Disease Of Nervous System Research Articles

Tryptophan Metabolism Disorder-Triggered Diseases, Mechanisms, and Therapeutic Strategies: A Scientometric Review.

Tryptophan is widely present in foods such as peanuts, milk, and bananas, playing a crucial role in maintaining metabolic homeostasis in health and disease. Tryptophan metabolism is involved in the development and progression of immune, nervous, and digestive system diseases. Although some excellent reviews on tryptophan metabolism exist, there has been no systematic scientometric study as of yet. This review provides and summarizes research hotspots and potential future directions by analyzing annual publications, topics, keywords, and highly cited papers sourced from Web of Science spanning 1964 to 2022. This review provides a scientometric overview of tryptophan metabolism disorder-triggered diseases, mechanisms, and therapeutic strategies. The gut microbiota regulates gut permeability, inflammation, and host immunity by directly converting tryptophan to indole and its derivatives. Gut microbial metabolites regulate tryptophan metabolism by activating specific receptors or enzymes. Additionally, the kynurenine (KYN) pathway, activated by indoleamine-2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase, affects the migration and invasion of glioma cells and the development of COVID-19 and depression. The research and development of IDO inhibitors help to improve the effectiveness of immunotherapy. Tryptophan metabolites as potential markers are used for disease therapy, guiding clinical decision-making. Tryptophan metabolites serve as targets to provide a new promising strategy for neuroprotective/neurotoxic imbalance affecting brain structure and function. In summary, this review provides valuable guidance for the basic research and clinical application of tryptophan metabolism.

BL-918 alleviates oxidative stress in rats after subarachnoid hemorrhage by promoting mitophagy through the ULK1/PINK1/Parkin pathway

Background and purposeOxidative stress plays a critical role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). The small molecule ULK1 agonist, BL-918, demonstrated neuroprotective effects in other central nervous system diseases; however, its role in SAH has not yet been explored. This study aimed to evaluate whether BL-918 could provide neuroprotective effects in rats following SAH. MethodsAn SAH model was established in Sprague-Dawley rats using endovascular perforation. BL-918 was administered intraperitoneally after SAH, while the ULK1 inhibitor SBI was given intraperitoneally prior to SAH modeling. PINK1 siRNA was administered into the lateral ventricle before SAH induction. The neuroprotective effects and mechanisms of BL-918 were assessed through SAH grading, brain water content measurement, blood-brain barrier permeability, neurobehavioral tests, Western blot, immunofluorescence, TUNEL staining, DHE staining, and transmission electron microscopy (TEM). ResultsAfter SAH, the expression levels of p-ULK1, PINK1, Parkin, and LC3Ⅱ increased, peaking at 24 h post-SAH. BL-918 treatment improved neurological function in rats, reduced brain water content and blood-brain barrier permeability, and exhibited anti-oxidative stress and anti-apoptotic effects. Western blot analysis revealed that BL-918 increased the expression of p-ULK1, PINK1, Parkin, LC3Ⅱ, Bcl-xl, and Bcl-2 while inhibiting the expression of Bax and Cleaved Caspase-3. Oxidative stress-related indicators showed that BL-918 alleviated oxidative stress. Immunofluorescence and TEM results demonstrated that BL-918 promoted mitophagy and preserved mitochondrial morphology. Furthermore, the positive effects of BL-918 were reversed by SBI and PINK1 siRNA, respectively. ConclusionBL-918 improved both short-term and long-term neurological impairments in rats after SAH and reduced oxidative stress by promoting mitophagy, at least partially through the ULK1/PINK1/Parkin signaling pathway.

Ubiquitin ligase signalling networks shape presynaptic development, function and disease.

Ubiquitin ligases are important regulators of nervous system development, function and disease. To date, numerous ubiquitin ligases have been discovered that regulate presynaptic biology. Here, we discuss recent findings on presynaptic ubiquitin ligases that include members from the three major ubiquitin ligase classes: RING, RBR and HECT. Several themes emerge based on findings across a range of model systems. A cadre of ubiquitin ligases is required presynaptically to orchestrate development and transmission at synapses. Multiple ubiquitin ligases deploy both enzymatic and non-enzymatic mechanisms, and act as hubs for signalling networks at the synapse. Both excitatory and inhibitory presynaptic terminals are influenced by ligase activity. Finally, there are several neurodevelopmental disorders and neurodegenerative diseases associated with presynaptic ubiquitin ligases. These findings highlight the growing prominence and biomedical relevance of the presynaptic ubiquitin ligase network.

CXCR2 mediated trafficking of neutrophils and neutrophil extracellular traps are required for myelin clearance after a peripheral nerve injury

Neutrophils are a vital part of the innate immune system. Many of their functions eliminate bacteria & viruses, like neutrophil extracellular traps (NETs), which trap bacteria, enhancing macrophage phagocytosis. It was surprising when it was demonstrated that neutrophils are a part of Wallerian degeneration, a process that is essential for nerve regeneration after a nerve injury. It is not known what signals attract neutrophils into the nerve and how they aid Wallerian degeneration. Neutrophils accumulate in the distal nerve within one day after an injury and are found in the nerve from one to three days. We demonstrate that CXCR2 mediates the trafficking of neutrophils into the distal nerve, and without CXCR2 Wallerian degeneration, as indicated by luxol fast blue staining, was reduced seven days after a sciatic nerve crush or transection injury. NETs were detected in the distal nerve after a sciatic nerve transection. NET formation has been shown to require protein arginine deiminase 4 (PAD4), which citrullinates histone 3. Inhibiting PAD4 reduced NET formation significantly in the distal nerve at two days and myelin clearance at seven days indicating that NETs aid myelin clearance. These results demonstrate another function for NETs other than clearing pathogens. Neutrophils have been detected after injuries to the central nervous system and diseases in humans and animal models. Our results demonstrate neutrophils aid myelin clearance, suggesting a role for their presence in central nervous system injuries and diseases.

Morphological Evaluation of Corpus Callosum Atrophy Over Time in Relapsing Remitting Multiple Sclerosis

Objective: Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease that generally affects young adults and is marked by inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI) is widely used diagnosis tool for relapsing remitting MS (RRMS). Corpus callosum (CC), the largest commissural tract in brain which is associated with both cognitive and physical impairment by atrophy in MS. Our study aimed to evaluate CC in RRMS patients using MR images and compare it to measurements from healthy controls within the same age. Methods: We manually measured changes in CC thickness in T1 brain MR images of RRMS patients in 2017, 2019, and 2022. Results: Our results showed that control group had greater thickness, length, and index values in all CC sections compared to patient group. Additionally, a significant difference was observed in thickness of genu and splenium sections and CC index between patient and control groups. However, no significant difference was detected in truncus part of CC or overall CC length. CC measurements in patient group decreased over time, with 1st MRI showing greater values than 2nd and 3rd MRI scans. Furthermore, there was a statistically significant difference in thickness of truncus part of CC and volume values of subcortical areas between 2nd-3rd and 1st-3rd MRI measurements. Conclusion: As a result of these findings, our study provides important information about changes in CC measurements for MS patients.

Effect of Fingolimod on Lymphocyte Subsets in Patients With Relapsing Multiple Sclerosis.

Background and aim Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS). This study aims to evaluate the effect of fingolimod on T and B lymphocytes in relapsing-remitting multiple sclerosis (RRMS) patients. Method Multiple sclerosis patients were selected from patients who were scheduled to start medication at the outpatient clinic of Kocaeli University, Kocaeli, Turkey, between February 2019 and February 2022. Venous blood samples were obtained before starting medication from the patients who agreed to participate in the study and who were to start treatment, simultaneous clinical and neurologic examinations were performed and the Expanded Disability Status Scale (EDSS) was calculated. After the six-month treatment, venous blood samples were taken again. Lymphocyte subgroup analyses were performed in the flow cytometry laboratory. Results The study included 48 patients in the fingolimod group and 33 patients as controls. Flow cytometry analyses showed there was no significant difference between the two groups in the numbers and percentages of CD19+, CD20+, and CD22+ cells at baseline, while a significant decrease was observed in all of these parameters in the fingolimod group after the six-month treatment. Discussion Our findings support that the fingolimod treatment has significant effects on both lymphocyte counts and lymphocyte subgroup ratios. The results show the mechanism of action of fingolimod is unaccountable only through T lymphocytes, and it is effective in both B lymphocyte subgroups and T lymphocytes.

Ozone: complicated effects in central nervous system diseases.

Oxidative stress is closely related to various diseases. Ozone can produce redox reactions through its unique response. As a source of the oxidative stress response, the strong oxidizing nature of ozone can cause severe damage to the body. On the other hand, low ozone concentrations can activate various mechanisms to combat oxidative stress and achieve therapeutic effects. Some animal experiments and clinical studies have revealed the potential medical value of ozone, indicating that ozone is not just a toxic gas. By reviewing the mechanism of ozone and its therapeutic value in treating central nervous system diseases (especially ischemic stroke and Alzheimer's disease) and the toxic effects of ozone, we find that ozone inhalation and a lack of antioxidants or excessive exposure lead to harmful impacts. However, with adequate antioxidants, ozone can transmit oxidative stress signals, reduce inflammation, reduce amyloid β peptide levels, and improve tissue oxygenation. Similar mechanisms to those of possible new drugs for treating ischemic stroke and Alzheimer's disease indicate the potential of ozone. Nevertheless, limited research has restricted the application of ozone. More studies are needed to reveal the exact dose-effect relationship and healing effect of ozone.

Implementation of Data Mining for Vertigo Disease Classification Using the Support Vector Machine (SVM) Method

This research aims to implement advanced data mining techniques for the classification of vertigo disorders using the Support Vector Machine (SVM) method. Vertigo, characterized by a spinning sensation, can be triggered by various factors such as nervous system disorders and inner ear infections. With the rising prevalence of vertigo patients, there is a pressing need for more effective and efficient diagnostic tools. This study was conducted at Puskesmas Jangka in Bireuen Regency, involving the collection of vertigo patient data from the years 2023-2024. The collected data underwent a comprehensive preprocessing pipeline, including data cleaning, partitioning into training and testing datasets, and subsequent implementation of the SVM algorithm. The performance of the model was evaluated using the Mean Absolute Percentage Error (MAPE), resulting in a MAPE value of 28.47%.

Gene-diet interactions in carbonated sugar-sweetened beverage consumption and metabolic syndrome risk: A machine learning analysis in a large hospital-based cohort

Background and aimCarbonated sugar-sweetened beverages (CSSB) intake has been increasingly linked to metabolic diseases. To investigate the association between CSSB intake and metabolic syndrome (MetS) risk, and the interaction between genetic predisposition to CSSB intake and dietary patterns. MethodsWe examined a hospital-based cohort of 57,940 participants, categorized into low-CSSB (n=52,848) and high-CSSB (n=5,092) groups based on a 50 ml daily consumption cutoff. A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) associated with CSSB intake, and SNP-SNP/SNP-environment interactions were explored. Using XGBoost and deep neural network (DNN) approaches, we developed prediction models for CSSB intake. ResultsThe low- and high-CSSB groups daily consumed an average of 0.56 and 8.91 g sugar from the soda, respectively. The high-CSSB group had unhealthy dietary habits and a lower intake of carotenoids, folate, vitamins C and D, calcium, flavonoids, and phenols than the low-CSSB group, consistent with the results of the prediction models. A polygenic risk score (PRS) based on 6 selected SNPs, linked to genes involved in obesity, diabetes, and nervous system disorders, showed the strongest association with CSSB intake and insulin resistance. Notably, carbohydrate, fat, and Western-style diet (WSD) intake interacted with the PRS, with lower carbohydrate and higher fat and WSD intakes associated with a stronger PRS-sugar intake relationship. The prediction models by XGboost and DNN mainly included dietary factors to explain CSSB intake. ConclusionsA significant interplay between genetic predisposition and poor dietary habits, particularly increased CSSB intake associated with WSD, contributed to MetS risk. It suggested that personalized dietary interventions based on genetic profiles could mitigate MetS risk, especially in populations transitioning to Westernized diets.

Neonicotinoids, Agriculture And Food Security Of Brazilian Honey: A Review

Pesticides used in agriculture have the function of controlling pests, diseases and preventing the development and growth of weeds, increasing the quality and productivity of crops. However, when they reach unwanted targets, such as bees, humans and other living beings, they cause harmful damage to ecosystems. Neonicotinoids, insecticides widely used in monocultures, such as soybeans and corn in Brazil, are especially harmful to bees, whether native or exotic, interfering with the foraging and pollination performance of plants. The global decline in the bee population is related to the use of insecticides, a fact that directly threatens the production of various foods. Honey, the main beekeeping product , is not only a source of food for bees, humans and other animals, but also an indicator of environmental quality, as its composition reflects the conditions of the environment in which it was produced, and determinations made therein can reveal the presence of contaminants such as pesticides and toxic metals providing information about ecosystem health and the presence of environmental contaminants. Furthermore, consuming pesticide-free foods is crucial for human health and environmental sustainability, as the intake of neonicotinoids is associated with several health problems such as hormonal disorders and nervous system diseases and is especially dangerous for children. This article reviews the neonicotinoid insecticides imidacloprid and thiamethoxam and the contamination they cause in the honey of bees Apis mellifera Linnaeus (1758) and Tetragonisca angustula Latreille (1811) in Brazil, evaluating the impacts of these insecticides on bees, the implications for ecosystems and safety to feed

The Dopamine Transporter Is a New Target for Ischemic Stroke.

Dopamine transporter (DAT) can regulate DA homeostasis and has been implicated in many nervous system diseases. Whether DAT is involved in the protection against ischemic stroke is unclear. In vivo microdialysis measurements of DA were recorded in the ischemic penumbral area of mice with middle cerebral artery occlusion (MCAO). DAT coding gene, Slc6a3 mutation, and DAT overexpression animals were performed MCAO. Madopar (compound formulation of levodopa) and nomifensine (DA reuptake inhibitor) were administered in MCAO animals. Brain slices were prepared in Slc6a3 mutation or wild-type (WT) animals with MCAO to record miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs). The effects of DA and its dopamine-1 receptor (D1R) antagonists (SCH-23390) on mEPSCs, mIPSCs, and neurons protection were recorded. MCAO caused a prominent increase in DA. Slc6a3 mutation significantly attenuated the ischemic injury, whereas DAT overexpression aggravated this injury. Both nomifensine and madopar protected against brain injury. Slc6a3 mutation and DA restored the disturbance of mEPSCs and mIPSC, and protected against neuron death, which was abolished by SCH-23390. DAT inhibition might be explored as a strategy for ischemic stroke prevention. DA and D1R involve in the restoration of synaptic dysfunction and neuron protection.

Advancements and mechanisms of stem cell-based therapies for spinal cord injury in animals.

Spinal cord injury (SCI) is a neurodegenerative disorder of the central nervous system (CNS) that can lead to permanent loss of sensation and voluntary movement beyond the affected area. Extensive preclinical and clinical trials have been conducted to evaluate the safety and effectiveness of stem cells for the treatment of various CNS diseases or disorders, including SCI. However, several challenges hinder nerve cell regeneration in the injured spinal cord, such as extensive cell loss, limited neural cell regeneration capacity, axonal disruption, and the presence of growth-inhibiting molecules, particularly astroglial scarring or glial scars at the injury site in chronic cases. These obstacles pose significant challenges for physicians in restoring normal motor and sensory nerve function in both humans and animals following SCI. This review focuses on SCI pathogenesis, the mechanisms underlying the therapeutic potential of Mesenchymal Stem Cells (MSCs) in SCI, and the potential of stem cell-based therapies as promising avenues for treatment. This review article also included relevant preclinical and clinical data from animal studies.

NAD+ supplement relieved chronic sleep restriction (CSR)-induced microglial proinflammation in vivo and in vitro

Sleep insufficiency is a significant health problem worldwide and can induce multiple neurodevelopmental disorders in the central nervous system (CNS). Sleep deprivation (SD), especially chronic SD, leads to cognition and memory loss and worsens neurodegenerative disease liability. Microglia are the main inflammation-dominant glia and play a crucial role in SD-induced neurological impairments. Nicotinamide adenine dinucleotide (NAD+) is a redox reaction coenzyme that exerts anti-inflammatory and mitochondria-protective effects in microglia. Whether NAD+ mitigated SD-induced neurological disorders by regulating microglial functions is still unknown. In the current study, we designed an in vivo and in vitro model to evaluate the neuroprotective effect of NAD+ on chronic sleep restriction (CSR) and further investigate the underlying mechanisms. Behavioral tests and immunofluorescence staining were applied to investigate the cognition impairments and microglial activation. Biochemical experiments were tested to analyze the oxidative status and possible mechanism. In vitro data were used to verify the in vivo data. Our results displayed that NAD+ supplement mitigated CSR-induced cognitive decline and microglial activation response by suppressing the expression of pro-inflammatory cytokines in vivo. NAD+ administration also decreased oxidative stress and mitochondrial impairments in microglia. In vitro results showed that NAD+ treatment inhibited ROS production and prompted M1 conversion to M2 phenotype. cGAS-STING/NF-κB pathways were significantly activated but down-regulated by NAD+ administration. H151, a STING antagonist, was applied to validate that NAD+ treatment alleviates neuroinflammation partially by regulating cGAS-STING pathways in microglia. Our findings suggest that NAD+ supplement is a promising therapy for sleep disorders-induced neurological problems, and cGAS-STING pathway may act as a critical regulator in microglial proinflammation.

Comparison of the effects of nursing and peer education on quality of life and resilience in patients with multiple sclerosis: A randomized clinical trial

BackgroundMultiple sclerosis (MS) is a prevalent disease of the central nervous system that often leads to diminished resilience and quality of life in affected individuals. This study aims to compare the effects of nursing and peer education on improving the quality of life and resilience in patients with multiple sclerosis. Materials and methodsThis three-group clinical trial study was conducted before and after interventions at the MS Society in Hamedan, Iran. In this study, 120 patients with MS were randomly selected and assigned to three groups: nurse education, peer education, and control. Quality of life and resilience questionnaires were self-reported before and two months after the completion of the intervention. The educational sessions were conducted over five meetings, each lasting between 45 and 60 min, held every two days. Group one received education led by nurses, while group two participated in peer-led education sessions. ResultsThe results indicated that before the intervention, there were no significant statistical differences in demographic variables, resilience, and quality of life among the three groups (p > 0.05). However, after the intervention, both the peer and nurse groups showed a significant increase in quality of life and resilience compared to the control group (p < 0.05). Nevertheless, no differences were observed between the nurse and peer groups regarding these variables (p > 0.05). ConclusionsBoth nursing and peer education methods had an equal impact on enhancing the resilience and quality of life of patients with MS. It is recommended that peer support be utilized to empower MS patients, especially in contexts where there is a shortage of nurses.

Identification of JC polyomavirus in upper respiratory samples from Portuguese children

BackgroundJC polyomavirus (JCPyV) is ubiquitous in the human population and the causative agent of a rare, fatal and demyelinating disease of the central nervous system named Progressive Multifocal Leukoencephalopathy (PML). The route of JCPyV transmission remains unclear, but high values of seroprevalence suggest an easy and frequent mode, such as respiratory route. ObjectivesThe present study aims to investigate the presence of JCPyV in upper respiratory samples and contribute to the elucidation of the JCPyV transmission pathway. Study designNasopharyngeal swabs from 587 Portuguese individuals, including 380 children (≤18 years) and 207 adults (>18 years), collected for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis between September and November 2021 were evaluated for the presence of JCPyV DNA. ResultsJCPyV DNA was detected in 3.1 % of the nasopharyngeal swabs analysed, with higher frequency of detection in samples from children (4.5 %) than from adults (0.5 %) (p = 0.005). Infection with SARS-CoV-2 does not potentiate the presence of JCPyV in upper respiratory tract, once only one adult of 28 years with confirmed SARS-CoV-2 infection showed detectable JCPyV DNA. JCPyV DNA was more frequently detected in respiratory samples from children without SARS-CoV-2 infection (6.4 %). As for this group, children under six years of age presents the highest frequency of detection (10.3 %). ConclusionsThe present study demonstrates that upper respiratory secretions of children, particularly under the age of six, may be implicated in JCPyV transmission, regardless of SARS-CoV-2 infection.

Efficacy and Safety of Inebilizumab, an Anti-CD19 Monoclonal Antibody, for the Treatment of Neuromyelitis Optica Spectrum Disorder: Based on the N-MOmentum Trial

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathic disease of the central nervous system characterized by severe optic neuritis and transverse myelitis. The antibody against aquaporin 4 (AQP4), a water channel mainly expressed in astrocytes, is specific to NMOSD and may be detected in >70% of all cases. Inebilizumab is a humanized IgG1 monoclonal antibody against CD19. Anti-AQP4 antibodies are produced by CD19-positive plasmablasts, and inebilizumab administration significantly reduces the number of CD19-positive B cells and has therapeutic effects on NMOSD. The efficacy and safety of inebilizumab have been verified in the N-MOmentum trial, an international double-blind, placebo-controlled phase II/III study, in which Japanese patients also participated. Inebilizumab was approved for the treatment of NMOSD with AQP4-IgG in Japan in March 2021. In this review, we summarize the efficacy and safety of inebilizumab in the treatment of NMOSD and, focus on findings from the primary and additional analyses of the N-MOmentum trial. These results suggest that inebilizumab is effective and safe in preventing the recurrence of NMOSD in populations with different backgrounds and that long-term treatment with inebilizumab is beneficial.

Distinct chemical structures inhibit the CEMIP hyaluronidase and promote oligodendrocyte progenitor cell maturation

Growing evidence supports pathogenic roles for chronically elevated hyaluronidase activity in numerous conditions. Elevated expression of one such hyaluronidase, the Cell Migration Inducing and hyaluronan binding Protein (CEMIP), has been implicated in the pathogenesis and progression of several cancers as well as demyelinating diseases in the central nervous system (CNS). Developing effective and selective CEMIP inhibitors could therefore have efficacy in treating a variety of conditions where CEMIP is chronically elevated. Using two distinct screens for novel hyaluronidase inhibitors, we identified two synthetic thiocarbamates and one plant-derived flavonoid, sulfuretin, that effectively blocked CEMIP activity in live cells, including a tumorigenic cell line and primary cultures of oligodendrocyte progenitor cells (OPCs). None of these agents influenced cell proliferation, but they had differential dose-dependent and cell type specific effects on cell survival. Furthermore, we found that each of these agents could promote oligodendrocyte maturation by OPCs in the presence of high molecular weight (>2 Mda) hyaluronan, the accumulation of which is linked to the inhibition of OPC maturation and remyelination failure in demyelinating diseases. These findings indicate that CEMIP can be inhibited through distinct chemical interactions, and that CEMIP inhibitors have potential efficacy for treating demyelinating diseases or other conditions where CEMIP is elevated.

The Antidiabetic Drug Metformin Attenuated Depressive and Anxietylike Behaviors and Oxidative Stress in the Brain in a Rodent Model of Inflammation Induced by Lipopolysaccharide in Male Rats.

Inflammation is considered to be a link between diabetes and central nervous system (CNS) disorders, including depression and anxiety. Metformin is suggested to have antioxidant, anti-inflammatory, and mood-improving effects. The aim of the current research was to investigate the effects of the antidiabetic drug metformin on depressive- and anxiety- like behaviors and oxidative stress in the brain in a rodent model of inflammation induced by lipopolysaccharide (LPS) in male rats. The rats were treated as follows: (1) Vehicle instead of metformin and lipopolysaccharide, (2) Lipopolysaccharide (1 mg/ kg) + vehicle instead of metformin, (3-5) Lipopolysaccharide + 50, 100, or 150 mg/ kg of metformin. After the behavioral tests, including open field (OF), elevated pulse maze (EPM), and force swimming (FS) tests, the brains were removed, and malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol, catalase (CAT) activity, interleukin-6 (IL-6) and superoxide dismutase (SOD) activity were determined. In the EPM, metformin increased the open arm time and entry and decreased closed arm time and entry. In the FS test, metformin lowered the immobility and increased active time compared to lipopolysaccharide. In the OF test, metformin increased total crossing and total distance, time spent, traveled distance, and crossing number in the central zone. As a result of metformin administration, IL-6, MDA, and NO metabolites were decreased while thiol content, SOD, and CAT activity were increased. The results indicated that the well-known antidiabetic drug metformin attenuated depressive- and anxiety-like behaviors induced by inflammation in rats. These beneficial effects are suggested to be due to their attenuating effects on neuroinflammation, oxidative stress, and NO in the brain.

Outcome of patients with diffuse large B-cell lymphoma and testicular involvement - real world data.

Patients with testicular lymphoma are at an increased risk of central nervous system (CNS) disease. Optimal strategy for CNS relapse prevention is unknown. We analyzed treatment strategies, cumulative incidence of CNS relapse and prognosis in 229 patients with diffuse large B-cell lymphoma (DLBCL) and testicular involvement: 157 primary testicular lymphomas (PTL) in clinical stages IE/IIE and 72 patients in advanced stages (T-DLBCL) IIIE/IV. Treatments for PTL vs. T-DLBCL included: rituximab-based chemotherapy (80.9% vs. 90.3%), orchiectomy (94.3% vs. 65.3%) and contralateral testicular irradiation (59.8% vs. 44.4%). Majority (84.3%) received CNS prophylaxis with similar rates of prophylactic methotrexate (intravenous 19.1% vs. 16.6%, intrathecal 40.8% vs. 40.4%, or both 24.2% vs. 27.8%) between PTL and T-DLBCL (p = 0.89). Median follow-up was 51.8 months. CNS relapses occurred in 14 (6.1%) of 63 relapsing patients. The 5-year cumulative incidence of CNS relapse in PTL was 4.5% and in T-DLBCL 12.1%. Median time to CNS relapse was 21.9 months. In univariate analyses, orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (HR = 0.11 [95% CI, 0-0.124], p = 0.001). Rituximab significantly reduced CNS relapse risk in T-DLBCL (HR = 0.1002, p = 0.0005). Median progression-free survival (PFS) and overall survival (OS) following CNS relapse was dismal in T-DLBCL compared to PTL (PFS 1.6 vs. 37.8 months, p = 0.04 and OS 2.3 vs. 37.8 months, p = 0.05). This study confirmed a favorable impact of rituximab in prevention of CNS relapse in T-DLBCL. Methotrexate prophylaxis did not alter CNS relapse risk. Prognosis of CNS relapse is particularly poor in T-DLBCL.

Evaluating the Regional and Demographic Variations in Dementia-Related Mortality Trends in the United States: 1999 to 2020.

Dementia, a term for a range of cognitive impairments impacting memory, thinking, and social abilities, represents a formidable challenge to healthcare systems worldwide. Analysing the temporal trends in dementia-related mortality among individuals, identifying the populations at high risk, and guiding the implementation of tailored interventions to address the escalating effects of dementia on public health. Data from CDC WONDER database was examined from 1999 to 2020 for the four causes of dementia mortality: unspecified dementia (F03), Alzheimer's disease (G30), vascular dementia (F01), and other degenerative diseases of nervous system not elsewhere classified (G31). Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated and stratified by geographic region, year, age groups, sex, and race/ethnicity. A total of 4,077,973 reported deaths were related to dementia from 1999 to 2020 in the United States. The greatest proportion of deaths was associated with Alzheimer's disease (45.9%), followed by unspecified dementia (43.8%). Very low proportion of deaths were associated with vascular dementia (4.9%) or other neurodegenerative diseases (5.3%). The AAMR increased in two distinct periods: a steep incline from 1999 to 2010 (APC: 6.95, 95% CI: 6.00-7.90), followed by a modest incline till 2020 (APC: 1.41, 95% CI: 0.80-2.04). Overall, females had a higher AAMR than males. AAMRs were highest among NH Whites patients and lowest in NH Asians or Pacific Islanders. A significant geographical difference was also observed among different US census regions. Nearly equal AAMRs were seen in non-metropolitan areas and metropolitan areas. States with AAMRs in the top 90th percentile included South Carolina, North Carolina, Maine, Tennessee, Georgia, and Alabama while states with AAMRs in the bottom 10th percentile included South Dakota, Florida, Hawaii, New Jersey, District of Columbia, and New York (33.1). Individuals aged above 85 had the highest AAMRs. Most deaths occurred in nursing homes and least in hospice facilities. The dementia related deaths are continuously increasing. Highest AAMRs were observed among the NH White people, females, and in the southern areas of the United States. People aged 85+ were most affected. To stop the rising death rates, targeted interventions and awareness are required for both prevention and treatment of dementia.