This study aims to engineer a novel developed superabsorbent (NDS) as potent hemostatic agent. NDS induces coagulation process due to the high adhesion affinity to the wet tissue, high swelling ratio ...and clotting potency. NDS controls massive bleedings by inducing the red blood cells accumulation, platelets aggregation and fibrin network formation at the site of bleeding.
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•NDS acts as brilliant superabsorbent that absorb 60 g of blood per one g of NDS.•NDS as a powerful hemostatic agents activated coagulation cascade process.•Biochemical, hematological, and pathological results didn’t show toxic effects.
Engineering of effective and biocompatible hemostatic materials to control massive bleeding is one of the interesting research fields. Herein, cellulose-based polymer modified by silica aerogel and calcium chloride was used for suitable control of bleeding. Novel developed superabsorbent (NDS) was synthesized by chemical and physical cross-linking methods. NDS not only quickly absorbs a high amount of blood component (60 g/g), but it can also adhere strongly (~90 KPa) to damaged tissue. The contributions of the freeze-drying method and presence of silica aerogel as structural modifiers led to the creation of a superabsorbent with a porosity percentage of 70% which creates a significant ability to absorb blood cells. NDS negative surface charge and presence of silica nanoparticles and calcium ions accelerate activation of the coagulation cascade process. Superior hemostatic ability of NDS compared to commercial hemostatic powder (Gelita-Cel® and Traumastem®) was proved by complementary tests such as blood absorption content, RBC attachment, blood clotting index (BCI), platelet adhesion, clotting time test and partial thromboplastin time (PTT). In vivo study results demonstrate that the NDS could successfully decrease bleeding time and blood loss amount in Wistar rat’s cut-out femoral artery, 2.25 and 4.3 fold better than Gelita-Cel® and 2.13 and 4.4 fold better than Traumastem®. NDS biodegradability was proved by its implantation inside the Wistar rat's body during 14 days. Biochemical, hematological, and pathological tests did not show inflammation and toxic effects in the liver and renal tissues, skin tissues, and alteration in complete blood count parameters (CBC) in NDS treated Wistar rats. In conclusion, the cellulose-based NDS hemostatic biomaterial is suggested for future clinical trial studies due to its powerful ability in bleeding control.
Summary
There is ongoing debate on how B cells contribute to the pathogenesis of multiple sclerosis (MS). The success of B‐cell targeting therapies in MS highlighted the role of B cells, particularly ...the antibody‐independent functions of these cells such as antigen presentation to T cells and modulation of the function of T cells and myeloid cells by secreting pathogenic and/or protective cytokines in the central nervous system. Here, we discuss the role of different antibody‐dependent and antibody‐independent functions of B cells in MS disease activity and progression proposing new therapeutic strategies for the optimization of B‐cell targeting treatments.
B cells can contribute to MS pathogenesis via production of antibodies against CNS antigens. The success of B‐cell targeting therapies in MS highlighted the antibody‐independent functions of B cells in MS. B cells can contribute to MS through antigen presentation to T cells and modulation of the function of T cells and myeloid cells by secreting pathogenic and/or protective cytokines.
Cognitive deficits due to spinal cord injury (SCI) have been elucidated in both animals and humans with SCI. Such disorders may cause concomitant oscillatory changes in regions of the brain involving ...in cognition; a subject that has not been directed mechanistically. One of the crucial oscillations, having a prominent role in cognition, particularly spatial memory, is hippocampal theta rhythm. Our research revealed that SCI could induce changes not only in the neurogenesis and apoptosis rate of the hippocampus but also in theta power as well as receptors involving in the generation of this rhythm. Herein we used 24 male Wistar rats (Sham/SCI = 12) and examined the effect of spinal cord contusion on hippocampal theta rhythm, spatial memory, and neurodegeneration. We proved that SCI eliminates hippocampus‐dependent theta power through spatial working memory, and correlates significantly with neurodegeneration and expression of receptors (NMDA, GABAA, Muscarinic1/M1), which are in turn essential in generation of theta rhythm. The immunohistochemistry analysis also demonstrated a significant decrease in DCX+ and BrdU+ cells; however, according to TUNEL assay, apoptosis is significantly higher in SCI‐induced animals. The western blotting analysis further showed a significant reduction of the abovementioned receptors in the hippocampus. We also verified that SCI impairs the spatial memory, proved by poor performance in the Y‐maze task. As well as, based on the local field potential recordings analysis, SCI decreases the power of theta rhythm. Eventually, this study demonstrated that chronic brain neurodegeneration occurs after SCI accompanied by theta rhythm and cognitive deficiency.
(a) Spatial memory, neurogenesis, apoptosis, and theta power alteration following spinal cord injury in rats. (b) The correlation coefficient of spatial memory and theta power (movement/no‐movement) with receptor (GABAA, NMDA, Muscarinic1) expression, BrdU+ cells, and DCX+ cells.
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.
Aluminium oxide (Al2O3) nanoparticles (AlNPs) are class of metal oxide nanoparticles that have diverse biomedical applications owing to their exceptional physicochemical and structural features such ...as resistance towards wear, chemicals, mechanical stresses as well as their favourable optical properties and a porous vast surface area. Other reasons for widespread applications of AlNPs are their low cost of preparation and easy handling. Therefore, owing to the economic importance, the recent achievements and possible health risks associated with the biomedical applications of AlNPs are overviewed in this work.
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•Spinal cord injury (SCI) leads to the decrease of DCX expression in the hippocampus.•SCI leads to the decrease of hippocampal rhythms (Delta, Theta, Beta, Gamma) power.•Decreased ...hippocampal neurogenesis is correlated with rhythms power after the SCI.•NMDA, M1, and GABA A receptors expression decrease in the hippocampus after the SCI.•SCI increases the apoptotic cells of hippocampus in the CA1, CA3 and DG areas.
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.
Abstract Dipeptidyl peptidase IV (DPPIV), on the surface of certain cells, where it is also referred to as CD26, is involved in a vast majority of biological and pathological processes. CD26/DPPIV ...function contributes to cancer and tumor metastasis as well as inhibition of its expression which alters the expression of immune response-related genes. CD26/DPPIV is a widely distributed multifunctional integral membrane and secreted protein that is defined as early predictive biomarker in HIV, cancer and autoimmunity diseases like diabetes and multiple sclerosis. CD26/DPPIV-chemokine interaction may have a functional role in T-cells and overall immune function. It is expressed at low density on resting T cells, but is upregulated with T cell activation. In this review, we summarize valuable information about detailed biological aspects and pharmacokinetic characteristics of CD26/DPPIV and its clinical efficacy, focusing particularly on the role of CD26/DPPIV in immunological and non-immunological diseases. We also describe our recent work about umbilical cord blood (UCB) hematopoietic stem cell transplantation strategies in which identified CD26+ cells can be differentiated to immune cells under certain culture condition.
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•trans-Chalcone protects rats against high-fat diet-induced NASH development.•trans-Chalcone improves hepatic lipid metabolism.•NASH induction increases SREBP-1c, SREBP-2, PPAR-γ2, ...and FAS enzyme levels.•NASH induction reduces hepatic PPAR-α expression level.•trans-Chalcone prevents NASH-related changes in SREBPs, FAS enzyme, and PPARs levels.
Non-alcoholic steatohepatitis (NASH) is an inflammatory and progressive form of non-alcoholic fatty liver disease. However, there are no FDA-approved drugs for this condition. Lipids accumulated in NASH have a direct role in the progression of this disease. Therefore, this study for the first time explored the preventive effect of trans-chalcone on NASH through the modulation of sterol regulatory element binding protein (SREBP)-1c, SREBP-2, hepatic fatty acid synthesis (FAS) enzyme, proliferator-activated receptor (PPAR)-α, and PPAR-γ2 levels, which are involved in hepatic lipid metabolism. In this study, male rats were randomly divided into three groups (n = 7): Control, received 10% tween 80; NASH, received 10% tween 80 and 10 ml/kg high-fat emulsion (high-fat diet, HFD); and NASH + TC, received 20 mg/kg trans-chalcone and 10 ml/kg HFD. All treatments were performed by once-daily oral gavage for 6 weeks. Liver and blood samples were collected and serum levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol, as well as hepatic levels of SREBP-1c, SREBP-2, FAS, PPAR-α, and PPAR-γ2, were measured. Moreover, hematoxylin and eosin stained tissues were used for histological analysis. In this study, treatment of HFD-fed rats with trans-chalcone significantly reduced abnormalities in liver histology, serum levels of liver injury markers, liver index, and hepatic levels of SREBP-1c, SREBP-2, FAS, and PPAR-γ2. Furthermore, trans-chalcone significantly increased hepatic PPARα levels in these rats. Therefore, it seems that trans-chalcone protects the liver of HFD-fed rats against NASH development through reduction of SREBP-1c/ FAS- and PPAR-γ2-related lipogenesis, attenuation of SREBP-2-related cholesterol synthesis, and elevation of PPARα-related fatty acid oxidation.
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 α4β2 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-1β, 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-1β, 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.
•Varenicline improves learning and memory impairment in the mouse model of mPFC ischemia.•Varenicline blocks inflammation and apoptosis in the mouse model of mPFC ischemia.•Varenicline improves synaptic dynamics in the mouse model of mPFC ischemia.•Varenicline diminishes tissue damage in the mouse model of mPFC ischemia.
The loss of spinal sensorimotor pathways following spinal cord injury (SCI) can induce retrograde neurodegeneration in the primary motor cortex (M1). However, the effect of thoracic SCI on forelimb ...motor skills has not been studied clearly. So, herein we aimed to examine the effects of the thoracic SCI model on forelimb motor skills learning, parallel with dopaminergic and oscillatory changes in hindlimb and forelimb areas (HLA and FLA) of M1 in rats. Male Wistar rats were randomly subjected to laminectomy (Control) or contusion SCI at the thoracic (T10) level. Oscillatory activity and motor skills performance were evaluated for six consecutive days using local field potential (LFP) recording and skilled forelimb reaching task, respectively. Dopamine (DA) levels and expression of dopamine receptors (D1R and D2R) were determined in HLA and FLA by ELISA and western blotting. LFP recording results showed a sustained increase of LFP power in SCI rats compared with uninjured rats through skilled reaching training. Also, the SCI group had a lower reaching performance and learning rate in contrast to the Control group. Biochemical analysis of HLA and FLA showed a reduction in DA levels and expression of D1R and D2R after SCI. According to these findings, thoracic SCI causes aberrant changes in the oscillatory activity and dopaminergic system of M1, which are not restricted to HLA but also found in FLA accompanied by a deficit in forelimb motor skills performance.
Summary statement: The reorganization of the primary motor cortex, following spinal cord injury, is not restricted to the hind limb area, and interestingly extends to the forelimb limb area, which appears as a dysfunctional change in oscillations and dopaminergic system, associated with a deficit in motor skills learning of forelimb.
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