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Abstract: Metal-organic frameworks (MOFs) have significant advantages over other candidate classes of chemo-sensory materials owing to their extraordinary structural tunability and character-istics. MOF-based biosensing is a simple and convenient method for identifying various species. Biomarkers are molecular or cellular processes that link environmental exposure to a health out-come. Biomarkers are important in understanding the links between environmental chemical expo-sure and the development of chronic diseases, as well as in identifying disease-prone subgroups. Until now, several species, including nanoparticles (NPs) and their nanocomposites, small mole-cules, and unique complex systems, have been used for the chemical sensing of biomarkers. Follow-ing the overview of the field, we discussed the various fabrication methods for MOFs development in this review. We provide a thorough overview of the previous five years of progress to broaden the scope of analytes for future research. Several enzymatic and non-enzymatic sensors are offered, together with a mandatory measuring method that includes detection range and dynamic range. In addition, we reviewed the comparison of enzymatic and non-enzymatic biosensors, inventive edges, and the difficulties that need to be solved. This work might open up new possibilities for material production, sensor development, medical diagnostics, and other sensing fields.

Diabetes mellitus affects almost half a billion patients worldwide and results from either destruction of β-cells responsible for insulin secretion or increased tissue resistance to insulin stimulation and the reduction of glycemic control. Novel drug delivery systems can improve treatment efficacy in diabetic patients. The low aqueous solubility of most oral antidiabetic drugs decreases drug bioavailability; therefore, there is a demand for the use of novel methods to overcome this issue. The application of bile acids mixed micelles and bilosomes can provide an enhancement in drug efficacy. Bile acids are amphiphilic steroidal molecules that contain a saturated tetracyclic hydrocarbon cyclopentanoperhydrophenanthrene ring, and consist of three 6-membered rings and a 5-membered ring, a short aliphatic side chain, and a tough steroid nucleus. This review offers a comprehensive and informative data focusing on the great potential of bile acid, their salts, and their derivatives for the development of new antidiabetic drug delivery system.

Anti-metabolite drugs prevent the synthesis of essential cell growth compounds. 5-fluorouracil is used as an anti-metabolic drug in various cancers in the first stage of treatment. Unfortunately, in some cancers, 5-fluorouracil has low effectiveness because of its drug resistance. Studies have shown that drug resistance to 5-fluorouracil is due to the activation of specific signaling pathways and increased expressions of enzymes involved in drug metabolites. However, when 5-fluorouracil is used in combination with other drugs, the sensitivity of cancer cells to 5-fluorouracil increases, and the effect of drug resistance is reversed. This study discusses how the function of 5-fluorouracil in JAK/STAT, Wnt, Notch, NF-κB, and hedgehogs in some cancers.

Tropisetron, an antagonist of 5-HT3 receptor (5-HT3R), has exhibited a number of beneficial effects on the treatment of several diseases; however, its effect on diabetic cardiomyopathy, which is an important causal factor in morbidity and mortality among diabetic patients, remains to be fully elucidated. Therefore, this study was designed to investigate the effect of tropisetron on diabetes-induced cardiomyopathy and the molecular mediators possibly involved. Twenty-four male wistar rats were assigned into three groups, control, diabetic, and tropisetron–treated diabetic groups. After 14 days of treatment, the results revealed a significant increase in calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) total and isoforms δ2 and δ3 of CaMKIIδ, as well as myosin heavy chain (MHC)-β. Furthermore, it decreased MHC-α gene expression among the diabetic group compared to the control group. Western blot analysis showed a significant increase in Bax and cleaved caspase 3 protein levels and a significant decrease in Bcl-2 contents in heart tissue of diabetic rats in comparison to the control rats. Moreover, the levels of Tumor necrosis factor alpha (TNF-α), ICAM-1, and CaMKII in heart tissue of diabetic rats were significantly higher than those in the control rats. Significant amelioration of alteration in the genes expression and protein changes along with restoration of the elevated levels of TNF-α, ICAM-1, and CaMKII were found in the tropisetron–treated diabetic group compared to the diabetic group. Collectively, our study provided strong evidence that 5-HT3 antagonist tropisetron was capable of attenuating the development of experimental diabetic cardiomyopathy associated with the reduction of intramyocardial MHCs and CaMKIIδ gene expression, inflammation and cardiac hypertrophy.

The world is grappling with an unprecedented public health crisis COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2. Due to the high transmission/mortality rates and socioeconomic impacts of the COVID-19, its control is crucial. In the absence of specific treatment, vaccines represent the most efficient way to control and stop the pandemic. Many companies around the world are currently making efforts to develop the vaccine to combat COVID-19. This review outlines key strategies for generating SARS-CoV-2 vaccine candidates, along with the mechanism of action, advantages, and potential limitations of each vaccine. The use of nanomaterials and nanotechnology for COVID-19 vaccines development will also be discussed.

Colorectal cancer is globally one of the most common cancers in all age groups. The current chemotherapy combinations for colorectal cancer treatment include 5-fluorouracil-based regimens; however, drug resistance remains one of the main reasons for chemotherapy failure and disease recurrence. Many studies have determined colorectal cancer chemoresistance mechanisms such as drug efflux, cell cycle arrest, DNA damage repair, apoptosis, autophagy, vital enzymes, epigenetic, epithelial-mesenchymal transition, stem cells, and immune system suppression. Several microRNAs affect drug resistance by regulating the drug resistance-related target genes in colorectal cancer. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with colorectal cancer. This work reviews and discuss the role of selected microRNAs in 5-fluorouracil resistance and their molecular mechanisms in colorectal cancer.

Wound healing is a serious obstacle due to the complexity of evaluation and management. While novel approaches to promoting chronic wound healing are of critical interest at the moment, several studies have demonstrated that combination therapy is critical for the treatment of a variety of diseases, particularly chronic wounds. Among the various approaches that have been proposed for wound care, regenerative medicine-based methods have garnered the most attention. As is well known, regenerative medicine's three primary tools are gene/cell therapy, biomaterials, and tissue engineering. Multifunctional biomaterials composed of synthetic and natural components are highly advantageous for exosome carriers, which utilizing them is an exciting wound healing method. Recently, stem cell-secreted exosomes and certain biomaterials have been identified as critical components of the wound healing process, and their combination therapy appears to produce significant results. This paper presents a review of literature and perspectives on the use of stem cell-derived exosomes and biomaterials in wound healing, particularly chronic wounds, and discusses the possibility of future clinical applications.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new coronavirus named by the International Committee on Taxonomy of Viruses. COVID-19 patients have high mortality due to respiratory failure from acute respiratory distress syndrome (ARDS) induced by SARS-CoV-2. The abnormal activation of P21-activated kinase (PAK1, RAC/CDC42-activated kinase 1) is reported in COVID-19. The PAK1 induces nuclear factor kappa B (NF-κB) activation as well as inflammatory pathways through its stimulation. BAY 11-7082 {(E) 3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile is one of the therapies that inhibit inflammation via mentioned signaling pathway, therefore, we suggest that this drug can potentially be effective in treating COVID-19.

Neurodegenerative diseases (NDD) are caused by the destruction of nerve cells in the central nervous system and are severely debilitating. The incidence of NDDs increases, and they are expected to become more prevalent with life expectancy. Depending on the number of neurons involved, there are various types of NDDs, and one of the most common NDDs is Alzheimer's disease (AD). Due to the lack of treatment, NDDs had become a significant neurobiology challenge. Therefore, identifying accurate, early, and non-invasive biomarkers of NDDs, are an unmet challenge. The growing importance of microRNAs (miRNAs) in biology has led scientists to investigate their potential relevance to neurodegeneration to identify novel therapeutic targets. Recent discoveries have found the role of miRNAs in many model organisms during aging and have revealed potential miRNA biomarkers of NDDs. Among the various miRNAs, the data confirm that miR-155 as so-called inflamma-miR, a potent activator of inflammation, is the fundamental miR in the pathogenesis of autoimmune diseases because it influences myeloid cell polarization to a phenotypic and functional proinflammatory form. miR-155 dysregulation also plays an essential role in many human cancers, hematological malignancies, and responses to viral infections. Here, we discuss this new field of miR-155 related to NDDs, focusing on AD and prospects.

Purpose: Despite the high prevalence of gastric cancer (GC), drug resistance is a major problem for effective chemotherapy. B7-H7 is a novel member of the B7 superfamily and is expressed in most common cancers. However, the role of B7-H7 on the aggressiveness of GC and chemo-sensitivity has remained unknown. Therefore, this study was designed to assess the effect of B7-H7 suppression using small interference RNA (siRNA) in combination with Docetaxel on GC cells. Methods: MTT test was applied to determine the IC50 of Docetaxel and the combined effect of B7-H7 siRNA and Docetaxel on the viability of the MKN-45 cells. To determine B7-H7, BCL-2, BAX, and Caspase-3-8-9 genes expression, qRT-PCR was performed. Furthermore, flow cytometry was applied to evaluate apoptosis and the cell cycle status. Finally, to evaluate the effect of this combination therapy on migratory capacity and colony‑forming ability, wound healing assay and colony formation test were employed, respectively. Results: B7-H7 suppression increased the chemo-sensitivity of MKN-45 cells to Docetaxel. The expression of B7-H7 mRNA was reduced after using B7-H7 siRNA and Docetaxel in MKN-45 GC cells. Also, B7-H7 suppression alongside Docetaxel reduced cell migration and colony formation rate, arrested the cell cycle at the G2-M phase, and induced apoptosis by modulating the expression of apoptotic target genes. Conclusion: B7-H7 plays a significant role in the chemo-sensitivity and pathogenesis of GC. Therefore, B7-H7 suppression, in combination with Docetaxel, may be a promising therapeutic approach in treating GC.

Genome-wide studies related to neurological disorders and neurodegenerative diseases have pointed to the role of epigenetic changes such as DNA methylation, histone modification, and noncoding RNAs. DNA methylation machinery controls the dynamic regulation of methylation patterns in discrete brain regions.This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approachesA Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022.For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies.This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy.

Early diagnosis and treatment of diseases are crucial research areas of human health. For early diagnosis, one method that has proven efficient is the detection of biomarkers which can provide real-time and accurate biological information. Most biomarker detection is currently carried out at localised dedicated laboratories using large and automated analysers, increasing waiting time and costs. Smaller, faster, and cheaper devices could potentially replace these time-consuming laboratory analyses and make analytical results available as point-of-care diagnostics. Innovative biosensor-based strategies could allow biomarkers to be tested reliably in a decentralised setting. Early diagnosis of COVID-19 patients has a key role in order to use quarantine and treatment strategies in a timely manner. Raised levels of several biomarkers in COVID-19 patients are associated with respiratory infections or dysfunction of various organs. Through clinical studies of COVID-19 patient biomarkers such as ferritin, Interleukins, albumin and …are found to reveals significant differences in their excretion ranges from healthy patients and patients with SARS-CoV-2, in addition to the development of biomarkers based biosensor such as stated biomarkers can be used and to investigate more specific biomarkers further proteomic analysis can be performed. This review presents several biomarker alterations in COVID-19 patients such as salivary, circulatory, coagulation, cardiovascular, renal, liver, C-reactive protein (CRP), immunological and inflammatory biomarkers. Also, biomarker sensors based on electrochemical, optical, and lateral flow characteristics which have potential applications for SARS-COV-2 in the recent COVID-19 pandemic, will be discussed.

Hepatocellular carcinoma (HCC), the most prevalent kind of liver cancer, remains one of the world's main causes of death. The alpha7 nicotinic acetylcholine receptor (α7nAchR) has been recognized to be overexpressed in malignancies and chemoresistance. Since little is known about the role of α7nAchR expression in drug-resistant cells, this study was designed to investigate the effect of α7nAchR suppression in combination with Sorafenib (SOR) on SOR-resistant HCC cells. First, SOR-resistant HCC cells were generated. To suppress the expression of α7nAchR, cells were treated with SOR following siRNA transfection. qRT-PCR was used to examine the expression of α7nAchR and apoptotic genes by evaluating the IC50 of SOR and the combination of α7nAchR siRNA and SOR on the survival of resistant cells. Moreover, apoptosis, autophagy, and cell cycle analysis for resistant HCC cells were performed using flow cytometry. Cell migration and colony formation assays were also used for further confirmation. Our results suggest that inhibiting α7nAchR can lead resistant HCC cells to become sensitive. Furthermore, when siRNA and SOR were treated together, HCC-resistant cells showed a considerable reduction in α7nAchR mRNA gene expression. In addition, when α7nAchR was downregulated in combination with SOR, migration and colony formation were inhibited. Apoptosis was triggered by modulating the expression of apoptotic target genes, and cell cycle arrest was observed in the G2-M and subG1 phases. Overexpression of α7nAchR in SOR-resistant HCC cells suggests that it might be a therapeutic target for HCC cell resistance therapy.

Deciphering the molecular downstream consequences of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is important for a greater understanding of the disease and treatment planning. Furthermore, greater understanding of the underlying mechanisms of diagnostic and therapeutic strategies can help in the development of vaccines and drugs against COVID-19. At present, the molecular mechanisms of SARS-CoV-2 in the host cells are not sufficiently comprehended. Some of the mechanisms are proposed considering the existing similarities between SARS-CoV-2 and the other members of the β-CoVs, and others are explained based on studies advanced in the structure and function of SARS-CoV-2. In this review, we endeavored to map the possible mechanisms of the host response following SARS-CoV-2 infection and surveyed current research conducted by in vitro, in vivo and human observations, as well as existing suggestions. We addressed the specific signaling events that can cause cytokine storm and demonstrated three forms of cell death signaling following virus infection, including apoptosis, pyroptosis, and necroptosis. Given the elicited signaling pathways, we introduced possible pathway-based therapeutic targets; ADAM17 was especially highlighted as one of the most important elements of several signaling pathways involved in the immunopathogenesis of COVID-19. We also provided the possible drug candidates against these targets. Moreover, the cytokine-cytokine receptor interaction pathway was found as one of the important cross-talk pathways through a pathway-pathway interaction analysis for SARS-CoV-2 infection., Graphical abstract

Background Many eukaryote cells produce membrane-enclosed extracellular vesicles (EVs) to establish cell-to-cell communication. Plant-derived EVs (P-EVs) contain proteins, RNAs, lipids, and other metabolites that can be isolated from the juice, the flesh, and roots of many species. Methods In the present review study, we studied numerous articles over the past two decades published on the role of P-EVs in plant physiology as well as on the application of these vesicles in different diseases. Results Different types of EVs have been identified in plants that have multiple functions including reorganization of cell structure, development, facilitating crosstalk between plants and fungi, plant immunity, defense against pathogens. Purified from several edible species, these EVs are more biocompatible, biodegradable, and extremely available from many plants, making them useful for cell-free therapy. Emerging evidence of clinical and preclinical studies suggest that P-EVs have numerous benefits over conventional synthetic carriers, opening novel frontiers for the novel drug-delivery system. Exciting new opportunities, including designing drug-loaded P-EVs to improve the drug-delivery systems, are already being examined, however clinical translation of P-EVs-based therapies faces challenges. Conclusion P-EVs hold great promise for clinical application in the treatment of different diseases. In addition, despite enthusiastic results, further scrutiny should focus on unravelling the detailed mechanism behind P-EVs biogenesis and trafficking as well as their therapeutic applications.

It has been recently revealed that Histone Deacetylase (HDAC) 3, a unique member of the HDACs family, can trigger and progress cancers by alternation in genes expression and proteins activity. Epigenetic modifications by HDACs have been studied well in various cancer cells. Recent studies have focused on the HDAC enzymes as a possible target in cancer therapy. There are significant documents on upregulation of HDAC3 in breast cancer (BC) cells which suggest an oncogenic role for this enzyme. Interestingly, some studies showed that HDAC3 inhibition could be considered as a promising target in breast cancer therapy, and thus far, several inhibitors from different nature have been introduced. In this review, we discussed the function and highlight the existing inhibitors of HDAC3 in BC pathogenesis and therapy.

Cytokine storms and extra-activated cytokine signaling pathways can lead to severe tissue damage and patient death. Activation of inflammatory signaling pathways during Cytokine storms are an important factor in the development of acute respiratory syndrome (SARS-CoV-2), which is the major health problem today, causing systemic and local inflammation. Cytokine storms attract many inflammatory cells that attack the lungs and other organs and cause tissue damage. Angiotensin-converting enzyme 2 (ACE2) are expressed in a different type of tissues. inhibition of ACE2 activity impairs renin-angiotensin (RAS) function, which is related to the severity of symptoms and mortality rate in COVID-19 patients. Different signaling cascades are activated, affecting various organs during SARS-CoV-2 infection. Nowadays, there is no specific treatment for COVID-19, but scientists have recognized and proposed several treatment alternatives, including applying cytokine inhibitors, immunomodulators, and plasma therapy. Herein, we have provided the detailed mechanism of SARS-CoV-2 induced cytokine signaling and its connection with pathophysiological features in different organs. Possible treatment options to cope with the severe clinical manifestations of COVID-19 are also discussed.

Recently, circular RNAs (circRNAs) have appealed to a growing interest due to their abundant expression and potential functions in cancer development. The most biological function of circRNAs may include acting as a sponge for miRNAs and proteins in different physio/pathological conditions. CircRNAs promote cancer progression by regulating several procedures such as growth, invasion, metastasis, angiogenesis, and drug resistance. Emerging evidence has shown that circRNAs frequently have tumor-specific expression, proposing these molecules serve as diagnostic and prognostic cancer biomarkers. Furthermore, circRNAs may be used as a potential target for the treatment of cancers as they can sponge oncogenic miRNAs and proteins. Exosomes, a subtype of extracellular vesicles mediate intercellular communication, contain circRNAs and deliver them to target cells inducing cancer development through different signaling pathways. Exosomal circRNAs may serve as a diagnostic and prognostic biomarker for cancers. Targeting exosomes may represent novel approaches for the treatment of cancers through using them as cell-free therapy and drug-delivery system and inhibiting their biogenesis and distribution. However, research on circRNAs biology is advancing and some concerns such as technical issues in the characterization and analysis of circRNAs along with biological understanding gaps necessary to be considered to transfer this undeveloped field to the vanguard of clinical studies. In this review, we discuss the existing information on the formation of circRNA and its roles in the tumor as a biomarker and treatment target. Furthermore, we describe tumor-derived exosomes enclosed circRNAs and their possible roles in cancer development and their potential as biomarkers and therapeutic approaches.

Cancer is one of the leading causes of death worldwide, and its incidence is steadily increasing. Although years of research have been conducted on cancer treatment, clinical treatment options for cancers are still limited. Animal cancer models have been widely used for studies of cancer therapeutics, but these models have been associated with many concerns, including inaccuracy in the representation of human cancers, high cost and ethical issues. Therefore, in vitro human cancer models are being developed quickly to fulfill the increasing demand for more relevant models in order to get a better knowledge of human cancers and to find novel treatments. This review summarizes the development of in vitro human cancer models for biomedical applications. We first review the latest development in the field by detailing various types of in vitro human cancer models, including transwell-based models, tumor spheroids, microfluidic tumor-microvascular systems and scaffold-based models. The advantages and limitations of each model, as well as their biomedical applications, are summarized, including therapeutic development, assessment of tumor cell migration, metastasis and invasion and discovery of key cancer markers. Finally, the existing challenges and future perspectives are briefly discussed.