Role of microRNA-363 during tumor progression and invasion.

Recent progresses in diagnostic and therapeutic methods have significantly improved prognosis in cancer patients. However, cancer is still considered as one of the main causes of human deaths in the world. Late diagnosis in advanced tumor stages can reduce the effectiveness of treatment methods and increase mortality rate of cancer patients. Therefore, investigating the molecular mechanisms of tumor progression can help to introduce the early diagnostic markers in these patients. MicroRNA (miRNAs) has an important role in regulation of pathophysiological cellular processes. Due to their high stability in body fluids, they are always used as the non-invasive markers in cancer patients. Since, miR-363 deregulation has been reported in a wide range of cancers, we discussed the role of miR-363 during tumor progression and metastasis. It has been reported that miR-363 has mainly a tumor suppressor function through the regulation of transcription factors, apoptosis, cell cycle, and structural proteins. MiR-363 also affected the tumor progression via regulation of various signaling pathways such as WNT, MAPK, TGF-ß, NOTCH, and PI3K/AKT. Therefore, miR-363 can be introduced as a probable therapeutic target as well as a non-invasive diagnostic marker in cancer patients.

Advances and challenges of the cell-based therapies among diabetic patients.

Diabetes mellitus is a significant global public health challenge, with a rising prevalence and associated morbidity and mortality. Cell therapy has evolved over time and holds great potential in diabetes treatment. In the present review, we discussed the recent progresses in cell-based therapies for diabetes that provides an overview of islet and stem cell transplantation technologies used in clinical settings, highlighting their strengths and limitations. We also discussed immunomodulatory strategies employed in cell therapies. Therefore, this review highlights key progresses that pave the way to design transformative treatments to improve the life quality among diabetic patients.

Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies.

Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.

Therapeutic potential of lipid-lowering probiotics on the atherosclerosis development.

Hypercholesterolemia is a critical risk factor for atherosclerosis, mostly attributed to lifestyle behavior such as diet. Recent advances have emphasized the critical effects of gastrointestinal bacteria in the pathology of hypercholesterolemia and atherosclerosis, suggesting that the gastrointestinal microbiome can therefore provide efficient therapeutic targets for preventing and treating atherosclerosis. Thus, interventions, such as probiotic therapy, aimed at altering the bacterial composition introduce a promising therapeutic procedure. In the current review, we will provide an overview of anti-atherogenic probiotics contributing to lipid-lowering, inhibiting atherosclerotic inflammation, and suppressing bacterial atherogenic metabolites.

Advances in Treatments for Epidermolysis Bullosa (EB): Emphasis on Stem Cell-Based Therapy.

Epidermolysis bullosa (EB) is a rare genetic dermatosis characterized by skin fragility and blister formation. With a wide phenotypic spectrum and potential extracutaneous manifestations, EB poses significant morbidity and mortality risks. Currently classified into four main subtypes based on the level of skin cleavage, EB is caused by genetic mutations affecting proteins crucial for maintaining skin integrity. The management of EB primarily focuses on preventing complications and treating symptoms through wound care, pain management, and other supportive measures. However, recent advancements in the fields of stem cell therapy, tissue engineering, and gene therapy have shown promise as potential treatments for EB. Stem cells capable of differentiating into skin cells, have demonstrated positive outcomes in preclinical and early clinical trials by promoting wound healing and reducing inflammation. Gene therapy, on the other hand, aims to correct the underlying genetic defects responsible for EB by introducing functional copies of mutated genes or modifying existing genes to restore protein function. Particularly for severe subtypes like Recessive Dystrophic Epidermolysis Bullosa (RDEB), gene therapy holds significant potential. This review aims to evaluate the role of new therapeutic approaches in the treatment of EB. The review includes findings from studies conducted on humans. While early studies and clinical trials have shown promising results, further research and trials are necessary to establish the safety and efficacy of these innovative approaches for EB treatment.

Synthesis of bone biocompatible implants using human adipose-derived mesenchymal stem cells (hADMSCs) and PCL/laminin scaffold substrate.

Objectives: Bone tissue engineering is considered a new method in the treatment of bone defects and can be an effective alternative to surgery and bone grafting. The use of adipose tissue mesenchymal stem cells (ADMSCs) on synthetic polymer scaffolds is one of the new approaches in bone tissue engineering. In this study, we aimed to investigate the effect of laminin coating on biocompatibility and osteogenic differentiation of ADMSCs seeded on polycaprolactone (PCL) scaffolds. Materials and Methods: The morphology of the electrospun scaffold was evaluated using a scanning electron microscope (SEM). Cell proliferation and cytotoxicity were determined by MTT assay. The adipogenic and osteogenic differentiation potential of the cells was evaluated. The osteogenic differentiation of ADMSCs cultured on the PCL scaffold coated with laminin was assessed by evaluating the level of alkaline phosphatase (ALP) activity, intracellular calcium content, and expression of bone-specific genes. Results: The results showed that the ADMSCs cultured on PCL/laminin showed enhanced osteogenic differentiation compared to those cultured on non-coated PCL or control medium (P<0.05). Conclusion: It seems that laminin enhances the physicochemical properties and biocompatibility of PCL nanofiber scaffolds; and by modifying the surface of the scaffold, improves the differentiation of ADMSCs into osteogenic cells.

Recent Approaches to Enhance Osteogenesis of Dental Pulp Stem Cells on Electrospun Scaffolds.

Critical-sized bone defects are a challenging issue during bone regeneration. Bone tissue engineering is aimed to repair such defects using biomimicking scaffolds and stem cells. Electrospinning allows the fabrication of biocompatible, biodegradable, and strengthened scaffolds for bone regeneration. Natural and synthetic polymers, alone or in combination, have been employed to fabricate scaffolds with appropriate properties for the osteogenic differentiation of stem cells. Dental pulps are rich in stem cells, and dental pulp stem cells (DPSCs) have a high capacity for proliferation, differentiation, immunomodulation, and trophic factor expression. Researchers have tried to enhance osteogenesis through scaffold modification approaches, including incorporation or coating with mineral, inorganic materials, and herbal extract components. Among them, the incorporation of nanofibers with hyaluronic acid (HA) has been widely used to promote osteogenesis. In this review, the electrospun scaffolds and their modifications used in combination with DPSCs for bone regeneration are discussed.

Effect of resveratrol and curcumin and the potential synergism on hypertension: A mini-review of human and animal model studies.

Resveratrol (RES) and curcumin (CUR) are two of the most extensively studied bioactive compounds in cardiovascular research from the past until today. These compounds have effectively lowered blood pressure by downregulating the renin-angiotensin system, exerting antioxidant effects, and exhibiting antiproliferative activities on blood vessels. This study aims to summarize the results of human and animal studies investigating the effects of CUR, RES, and their combination on hypertension and the molecular mechanisms involved. The published trials' results are controversial regarding blood pressure reduction with different doses of RES and CUR, highlighting the need to address this issue.

Evaluation of osteoconductive effect of polycaprolactone (PCL) scaffold treated with Aloe vera on adipose-derived mesenchymal stem cells (ADSCs).

BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) hold promise for bone tissue engineering because of their ability to differentiate into a variety of cell lineages. In tissue engineering, composite scaffolds made of natural and synthetic polymers have also attracted interest. Modification of scaffolds with various substances, including Aloe Vera, is expected to play a useful role in the repair of damaged tissues, including bone. METHOD: ADSCs were isolated and seeded in three groups on an Aloe Vera-modified PCL scaffold: 1. Polycaprolactone (PCL) scaffold group, 2. PCL/Aloe Vera scaffold group, and 3. TCPS (Tissue Culture Polystyrene) group. Subsequently, staining with Oil red and Alizarin Red was performed to assess the ability of ADSCs to differentiate into fat and bone cells. Cell viability was determined by the resazurin assay on days 1, 3, and 5. Calcium content and alkaline phosphatase activity (ALP) were determined with kits on days 7, 14, and 21. RNA was extracted, and cDNA was synthesized. Finally, the expression of marker genes for bone differentiation like osteogenic markers such as Osteonectin (ON), Osteocalcin (OC), RUNX Family Transcription Factor 2 (RUNX2), Collagen type I alpha 1 (COL1) was evaluated by real-time PCR. RESULTS: Aloe vera-treated PCL scaffolds showed improved biocompatibility compared with untreated scaffolds (P<0.05). In addition, treated scaffolds promoted osteogenic differentiation of ADSCs, as evidenced by increased expression of osteogenic markers such ON, OC, RUNX2, COL1 compared with PCL scaffold and TCPS (P<0.05). Furthermore, ALP and calcium content assay confirmed improved mineral deposition on PCL scaffolds treated with Aloe vera, indicating enhanced osteoconductivity (P<0.05). CONCLUSION: Our data suggest that a PCL scaffold mixed with Aloe Vera gel has promising osteoconductive potential, which can be used as a natural polymer for tissue engineering of bone and promote bone regeneration.

Effect of a combined program of running exercise and environmental enrichment on memory function and neurogenesis markers in amyloid-beta-induced Alzheimer-like model.

Objectives: It is urgent to develop non-pharmacological interventions or multifactor combination approaches to combat Alzheimer's disease (AD). The effect of exercise (EX) combined with environmental enrichment (EE) on behavioral phenotypes and neurogenesis markers in an Alzheimer-like rat model was investigated. Materials and Methods: The groups consisted of AD, sham-operated, AD+EX, AD+EE, and AD+EX+EE. AD was produced by injection of amyloid-beta (1-42, 6 µg) intrahippocampally, and a daily treadmill for 3 consecutive weeks was used for EX animals. EE was a large cage (50× 50× 50 cm) containing differently shaped objects. Spatial learning and memory were evaluated in the Morris water maze (MWM), and a shuttle box was used to evaluate inhibitory avoidance memory. RT-PCR was performed to assess the expression of early neurogenesis markers, DCX, and Sox2 within the hippocampus. Results: Pretreatment with exercise and EE, both individually and in combination, could provide protection from memory impairments in AD rats. Combined treatment led to a significantly more pronounced improvement in memory deficits of AD rats than either paradigm alone. Combination therapy with exercise and EE could also reverse the passive avoidance memory impairment and hippocampal DCX expression of AD rats to the control levels. Conclusion: These data suggest that exercise in combination with cognitive engagement can provide a non-pharmacological and multidomain policy that may prevent or delay AD symptoms.

A novel approach to design a multiepitope peptide as a vaccine candidate for Bordetella pertussis.

Bordetella pertussis is a very contagious pathogen in humans, causing pertussis disease. Pertussis is one of the 10 leading causes of death due to infectious diseases, especially among infants and children. Antibiotic-resistant strains have recently emerged in this bacterium, and despite the high vaccination coverage, the prevalence of this disease has been increasing recently in both developed and developing countries. The objective of this study is to introduce a novel in silico vaccine candidate aimed at countering B. pertussis effectively. Differing from other comparable studies, this research employed a computational screening methodology to assess the genome of 'Bordetella pertussis 18323.' The purpose was to identify an innovative antigen for the development of a vaccine against B. pertussis. Notably, our investigation introduces an innovative antigen distinguished by its elevated immunogenicity score. Importantly, this antigen lacks toxicity and allergenicity, making it recognizable to the immune system and thus capable of inducing a robust immune response. In the subsequent phase, our antigen was utilized to identify potential epitopes conducive to the construction of a B. pertussis vaccine. These epitopes, alongside linkers, his-tag and adjuvants, were amalgamated to form the vaccine candidate. Subsequently, a comprehensive evaluation of the vaccine was conducted, encompassing various computational tests such as secondary and tertiary structure analysis, physicochemical examination, and structural analysis involving docking and molecular dynamics simulations. Importantly, our vaccine successfully passed all in silico tests.Communicated by Ramaswamy H. Sarma.

The crosstalk between non-coding RNA polymorphisms and resistance to lung cancer therapies.

Lung cancer (LC) is one of the most common cancer-related mortality in the world. Even with intensive multimodality therapies, lung cancer has a poor prognosis and a high morbidity rate. This review focused on the role of non-coding RNA polymorphisms such as lncRNAs and miRNAs in the resistance to LC therapies, which could open promising avenue for better therapeutic response. Of note, there is currently no valid biomarker to predict lung cancer sensitivity in patients during treatment. Since genetic variations cause many challenges in treating patients, genotyping of known polymorphisms must be thoroughly explored to find desirable treatment platforms. With this knowledge, individualized treatments could become more possible in management of LC.

Targeting transforming growth factor beta (TGF-ß) using Pirfenidone, a potential repurposing therapeutic strategy in colorectal cancer.

The modulating factors within the tumor microenvironment, for example, transforming growth factor beta (TGF-ß), may limit the response to chemo and immunotherapy protocols in colorectal cancer (CRC). In the current study, the therapeutic potential of targeting the TGF-ß pathway using Pirfenidone (PFD), a TGF-ß inhibitor, either alone or in combination with five fluorouracil (5-FU) has been explored in preclinical models of CRC. The anti-proliferative and migratory effects of PFD were assessed by MTT and wound-healing assays respectively. Xenograft models were used to study the anti-tumor activity, histopathological, and side effects analysis. Targeting of TGF-ß resulted in suppression of cell proliferation and migration, associated with modulation of survivin and MMP9/E-cadherin. Moreover, the PFD inhibited TGF-ß induced tumor progression, fibrosis, and inflammatory response through perturbation of collagen and E-cadherin. Targeting the TGF-ß pathway using PFD may increase the anti-tumor effects of 5-FU and reduce tumor development, providing a new therapeutic approach to CRC treatment.

Effect of melatonin on male offspring testis and sperm parameters in BALB/c mice after exposing their mother to METHamphetamine during pregnancy and lactation.

Objectives: Methamphetamine (METH) is a psychostimulant that has harmful effects on all organs, the nervous system, cardiovascular system, and reproductive system. Since many METH consumers are young people of reproductive age, it poses a risk to the next generation of METH consumers. METH can pass through the placenta and is also secreted into breast milk. Melatonin (MLT) is the primary hormone of the pineal gland that regulates the circadian cycle, and it is also an antioxidant that can mitigate the effects of toxic substances. This study aims to investigate the protective effect of melatonin against the detrimental effects that METH has on the reproductive system of male newborns, whose mothers consumed METH during pregnancy and lactation. Materials and Methods: In the current study, 30 female adult balb/c mice were divided into three groups: control group, vehicle group that received normal saline, and the experimental group that received 5 mg/kg METH intraperitoneally during gestation and lactation. After lactation, the male offspring of each group were randomly divided into two subgroups, one of which received 10 mg/kg melatonin intragastrically for 21 days (corresponding to the lactation period of the mice) (METH-MLT) and the other did not (METH -D.W). After treatment, the mice were sacrificed and testicular tissue and epididymis were obtained for the following tests. Results: The diameter of seminiferous tubules, SOD activity, total Thiol groups concentration, catalase activity, sperm count, and PCNA and CCND gene expression were significantly increased in the METH-MLT group compared with the METH-DW. Apoptotic cells and MDA level ameliorated in the METH-MLT group compared with METH-D.W, and testicular weight had no notable change. Conclusion: The current study represents that consumption of METH during pregnancy and lactation can have adverse effects on the histological and biochemical factors of testis and sperm parameters of male newborns, which can be mitigated by taking melatonin after the end of the breastfeeding period.

Applications of poly(lactic acid) in bone tissue engineering: A review article.

BACKGROUND: Bone tissue engineering is a promising approach to large-scale bone regeneration. This involves the use of an artificial extracellular matrix or scaffold and osteoblasts to promote osteogenesis and ossification at defect sites. Scaffolds are constructed using biomaterials that typically have properties similar to those of natural bone. METHOD: In this study, which is a review of the literature, various evidences have been discussed in the field of Poly Lactic acid (PLA) polymer application and modifications made on it in order to induce osteogenesis and repair bone lesions. RESULTS: PLA is a synthetic aliphatic polymer that has been extensively used for scaffold construction in bone tissue engineering owing to its good processability, biocompatibility, and flexibility in design. However, PLA has some drawbacks, including low osteoconductivity, low cellular adhesion, and the possibility of inflammatory reactions owing to acidic discharge in a living environment. To overcome these issues, a combination of PLA and other biomaterials has been introduced. CONCLUSIONS: This short review discusses PLA's characteristics of PLA, its applications in bone regeneration, and its combination with other biomaterials.

Revisiting Recent Tissue Engineering Technologies in Alveolar Cleft Reconstruction.

Tissue engineering and regenerative medicine have received significant attention in treating degenerative disorders and presented unique opportunities for researchers. The latest research on tissue engineering and regenerative medicine to reconstruct the alveolar cleft has been reviewed in this study. Three approaches have been used to reconstruct alveolar cleft: Studies that used only stem cells or biomaterials and studies that reconstructed alveolar defects by tissue engineering using a combination of stem cells and biomaterials. Stem cells, biomaterials, and tissue-engineered constructs have shown promising results in the reconstruction of alveolar defects. However, some contrary issues, including stem cell durability and scaffold stability, were also observed. It seems that more prospective and comprehensive studies should be conducted to fully clarify the exact dimensions of the stem cells and tissue engineering reconstruction method in the therapy of alveolar cleft.

The differentiation and generation of glucose-sensitive beta like-cells from menstrual blood-derived stem cells using an optimized differentiation medium with platelet-rich plasma (PRP).

Regarding their reversible damage of insulin-producing cells (IPCs) and the inefficiency of treatment methods for type 1 diabetes mellitus (T1DM), scientists decided to produce IPCs from an unlimited source of cells. But the production of these cells is constantly faced with problems such as low differentiation efficiency in cell therapy and regenerative medicine. This study provided an ideal differentiation medium enriched with plasma-rich platelet (PRP) delivery to produce IPCs from menstrual blood-derived stem cells (MenSCs). We compared them with and without PRP differentiation medium. MenSCs were then cultured in two experimental groups: with/without PRP differentiation medium and a control group (undifferentiated MenSCs). After 18 days, differentiated cells were analyzed for expression of pancreatic gene markers by real-time PCR. Immunocytochemical staining was used to detect the presence of insulin and Pdx-1 in the differentiated cells, and insulin and C-peptide secretion response to glucose were tested by ELISA. Finally, the morphology of differentiated cells was examined by an inverted microscope. In vitro studies showed that MenSCs differentiated in the PRP differentiation medium had strong properties of IPCs such as pancreatic islet-like structure. The expression of pancreatic markers at both RNA and protein levels showed that the differentiation efficiency was higher in the PRP differentiation medium. In both experimental groups, the differentiated cells were functional and secreted C-peptide and insulin on glucose stimulation, but the secretion of C-peptide and insulin in the PRP group was higher than those cultured in the without PRP differentiation medium. Our findings showed that using of PRP enriched differentiation medium can promote the differentiation of MenSCs into IPCs compared to the without PRP culture group. Therefore, the use of PRP into differentiation media can be proposed as a new approach to producing IPCs from MenSCs and used in cell-based therapies for T1DM.

The therapeutic effect of melatonin on female offspring ovarian reserve and quality in BALB/c mice after exposing their mother to methamphetamine during pregnancy and lactation.

Objectives: Nowadays, methamphetamine (METH) abuse as a psychotropic drug is increasing. There is insufficient information about its adverse effects on the ovarian reserve of the next generation. Herein, we tried to investigate the effect of METH abuse during pregnancy and lactation and, subsequently, the therapeutic effect of melatonin on ovarian reserve in offspring. Materials and Methods: In the present study, BALB/c pregnant female mice were divided into 3 groups: Control, Saline, and METH (5mg/Kg). METH was injected during pregnancy and lactation, and the female offspring of each group was divided into 2 subgroups: A) treated with 10 mg/kg Melatonin daily until puberty (6 weeks old) and B) received distilled water. The animals were sacrificed at 6 weeks of age, and blood samples were collected for hormonal assessments; the right ovaries were removed and fixed for TUNEL and Hematoxylin & Eosin staining, and the left ovaries were removed and stored for gene expression and oxidative stress evaluation. Results: In the MTEH group, two indicators of ovarian reserve (including anti-Müllerian hormone (AMH) and primordial follicle, and Cyclin D1 (CCND-1) and proliferating cell nuclear antigen (PCNA) genes expression significantly decreased, and the oxidative stress and apoptosis significantly increased in comparison with other groups. After lactation in the MTEH group, melatonin treatment significantly improved the ovarian reserve and gene expression and declined apoptosis and oxidative stress. Conclusion: METH abuse during pregnancy and lactation decreased ovarian reserve in offspring. The administration of melatonin as an anti-oxidant agent after lactation can counteract the adverse effects of METH on offspring ovaries.

Cell cycle related long non-coding RNAs as the critical regulators of breast cancer progression and metastasis.

Cell cycle is one of the main cellular mechanisms involved in tumor progression. Almost all of the active molecular pathways in tumor cells directly or indirectly target the cell cycle progression. Therefore, it is necessary to assess the molecular mechanisms involved in cell cycle regulation in tumor cells. Since, early diagnosis has pivotal role in better cancer management and treatment, it is required to introduce the non-invasive diagnostic markers. Long non-coding RNAs (LncRNAs) have higher stability in body fluids in comparison with mRNAs. Therefore, they can be used as efficient non-invasive markers for the early detection of breast cancer (BCa). In the present review we have summarized all of the reported lncRNAs involved in cell cycle regulation in BCa. It has been reported that lncRNAs mainly affect the cell cycle in G1/S transition through the CCND1/CDK4-6 complex. Present review paves the way of introducing the cell cycle related lncRNAs as efficient markers for the early detection of BCa.

The role of HLA genotypes in understanding the pathogenesis of severe COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has caused human tragedy through the global spread of the viral pathogen SARS-CoV-2. Although the underlying factors for the severity of COVID-19 in different people are still unknown, several gene variants can be used as predictors of disease severity, particularly variations in viral receptor genes such as angiotensin-converting enzyme 2 (ACE2) or major histocompatibility complex (MHC) genes. The reaction of the immune system, as the most important defense strategy in the case of viruses, plays a decisive role. The innate immune system is important both as a primary line of defense and as a trigger of the acquired immune response. The HLA-mediated acquired immune response is linked to the acquired immune system. In various diseases, it has been shown that genetic alterations in components of the immune system can play a crucial role in how the body responds to pathogens, especially viruses. One of the most important host genetic factors is the human leukocyte antigen (HLA) profile, which includes HLA classes I and II and may be symbolic of the diversity of immune response and genetic predisposition in disease progression. COVID-19 will have direct contact with the acquired immune system as an intracellular pathogen after exposure to the proteasome and its components through class I HLA. Therefore, it is assumed that in different genotypes of the HLA-I class, an undesirable supply causes an insufficient activation of the immune system. Insufficient binding of antigen delivered by class I HLA to host lymphocytes results in uncertain identification and insufficient activation of the acquired immune system. The absence of secretion of immune cytokines such as interferons, which play an important role in controlling viral infection in the early stages, is a complication of this event. Understanding the allelic diversity of HLA in people infected with coronavirus compared with uninfected people of one race not only allows identification of people with HLA susceptible to COVID-19 but also provides better insight into the behavior of the virus, which helps to take effective preventive and curative measures earlier.