Changes In Brain Tissue Research Articles

The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke. This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH. The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes. The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH. AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.

Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.

All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment. EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation. The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.

Noise and mental health: evidence, mechanisms, and consequences.

The recognition of noise exposure as a prominent environmental determinant of public health has grown substantially. While recent years have yielded a wealth of evidence linking environmental noise exposure primarily to cardiovascular ailments, our understanding of the detrimental effects of noise on the brain and mental health outcomes remains limited. Despite being a nascent research area, an increasing body of compelling research and conclusive findings confirms that exposure to noise, particularly from sources such as traffic, can potentially impact the central nervous system. These harms of noise increase the susceptibility to mental health conditions such as depression, anxiety, suicide, and behavioral problems in children and adolescents. From a mechanistic perspective, several investigations propose direct adverse phenotypic changes in brain tissue by noise (e.g. neuroinflammation, cerebral oxidative stress), in addition to feedback signaling by remote organ damage, dysregulated immune cells, and impaired circadian rhythms, which may collectively contribute to noise-dependent impairment of mental health. This concise review linking noise exposure to mental health outcomes seeks to fill research gaps by assessing current findings from studies involving both humans and animals.

Changes in Expression of Key Genes in Alzheimer's Disease: A Specific Brain Tissue Change.

Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.

Association of mild and complex multimorbidity with structural brain changes in older adults: A population-based study.

We quantified the association of mild (ie, involving one or two body systems) and complex (ie, involving ≥3 systems) multimorbidity with structural brain changes in older adults. We included 390 dementia-free participants aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen who underwent brain magnetic resonance imaging at baseline and after 3 and/or 6 years. Using linear mixed models, we estimated the association between multimorbidity and changes in total brain tissue, ventricular, hippocampal, and white matter hyperintensities volumes. Compared to non-multimorbid participants, those with complex multimorbidity showed the steepest reduction in total brain (β*time -0.03, 95% CI -0.05, -0.01) and hippocampal (β*time -0.05, 95% CI -0.08, -0.03) volumes, the greatest ventricular enlargement (β*time 0.03, 95% CI 0.01, 0.05), and the fastest white matter hyperintensities accumulation (β*time 0.04, 95% CI 0.01, 0.07). Multimorbidity, particularly when involving multiple body systems, is associated with accelerated structural brain changes, involving both neurodegeneration and vascular pathology. Multimorbidity accelerates structural brain changes in cognitively intact older adults These brain changes encompass both neurodegeneration and cerebrovascular pathology The complexity of multimorbidity is associated with the rate of brain changes' progression.

Protective role of virgin coconut oil on potent biochemical biomarkers in Wistar rat model of comorbid depression.

Chronic stress arises from stressful situations in day-to-day life that are ignored or managed incorrectly. Long-term stress can have negative effects, especially when it plays a role in the development of neurological illnesses. Severe stress can also negatively impact emotional well-being. Virgin coconut oil (VCO) has numerous health advantages. The aim of this study was to assess how VCO affected the biochemical and behavioral characteristics of Wistar albino rats exposed to chronic, unpredictable stress. Healthy Wistar albino rats (150-200 gm) were split into two groups: experimental group and control group. Based on stress exposure and treatment with VCO and antidepressants, they were further divided into various subgroups. A chronic, unpredictable stress procedure was given for 21 days. After the experimental procedure, the rats were anesthetized, and through a cardiac puncture, blood was collected. The liver and brain were dissected to estimate different biochemical markers. VCO proved to be a protective agent against chronic, unpredictable stress-induced changes in the biochemical parameters, hepatic enzyme activity, lipid profile, oxidative stress, and cognition. VCO might be helpful as an effective natural treatment that can be utilized to effectively combat chronic, unpredictable stress-induced changes in brain and liver tissue.

Structural Changes in Human Brain Tissue in Prenatal Alcoholization at Different Periods of Intrauterine Development

Structural Changes in Human Brain Tissue in Prenatal Alcoholization at Different Periods of Intrauterine Development

Gender-Dependent Cholinergic System Alterations in a Phenylketonuria Model

Introduction: Phenylketonuria (PKU) is a rare inherited metabolic disorder characterized by a deficiency of the enzyme phenylalanine hydroxylase. The absence of this enzyme leads to elevated levels of phenylalanine in the blood, causing accumulation in the brain and resulting in permanent brain damage. To investigate the neurological effects of PKU, an experimental PKU model was developed, and cholinergic parameters were analyzed in brain tissue and serum from both female and male rats. Serum AChE, BChE, and total ChE activities were examined, while AChE activity was specifically analyzed in hippocampal tissue. Material and Methods: Brain tissue and serum samples were collected from female and male rats from an induced phenylketonuria model for analysis. AChE, BChE, and total ChE activities were measured in serum samples, while AChE activity was examined in hippocampal tissue. Enzyme activities were measured according to Ellman assay. The data analysis and graphical presentations were done by GraphPad prism. Results: Hippocampal AChE activity was significantly increased in both PKU groups compared to the control groups (Male ***p=0.0001; female *p=0.046). Serum analysis revealed decreased total serum cholinergic activity in both the female and male PKU groups compared with the control groups (**p≤0.002 and ***p≤0.0003, respectively). These results were consistent with findings from total serum cholinergic activity analysis. Additionally, the AChE activity in both the female and male PKU groups was decreased compared to their respective control groups (***p≤0.002 and ***p≤0.0006, respectively). It was also found that BChE activity in the serum of male rats in the PKU group was decreased compared to male rats in the control group (*p=0.038). Conclusion: These findings indicate that the cholinergic system in the phenylketonuria model may vary according to gender. The observed changes in both brain tissue and serum provide new insights into the gender-dependent neurological effects of PKU. Keywords: Phenylketonuria, cholinergic system, enzyme activity, hippocampal tissue, gender differences

Hsp90 participates in the necroptosis of mouse neural cells induced by aluminum through the RIP1/RIP3/MLKL pathway

Objective: To investigate whether heat shock protein 90 (HSP90) participates in the necroptosis of C57BL/6 mouse neurons and spatial memory impairment induced by Aluminum maltol [Al (mal) (3)] through RIP1/RIP3/MLKL pathway. Methods: In March 2022, Thirty-two C57 mice were randomly divided into control group, Low dose group, a medium dose group, and a high-dose group, with 8 mice in each group, and injected intraperitoneally with physiological saline, 20, 40, and 80, respectivelyμmol/kgAl (mal) (3) was administered, it was injected 5 days a week and discontinued 2 days for 60 days. Morris water maze test was used to test the spatial learning and memory ability of mice. Nissl staining was used to observe the pathological changes of brain tissue. The protein expression levels of RIP1, RIP3, MLKL and HSP90 in hippocampus were determined by Western blotting. Results: In the water maze experiment, compared with the control group, the number of mice crossing the platform decreased in each dose group, the difference was statistically significant (H=9.50, P=0.023), and the number of mice crossing the platform was statistically significant among each dose group (P <0.05). Compared with the control group, the number of hippocampal nerve cells in each dose group decreased, the arrangement was disordered, and the Nissellite bodies decreased. Western blotting results showed that compared with the control group, the expression level of RIP1 protein in the hippocampus of mice in high-dose group was higher, and the difference was statistically significant (P <0.05). The expression levels of RIP3, MLKL and HSP90 in hippocampal tissue of mice in medium and high dose groups were increased, and the differences were statistically significant (P<0.05). After siRNA intervention decreased the expression of HSP90 protein, the expressions of HSP90, RIP1, RIP3 and MLKL in Al (mal) (3) groups were increased, and the differences were statistically significant (P<0.05) . Conclusion: Through RIP1/RIP3/MLKL pathway, HSP90 is involved in neuronal programmed necrosis and spatial memory impairment induced by maltol aluminum in C57 mice.

Upregulated Chaperone-Mediated Autophagy May Perform a Key Role in Reduced Cancer Incidence in Huntington's Disease.

Incidence of cancer is markedly reduced in patients with the hereditary neurodegenerative polyglutamine (polyQ) diseases. We have very poor knowledge of the underlying molecular mechanisms, but the expanded polyQ sequence is assumed to play a central role, because it is common to the respective disease related proteins. The inhibition seems to take place in all kinds of cells, because the lower cancer frequency applies to nearly all types of tumors and is not related with the characteristic pathological changes in specific brain tissues. Further, the cancer repressing mechanisms appear to be active early in life including in pre-symptomatic and early phase polyQ patients. Autophagy plays a central role in clearing proteins with expanded polyQ tracts, and autophagy modulation has been demonstrated and particularly investigated in Huntington's disease (HD). Macroautophagy may be dysfunctional due to defects in several steps of the process, whereas increased chaperone-mediated autophagy (CMA) has been shown in HD patients, cell and animal models. Recently, CMA is assumed to play a key role in prevention of cellular transformation of normal cells into cancer cells. Investigations of normal cells from HD and other polyQ carriers could therefore add further insight into the protective mechanisms of CMA in tumorigenesis, and be important for development of autophagy based strategies to prevent malignant processes leading to cancer and neurodegeneration.

Naotaifang III Protects Against Cerebral Ischemia Injury Through LPS/TLR4 Signaling Pathway in the Microbiota-Gut-Brain Axis.

Ischemic stroke (IS) is a leading cause of mortality worldwide. Naotaifang III is a new Chinese herbal formula to treat IS. Previous studies have shown that Astragali Radix, Puerariae Lobatae Radix, Chuanxiong Rhizoma, and Rhei Radix Et Rhizoma in Naotaifang III were able to regulate the imbalance of intestinal microbiota during cerebral ischemia injury. Rats were randomly divided into sham operation group, normal control group, middle cerebral artery occlusion (MCAO) group, intestinal microbiota imbalance MCAO group, Naotaifang III group, and normal bacteria transplantation group, with 15 rats in each group. Then, neurological function scores and cerebral infarction volume were detected; haematoxylin and eosin staining and Golgi silver staining were used to observe morphological changes in brain tissue. Meanwhile, the lipopolysaccharide (LPS) and cerebral cortex interleukin (IL)-1β were detected by enzyme-linked immunosorbent assay (ELISA); the expressions of Toll-like receptor (TLR)-4 and nuclear factor kappa-B (NF-κB) proteins were detected by immunofluorescence and Western blot. The cecal flora was detected by 16S rDNA. The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1β, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis. In summary, Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis. The results showed that gut dysbiosis aggravated cerebral ischemic injury and significantly increased the expression of LPS, TLR4, NF-κB, and IL-1β, which could be significantly reversed by Naotaifang III or normal bacterial transplantation. Naotaifang III may exert a protective effect on neuroinflammatory injury after MCAO through the LPS/TLR4 signaling pathway in the microbe-gut-brain axis. Naotaifang III may induce anti-neuroinflammatory molecular mechanisms and signaling pathways through the microbe-gut-brain axis.

Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS/TLR4/MyD88/NF-κB pathway.

Gas explosions (GE) are a prevalent and widespread cause of traumatic brain injury (TBI) in coal miners. However, the impact and mechanism of curcumin on GE-induced TBI in rats remain unclear. In this study, we simulated GE-induced TBI in rats and administered curcumin orally at a dose of 100mg/kg every other day for 7days to modulate the gut microbiota in TBI rats. We employed 16S rRNA sequencing and LC-MS/MS metabolomic analysis to investigate changes in the intestinal flora and its metabolic profile. Additionally, we utilized ELISA, protein assays, and immunohistochemistry to assess neuroinflammatory signaling molecules for validation. In a rat TBI model, GE resulted in weight loss, pathological abnormalities, and cortical hemorrhage. Treatment with curcumin significantly mitigated histological abnormalities and microscopic mitochondrial structural changes in brain tissue. Furthermore, curcumin treatment markedly ameliorated GE-induced brain dysfunction by reducing the levels of several neuroinflammatory signaling molecules, including neuron-specific enolase, interleukin (IL)-1β, IL-6, and cryptothermic protein 3. Notably, curcumin reshaped the gut microbiome by enhancing evenness, richness, and composition. Prevotella_9, Alloprevotella, Bacilli, Lactobacillales, Proteobacteria, and Gammaproteobacteria were identified as prominent members of the gut microbiota, increasing the linear discriminant analysis scores and specifically enhancing the abundance of bacteria involved in the nuclear factor (NF)-κB signaling pathway, such as Lachnospiraceae and Roseburia. Additionally, there were substantial alterations in serum metabolites associated with metabolic NF-κB signaling pathways in the model group. Curcumin administration reduced serum lipopolysaccharide levels and downregulated downstream Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling. Furthermore, curcumin alleviated GE-induced TBI in rats by modulating the gut microbiota and its metabolites. Based on these protective effects, curcumin may exert its influence on the gut microbiota and the TLR4/MyD88/NF-κB signaling pathways to ameliorate GE-induced TBI.

Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/β-catenin Pathway in Hypoxic-Ischemic Neonatal Rats.

Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in the central nervous system and are profoundly involved in neuroinflammation. Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear. This study aimed to clarify the effect and mechanism of atorvastatin on the regulation of microglia function in neonatal hypoxic-ischemic brain damage (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD model was established. Atorvastatin, recombinant sclerostin protein (SOST), and XAV939 (degradation of β-catenin) were administered to OGD microglia and HIBD rats. The pathological changes of brain tissue, cerebral infarction volume, learning and memory ability of rats, pro-inflammatory (CD16+/Iba1+) and anti-inflammatory (CD206+/Iba1+) microglia markers, inflammation-related indicators (Inos, Tnfα, Il6, Arg1, Tgfb, and Mrc1), and Wnt/β-catenin signaling molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory microglia and pro-inflammatory factors, while increasing anti-inflammatory microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. Mechanistically, atorvastatin decreased SOST expression and activated the Wnt/β-catenin signaling pathway, and the administration of recombinant SOST protein or XAV939 inhibited Wnt/β-catenin signaling and attenuated the anti-inflammatory effect of atorvastatin. Atorvastatin promotes the pro/anti-inflammatory phenotypic transformation of microglia via the Wnt/β-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a potent agent for the treatment of HIE in neonates.

Cranium bifidum with meningocele in ruminants: a clinical insight

Cranium bifidum is an incomplete closure of the skull at the suture lines, leaving a space through which the intracranial tissues can protrude. Meningocele is the herniation of the meninges containing cerebrospinal fluid through the cranium bifidum. This congenital defect is attributed to the intake of certain poisonous plants, genetic abnormalities, hereditary factors, malnutrition, bovine viral diarrhea, and others. The obvious clinical sign is a floating saccular protrusion of varied size and volume and is typically associated with cranium bifidum in the frontal or parietal region. Surgical management involves exposing the effective cranial opening and suturing the dura mater in a simple continuous pattern. Prognosis depends on the presence or absence of neurological signs; neurological signs are associated with morphological changes in brain tissue with poor prognosis.

Milk fat globule membrane promotes brain development in piglets by enhancing the connection of white matter fiber trace

IntroductionBrain development during infancy is crucial for later health and development. Although Milk Fat Globule Membrane (MFGM) has been demonstrated to enhance brain development, further investigation is needed to determine the optimal dose.MethodsIn this study, 80 piglets aged 2 days were randomly assigned to four groups: Control group, MFGM-L (1.74 g MFGM per 100 g diet), MFGM-M (4.64 g MFGM per 100 g diet), and MFGM-H (6.09 g MFGM per 100 g diet). Daily body weight and milk intake of the piglets were recorded until 31 days postnatal. Learning and memory abilities were evaluated using the spatial T-maze test on day 15. MRI analysis was conducted to assess functional and structural changes in brain tissues. Additionally, mRNA and protein expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF-3) in the hippocampus and prefrontal cortex were evaluated.ResultsThe results indicated that the MFGM supplemented diet significantly improved the accuracy of the piglets in the T-maze test, with the MFGM-L group exhibiting the best performance. MRI showed no volumetric differences in the gray and white matter between the groups. However, the fractional anisotropy in the left and right hippocampus of piglets in the MFGM-L group was significantly higher than in the other three groups. Furthermore, there was a strong correlation between the accuracy of the T-maze test and hippocampal fractional anisotropy.DiscussionThe MFGM supplemented diet also increased the expression of BDNF in the cerebral cortex. However, the changes in BDNF were not consistent with the results of the T-maze test. In conclusion, adding 1.74 g MFGM per 100 g diet can significantly improve neonatal piglets’ learning and memory abilities, potentially by enhancing the connection of white matter fiber bundles in the brain.

Ultrastructural Changes in Brain Tissue in Drug-Resistant Mesial Temporal Lobe Epilepsy in Humans: A Mini-Review

Epilepsy is a group of chronic neurological diseases of the brain characterized by a persistent predisposition to epileptic seizures, affecting more than 70 million people worldwide. Drug-resistance is a key problem in the theory and practice of epileptology. The literature contains many publications devoted to ultrastructural changes in brain tissue in experimental animal models, but the features of ultrastructural changes in human brain tissue in drug-resistant mesial Temporal Lobe Epilepsy (TLE) remain unknown. This brief review presents the current state of the art of problems devoted to the study of the ultrastructure of neurons, glia, and blood vessels in patients with drug-resistant mesial TLE.

The effect of evening primrose oil on some biochemical parameters in brain tissue in a model of metabolic syndrome induced with fructose in rats

Objective: Metabolic syndrome is a disease characterized by hypertension, dyslipidemia and insulin resistance, and constitutes an important risk factor for cardiovascular disorders. The effect of evening primrose oil (EPO) on insülin, adiponectin and resistin levels in brain tissue was investigated in a fructose-related metabolic syndrome model. &#x0D; Materials and Methods: The rats were divided into 4 groups as control, evening primrose oil (orally at a dose of 0.1 ml/rat/day), fructose (20% fructose added), fructose+evening primrose oil for 57 days. At the end of the experiment, brain samples were taken and homogenized. Then, insülin, adiponectin and resistin levels were determined by ELISA. &#x0D; Results: Plasma insulin and resistin levels of the fructose group increased (p≤0.05 ) compared to the controls, on the contrary, adiponectin levels were significantly decreased (p≤0.05 ) in the fructose group. When EPO was given to rats given fructose, increased insulin and resistin levels decreased, while decreased adiponectin levels were increased. &#x0D; Conclusion: Fructose-induced impaired metabolic changes in brain tissue were partially ameliorated when EPO was administered. Accordingly, the use of EPO in the medical setting may be recommended by clinicians to reduce the harmful effects on the brain, since metabolic changes in the brains of rat fed with high fructose content can also occur with the intake of fructose from various foods in humans.

LncRNA-AC020978 Promotes Metabolic Reprogramming in M1 Microglial Cells in Postoperative Cognitive Disorder via PKM2.

The present work aimed to explore the role of long non-coding RNA (lncRNA)-AC020978 in postoperative cognitive disorder (POCD) and the underlying mechanism. The POCD mouse model was constructed through isoflurane anesthesia + abbreviated laparotomy. The AC020978 expression in brain tissue was silenced after lentivirus injection, then Morris water maze test was conducted to detect the cognitive disorder level, flow cytometry was performed to analyze M1 macrophage level, ELISA was carried out to measure inflammatory factor levels, H&E, Nissl and immunohistochemical staining was performed to detect the pathological changes in brain tissue, and Western blotting assay was adopted to detect protein expression. In addition, microglial cells were cultured in vitro, after lentivirus infection, the effect of AC020978 on the M1 polarization of microglial cells and glycolysis was observed. AC020978 overexpression promoted POCD progression and aggravated cognitive disorder in mice; in addition, the proportion of peripheral and central M1 cells increased, the inflammatory factor levels were upregulated, and microglial cells were activated. By contrast, AC020978 silencing led to cognitive disorder in mice and suppressed microglial cell activation and M1 polarization. In vitro experimental results indicated that AC020978 promoted the expression and phosphorylation of PKM2, which promoted inflammatory response through enhancing microglial cell glycolysis and M1 polarization. AC020978 interacts with PKM2 to promote the glycolysis and M1 polarization of microglial cells, thus regulating cognitive disorder and central inflammation in POCD.

Protein Banding Pattern Changes in Muscle and Brain Tissues of Fresh Water Fish Labeo rohita (Hamilton) Exposed to Malathion in Gel Electrophoresis

The impact of the organophosphate malathion on the protein electrophoretic patterns of the freshwater fish Labeo rohita (Hamilton) brain and muscle tissues were examined. Over 10 days, fish were given sub-lethal dosages of malathion (2 percent) at 24-, 48-, 72-, and 96-hour intervals. For example, muscle and brain tissue proteins, were run on 7.5% SDS -PAGE to look for alterations in protein structure. Ten protein bands were found to be responsible for controlling skeletal muscle and brain function. At various times after Malathion exposure, the quantity and intensity of protein bands were reduced in the fish. There were also new protein bands found to be antagonistic to pesticides. Standard marker proteins were used to determine protein banding patterns, and Rm values were then determined. Electrophoretogram data from this investigation demonstrated that protein bands in gills and muscles were similar, with very slight differences.

The Role of Cystathionine-β-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies.

We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-β-synthase (CBS), and hydrogen sulfide (H2S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15min (mild) and 30min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin-eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia-ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H2S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H2S. H2S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.