hsa-miR-124 and miR-16 have potential for use as therapeutic candidates in the treatment of atherosclerosis

New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs

Non-coding RNAs (ncRNAs) have critical role in the pathophysiology as well as recovery after ischemic stroke. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are critical for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. Moreover, exosomes have been considered as nanocarriers capable of transferring various cargos, such as lncRNAs and miRNAs to recipient cells, with prominent inter-cellular roles in the mediation of neuro-restorative events following strokes and neural injuries. In this review, we summarize the pathogenic role of ncRNAs and exosomal ncRNAs in the stroke