Design and synthesis of nano-biomaterials based on graphene and local delivery of cerebrolysin into the injured spinal cord of mice, promising neural restoration.

Spinal cord injury (SCI) is an incurable and catastrophic health issue with no clinical solution. As part of cascade reactions, the inflammatory process and fibrous glial scar production aggravate the amount of lesion through a secondary damage mechanism, encouraging scientists from other disciplines to investigate new paths for solving this problem. Graphene oxide (GO) and its derivatives are among the most promising biomedical and nerve tissue regeneration materials due to their remarkable chemical, mechanical, and electrical properties. This paper designs and introduces a new GO-based nanomaterial to minimize inflammation and stimulate neurite regrowth. To improve biocompatibility, biodegradability, and cell proliferation, GO plates were modified with polyethylene glycol (PEG) and Au nanoparticles as neuroprotective and antibacterial agents, respectively. Preliminary biological investigations on bone marrow derived mesenchymal stem cells (BM-MSCs) with various concentrations of a graphenic nanocarrier indicated a lack of cell toxicity and an enhancement in BM-MSC proliferation of about 10% after 48 hours. Therapeutic nanostructures were used in the T10 segment of a mouse SCI model. The pathological and immunohistochemical data revealed that refilling tissue cavities, decreasing degeneration, and establishing neuroregeneration resulted in a considerable improvement of hind limb motor function. Furthermore, compared to the nanocomposite mixture alone, the intraspinal delivery of cerebrolysin (CRL) had a more satisfying impact on nerve regrowth, cystic cavity, hemorrhage avoidance, and motor function enhancement. This study demonstrates the potential of graphenic nanomaterials for SCI treatment and neuroregeneration applications.

Global trend in exosome isolation and application: an update concept in management of diseases.

Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype of EVs, 40-150 nm spherical vesicles with a lipid layer derived from endosomes. Exosomes, which are involved in signal transduction and maintain homeostasis, are released from almost all cells, tissues, and body fluids. Although several methods exist to isolate and characterize EVs and exosomes, each technique has significant drawbacks and limitations that prevent progress in the field. New approaches in the biology of EVs show great potential for isolating and characterizing EVs, which will help us better understand their biological function. The strengths and limitations of conventional strategies and novel methods (microfluidic) for EV isolation are outlined in this review. We also present various exosome isolation techniques and kits that are commercially available and assess the global market demand for exosome assays.

Nutritional knowledge, attitude, and practice of professional athletes in an Iranian population (a cross-sectional study).

BACKGROUND: Proper nutrition is vital in promoting community health, yet insufficient knowledge and improper dietary practices can lead to deficiencies and diseases. Professional athletes depend on optimal nutrition for their performance and recovery, but a lack of understanding can impede their potential. The nutritional status of athletes impacts their overall health and sports performance. Inadequate sports nutrition knowledge may result in suboptimal practices, reducing strength, power, endurance, and immunity. Additionally, disordered attitudes can lead to dietary imbalances and an increased risk of injury. This study, conducted in Qazvin, Iran, examined athletes' nutritional knowledge, attitudes, and practices. By addressing these factors, there is potential to enhance dietary behaviors and ultimately improve athletes' performance. METHODS: The study employed a descriptive-analytical, cross-sectional design to investigate the nutritional knowledge, attitude, and practice (KAP) of professional athletes in Qazvin, Iran. A total of 320 purposefully selected professional athletes (68.13% male, 31.87% female) from various sports fields participated in the research. The data collection tool consisted of demographic questions and a KAP questionnaire, including 27 nutritional knowledge questions, 16 nutritional attitude questions, and 14 nutritional performance questions. The quota sampling method was used to estimate sample sizes. Data analysis was carried out by SPSS v.26 using one sample t-test, one-way ANOVA, and Pearson's correlation coefficient test. RESULTS: The results showed that nutritional knowledge (the mean value was 79.594 ± 7.015 - the optimal knowledge level = 84) and attitude (the mean value was 23.347 ± 5.300 - the optimal attitude level = 26) for athletes are low, but their nutritional practice (the mean value was 21.788 ± 3.450 - the optimal performance level = 24) was moderate. Also, professional athletes' nutritional knowledge, attitude, and practice were lower than normal (p < 0.05). Significant positive correlations were among knowledge, attitude, and practice (p < 0.05). However, there were no significant differences in nutritional knowledge, attitude, and practice among the subjects of different age groups, genders, and sports types (p > 0.05). CONCLUSION: This study showed that the nutritional knowledge, attitude, and practice of professional Iranian athletes in Qazvin province were low; therefore, the implementation of more theoretical and applied nutrition education, such as using knowledge assessment tools and interventions, irrespective of their age, sport's field, and gender, is compelling.

Synergistic effect of chitosan-alginate composite hydrogel enriched with ascorbic acid and alpha-tocopherol under hypoxic conditions on the behavior of mesenchymal stem cells for wound healing.

BACKGROUND: In regenerative medicine, especially skin tissue engineering, the focus is on enhancing the quality of wound healing. Also, several constructs with different regeneration potentials have been used for skin tissue engineering. In this study, the regenerative properties of chitosan-alginate composite hydrogels in skin wound healing under normoxic and hypoxic conditions were investigated in vitro. METHODS: The ionic gelation method was used to prepare chitosan/alginate (CA) hydrogel containing CA microparticles and bioactive agents [ascorbic acid (AA) and α-tocopherol (TP)]. After preparing composite hydrogels loaded with AA and TP, the physicochemical properties such as porosity, pore size, swelling, weight loss, wettability, drug release, and functional groups were analyzed. Also, the hemo-biocompatibility of composite hydrogels was evaluated by a hemolysis test. Then, the rat bone marrow mesenchymal stem cells (rMSCs) were seeded onto the hydrogels after characterization by flow cytometry. The survival rate was analyzed using MTT assay test. The hydrogels were also investigated by DAPI and H&E staining to monitor cell proliferation and viability. To induce hypoxia, the cells were exposed to CoCl2. To evaluate the regenerative potential of rMSCs cultured on CA/AA/TP hydrogels under hypoxic conditions, the expression of the main genes involved in the healing of skin wounds, including HIF-1α, VEGF-A, and TGF-ß1, was investigated by real-time PCR. RESULTS: The results demonstrated that the prepared composite hydrogels were highly porous, with interconnected pores that ranged in sizes from 20 to 188 µm. The evaluation of weight loss showed that the prepared hydrogels have the ability to biodegrade according to the goals of wound healing. The reduction percentage of CA/AA/TP mass in 21 days was reported as 21.09 ± 0.52%. Also, based on wettability and hemolysis tests of the CA/AA/TP, hydrophilicity (θ = 55.6° and 53.7°) and hemocompatibility with a hemolysis ratio of 1.36 ± 0.19 were evident for them. Besides, MTT assay, DAPI, and H&E staining also showed that the prepared hydrogels provide a suitable substrate for cell growth and proliferation. Finally, based on real-time PCR, increased expression levels of VEGF and TGF-ß1 were observed in rMSCs in hypoxic conditions cultured on the prepared hydrogels. CONCLUSIONS: In conclusion, this study provides evidence that 3D CA/AA/TP composite hydrogels seeded by rMSCs in hypoxic conditions have great potential to improve wound healing.

A new insight into the role of pericytes in ischemic stroke.

The functional structure of the blood-brain barrier (BBB) deteriorates after stroke by developing diffuse microvascular and neurovascular dysfunction and loss of white matter integrity. This causes nervous tissue injury and causes sensory and motor disabilities in stroke patients. Improving the integrity of the BBB and neurovascular remodeling after stroke can promote post-stroke injury conditions. Pericytes are contractile cells abundant in the BBB and sandwiched between astrocytes and endothelial cells of the microvessels. Stroke could lead to the degeneration of pericytes in the BBB. However, recent evidence shows that promoting pericytes enhances BBB integrity and neurovascular remodeling. Furthermore, pericytes achieve multipotent properties under hypoxic conditions, allowing them to transdifferentiate into the brain resident cells such as microglia. Microglia regulate immunity and inflammatory response after stroke. The current review studies recent findings in the intervening mechanisms underlying the regulatory effect of pericytes in BBB recovery after stroke.

Tau Protein Biosensors in the Diagnosis of Neurodegenerative Diseases.

Tau protein plays a crucial role in diagnosing neurodegenerative diseases. However, performing an assay to detect tau protein on a nanoscale is a great challenge for early diagnosis of diseases. Enzyme-linked immunosorbent assay (ELISA), western-blotting, and molecular-based methods, e.g., PCR and real-time PCR, are the most widely used methods for detecting tau protein. These methods are subject to certain limitations: the need for advanced equipment, low sensitivity, and specificity, to name a few. With the above said, it is necessary to discover advanced and novel methods for monitoring tau protein. Counted among remarkable approaches adopted by researchers, biosensors can largely eliminate the difficulties and limitations associated with conventional methods. The main objective of the present study is to review the latest biosensors developed to detect the tau protein. Furthermore, the problems and limitations of conventional diagnosis methods were discussed in detail.

Synthesis, characterization, and evaluation of pH-sensitive doxorubicin-loaded functionalized graphene oxide in osteosarcoma cells.

Introduction: Doxorubicin (DOX) is one of the most common drugs in cancer treatment. However, its partial solubility along with the high incidence of side effects remains a challenge to tackle. To address these issues, we designed a formulation based on graphene oxide (GO) and used it as an anticancer drug delivery system. Methods: The physical and chemical properties of the formulation were studied using FTIR, SEM, EDX, Mapping, and XRD. Release studies in the in vitro condition were used to evaluate the pH sensitivity of drug release from nanocarriers. Other in vitro studies, including uptake assay, MTT, and apoptosis assay were carried out on the osteosarcoma cell line. Results: in vitro release studies confirmed that the synthesized formulation provides a better payload release profile in acidic conditions, which is usually the case in the tumor site. On the OS cell line, the cytotoxicity of the DOX-loaded nanocarrier (IC50=0.293 µg/mL) and early apoptosis rate (33.80 % ) were higher in comparison to free DOX (IC50=0.472 µg/mL, and early apoptosis rate= 8.31 % ) after 48 hours. Conclusion: In summary, our results suggest a DOX-loaded graphene oxide carrier as a potential platform for targeting cancer cells.

Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles.

Introduction: Blood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers. As a correlate, designing high-efficiency biocarriers for gene delivery is challenging. This study aimed to deliver pEGFP-N1 plasmid into the brain parenchyma using CDX-modified chitosan (CS) nanoparticles (NPs). Methods: Herein, we attached CDX, a 16 amino acids peptide, to the CS polymer using bifunctional polyethylene glycol (PEG) formulated with sodium tripolyphosphate (TPP), by ionic gelation method. Developed NPs and their nanocomplexes with pEGFP-N1 (CS-PEG-CDX/pEGFP) were characterized using DLS, NMR, FTIR, and TEM analyses. For in vitro assays, a rat C6 glioma cell line was used for cell internalization efficiency. The biodistribution and brain localization of nanocomplexes were studied in a mouse model after intraperitoneal injection using in vivo imaging and fluorescent microscopy. Results: Our results showed that CS-PEG-CDX/pEGFP NPs were uptaken by glioma cells in a dose-dependent manner. In vivo imaging revealed successful entry into the brain parenchyma indicated with the expression of green fluorescent protein (GFP) as a reporter protein. However, the biodistribution of developed NPs was also evident in other organs especially the spleen, liver, heart, and kidneys. Conclusion: Based on our results, CS-PEG-CDX NPs can provide a safe and effective nanocarrier for brain gene delivery into the central nervous system (CNS).

STA-21, a small molecule STAT3 inhibitor, ameliorates experimental autoimmune encephalomyelitis by altering Th-17/Treg balance.

BACKGROUND: Numerous studies have demonstrated the role of T helper (Th) 17 and T regulatory (reg) cells and pro-inflammatory and anti-inflammatory cytokines related to these cells in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). STAT3 is one of the downstream signaling proteins of IL-23, IL-6, and IL-21 that are required for Th17 cells differentiation. STA-21 is a STAT3 inhibitor that functions by inhibiting STAT3 dimerization and binding to DNA impairing the expression of STAT3 target genes including, RORγt, IL-21 and IL-23R that are also required for Th17 cell differentiation. AIM: In this study, we evaluated the effect of STA-21 on EAE Model and investigated how this small molecule can change Th17/Treg balance leading to amelioration of disease. METHODS: After EAE induction and treatment with STA-21, its effects were assessed. Major assays were H&E and LFB staining, Flow cytometric analysis, Reverse transcription-PCR (RT-PCR), and ELISA. RESULTS: STA-21 ameliorated the EAE severity and decreased the EAE inflammation and demyelination. It also decreased STAT3 phosphorylation, the proportion of Th17 cells and the protein level of IL-17. In contrast, the balance of Tregs and the level of anti-inflammatory cytokine, IL-10 increased in STA-21-treated mice. Moreover, STA-21 significantly decreased the expression of Th17 related transcription factors, RORɣt and IL-23R while FOXP3 expression associated with Treg differentiation was increased. CONCLUSION: This study showed that STA-21 has therapeutic effects in EAE by reducing inflammation and shifting inflammatory immune responses to anti-inflammatory and can be used as a suitable treatment strategy for the treatment of EAE. The effectiveness of inhibiting or strengthening the functional cells of the immune system by these small molecules in terms of easy to access, simple construction and inexpensive expansion make them as a suitable tool for the treatment of inflammatory and autoimmune diseases.

CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice.

Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE). Results showed the suitability of the present protocol in the synthesis of Fin-loaded CDX-modified chitosan (CS) nanoparticles (NPs) (Fin@CSCDX) with suitable physicochemical features. Confocal microscopy confirmed the appropriate accumulation of synthesized NPs within the brain parenchyma. Compared to the control EAE mice, INF-γ levels were significantly reduced in the group that received Fin@CSCDX (p < 0.05). Along with these data, Fin@CSCDX reduced the expression of TBX21, GATA3, FOXP3, and Rorc associated with the auto-reactivation of T cells (p < 0.05). Histological examination indicated a low-rate lymphocyte infiltration into the spinal cord parenchyma after the administration of Fin@CSCDX. Of note, HPLC data revealed that the concentration of nano-formulated Fin was about 15-fold less than Fin therapeutic doses (TD) with similar reparative effects. Neurological scores were similar in both groups that received nano-formulated fingolimod 1/15th of free Fin therapeutic amounts. Fluorescence imaging indicated that macrophages and especially microglia can efficiently uptake Fin@CSCDX NPs, leading to the regulation of pro-inflammatory responses. Taken together, current results indicated that CDX-modified CS NPs provide a suitable platform not only for the efficient reduction of Fin TD but also these NPs can target the brain immune cells during neurodegenerative disorders.

Improvement of spinal cord injury symptoms by targeting the Bax/Bcl2 pathway and modulating TNF-α/IL-10 using Platelet-Rich Plasma exosomes loaded with dexamethasone.

Spinal cord injury (SCI) is a debilitating condition that results in impaired sensory and motor function due to the limited self-regenerative ability of the spinal cord. To address this issue, combination therapy has been proposed as an effective treatment strategy for SCI regeneration. In this study, Platelet-Rich Plasma (PRP)-derived exosomes loaded with dexamethasone were utilized in a mouse model of SCI compression. PRP-derived exosomes loaded with dexamethasone (Dex) were prepared using ultracentrifugation and sonication methods and were administered to the mice via intravenous injection. Following a four-week duration, behavioral assessments were administered to assess functional recuperation, and diverse metrics encompassing the expression of genes associated with apoptosis and antiapoptosis, serum cytokine concentrations and tissue sampling were subjected to thorough examination. The results of this study demonstrated that mice treated with PRP-derived exosomes loaded with Dex (ExoDex) exhibited altered levels of TNF-α and IL-10, along with decreased Bax and increased Bcl2 expression in comparison to the model group. Furthermore, intravenously injected ExoDex reduced the size of the lesion site, lymphocyte infiltration, vacuolation, cavity size and tissue disorganization while also improving locomotor recovery. We propose that the utilization of exosome-loaded Dex therapy holds potential as a promising and clinically relevant approach for injured spinal cord repair. However, further extensive research is warranted in this domain to validate and substantiate the outcomes presented in this study.

Protective Role of trans-Chalcone against the Progression from Simple Steatosis to Non-alcoholic Steatohepatitis: Regulation of miR-122, 21, 34a, and 451.

Purpose: Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder and an aggressive form of fatty liver disease. Certain microRNAs, including miR-122, 21, 34a, and 451, are involved in the transition from steatosis to NASH. This study examined how trans-chalcone (the core of chalcone derivatives) affects NAFLD progression by regulating miRNAs. Methods: Male rats were divided into three groups (n = 7/group) as follows: control, rats were gavaged with 10% tween 80 (for two weeks); NASH, rats were gavaged with a high-fat liquid diet (HFD; for six weeks) and 10% tween 80 (for two weeks); NASH + Chal, rats were gavaged with the HFD (for six weeks) and trans-chalcone (for two weeks). Hepatic expression levels of miR-122, 21, 34a, and 451 were determined. Results: trans-Chalcone reversed histological abnormalities, reduced liver injury markers, and attenuated insulin resistance in HFD-fed rats. In the liver, HFD-induced NASH increased the expression level of miR-34a and decreased expression levels of miR-122, 21, and 451. However, trans-chalcone inhibited HFD-induced changes in expression levels of these miRNAs. Conclusion: trans-Chalcone could inhibit the transition from steatosis to NASH through the modulation of miR-122, 21, 34a, and 451 expression levels in the liver.

Sensitive and convenient detection of miRNA-145 using a gold nanoparticle-HCR coupled system: computational and in vitro validations.

Multiple sclerosis (MS) remains a challenging disease that requires timely diagnosis. Therefore, an ultrasensitive optical biosensor based on hybridization chain reaction (HCR) was developed to detect microRNA-145 (miRNA-145) as an MS biomarker. To construct such a sensor, HCR occurred between specific hairpin probes, as MB1 contains a poly-cytosine nucleotide loop and MB2 has a poly-guanine nucleotide sticky end. By introducing miR-145 as a target sequence, long-range dsDNA polymers are formed. Then, positively charged gold nanoparticles (AuNPs) were incubated with the HCR product, which adsorbed onto the dsDNA polymers due to electrostatic adsorption. This resulted in the precipitation of the AuNPs. By incubating different concentrations of miR-145 with AuNPs, the changes in the UV-vis spectrum of the supernatant were analyzed. The proposed biosensor showed a great ability to detect miR-145 in a wide linear range from 1 pM-1 nM with an excellent detection limit (LOD) of 0.519 nM. Furthermore, the developed biosensor indicated considerable selectivity in discriminating between miR-145 and mismatched sequences. It shows high selectivity in differentiating targets. Interestingly, the proposed method was also able to detect miRNA-145 in the diluted serum samples. In conclusion, this sensing platform exhibits high selectivity and specificity for the detection of circulating microRNAs, which holds great promise for translation to routine clinical applications.

Varenicline improves cognitive impairment in a mouse model of mPFC ischemia: The possible roles of inflammation, apoptosis, and synaptic factors.

Ischemia in the medial prefrontal cortex (mPFC) causes cognitive impairment in stroke cases. This study aimed to examine the effects of varenicline as α7 and α4ß2 nicotine acetylcholine receptors (nAChRs) agonist, on cognitive impairment, inflammation, apoptosis, and synaptic dysfunction in mPFC ischemia. Mice were divided to three groups of control, sham, or photothrombotic mPFC ischemia model. The control and sham groups received 2 ml/kg of normal saline for a 14-day period. As well, the animals in the ischemia groups received normal saline (2 ml/kg) or varenicline at 0.1, 1, and 3 mg/kg doses for a 14-day period. Anxiety-like behaviors were then assessed by open field (OFT) and elevated plus-maze (EPM) tests. Memory was also evaluated using Morris water maze (MWM) and novel object recognition (NOR) tests. The levels of inflammatory (IL-1ß, TNF-α), apoptotic (Bax, caspase3, BCL-2), and synaptic (SYP, PSD-95, and GAP-43) proteins were examined using the western blot method. In addition, the histological evaluation was performed to assess tissue damage. The administration of Varenicline at the dose of 3 mg/kg reduced the IL-1ß, TNF-α, Bax, and caspase3 levels. Moreover, it increased BCL-2, SYP, PSD-95, and GAP-43 levels at the same dose and ameliorated memory impairment and anxiety-like behaviors in mPFC ischemic mice. Varenicline improved cognitive impairment by blocking inflammation and apoptosis, improving synaptic factors, and diminishing tissue damage in the mPFC ischemic mice.

Young Plasma Induces Antidepressant-Like Effects in Aged Rats Subjected to Chronic Mild Stress by Suppressing Indoleamine 2,3-Dioxygenase Enzyme and Kynurenine Pathway in the Prefrontal Cortex.

Pathophysiology of depression in elderlies is linked to aging-associated increase in indoleamine 2,3-dioxygenase (IDO) levels and activity and kynurenine (Kyn) metabolites. Moreover, these aging-induced changes may alter the brain's responses to stress. Growing evidence suggested that young plasma can positively affect brain dysfunctions in old age. The present study aimed to investigate whether the antidepressant effects of young plasma administration in aged rats subjected to chronic unpredictable mild stress (CUMS) and underlying mechanisms, focusing on the prefrontal cortex (PFC). Young (3 months old) and aged (22 months old) male rats were divided into five groups; young control, aged control, aged rats subjected to CUMS (A + CUMS), aged rats subjected to CUMS and treated with young plasma (A + CUMS + YP), and aged rats subjected to CUMS and treated with old plasma (A + CUMS + OP). Plasma was injected (1 ml, intravenously) three times per week for four weeks. Young plasma significantly improved CUMS-induced depressive-like behaviors, evidenced by the increased sucrose consumption ratio in the sucrose preference test and the reduced immobility time in the forced swimming test. Furthermore, young plasma markedly reduced the levels of interferon-gamma (IFN-γ), IDO, Kyn, and Kyn to tryptophan (Kyn/Trp) ratio in PFC tissue. Expression levels of the serotonin transporter and growth-associated protein (GAP)-43 were also significantly increased after chronic administration of young plasma. These findings provide evidence for the antidepressant effect of young plasma in old age; however, whether it improves depressive behaviors or faster recovery from stress-induced deficits is required to be elucidated.

An Overview of the Epidemiologic, Diagnostic and Treatment Approaches of COVID-19: What do We Know?

Background: In late December 2019, a new infectious respiratory disease (COVID-19) was reported in a number of patients with a history of exposure to the Huanan seafood market in China. The World Health Organization officially announced the COVID-19 pandemic on March 11, 2020. Here, we provided an overview of the epidemiologic, diagnostic and treatment approaches associated with COVID-19. Methods: We reviewed the publications indexed in major biomedical databases by December 20, 2020 or earlier (updated on May 16, 2021). Search keywords included a combination of: COVID-19, Coronavirus disease 2019, SARS-CoV-2, Epidemiology, Prevention, Diagnosis, Vaccine, and Treatment. We also used available information about COVID-19 from valid sources such as WHO. Results and Conclusion: At the time of writing this review, while most of the countries authorized COVID-19 vaccines for emergency use starting December 8, 2020, there is no a definite cure for it. This review synthesizes current knowledge of virology, epidemiology, clinical symptoms, diagnostic approaches, common treatment strategies, novel potential therapeutic options for control and prevention of COVID-19 infection, available vaccines, public health and clinical implications.

The role of miRNAs in the regulation of autophagy in autoimmune diseases.

Autoimmune diseases (AD), which are classified as chronic injuries, are caused by a specific auto-reactive reaction. The etiology of most ADs is not well understood. Meanwhile, Autophagy is a protective response defining as a catabolic method by lysosomes tending to maintain homeostasis acts by recycling and discrediting cell compartments. Autophagy plays a crucial role in controlling immune homeostasis by eliminating intracellular pathogens and presenting antigens to immune cognition. MicroRNAs are commonly known as endogenous non-coding small RNAs, which span 18-25 nt and take part in the gene expression at the post-transcriptional level regulation. miRNAs play important roles in different processes like, cell differentiation, duplicating, and apoptosis. Moreover, miRNAs are the critical molecules for the regular function of the immune system by modulating immune tolerance mechanisms and autoimmunity. Recent findings support the role of dysregulated miRNAs in the pathogenesis of ADs and in the regulation of autophagy. In this review, we will focus on the role of the miRNAs in the regulation of autophagy and then will explain the role of dysregulated miRNAs in the initiation of the ADs by modulating autophagy.

Hippocampal neurodegeneration and rhythms mirror each other during acute spinal cord injury in male rats.

Spinal Cord Injury (SCI), triggers neurodegenerative changes in the spinal cord, and simultaneously alters oscillatory manifestations of motor cortex. However, these disturbances may not be limited to motor areas and other parts such as hippocampus, which is vital in the neurogenesis and cognitive function, may be affected in the neurogenic and oscillatory manners. Addressing this remarkable complication of SCI, we evaluated the hippocampal neurogenesis and rhythms through acute phase of SCI. In the present study, we used 40 male rats (Sham.W1 = 10, SCI.W1 = 10, Sham.W2 = 10, SCI.W2 = 10), and findings revealed that contusive SCI declines hippocampal rhythms (Delta, Theta, Beta, Gamma) power and max-frequency. Also, there was a significant decrease in the DCX + and BrdU + cells of the dentate gyrus; correlated significantly with rhythms power decline. Considering the TUNEL assay analysis, there were significantly greater apoptotic cells, in the CA1, CA3, and DG regions of injured animals. Furthermore, according to the western blotting analysis, the expression of receptors (NMDA, GABAA, Muscarinic1), which are essential in the neurogenesis and generation of rhythms significantly attenuated following SCI. Our study demonstrated that acute SCI, alters the power and max-frequency of hippocampal rhythms parallel with changes in the hippocampal neurogenesis, apoptosis, and receptors expression.

Ruxolitinib attenuates experimental autoimmune encephalomyelitis (EAE) development as animal models of multiple sclerosis (MS).

AIMS: STAT3 signaling is critical for Th17 development that plays an important role in multiple sclerosis pathogenesis. To evaluate the anti-inflammatory and regulatory T cells effects of JAK1/2 and STAT3 inhibition, we assessed the JAK 1/2 inhibitor ruxolitinib effects on Th17 cell/Tregs balance. MAIN METHODS: Ruxolitinib was administered to experimental autoimmune encephalomyelitis (EAE) mice via oral gavage, and its effects were assessed. The expression of pro-inflammatory and anti-inflammatory cytokines, including IL-17A and IL-10, were analyzed by real-time PCR. The frequency of Th17 cells and Tregs were evaluated by flow cytometry. KEY FINDING: Ruxolitinib ameliorated the EAE severity and decreased the proportion of Th17 cells and inflammatory markers levels. In contrast, the balance of Tregs and the level of anti-inflammatory cytokine were increased in ruxolitinib-treated mice. Furthermore, ruxolitinib markedly decreased the expression of Th17 related transcription factor, RORÉ£t, whereas FOXP3 expression associated with Treg differentiation was increased. SIGNIFICANCE: Our results show that ruxolitinib may be a promising therapeutic strategy for multiple sclerosis.