Tumor Microenvironment-Responsive Biodegradable Nanomedicine for Self-Enhanced Synergistic Chemo-, Photothermal, and Chemodynamic Therapy.

The nanoscale multidrug codelivery system for synergistic therapy is an effective strategy for tumor treatment. However, the low drug delivery efficiency and poor therapeutic effects limit its application. Here, based on the coordination effect of Artemisinin (Art), quercetin (Qc), and Fe3+, we had constructed a safe and efficient carrier-free hyaluronic acid (HA)-modified Art-Fe-Qc nanoparticles (AFQ@HA NPs) for enhanced chemotherapy/photothermal therapy (PTT)-chemodynamic therapy (CDT) synergistic therapy, which achieved an ultrahigh drug loading efficiency and a multifunction anticancer strategy. The results showed that high drug loading was achieved based on drug coordination self-assembly, with Art and Qc contents of 38.6 and 42.7%, respectively. At the same time, based on the Qc-Fe coordination molecular network, the system had excellent photothermal conversion performance with an efficiency of 57.3% and could effectively inhibit the expression of HSP70, achieving enhanced PTT. Further, under the stimulation of excessive H2O2 and glutathione (GSH) in the tumor microenvironment, the AFQ@HA NPs were continuously degraded, while releasing Art and Fe3+/Fe2+ to achieve iron ion-enhanced CDT. The results of in vitro and in vivo experiments showed that AFQ@HA NPs could achieve chemotherapy-PTT-CDT synergistic therapy in response to tumor microenvironment by passively targeting and actively targeting tumor cells with CD44, demonstrating its excellent targeted antitumor effects.

Antidepressant Properties of a Four-compound Cocktail Identified from Si-Ni-San by HIF-1 Pathway Modulation.

BACKGROUND: Si-Ni-San (SNS) is the formula prescription of Traditional Chinese Medicine (TCM) with anti-depression properties, but its underlying mechanisms remain unclear. OBJECTIVE: This study provides novel approaches for the study of Traditional Chinese Medicine (TCM) and offers new opportunities for exploring the pharmacological properties of SNS. METHODS: The ingredients in SNS implicated in the treatment of depression were identified and studied using network pharmacology. SwissTargetPrediction and molecular docking were used to study the interaction of SNS ingredients and their targets. The protective effect of these ingredients and their cocktail in rat pheochromocytoma cells (PC12) exposed to corticosterone (Cor) were evaluated using the CCK-8 assay, Hoechst 33342 staining, 2',7'-dichlorodihydro fluorescein diacetate (H2DCFDA) staining, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and in-cell Western analysis. RESULTS: The network pharmacology study showed that the HIF-1 signaling pathway was the most crucial pathway implicated in the anti-depressive property of SNS. MAPK1 (ERK2), MAPK3 (ERK1), AKT1, VEGFA, STAT3, and EGF were identified as hub target proteins in the HIF-1 signaling pathway. Quercetin, naringenin, licochalcone A, and kaempferol from SNS, which targeted the six proteins mentioned above, were used to create a cocktail. This cocktail exerted protective properties, decreased the oxidative stress in PC12 exposed to Cor, and successfully regulated the expressions of AKT1, p-AKT1, ERK1, ERK2, p-ERK1/2, STAT3, p- STAT3, and VEGFA induced by Cor exposure. The SwissTargetPrediction and molecular docking study showed that the cocktail may regulate the HIF-1 signaling pathway by directly binding with AKT1 and MAPK1. CONCLUSION: The cocktail from SNS comprised of quercetin, naringenin, licochalcone A, and kaempferol exerts anti-depression potentiality by modulating the HIF-1 signaling pathway via direct interactions with AKT1 and MAPK1.

Dietary inflammation influences the prevalence of cardiovascular diseases in prediabetes and diabetes patients: findings from the National Health and Nutrition Examination Survey (NHANES 2001-2018).

Prediabetes is an early phase before diabetes. Diabetes and dietary inflammation are two crucial factors that are strongly associated with cardiovascular diseases (CVDs). Dietary interventions slowed the progression of diabetes and CVD. However, the associations between CVDs and dietary inflammation in different stages of pathoglycaemia have not been investigated. To explore the effect of a proinflammatory diet on CVD incidence at different stages of diabetes, NHANES (2001-2018) data were collected and analysed. A total of 3137 CVD patients with a comparable non-CVD group (n = 3137) were enrolled after propensity score matching (PSM) analysis. These patients were subsequently categorized into three subgroups: those with diabetes (n = 3043), those with prediabetes (n = 1099) and those with normoglycemia (n = 2132). The DII (Dietary inflammatory index) is a risk factor for CVD, both in overall individuals and in each subgroup of population-based information. In diabetic individuals, the odds ratios (ORs) (95% CIs) of CVD incidence for the DII were 1.10 (1.05, 1.15) and 1.08 (1.03, 1.13) according to the crude and adjusted models, respectively. For individuals with prediabetes, the ORs (95% CIs) of CVD risk for DII were 1.05 (0.97, 1.14) and 1.11 (1.01, 1.22) according to the crude and adjusted models, respectively. After adjusting for population-based information and hypertension status, the DII appeared to have the highest OR for individuals with prediabetes, and no significant association was found between the DII score and CVD risk in the normoglycemia group. Moreover, the OR of CVD for DII in the uncontrolled diabetes group was 1.06 (0.98, 1.16)*. These results suggest that the DII is more closely associated with the risk of CVDs in prediabetic and diabetic populations, and we should pay more attention to diet control before a person develops diabetes to prevent CVD progression.

The influence of open-skill and closed-skill sports on executive functions: a systematic review.

Aims/Background Open-skill sports are reportedly more effective than closed-skill sports in improving executive functions. However, it remains unclear as to its superiority in specific components of executive functions and specific populations. This review aims to explore the degree to which specific components of executive functions are affected by different sport types, open-skill sports and closed-skill sports, among different age groups. Methods Relevant articles published from 1st January 2000 to 31st December 2023 were searched and obtained from four databases, namely EBSCO, PubMed, Web of Science, and Science Direct. These studies were selected through a carefully established article-filtering workflow, governed by a set of inclusion and exclusion criteria, and the quality assessment was carried out independently by each researcher. Results Out of the 30 studies included for this systematic review, eight studies demonstrated the beneficial impacts of open-skill sports on adults by improving three executive functions subcomponents, as compared with closed-skill sports. Six studies found that open-skill sports are conducive to inhibitory control and cognitive flexibility among children and adolescents, while four studies showed that open-skill sports greatly enhance inhibitory control in elderly individuals. Conclusion Compared with closed-skill sports, open-skill sports have a favourable impact on inhibitory control and cognitive flexibility in children, adolescents, and adults, marked by shorter response time in inhibitory control tasks, as well as shorter response time and lower switch costs in cognitive flexibility tasks. In addition, relative to closed-skill sports, open-skill sports heightens accuracy in working memory tasks among adults.

Highly Efficient Adsorption of Norfloxacin by Low-Cost Biochar: Performance, Mechanisms, and Machine Learning-Assisted Understanding.

This study employed potassium carbonate (K2CO3) activation using ball milling in conjunction with pyrolysis to produce biochar from one traditional Chinese herbal medicine Atropa belladonna L. (ABL) residue. The resulting biochar KBC800 was found to possess a high specific surface area (S BET = 1638 m2/g) and pore volume (1.07 cm3/g), making it effective for removing norfloxacin (NOR) from wastewater. Batch adsorption tests confirmed its effectiveness in eliminating NOR, along with its excellent resistance to interference from impurity ions or antibiotics. Notably, the maximum experimental NOR adsorption capacity on KBC800 was 666.2 mg/g at 328 K, surpassing those of other biochar materials reported. The spontaneous and endothermic adsorption of NOR on KBC800 could be better suited to the Sips model. Additionally, KBC800 adsorbs NOR mainly by pore filling, with electrostatic attraction, π-π EDA interactions, and hydrogen bonds also contributing significantly. The machine learning model revealed that NOR adsorption on the biochar was significantly affected by the initial concentration, followed by S BET and average pore size. Based on the random forest model, it is demonstrated that biochar is able to adsorb NOR effectively. It is noteworthy that the use of low-cost pharmaceutical wastes to produce adsorbents for emerging contaminants such as antibiotics could have greater potential for future practical applications under the ongoing dual carbon policy.

Biomarkers of occupational benzene exposure: A Systematic Review to estimate the exposure levels and individual susceptibility at low doses.

Benzene is associated with diverse occupational and public health hazards. It exhibits an ability to rapidly permeate the skin and contaminate water and food sources, leading to dermal and ingestion exposures. Despite numerous studies examining the associations between benzene and various indicators of harm, the findings have yielded inconsistent results. Furthermore, relying solely on air concentration as a measure of benzene exposure is limited, as it fails to account for internal exposure dose and individual susceptibility. This study aimed to conduct a comprehensive review in order to present current knowledge on benzene biomarkers and their significance in evaluating exposure levels and associated health hazards. The search methodology adhered to the PRISMA guidelines and involved the application of specific inclusion and exclusion criteria across multiple databases including PubMed, Embase, and Web of Science. Two researchers independently extracted and evaluated the relevant data based on predetermined criteria. Following the screening process, a total of 80 articles were considered eligible out of the initially retrieved 1053 articles after undergoing screening and assessment for inclusion. As the level of exposure decreased, specific biomarkers demonstrated a gradual increase in limitations, including heightened background concentrations and vulnerability to confounding factors. The advancement of sampling and analysis techniques will yield new biomarkers. Additionally, when conducting practical work, it is crucial to employ a comprehensive utilization of diverse biomarkers while excluding individual metabolic variations and combined exposure factors.

Exploring the Potential of Biochar Derived from Chinese Herbal Medicine Residue for Efficient Removal of Norfloxacin.

One-step carbonization was explored to prepare biochar using the residue of a traditional Chinese herbal medicine, Atropa belladonna L. (ABL), as the raw material. The resulting biochar, known as ABLB4, was evaluated for its potential as a sustainable material for norfloxacin (NOR) adsorption in water. Subsequently, a comprehensive analysis of adsorption isotherms, kinetics, and thermodynamics was conducted through batch adsorption experiments. The maximum calculated NOR adsorption capacity was 252.0 mg/g at 298 K, and the spontaneous and exothermic adsorption of NOR on ABLB4 could be better suited to a pseudo-first-order kinetic model and Langmuir model. The adsorption process observed is influenced by pore diffusion, π-π interaction, electrostatic interaction, and hydrogen bonding between ABLB4 and NOR molecules. Moreover, the utilization of response surface modeling (RSM) facilitated the optimization of the removal efficiency of NOR, yielding a maximum removal rate of 97.4% at a temperature of 304.8 K, an initial concentration of 67.1 mg/L, and a pH of 7.4. Furthermore, the biochar demonstrated favorable economic advantages, with a payback of 852.5 USD/t. More importantly, even after undergoing five cycles, ABLB4 exhibited a consistently high NOR removal rate, indicating its significant potential for application in NOR adsorption.

A dual-responsive RhB-doped MOF probe for simultaneous recognition of Cu2+ and Fe3.

Based on the dual response of RhB@UiO-67 (1:6) to Cu2+ and Fe3+, a proportional fluorescent probe with (I392/I581) as the output signal was developed to recognize Cu2+ and Fe3+. Developing highly sensitive and selective trace metal ions probes is crucial to human health and ecological sustainability. In this work, a series of ratio fluorescent probes (RhB@UiO-67) were successfully synthesized using a one-pot method to enable fluorescence sensing of Cu2+ and Fe3+ at low concentrations. The proportional fluorescent probe RhB@UiO-67 (1:6) exhibited simultaneous quenching of Cu2+ and Fe3+, which was found to be of interest. Furthermore, the limits of detection (LODs) for Cu2+ and Fe3+ were determined to be 2.76 µM and 0.76 µM, respectively, for RhB@UiO-67 (1:6). These values were significantly superior to those reported for previous sensors, indicating the probe's effectiveness in detecting Cu2+ and Fe3+ in an ethanol medium. Additionally, RhB@UiO-67 (1:6) demonstrated exceptional immunity and reproducibility towards Cu2+ and Fe3+. The observed fluorescence quenching of Cu2+ and Fe3+ was primarily attributed to the mechanisms of fluorescence resonance energy transfer (FRET), photoinduced electron transfer (PET), and competitive absorption (CA). This work establishes a valuable foundation for the future study and utilization of Cu2+ and Fe3+ sensing technologies.

Identification of volatile biomarkers for lung cancer from different histological sources: A comprehensive study.

The identification of noninvasive volatile biomarkers for lung cancer is a significant clinical challenge. Through in vitro studies, the recognition of altered metabolism in cell volatile organic compound (VOC) emitting profile, along with the occurrence of oncogenesis, provides insight into the biochemical pathways involved in the production and metabolism of lung cancer volatile biomarkers. In this research, for the first time, a comprehensive comparative analysis of the volatile metabolites in NSCLS cells (A549), SCLC cells (H446), lung normal cells (BEAS-2B), as well as metabolites in both the oxidative stress (OS) group and control group. Specifically, the combination of eleven VOCs, including n-dodecane, acetaldehyde, isopropylbenzene, p-ethyltoluene and cis-1,3-dichloropropene, exhibited potential as volatile biomarkers for lung cancer originating from two different histological sources. Furthermore, the screening process in A549 cell lines resulted in the identification of three exclusive biomarkers, isopropylbenzene, formaldehyde and bromoform. Similarly, the exclusive biomarkers 1,2,4-trimethylbenzene, p-ethyltoluene, and cis-1,3-dichloropropene were present in the H446 cell line. Additionally, significant changes in trans-2-pentene, acetaldehyde, 1,2,4-trimethylbenzene, and bromoform were observed, indicating a strong association with OS. These findings highlight the potential of volatile biomarkers profiling as a means of noninvasive identification for lung cancer diagnosis.

Unlocking the potential of Chinese herbal medicine residue-derived biochar as an efficient adsorbent for high-performance tetracycline removal.

This study employed hydrothermal carbonization (HTC) in conjunction with ZnCl2 activation and pyrolysis to produce biochar from one traditional Chinese medicine astragali radix (AR) residue. The resultant biochar was evaluated as a sustainable adsorbent for tetracycline (TC) elimination from water. The adsorption performance of TC on two micropore-rich AR biochars, AR@ZnCl2 (1370 m2 g-1) and HAR@ZnCl2 (1896 m2 g-1), was comprehensively evaluated using adsorption isotherms, kinetics, and thermodynamics. By virtue of pore diffusion, π-π interaction, electrostatic attraction, and hydrogen bonding, the prepared AR biochar showed exceptional adsorption properties for TC. Notably, the maximum adsorption capacity (930.3 mg g-1) of TC on HAR@ZnCl2 can be achieved when the adsorbent dosage is 0.5 g L-1 and C0 is 500 mg L-1 at 323 K. The TC adsorption on HAR@ZnCl2 took place spontaneously. Furthermore, the impact of competitive ions behavior is insignificant when coexisting ion concentrations fall within the 10-100 mg L-1 range. Additionally, the produced biochar illustrated good economic benefits, with a payback of 701 $ t-1. More importantly, even after ten cycles, HAR@ZnCl2 still presented great TC removal efficiency (above 77%), suggesting a good application prosperity. In summary, the effectiveness and sustainability of AR biochar, a biowaste-derived product, were demonstrated in its ability to remove antibiotics from water, showing great potential in wastewater treatment application.

Comprehensive Analysis of Fatty Acid Metabolism in Diabetic Nephropathy from the Perspective of Immune Landscapes, Diagnosis and Precise Therapy.

Objective: Diabetic nephropathy (DN) represents the principal cause of end-stage renal diseases worldwide, lacking effective therapies. Fatty acid (FA) serves as the primary energy source in the kidney and its dysregulation is frequently observed in DN. Nevertheless, the roles of FA metabolism in the occurrence and progression of DN have not been fully elucidated. Methods: Three DN datasets (GSE96804/GSE30528/GSE104948) were obtained and combined. Differentially expressed FA metabolism-related genes were identified and subjected to DN classification using "ConsensusClusterPlus". DN subtypes-associated modules were discovered by "WGCNA", and module genes underwent functional enrichment analysis. The immune landscapes and potential drugs were analyzed using "CIBERSORT" and "CMAP", respectively. Candidate diagnostic biomarkers of DN were screened using machine learning algorithms. A prediction model was constructed, and the performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The online tool "Nephroseq v5" was conducted to reveal the clinical significance of the candidate diagnostic biomarkers in patients with DN. A DN mouse model was established to verify the biomarkers' expression. Results: According to 39 dysregulated FA metabolism-related genes, DN samples were divided into two molecular subtypes. Patients in Cluster B exhibited worse outcomes with a different immune landscape compared with those in Cluster A. Ten potential small-molecular drugs were predicted to treat DN in Cluster B. The diagnostic model based on PRKAR2B/ANXA1 was created with ideal predictive values in early and advanced stages of DN. The correlation analysis revealed significant association between PRKAR2B/ANXA1 and clinical characteristics. The DN mouse model validated the expression patterns of PRKAR2B/ANXA1. Conclusion: Our study provides new insights into the role of FA metabolism in the classification, immunological pathogenesis, early diagnosis, and precise therapy of DN.

ERRα regulates synaptic transmission through reactive oxygen species in hippocampal neurons.

Reactive oxygen species (ROS) play multiple roles in synaptic transmission, and estrogen-related receptor α (ERRα) is involved in regulating ROS production. The purpose of our study was to explore the underlying effect of ERRα on ROS production, neurite formation and synaptic transmission. Our results revealed that knocking down ERRα expression affected the formation of neuronal neurites and dendritic spines, which are the basic structures of synaptic transmission and play important roles in learning, memory and neuronal plasticity; moreover, the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were decreased. These abnormalities were reversed by overexpression of human ERRα. Additionally, we also found that knocking down ERRα expression increased intracellular ROS levels in neurons. ROS inhibitor PBN rescued the changes in neurite formation and synaptic transmission induced by ERRα knockdown. These results indicate a new possible cellular mechanism by which ERRα affects intracellular ROS levels, which in turn regulate neurite and dendritic spine formation and synaptic transmission.

Telbivudine-induced rhabdomyolysis in a patient undergoing haemodialysis: A case report and review of literature.

Herein, we describe a case of acute rhabdomyolysis in a man in his early 50s undergoing haemodialysis and receiving the antiviral drug, telbivudine, for chronic hepatitis B virus (HBV) infection. Following diagnosis by electromyography (EMG), magnetic resonance image (MRI) scans and laboratory data (i.e., elevated serum creatinine kinase (CK) and myoglobin) telbivudine was discontinued and the patient was treated with methylprednisolone. While his CK and myoglobin levels decreased rapidly, his muscle weakness and pain improved slowly. Learning points include: patients undergoing haemodialysis and concomitantly receiving antiviral treatment for HBV, should have their serum levels of CK and myoglobin monitored regularly; treatment with corticosteroids maybe required; relief from rhabdomyolysis-induced muscle weakness and pain may be slow due to nerve fibre damage.

Primary Plasmablastic Lymphoma of The Paranasal Sinuses: A Rare Case Report.

Plasmablastic lymphoma (PBL) is a rare and highly invasive type of non-Hodgkin's lymphoma. It is usually associated with immunosuppression and human immunodeficiency virus infection. PBL most commonly occurs in the oral cavity, lymph nodes, and in other extranodal sites. However, it rarely originates from bilateral sinuses. Herein, we report the case of a 59-year-old man diagnosed with primary PBL of the sinuses confirmed by endoscopic biopsy, imaging materials, histopathological examination, and immunohistochemistry. The patient underwent 4 cycles of chemotherapy and 22 rounds of radiation therapy for 8 months. Re-examination by sinus computed tomography revealed no obvious tumor tissue in the nasal cavity and sinuses, suggesting that treatment was effective. No local recurrence or distant metastasis was detected at 6-month follow-up after the end of treatment.

CXCR5 Regulates Neuronal Polarity Development and Migration in the Embryonic Stage via F-Actin Homeostasis and Results in Epilepsy-Related Behavior.

Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism. Here, we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with epilepsy. Subsequently, we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol- and kainic acid-induced seizures, whereas CXCR5 overexpression had the opposite effect. CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons. Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model, we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment. Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability, resulting in an increased number of seizures. Finally, our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism, namely, the disruption of neuronal polarity.

Efficient Eu3+-Integrated UiO-66 Probe for Ratiometric Fluorescence Sensing of Styrene and Cyclohexanone.

The development of probes with sensitive and prompt detection of volatile organic compounds (VOCs) is of great importance for protecting human health and public security. Herein, we successfully prepared a series of bimetallic lanthanide metal-organic framework (Eu/Zr-UiO-66) by incorporating Eu3+ for fluorescence sensing of VOCs (especially styrene and cyclohexanone) using a one-pot method. Based on the multiple fluorescence signal responses of Eu/Zr-UiO-66 toward styrene and cyclohexanone, a ratiometric fluorescence probe using (I617/I320) and (I617/I330) as output signals was developed to recognize styrene and cyclohexanone, respectively. Benefitting from the multiple fluorescence response, the limits of detection (LODs) of Eu/Zr-UiO-66 (1:9) for styrene and cyclohexanone were 1.5 and 2.5 ppm, respectively. These are among the lowest reported levels for MOF-based sensors, and this is the first known material for fluorescence sensing of cyclohexanone. Fluorescence quenching by styrene was mainly owing to the large electronegativity of styrene and fluorescence resonance energy transfer (FRET). However, FRET was accounted for fluorescence quenching by cyclohexanone. Moreover, Eu/Zr-UiO-66 (1:9) exhibited good anti-interference ability and recycling performance for styrene and cyclohexanone. More importantly, the visual recognition of styrene and EB vapor can be directly realized with the naked eyes using Eu/Zr-UiO-66 (1:9) test strips. This strategy provides a sensitive, selective, and reliable method for the visual sensing of styrene and cyclohexanone.

Primary nasal tuberculosis: A rare case report.

Nasal primary tuberculosis (TB) of the upper respiratory tract is rare and barely reported in literature. Herein, we report a complicated case of nasal primary TB with otitis media. The patient visited the ENT clinic due to left-side nasal obstruction accompanied by rhinorrhea, and intermittent headaches. The diagnosis of nasal TB was confirmed with an acid-fast bacterial test and histopathological examination. After 3 months of treatment with anti-TB drugs, patient's symptoms of nasal obstruction, rhinorrhea, and other symptoms were remarkably relieved. The left ear purulence substantially reduced. The patient recovered well and had no recurrence post half a year of follow-up. Our case emphasizes the importance of accurate diagnosis and initiation of timely treatment. Additionally, when a patient has nasal TB complicated with otitis media, it is important to consider a diagnosis of middle ear TB.

MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription.

Epilepsy is considered to result from an imbalance between excitation and inhibition of the central nervous system. Pathogenic mutations in the methyl-CpG binding domain protein 5 gene (MBD5) are known to cause epilepsy. However, the function and mechanism of MBD5 in epilepsy remain elusive. Here, we found that MBD5 was mainly localized in the pyramidal cells and granular cells of mouse hippocampus, and its expression was increased in the brain tissues of mouse models of epilepsy. Exogenous overexpression of MBD5 inhibited the transcription of the signal transducer and activator of transcription 1 gene (Stat1), resulting in increased expression of N-methyl-d-aspartate receptor (NMDAR) subunit 1 (GluN1), 2A (GluN2A) and 2B (GluN2B), leading to aggravation of the epileptic behaviour phenotype in mice. The epileptic behavioural phenotype was alleviated by overexpression of STAT1 which reduced the expression of NMDARs, and by the NMDAR antagonist memantine. These results indicate that MBD5 accumulation affects seizures through STAT1-mediated inhibition of NMDAR expression in mice. Collectively, our findings suggest that the MBD5-STAT1-NMDAR pathway may be a new pathway that regulates the epileptic behavioural phenotype and may represent a new treatment target.

TMT-based proteomics profile reveals changes of the entorhinal cortex in a kainic acid model of epilepsy in mice.

Experimental modeling and clinical neuroimaging of patients has shown that certain seizures are capable of causing neuronal death. Research into cell death after seizures has identified the induction of the molecular machinery of apoptosis. Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults, which is characterized by substantial pathological abnormalities in the temporal lobe, including the hippocampus and entorhinal cortex (EC). Although decades of studies have revealed numerous molecular abnormalities in the hippocampus that are linked to TLE, the biochemical mechanisms associated with TLE in EC remain unclear. In this study, we explored these early phenotypical alterations in the EC 5 days after mice were given a systemic injection of kainic acid (KA) to induce status epilepticus (KA-SE). we used the Tandem Mass Tag (TMT) combined with LC-MS/MS approach to identify distinct proteins in the EC in a mouse model of KA-SE model. According to the findings, 355 differentially abundant proteins including 199 upregulated and 156 downregulated differentially abundant proteins were discovered. The first-ranked biological process according to Gene Ontology (GO) analysis was "negative control of extrinsic apoptotic signaling". "Apoptosis" was the most significantly enriched Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway. Compared with those in control mice, BCL2L1, NTRK2 and MAPK10 abundance levels were reduced in KA mice. MAPK10 and NTRK2 act as upstream regulators to regulate BCL2L1, and BCL2L1 Inhibits cell death by blocking the voltage- dependent anion channel (VDAC) and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. However, ITPR1 was increased at the mRNA and protein levels in KA mice. Furthermore, there was no significant difference in ACTB, TUBA1A and TUBA4A levels between the two groups. Our results offer clues to help identify biomarkers for the development of pharmacological therapies targeted at epilepsy.