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In spinal cord injury, microglial activation plays an important role during the inflammatory process. Specifically, the cellular and molecular interactions between microglia and astrocytes are of critical importance. Cells can communicate with each other through the substances carried by exosomes, and overproliferated astrocytes would create a physical and chemical barrier that prevents neurite regeneration, thereby interfering with functional recovery. On the other hand, Smad3 is an important factor in the proliferation, migration, and apoptosis of astrocytes. In this study, supernatant and purified exosomes were collected from LPS-treated microglia and co-cultured with astrocytes. The results showed that astrocytic proliferation was promoted with higher levels of Smad3. Furthermore, miRNA sequencing analysis was performed on microglial exosomes after inflammation. The results revealed a differential expression of miR-145-5p in the exosomes. The Dual-Luciferase assay showed that miR-145-5p could bind to Smad3 mRNA and regulate the levels of Smad3 protein at the post-transcriptional level. Subsequently, exosomes were transfected with miR-145-5p mimics, and astrocytes after mechanical injury were cultured with these exosomes for 24 h. The levels of Smad3 and phosphor-Smad3 proteins were analyzed by western blot and qRT-PCR. CCK8 and flow cytometry showed lower proliferation of astrocytes after co-culturing with the exosomes transfected with the miR-145-5p mimic. This study finds that miR-145-5p was found to be a negative regulator of astrocyte proliferation, and that its downregulation promotes smad3 activity and thus astrocyte proliferation.Glucose and oxygen (O2) are vital to the brain. Glucose metabolism and mitochondria play a pivotal role in this process, culminating in the increase of reactive O2 species. Hexokinase (HK) is a key enzyme on glucose metabolism and is coupled to the brain mitochondrial redox modulation by recycling ADP for oxidative phosphorylation (OXPHOS). GABA shunt is an alternative pathway to GABA metabolism that increases succinate levels, a Krebs cycle intermediate. Although glucose and GABA metabolisms are intrinsically connected, their interplay coordinating mitochondrial function is poorly understood. Here, we hypothesize that the HK and the GABA shunt interact to control mitochondrial metabolism differently in the cortex and the hypothalamus. The GABA shunt stimulated mitochondrial O2 consumption and H2O2 production higher in hypothalamic synaptosomes (HSy) than cortical synaptosomes (CSy). The GABA shunt increased the HK coupled to OXPHOS activity in both population of synaptosomes, but the rate of activation was higher in HSy than CSy. Significantly, malonate and vigabatrin blocked the effects of the GABA shunt in the HK activity coupled to OXPHOS. It indicates that the glucose phosphorylation is linked to GABA and Krebs cycle reactions. Together, these data shed light on the HK and SDH role on the metabolism of each region fed by GABA turnover, which depends on the neurons' metabolic route.This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.Vincristine is a common chemotherapeutic agent in cancer treatment, while it often causes chemotherapy-induced peripheral neuropathy(CIPN), which brings patients a great disease burden and associated economic pressure. The mechanism under CIPN remains mostly unknown. The previous study has shown that cell-type-specific spinal synaptic plasticity in the dorsal horn plays a pivotal role in neuropathic pain. Downregulation of GABA transmission, which mainly acts as an inhibitory pathway, has been reported in the growing number of research. Our present study found that GAD67, responsible for > 90% of basal GABA synthesis, is down-regulated, while its relative mRNA remains unchanged in vincristine-induced neuropathy. Considering microRNAs (miRNAs) as a post-transcription modifier by degrading targeted mRNA or repressing mRNA translation, we performed genome-wide miRNA screening and revealed that miR-30d might contribute to GAD67 down-regulation. Further investigation confirmed that miR-30d could affect the fluorescence activity of GAD67 by binding to the 3 'UTR of the GAD67 gene, and intrathecal injection of miR-30d antagomir increased the expression of GAD67, partially rescued vincristine-induced thermal hyperalgesia and mechanical allodynia. In summary, our study revealed the molecule interactions of GAD67 and miR-30d in CIPN, which has not previously been discussed in the literature. The results give more profound insight into understanding the CIPN mechanism and hopefully helps pain control.Cardiac complications such as heart failure and arrhythmias caused by "iron-induced" cardiomyopathy are considered as the primary cause of death in the patients with β-thalassemia major. The aim of this study was to evaluate electrocardiography, echocardiography according cardiac T2* and ferritin findings of patients followed-up for β-thalassemia major, and to investigate the importance of these findings for early detection of cardiac complications. The study included 41 patients and 25 healthy individuals with matched age and gender. The cardiac T2* results revealed a cardiac iron load below 20 ms in 12 (29.27%) patients, and above 20 ms in 29 (70.73%) patients. All electrocardiography parameters significantly increased in the patient group when compared to the control group (p  20 ms (p  less then  0.05). Intraventricular septum thickness, left ventricular posterior wall thickness, left ventricular mass and left ventricular mass index detected by echocardiography were significantly higher in the group with T2*  less then  20 ms (p  less then  0.05). Electrocardiography, echocardiography, cardiac T2* and ferritin findings should be carefully evaluated in these patients in order to detect early signs of cardiac complications.The recognition and sensing of various analytes in aqueous and biological systems by using fluorometric or colorimetric chemosensors possessing high selectivity and sensitivity, low cost has gained enormous attention. Furthermore, thiophene derivatives possess exceptional photophysical properties compared to other heterocycles, and therefore they can be employed in chemosensors for analyte detection. In this review, we have tried to explore the design and detection mechanism of various thiophene-based probes, practical applicability, and their advanced models (design guides), which could be thoughtful for the synthesis of new thiophene-based probes. This review provides an insight into the reported chemosensors (2008-2020) for thiophene scaffold as effective emission and absorption-based chemosensors.A central question in drug discovery is how to select drug candidates from a large number of available compounds. This analysis presents a model-based approach for comparing and ranking combinations of radiation and radiosensitizers. The approach is quantitative and based on the previously-derived Tumor Static Exposure (TSE) concept. Combinations of radiation and radiosensitizers are evaluated based on their ability to induce tumor regression relative to toxicity and other potential costs. The approach is presented in the form of a case study where the objective is to find the most promising candidate out of three radiosensitizing agents. Data from a xenograft study is described using a nonlinear mixed-effects modeling approach and a previously-published tumor model for radiation and radiosensitizing agents. First, the most promising candidate is chosen under the assumption that all compounds are equally toxic. The impact of toxicity in compound selection is then illustrated by assuming that one compound is more toxic than the others, leading to a different choice of candidate.Left-truncated data are often encountered in epidemiological cohort studies, where individuals are recruited according to a certain cross-sectional sampling criterion. Length-biased data, a special case of left-truncated data, assume that the incidence of the initial event follows a homogeneous Poisson process. In this article, we consider an analysis of length-biased and interval-censored data with a nonsusceptible fraction. We first point out the importance of a well-defined target population, which depends on the prior knowledge for the support of the failure times of susceptible individuals. Given the target population, we proceed with a length-biased sampling and draw valid inferences from a length-biased sample. When there is no covariate, we show that it suffices to consider a discrete version of the survival function for the susceptible individuals with jump points at the left endpoints of the censoring intervals when maximizing the full likelihood function, and propose an EM algorithm to obtain the nonparametric maximum likelihood estimates of nonsusceptible rate and the survival function of the susceptible individuals. We also develop a novel graphical method for assessing the stationarity assumption. Selleck 5-Fluorouracil When covariates are present, we consider the Cox proportional hazards model for the survival time of the susceptible individuals and the logistic regression model for the probability of being susceptible. We construct the full likelihood function and obtain the nonparametric maximum likelihood estimates of the regression parameters by employing the EM algorithm. The large sample properties of the estimates are established. The performance of the method is assessed by simulations. The proposed model and method are applied to data from an early-onset diabetes mellitus study.The black-handed spider monkey (Ateles geoffroyi) is a platyrrhine primate distributed in southern Mexico, Central America, and part of South America. Two subspecies inhabit Mexico Ateles geoffroyi vellerosus and Ateles geoffroyi yucatanensis, both threatened with extinction. Serological evidence of exposure of spider monkeys to various groups of parasites such as Trypanosoma cruzi in México and Leishmania spp. in Brazil has been reported. The genus Leishmania encompasses about 23 species of flagellate protozoa that are transmitted by the bite of females of Phlebotominae sand flies. These parasites cause a zoonotic disease called leishmaniasis, which generates skin, mucocutaneous and/or visceral manifestations. The aim of the present study was to demonstrate the presence of Leishmania sp. in spider monkeys from the Tuxtlas Biosphere Reserve, Veracruz, Mexico. Blood samples from 10 free- ranging specimens of A. geoffroyi yucatanensis and 11 specimens in captivity of A. geoffroyi vellerosus were collected and used.