Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke.

Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it is as a substantial reason of morbidity and mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest as a potential treatment for cerebral ischemic damage, as shown in ischemic stroke, because of their potent intrinsic features, which include self-regeneration, immunomodulation, and multi-potency. Additionally, MSCs are easily obtained, isolated, and cultured. Despite this, there are a number of obstacles that hinder the effectiveness of MSC-based treatment, such as adverse microenvironmental conditions both in vivo and in vitro. To overcome these obstacles, the naïve MSC has undergone a number of modification processes to enhance its innate therapeutic qualities. Genetic modification and preconditioning modification (with medications, growth factors, and other substances) are the two main categories into which these modification techniques can be separated. This field has advanced significantly and is still attracting attention and innovation. We examine these cutting-edge methods for preserving and even improving the natural biological functions and therapeutic potential of MSCs in relation to adhesion, migration, homing to the target site, survival, and delayed premature senescence. We address the use of genetically altered MSC in stroke-induced damage. Future strategies for improving the therapeutic result and addressing the difficulties associated with MSC modification are also discussed.

Dietary caffeine intake is associated with favorable metabolic profile among apparently healthy overweight and obese individuals.

BACKGROUND: Recent studies have revealed some conflicting results about the health effects of caffeine. These studies are inconsistent in terms of design and population and source of consumed caffeine. In the current study, we aimed to evaluate the possible health effects of dietary caffeine intake among overweight and obese individuals. METHODS: In this cross-sectional study, 488 apparently healthy individuals with overweight and obesity were participated. Dietary intake was assessed by a Food Frequency Questionnaire (FFQ) and the amount of dietary caffeine was calculated. Body composition was determined by bioelectrical impedance analysis (BIA). Enzymatic methods were used to evaluate serum lipid, glucose, and insulin concentrations. RESULTS: Those at the highest tertile of dietary caffeine intake had lower percentage of fat mass, higher fat free mass and appetite score (P < 0.05). Also, lower total cholesterol (TC) and low density lipoprotein cholesterol (LDL-c) was observed in higher tertiles of dietary caffeine intake compared with lower tertiles. In multinomial adjusted models, those at the second tertile of dietary caffeine intake were more likely to have higher serum insulin (P = 0.04) and lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared with first tertile (P = 0.03) in crude model. While, in the age, body mass index (BMI), sex, physical activity, socio-economic status (SES) and energy intake -adjusted model (Model III), those at the third tertile of dietary caffeine intake were more likely to have low serum LDL concentrations [odds ratio (OR) = 0.957; CI = 0.918-0.997; P = 0.04]. With further adjustment to dietary vegetable, fiber and grain intake, those at the third tertile of dietary caffeine intake were more likely to have low systolic blood pressure (SBP), LDL and high HDL levels compared with those at the first tertile (P < 0.05). CONCLUSION: High intakes of dietary caffeine was associated with lower LDL, SBP, insulin resistance and higher HDL concentrations among overweight and obese individuals. However, due to observational design of the study, causal inference is impossible and further studies are warranted to confirm our findings.

Soluble receptor for advanced glycation end products (sRAGE) is associated with obesity rates: a systematic review and meta-analysis of cross-sectional study.

BACKGROUND: Several studies have highlighted the possible positive effects of soluble receptor for advanced glycation end products (sRAGE) against obesity. However, due to their inconsistent results, this systematic review and meta-analysis aimed to quantitatively evaluate and critically review the results of studies evaluating the relationship between sRAGE with obesity among adult population. METHODS: In the systematic search, the eligibility criteria were as follows: studies conducted with a cross-sectional design, included apparently healthy adults, adults with obesity, or obesity-related disorders, aged over 18 years, and evaluated the association between general or central obesity indices with sRAGE. RESULTS: Our systematic search in electronic databases, including PubMed, Scopus, and Embase up to 26 October, 2023 yielded a total of 21,612 articles. After removing duplicates, screening the titles and abstracts, and reading the full texts, 13 manuscripts were included in the final meta-analysis. According to our results, those at the highest category of circulating sRAGE concentration with median values of 934.92 pg/ml of sRAGE, had 1.9 kg/m2 lower body mass index (BMI) (WMD: -1.927; CI: -2.868, -0.986; P < 0.001) compared with those at the lowest category of sRAGE concentration with median values of 481.88 pg/ml. Also, being at the highest sRAGE category with the median values of 1302.3 pg/ml sRAGE, was accompanied with near 6 cm lower waist circumference (WC) (WMD: -5.602; CI: -8.820, -2.383; P < 0.001 with 86.4% heterogeneity of I2) compared with those at the lowest category of sRAGE concentration with median values of 500.525 pg/ml. Individuals with obesity had significantly lower circulating sRAGE concentrations (WMD: -135.105; CI: -256.491, -13.72; P = 0.029; with 79.5% heterogeneity of I2). According to the subgrouping and meta-regression results, country and baseline BMI were possible heterogeneity sources. According to Begg's and Egger's tests and funnel plots results, there was no publication bias. CONCLUSION: According to our results, higher circulating sRAGE concentrations was associated with lower BMI and WC among apparently healthy adults. Further randomized clinical trials are warranted for possible identification of causal associations.

Effect of sesame (Sesamum indicum L.) consumption on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

Conflicting evidence exists on the effect of sesame consumption on glucose metabolism in patients with type 2 diabetes (T2D). Therefore, this meta-analysis focuses on the relationship between sesame (Sesamum indicum L.) intervention and glycemic control in patients with T2D. Published literature was retrieved and screened from PubMed, Scopus, ISI Web of Science, and the Cochrane Library up to December 2022. Outcome measures included fasting blood sugar (FBS) concentrations, fasting insulin levels, and hemoglobin A1c (HbA1c) percentage. Pooled effect sizes were reported as weighted mean differences (WMDs) and 95% confidence intervals (CIs). Eight clinical trials (395 participants) were eligible for meta-analyses. Overall, sesame consumption significantly reduced serum FBS (WMD: -28.61 mg/dL, 95% CI: -36.07 to -21.16, p˂0.001; I2 = 98.3%) and HbA1c percentage (WMD: -0.99%, 95% CI: -1.22 to -0.76, p ≤ 0.001; I2 = 65.1%) in patients with T2D. However, sesame consumption did not significantly influence fasting insulin levels (Hedges's: 2.29, 95% CI: -0.06 to 4.63, p = 0.06; I2 = 98.1%). In summary, the current meta-analysis showed a promising effect of sesame consumption on glycemic control through reducing FBS and HbA1c, yet additional prospective studies are recommended, using higher doses and longer intervention period, to confirm the impact of sesame consumption on insulin levels in T2D patients.

Inhibitory Potential of the Ocimum sanctum Phytochemicals on Bruton's Tyrosine Kinase, a Well-Known Drug Target for Treatment of Chronic Lymphocytic Leukemia: An In Silico Investigation.

Chronic lymphocytic leukemia (CLL) is an incurable neoplasm of B-lymphocytes, which accounts for about one-third of all leukemias. Ocimum sanctum, an herbaceous perennial, is considered as one of the important sources of drugs for the treatment of various diseases, including cancers and autoimmune diseases. The present study was designed to screen various phytochemicals of O. sanctum for discovering their potential to inhibit Bruton's tyrosine kinase (BTK), a well-known drug target of CLL. Various phytochemicals of O. sanctum were screened for their potential to inhibit BTK using several in silico protocols. First, the molecular docking approach was used to calculate the docking scores of the selected phytochemicals. Then, the selected top-ranked phytochemicals were screened for their physicochemical characteristics using ADME analysis. Finally, the stability of the selected compounds in their corresponding docking complexes with BTK was analysed using molecular dynamics simulations. Primarily, our observations revealed that, out of the 46 phytochemicals of O. sanctum, six compounds possessed significantly better docking scores (ranging from -9.2 kcal/mol to -10 kcal/mol). Their docking scores were comparable to those of the control inhibitors, acalabrutinib (-10.3 kcal/mol), and ibrutinib (-11.3 kcal/mol). However, after ADME analysis of these top-ranked six compounds, only three compounds (Molludistin, Rosmarinic acid, and Vitexin) possessed drug likeliness characteristics. During the MD analysis, the three compounds Molludistin, Rosmarinic acid, and Vitexin were found to remain stable in the binding pocket in their corresponding docking complexes with BTK. Therefore, among the 46 phytochemicals of O. sanctum tested in this study, the three compounds, Molludistin, Rosmarinic acid, and Vitexin are the best inhibitors of BTK. However, these findings need to be confirmed by biological experiments in the laboratory.

Key transcription factors in the differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent cells that represent a promising source for regenerative medicine. MSCs are capable of osteogenic, chondrogenic, adipogenic and myogenic differentiation. Efficacy of differentiated MSCs to regenerate cells in the injured tissues requires the ability to maintain the differentiation toward the desired cell fate. Since MSCs represent an attractive source for autologous transplantation, cellular and molecular signaling pathways and micro-environmental changes have been studied in order to understand the role of cytokines, chemokines, and transcription factors on the differentiation of MSCs. The differentiation of MSC into a mesenchymal lineage is genetically manipulated and promoted by specific transcription factors associated with a particular cell lineage. Recent studies have explored the integration of transcription factors, including Runx2, Sox9, PPARγ, MyoD, GATA4, and GATA6 in the differentiation of MSCs. Therefore, the overexpression of a single transcription factor in MSCs may promote trans-differentiation into specific cell lineage, which can be used for treatment of some diseases. In this review, we critically discussed and evaluated the role of transcription factors and related signaling pathways that affect the differentiation of MSCs toward adipocytes, chondrocytes, osteocytes, skeletal muscle cells, cardiomyocytes, and smooth muscle cells.

Internal carotid artery ectasia: A case report of incidental diagnosis after post-traumatic headache.

Internal carotid artery ectasia (ICAE) is a rare vascular abnormality characterized by dilation and tortuosity of the internal carotid artery (ICA) beyond normal limits. ICAE is typically asymptomatic but can manifest with symptoms such as headache and dizziness. The exact cause of ICAE remains uncertain, but both congenital and acquired factors, including trauma, have been implicated. A 35-year-old female presented to the Emergency Room with severe headache and dizziness following a traumatic injury. Neurological examination revealed no deficits. Computed tomography (CT) scan showed an elongated and prominent right supraclinoid internal carotid artery with mural wall calcification. Subsequent magnetic resonance imaging (MRI) confirmed the diagnosis of internal carotid artery ectasia (ICAE) without significant stenosis or malformation. The patient remained asymptomatic during follow-up visits. Proactive monitoring was advised to detect potential complications at an early stage. This case emphasizes the incidental detection of ICAE in a patient with post-traumatic headache. ICAE is a rare condition with an elusive etiology, and its management depends on factors such as symptom severity and associated risks. Conservative management is often recommended for asymptomatic cases.

Mesenchymal stem cells and their extracellular vesicles as emerging therapeutic tools in the treatment of ischemic stroke.

Ischemic stroke (IS) is a neurological condition characterized by severe long-term consequences and an unfavorable prognosis for numerous patients. Despite advancements in stroke treatment, existing therapeutic approaches possess certain limitations. However, accumulating evidence suggests that mesenchymal stem/stromal cells (MSCs) hold promise as a potential therapy for various neurological disorders, including IS, owing to their advantageous properties, such as immunomodulation and tissue regeneration. Additionally, MSCs primarily exert their therapeutic effects through the release of extracellular vesicles (EVs), highlighting the significance of their paracrine activities. These EVs are small double-layered phospholipid membrane vesicles, carrying a diverse cargo of proteins, lipids, and miRNAs that enable effective cell-to-cell communication. Notably, EVs have emerged as attractive substitutes for stem cell therapy due to their reduced immunogenicity, lower tumorigenic potential, and ease of administration and handling. Hence, this review summarizes the current preclinical and clinical studies performed to investigate the safety and therapeutic potential of MSCs and their EVs derived from different sources, including bone marrow, adipose tissue, umbilical cord blood, and Wharton's jelly in IS.

A new vision of the efficacy of both CAR-NK and CAR-T cells in treating cancers and autoimmune diseases.

Chimeric Antigen Receptor (CAR) based therapies are becoming increasingly important in treating patients. CAR-T cells have been shown to be highly effective in the treatment of hematological malignancies. However, harmful therapeutic barriers have been identified, such as the potential for graft-versus-host disease (GVHD), neurotoxicity, and cytokine release syndrome (CRS). As a result, CAR NK-cell therapy is expected to be a new therapeutic option. NK cells act as cytotoxic lymphocytes, supporting the innate immune response against autoimmune diseases and cancer cells by precisely detecting and eliminating malignant cells. Genetic modification of these cells provides a dual approach to the treatment of AD and cancer. It can be used through both CAR-independent and CAR-dependent mechanisms. The use of CAR-based cell therapies has been successful in treating cancer patients, leading to further investigation of this innovative treatment for alternative diseases, including AD. The complementary roles of CAR T and CAR NK cells have stimulated exploration in this area. Our study examines the latest research on the therapeutic effectiveness of these cells in treating both cancer and ADs.

The pathophysiology of the cell cycle in cancer and treatment strategies using various cell cycle checkpoint inhibitors.

The cell cycle is the series of events that occur in a cell leading to its division and duplication. It can be divided into two main stages: interphase and mitosis. Interphase is the longest stage of the cell cycle and can be further divided into three phases: G1, S, and G2. During G1, the cell grows and prepares for DNA synthesis. In the S phase, DNA synthesis occurs, leading to the replication of the genetic material. In G2, the cell continues to grow and prepares for mitosis. After mitosis, the cell enters the final stage of the cell cycle, called cytokinesis, during which the cytoplasm is divided, resulting in two separate daughter cells. The cell cycle then begins again with interphase. Cell cycle dysregulation is a hallmark of cancer, and it can have several consequences that contribute to the development and progression of cancer. Cyclin inhibitors and checkpoint activators have shown promise in the treatment of cancer, particularly in combination with other therapies.

Knowledge, Attitude, and Behavior of Medical Students with Regard to Concussions: A Cross-Sectional Study.

BACKGROUND: Concussions, categorized as mild traumatic brain injuries, result from traumatic events and present a significant concern within the field of traumatic brain injuries. Understanding the multifaceted pathophysiology of concussions, their diverse symptomatology, and their appropriate management strategies is crucial for healthcare professionals. This study explores the knowledge, attitudes, and behaviors of medical students at King Faisal University in the Eastern Province of Saudi Arabia regarding concussions. METHODS: A cross-sectional study design was employed to assess a diverse group of medical students at King Faisal University in the Eastern Province of Saudi Arabia. Participants were surveyed using a questionnaire covering socio-demographic information, knowledge assessment, attitude assessment, and behavior assessment. RESULTS: Of the 315 participants, 68.3% demonstrated good knowledge about concussions. Participants generally recognized concussions as a type of traumatic brain injury (68.9%) and believed it was necessary to report concussion symptoms to a doctor (80.3%). However, certain misconceptions existed, such as the belief that all patients with concussion should rest for seven days (31.7%). Participants primarily obtained information from teachers (100%) and the internet and social media (81.6%). CONCLUSION: While medical students at King Faisal University in the Eastern Province of Saudi Arabia generally exhibited good knowledge about concussions, specific knowledge gaps and misconceptions were seen to exist. To ensure comprehensive understanding and promote appropriate management, continuous education, and awareness campaigns are essential, with healthcare providers playing a pivotal role in knowledge dissemination.

Comparative evaluation of natural neuroprotectives and their combinations on chronic immobilization stress-induced depression in experimental mice.

The present study evaluates the potential of neuroprotective phytochemicals-rutin (R), resveratrol (Res), 17ß-estradiol (17ß-E2), and their different combinations against chronic immobilization stress (CIS)-induced depression-like behaviour in male albino mice. Here, the mice were exposed to stress via immobilization of their four limbs under a restrainer for 6 h daily until 7 days of the induction after 30 min of respective drug treatment in different mice groups. The result found the protective effect of these phytoconstituents and their combinations against CIS-induced depression due to their ability to suppress oxidative stress, restore mitochondria, HPA-axis modulation, neurotransmitter level, stress hormones, and inflammatory markers. Also, the combination drug regimens of these phytoconstituents showed synergistic results in managing the physiological and biochemical features of depression. Thus, these neuroprotective could be utilized well in combination to manage depression-like symptoms during episodic stress. Furthermore, such results could be well justified when administered in polyherbal formulation with these neuroprotective as major components. In addition, an advanced study can be designed at the molecular and epigenetics level using a formulation based on these neuroprotective.

Antioxidant, LC-MS Analysis, and Cholinesterase Inhibitory Potentials of Phoenix dactylifera Cultivar Khudari: An In Vitro Enzyme Kinetics and In Silico Study.

We evaluated the therapeutic potentials of Khudari fruit pulp, a functional food and cultivar of Phoenix dactylifera, against neurological disorders. Our results demonstrate a good amount of phytochemicals (total phenolic content: 17.77 ± 8.21 µg GA/mg extract) with a high antioxidant potential of aqueous extract (DPPH assay IC50 = 235.84 ± 11.65 µg/mL) and FRAP value: 331.81 ± 4.56 µmol. Furthermore, the aqueous extract showed the marked inhibition of cell-free acetylcholinesterase (electric eel) with an IC50 value of 48.25 ± 2.04 µg/mL, and an enzyme inhibition kinetics study revealed that it exhibits mixed inhibition. Thereafter, we listed the 18 best-matched phytochemical compounds present in aqueous extract through LC/MS analysis. The computational study revealed that five out of eighteen predicted compounds can cross the BBB and exert considerable aqueous solubility. where 2-{5-[(1E)-3-methylbuta-1,3-dien-1-yl]-1H-indol-3-yl}ethanol (MDIE) indicates an acceptable LD50. value. A molecular docking study exhibited that the compounds occupied the key residues of acetylcholinesterase with ΔG range between -6.91 and -9.49 kcal/mol, where MDIE has ∆G: -8.67 kcal/mol, which was better than that of tacrine, ∆G: -8.25 kcal/mol. Molecular dynamics analyses of 100 ns supported the stability of the protein-ligand complexes analyzed through RMSD, RMSF, Rg, and SASA parameters. TRP_84 and GLY_442 are the most critical hydrophobic contacts for the complex, although GLU_199 is important for H-bonds. Prime/MM-GBSA showed that the protein-ligand complex formed a stable confirmation. These findings suggest that the aqueous extract of Khudari fruit pulp has significant antioxidant and acetylcholinesterase inhibition potentials, and its compound, MDIE, forms stably with confirmation with the target protein, though this fruit of Khudari dates can be a better functional food for the treatment of Alzheimer's disease. Further investigations are needed to fully understand the therapeutic role of this plant-based compound via in vivo study.

Biological Synthesis, Characterization, and Therapeutic Potential of S. commune-Mediated Gold Nanoparticles.

Green-synthesized gold nanoparticles demonstrate several therapeutic benefits due to their safety, non-toxicity, accessibility, and ecological acceptance. In our study, gold nanoparticles (AuNPs) were created using an extracellular extract from the fungus Schizophyllum commune (S. commune). The reaction color was observed to be a reddish pink after a 24 h reaction, demonstrating the synthesis of the nanoparticles. The myco-produced nanoparticles were investigated using transmission electron microscopy (TEM), dynamic light scattering (DLS), and UV-visible spectroscopy. The TEM pictures depicted sphere-like shapes with sizes ranging from 60 and 120 nm, with an average diameter of 90 nm, which is in agreement with the DLS results. Furthermore, the efficiency of the AuNPs' antifungal and cytotoxic properties, as well as their production of intracellular ROS, was evaluated. Our findings showed that the AuNPs have strong antifungal effects against Trichoderma sp. and Aspergillus flavus at increasing doses. Additionally, the AuNPs established a dose-dependent activity against human alveolar basal epithelial cells with adenocarcinoma (A549), demonstrating the potency of synthesized AuNPs as a cytotoxic agent. After 4 h of incubation with AuNPs, a significant increase in intracellular ROS was observed in cancer cells. Therefore, these metallic AuNPs produced by fungus (S. commune) can be used as an effective antifungal, anticancer, and non-toxic immunomodulatory delivery agent.

Factors Shaping Medical Students' Intentions Toward Neurosurgery: A Cross-Sectional Study.

Background Choosing a medical specialty poses a significant challenge for students, with initial fascinations often evolving during their academic journey. Despite its inherent appeal, neurosurgery faces hesitancy among undergraduate students, potentially due to perceived difficulties and time demands. This study aims to investigate the factors influencing medical students' intentions toward neurosurgery at two institutions in the eastern province of Saudi Arabia. Methodology A cross-sectional study design was employed, utilizing a validated, anonymous questionnaire distributed electronically to medical students and interns in the eastern province of Saudi Arabia. The questionnaire comprised two sections, namely, demographic and academic profiles, and participants' intentions, knowledge, and attitudes toward neurosurgery. Data analysis involved descriptive statistics, and chi-square tests to explore relationships and identify significant predictors. Results Of the participants, 197 (34.1%) expressed interest in neurosurgery, but only 94 (16.3%) had a comprehensive understanding of the field. Motivations included high income, specialty prestige, and positive impact on patients, while stress and work-life balance were common deterring factors. Age and academic years were associated with a gradual decrease in interest, except for initial medical school students. Participants were attracted to innovative technological aspects, while high competition and neurophobia were deterring factors. Conclusions This study provides a comprehensive analysis of determinants influencing medical students' and interns' interest in neurosurgery. Early exposure, clinical training, and personal motivations play significant roles in shaping career preferences. Challenges, such as perceived difficulties and concerns related to work-life balance, need targeted interventions to enhance neurosurgery's attractiveness. Considerations extend beyond technical and academic facets to encompass personal and lifestyle dimensions.

The microRNAs (miRs) overexpressing mesenchymal stem cells (MSCs) therapy in neurological disorders; hope or hype.

Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. One of the biggest concerns within gene-based therapy is the delivery of the therapeutic microRNAs to the intended place, which is obligated to surpass the biological barriers without undergoing degradation in the bloodstream or renal excretion. Hence, the delivery of modified and unmodified miRNA molecules using excellent vehicles is required. In this light, mesenchymal stem cells (MSCs) have attracted increasing attention. The MSCs can be genetically modified to express or overexpress a particular microRNA aimed with promote neurogenesis and neuroprotection. The current review has focused on the therapeutic capabilities of microRNAs-overexpressing MSCs to ameliorate functional deficits in neurological conditions.

Inflammatory diseases: Function of LncRNAs in their emergence and the role of mesenchymal stem cell secretome in their treatment.

One of the best treatments for inflammatory diseases such as COVID-19, respiratory diseases and brain diseases is treatment with stem cells. Here we investigate the effect of stem cell therapy in the treatment of brain diseases.Preclinical studies have shown promising results, including improved functional recovery and tissue repair in animal models of neurodegenerative diseases, strokes,and traumatic brain injuries. However,ethical implications, safety concerns, and regulatory frameworks necessitate thorough evaluation before transitioning to clinical applications. Additionally, the complex nature of the brain and its intricate cellular environment present unique obstacles that must be overcome to ensure the successful integration and functionality of genetically engineered MSCs. The careful navigation of this path will determine whether the application of genetically engineered MSCs in brain tissue regeneration ultimately lives up to the hype surrounding it.

Advancements in the Clinical Outcomes of Functional Neurosurgery With Deep Brain Stimulation for Movement Disorders: A Literature Review.

This literature review explores recent advancements in deep brain stimulation (DBS) surgery for movement disorders. It highlights notable improvements, including closed-loop stimulation techniques, optogenetics, and improved surgical targeting. Positive clinical outcomes with low complication rates and improved motor symptoms are consistently reported. The review emphasizes the importance of minimizing risks through meticulous surgical practices and discusses potential complications associated with DBS surgery. Future prospects focus on enhancing technology, refining surgical techniques, and conducting further research. Closed-loop stimulation optimizes DBS efficacy by tailoring stimulation parameters to individual patient needs. Optogenetics offers precise modulation of neural activity with light-sensitive proteins, enabling more targeted treatments. Cybersecurity measures are essential due to the integration of wireless and digital technologies in DBS systems. DBS surgery has significantly improved the management of movement disorders with its safety and effectiveness. Ongoing research in closed-loop stimulation, optogenetics, and cybersecurity is expected to further enhance DBS technology and outcomes, benefiting patients with treatment-resistant movement disorders.

Supporting wound healing by mesenchymal stem cells (MSCs) therapy in combination with scaffold, hydrogel, and matrix; State of the art.

Non-healing wounds impose a huge annual cost on the survival of different countries and large populations in the world. Wound healing is a complex and multi-step process, the speed and quality of which can be changed by various factors. To promote wound healing, compounds such as platelet-rich plasma, growth factors, platelet lysate, scaffolds, matrix, hydrogel, and cell therapy, in particular, with mesenchymal stem cells (MSCs) are suggested. Nowadays, the use of MSCs has attracted a lot of attention. These cells can induce their effect by direct effect and secretion of exosomes. On the other hand, scaffolds, matrix, and hydrogels provide suitable conditions for wound healing and the growth, proliferation, differentiation, and secretion of cells. In addition to generating suitable conditions for wound healing, the combination of biomaterials and MSCs increases the function of these cells at the site of injury by favoring their survival, proliferation, differentiation, and paracrine activity. In addition, other compounds such as glycol, sodium alginate/collagen hydrogel, chitosan, peptide, timolol, and poly(vinyl) alcohol can be used along with these treatments to increase the effectiveness of treatments in wound healing. In this review article, we take a glimpse into the merging scaffolds, hydrogels, and matrix application with MSCs therapy to favor wound healing.

Relationship between exposure to heavy metals on the increased health risk and carcinogenicity of urinary tract (kidney and bladder).

In today's society, with the continuous development of manufacturing industries and factories related to chemicals, the amount of heavy metals in the inhaled air of humans, water and even food consumption has increased dramatically. The aim of this study was investigation of relationship between exposure to heavy metals on the increased carcinogenicity risk of kidney and bladder. Databases used to for searched were the Springer, Google Scholar, Web of Science, Science Direct (Scopus) and PubMed. At the end after sieve we selected 20 papers. Identify all relevant studies published 2000-2021. The results of this study showed that exposure to heavy metals due to the bio accumulative properties of these metals can cause kidney and bladder abnormalities and provide the basis through various mechanisms for malignant tumors in these organs. Based on result this study, since a limited number of heavy metals including copper, iron, zinc and nickel in very small amounts as micronutrients play a very important role in the function of enzymes and the body cells biological reactions, but exposure to some of them like arsenic, lead, vanadium and mercury will cause irreversible effects on people's health and cause various diseases including cancers of the liver, pancreas, prostate, breast, kidney and bladder. The kidneys, ureter and bladder are the most important organs in the urinary tract on human. According to the result of this study, the duty of this urinary system is to remove toxins, chemicals and heavy metals from the blood, balance electrolytes, excrete excess fluid, produce urine and transfer it to the bladder. This mechanism causes the kidneys and bladder to be highly associated with these toxins and heavy metals, which can lead to various diseases in these two important organs. According to the finding the reducing exposure to heavy metals in various ways can prevent many diseases related to this system and reduce the incidence of kidney and bladder cancers.