Anti-PD-1/PD-L1 inhibitor therapy for melanoma brain metastases: a systematic review and meta-analysis.

Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases. This systematic review and meta-analysis followed PRISMA guidelines. PICO criteria targeted melanoma brain metastasis patients treated with PD-1/PD-L1 inhibitors, assessing overall survival, progression-free survival, and complications. Inclusion criteria were English studies on humans using PD-1/PD-L1 inhibitors for melanoma brain metastases with > 10 patients. A total of 22 trials involving 1523 melanoma brain metastase patients treated with anti-PD-1/PD-L1 inhibitors were thoroughly analyzed. Our findings show the 6-month OS rate of 0.75 [95%CI:0.67-0.84], the 6-months PFS rate of 0.42 [95%CI:0.31-0.52], the 1-year OS rate of 0.63 [95%CI:0.52-0.74], the 1-year PFS rate was 0.45 [95%CI:0.32-0.58], the 18-months OS rate of 0.52 [95%CI:0.37-0.67], the 2-year OS rate of 50% [95% CI: (34%-65%)], the 2 year PFS rate of 0.36 (95%CI:0.23-0.50), the 3-year OS rate of 0.42 (95%CI:0.17-0.67), the 4-year PFS rate of 0.35 [95%CI:0.08-0.61], the 4-year OS rate of 0.29 [95%CI:0.01-0.56], the 5-year OS rate of 0.29 (95%CI:0.09-0.50), and the 5-year PFS rate of 0.11 (95%CI:0.03-0.19). The combined disease stability rate was 0.13 [95%CI:0.05-0.20], the progressive disease rate was 0.49 [95%CI:0.37-0.62], the partial response rate was 0.14 [95%CI:0.07-0.20], the object response rate was 0.35 [95%CI:0.24-0.46], and the complete response rate was 0.22 [95%CI:0.12-0.32]. In conclusion, our meta-analysis provides compelling evidence supporting the efficacy of PD-1/PD-L1 inhibitors in patients with melanoma brain tumors, as evidenced by favorable survival outcomes and disease control rates.

Elderberry diet improves gut-brain axis dysfunction, neuroinflammation, and cognitive impairment in the rat model of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is related to a problem in the gut-brain axis. This experimental research aimed to shed light on the potential therapeutic application of elderberry (EB), which can work on the axis and get better the IBS symptoms. There were three groups (36 Sprague-Dawley rats) in this experiment, including control, IBS, and IBS with EB diet (IBS + EB). Making use of intracolonic instillation of 1 ml of 4% acetic acid for 30 s, IBS was induced. 7 days later, the EB extract (2%) was added to the diets of all animals for 8 weeks. Some histological, behavioral, and stereological techniques were used to detect the effects of EB on the gut and brain tissues. The findings showed that the EB diet improved locomotion and decreased anxiety-like behavior in the rat models of IBS. Moreover, the diet dropped the expression of TNF-α and increased mucosal layer thickness and the number of goblet and mast cells in colon tissue samples. In the hippocampal samples, administration of EB prevented astrogliosis and astrocyte reactivity. Although hippocampal and cortical neurons decreased markedly in the IBS group, EB prevented the drop in the number of neurons. Although lots of research is needed to elucidate the effectiveness of EB in IBS and its exact molecular mechanism, the result of this study showed that EB as an antioxidant and immune-modulatory agent could be a promising research target to prevent the impairment in the gut-brain axis, and could ameliorative classic IBS symptoms.

Grafted Sertoli cells prevent neuronal cell death and memory loss induced by seizures.

Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses.

COVID-19 causes neuronal degeneration and reduces neurogenesis in human hippocampus.

Recent investigations of COVID-19 have largely focused on the effects of this novel virus on the vital organs in order to efficiently assist individuals who have recovered from the disease. In the present study we used hippocampal tissue samples extracted from people who died after COVID-19. Utilizing histological techniques to analyze glial and neuronal cells we illuminated a massive degeneration of neuronal cells and changes in glial cells morphology in hippocampal samples. The results showed that in hippocampus of the studied brains there were morphological changes in pyramidal cells, an increase in apoptosis, a drop in neurogenesis, and change in spatial distribution of neurons in the pyramidal and granular layer. It was also demonstrated that COVID-19 alter the morphological characteristics and distribution of astrocyte and microglia cells. While the exact mechanism(s) by which the virus causes neuronal loss and morphology in the central nervous system (CNS) remains to be determined, it is necessary to monitor the effect of SARS-CoV-2 infection on CNS compartments like the hippocampus in future investigations. As a result of what happened in the hippocampus secondary to COVID-19, memory impairment may be a long-term neurological complication which can be a predisposing factor for neurodegenerative disorders through neuroinflammation and oxidative stress mechanisms.

An elderberry-supplemented diet improves spermatogenesis in mice with busulfan-induced azoospermia.

CONTEXT: Approximately 40-50% of all infertility cases are due to male infertility, and one of the most important causes of infertility is azoospermia. AIMS: This study aimed to evaluate the potential effect of elderberry on the spermatogenesis process in the azoospermia mice model. METHOD: Thirty adult male mice were randomised into three groups: control; busulfan (45mg/kg); and busulfan+elderberry (2%), 6mL orally per animal. Sperm samples were collected from the tail of the epididymis, and testis specimens were also collected and then subjected to sperm parameters analysis, histopathological evaluation, reactive oxygen species (ROS), and glutathione (GSH) measurement to determine the mRNA expression and hormonal assay. CONCLUSIONS: It can be concluded that the elderberry diet may be considered a complementary treatment to improve the spermatogenesis process in busulfan-induced azoospermic mice. IMPLICATIONS: Considering some limitations, the elderberry diet can be an alternate option for improving testicular damage following chemotherapy.

Neurological Symptoms, Comorbidities, and Complications of COVID-19: A Literature Review and Meta-Analysis of Observational Studies.

BACKGROUND: Recently, it has been shown that coronavirus disease 2019 (COVID-19), which has caused a pandemic since December 2019, can be accompanied by some neurological disorders. This study aimed to assess the prevalence of the most common neurological symptoms and comorbidities and systematically review the literature regarding the most prevalent neurological complications of COVID-19 infection. METHODS: All relevant studies had been collected from PubMed, Scopus, Embase, and Web of Science databases. All extracted data were analyzed using Stata version 11.2. The I2 index was applied, and a random-effects model or a fixed-effects model was used for pooled estimation to assess the heterogeneity of studies. Furthermore, Egger and Beeg's tests were used to evaluate the publication bias. RESULTS: Fifty-seven studies (26 observational and 31 case reports) were included (including 6,597 COVID-19 patients). The most prevalent general symptoms were fever, cough, and dyspnea with 84.6% (95% CI: 75.3-92.1; I2 = 98.7%), 61.3% (95% CI: 55.3-67.0; I2 = 94.6%), and 34.2% (95% CI: 25.6-43.4; I2 = 97.7%), respectively. Neurological symptoms observed among COVID-19 patients were fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea with 42.9% (95% CI: 36.7-49.3; I2 = 92.8%), 35.4% (95% CI: 11.2-64.4; I2 = 99.2%), 28.9% (95% CI: 19.9-38.8; I2 = 96.3%), 25.3% (95% CI: 1.6-63.4; I2 = 99.6%), 10.1% (95% CI: 2.7-21.0; I2 = 99.1%), 6.7% (95% CI: 3.7-10.5; I2 = 87.5%), and 5.9% (95% CI: 3.1-9.5; I2 = 94.5%). The most prevalent neurological comorbidity in COVID-19 was cerebrovascular disease with 4.3% (95% CI: 2.7-6.3; I2 = 78.7%). CONCLUSION: The most prevalent neurological manifestations of COVID-19 include fatigue, gustatory dysfunction, anorexia, olfactory dysfunction, headache, dizziness, and nausea. Cerebrovascular disorders can either act as a risk factor for poorer prognosis in COVID-19 patients or occur as a critical complication in these patients. Guillain-Barre syndrome, encephalitis, and meningitis have also been reported as complications of COVID-19.

Coronavirus disease and male fertility: a systematic review.

BACKGROUND: Based on the information from other SARS-CoV infections in the patients recovered from COVID-19, particularly cases in the reproductive age, gonadal function evaluation and andrological consultation comprising semen analysis are recommended. MAIN BODY: Based on the COVID-19 infected patients' seminal fluid analyses, SARS-CoV-2 may employ the male reproductive system as a transmission pathway. It has been also demonstrated that angiotensin-converting enzyme 2 (ACE2) can be strongly expressed at the protein levels in the testicular cells. The high expression of ACE2 in testes suggests that testes in the COVID-19 infected males can have an important role in the viral persistence and this subject needs further investigations. Several researchers have examined males recovered from COVID-19, but still, large-scale experiments are needed to determine the effects of SARS-CoV-2 on the male reproductive system as well as viral transmission risk. CONCLUSION: Comprehensive researches are required to figure out the presence of the SARS-CoV-2 virus in seminal fluid as well as its sexual transmissibility and impact on sperm characteristics.

Critical complications of COVID-19: A descriptive meta-analysis study.

The coronavirus disease 2019 (COVID-19) is a novel coronavirus infection that has rapidly spread worldwide, causing a pandemic. The main objective of this meta-analysis was to evaluate the prevalence of the most common symptoms and complications of COVID-19. All relevant studies on the clinical complications of COVID-19 have been identified by searching two web databases (i.e., PubMed and Scopus). Afterward, the relevant data were extracted from the selected studies, and then analyzed by the STATA (Version 14) random-effects model. The 30 studies selected for our meta-analysis covered 6,389 infected patients. The prevalence rates of the most common symptoms were as follows: fever: 84.30% (95% CI: 77.13-90.37; I2 = 97.74%), cough: 63.01% (95% CI: 57.63-68.23; I2 = 93.73%), dyspnea: 37.16% (95% CI: 27.31-47.57%; I2 = 98.32%), fatigue: 34.22% (95% CI: 26.29-42.62; I2 = 97.29%), and diarrhea: 11.47% (95% CI: 6.96-16.87; I2 = 95.58%). Moreover, the most prevalent complications were found to be acute respiratory distress syndrome (ARDS) with 33.15% (95% CI: 23.35-43.73; I2 = 98.56%), arrhythmia with 16.64% (95% CI: 9.34-25.5; I2 = 92.29%), acute cardiac injury with 15.68% (95% CI: 11.1-20.97; I2 = 92.45%), heart failure with 11.50% (95% CI: 3.45-22.83; I2 = 89.48%), and acute kidney injury (AKI) with 9.87% (95% CI: 6.18-14.25; I2 = 95.64%). In this study, we assessed the prevalence of the main clinical complications of COVID-19, and found that following respiratory complications, cardiac and renal complications are the most common clinical complications of COVID-19.

SARS-CoV-2 infection in patients with diabetes mellitus and hypertension: a systematic review.

After the emergence of the novel 2019 coronavirus disease in P. R. China, this highly contagious disease has been currently spread out to almost all countries, worldwide. Novel 2019 coronavirus disease, Middle East respiratory syndrome, and severe acute respiratory syndrome are reported to cause a higher risk for severe infections in patients with chronic comorbidities, such as hypertension and diabetes. These severe infections can contribute to higher rates of morbidity and mortality in these patients. In the present review, we discussed the role and underlying mechanisms of the two most common chronic diseases, type-2 diabetes mellitus and hypertension, in clinical manifestations and disease severity of novel 2019 coronavirus disease, Middle East respiratory syndrome and severe acute respiratory syndrome, with the hope to provide evidence for better decision-making in the treatment of this vulnerable population.

Coronavirus diseases and pregnancy: COVID-19,SARS, and MERS.

Around the end of December 2019, a new beta-coronavirus from Wuhan City, Hubei Province, China began to spread rapidly. The new virus, called SARS-CoV-2, which could be transmitted through respiratory droplets, had a range of mild to severe symptoms, from simple cold in some cases to death in others. The disease caused by SARS-CoV-2 was named COVID-19 by WHO and has so far killed more people than SARS and MERS. Following the widespread global outbreak of COVID-19, with more than 132758 confirmed cases and 4955 deaths worldwide, the World Health Organization declared COVID-19 a pandemic disease in January 2020. Earlier studies on viral pneumonia epidemics has shown that pregnant women are at greater risk than others. During pregnancy, the pregnant woman is more prone to infectious diseases. Research on both SARS-CoV and MERS-CoV, which are pathologically similar to SARS-CoV-2, has shown that being infected with these viruses during pregnancy increases the risk of maternal death, stillbirth, intrauterine growth retardation and, preterm delivery. With the exponential increase in cases of COVID-19 throughout the world, there is a need to understand the effects of SARS-CoV-2 on the health of pregnant women, through extrapolation of earlier studies that have been conducted on pregnant women infected with SARS-CoV, and MERS-CoV. There is an urgent need to understand the chance of vertical transmission of SARS-CoV-2 from mother to fetus and the possibility of the virus crossing the placental barrier. Additionally, since some viral diseases and antiviral drugs may have a negative impact on the mother and fetus, in which case, pregnant women need special attention for the prevention, diagnosis, and treatment of COVID-19.

A challenging transseptal mitral valve in valve case report: Success and safety.

Key Clinical Message: Transcatheter mitral valve implantation (TMVI) is considered a less-invasive approach than open-heart surgery, favored in high-risk patients elected for valve replacement. Although seemingly suitable, this procedure is highly operator-dependent. Abstract: Transcatheter mitral valve implantation (TMVI) is an alternative in high-risk patients. We reported a 72-year-old patient with mitral bioprosthesis degeneration successfully receiving TMVI. The procedure has lower morbidity and mortality rate than the surgical approach but can be accompanied by several complications, especially when conducted by an inexperienced operator.

Impact of Probiotics on Gastrointestinal Function and Metabolic Status After Roux-en-Y Gastric Bypass: A Double-Blind, Randomized Trial.

PURPOSE: Postoperative changes in gut microbiota may occur in patients undergoing Roux-en-Y gastric bypass surgery. In this study, we evaluate the impact of administering probiotic tablets on the gastrointestinal function and metabolic status of these patients. MATERIALS AND METHODS: This double-blinded randomized clinical trial was conducted from 2021 to 2022 on 135 Roux-en-Y surgery candidates. The intervention group underwent the surgical procedure and started receiving probiotic supplements (Familact Co.) 1 week after surgery; the control group received a placebo. The laboratory and anthropometric data were measured and analyzed before and 3 and 6 months after the intervention. GIQLI questionnaire was also used at the beginning and 6 months after the intervention to evaluate GI symptoms. RESULTS: We observed significantly reduced BMI in both groups after surgeries (P < 0.001). The levels of FBS and HbA1C were significantly lower in the probiotic group compared to the placebo in 3 months (P = 0.02 and P = 0.001, respectively) and 6 months (P < 0.001 for both) after the intervention. The levels of vitamin B12 increased significantly in the probiotic group (P < 0.001), and the values were substantially higher than the placebo group in 3 and 6 months (P < 0.001), respectively. Analysis of the GIQLI questionnaire before and 6 months after interventions also revealed significant improvement in the GIQLI score in both groups (P < 0.001 for probiotics and P = 0.03 for placebo). CONCLUSION: Probiotic supplement administration following RYGB improves patients' vitamin and metabolic profile, as well as GI function, although it cannot significantly affect weight loss.

Introducing fitting models for estimating age-specific dose and effective dose in paediatric patients undergoing head, chest and abdomen-pelvis imaging protocols: a patient study.

INTRODUCTION: Concerns regarding the adverse consequences of radiation have increased due to the expanded application of computed tomography (CT) in medical practice. Certain studies have indicated that the radiation dosage depends on the anatomical region, the imaging technique employed and patient-specific variables. The aim of this study is to present fitting models for the estimation of age-specific dose estimates (ASDE), in the same direction of size-specific dose estimates, and effective doses based on patient age, gender and the type of CT examination used in paediatric head, chest and abdomen-pelvis imaging. METHODS: A total of 583 paediatric patients were included in the study. Radiometric data were gathered from DICOM files. The patients were categorised into five distinct groups (under 15 years of age), and the effective dose, organ dose and ASDE were computed for the CT examinations involving the head, chest and abdomen-pelvis. Finally, the best fitting models were presented for estimation of ASDE and effective doses based on patient age, gender and the type of examination. RESULTS: The ASDE in head, chest, and abdomen-pelvis CT examinations increases with increasing age. As age increases, the effective dose in head and abdomen-pelvis CT scans decreased. However, for chest scans, the effective dose initially showed a decreasing trend until the first year of life; after that, it increases in correlation with age. CONCLUSIONS: Based on the presented fitting model for the ASDE, these CT scan quantities depend on factors such as patient age and the type of CT examination. For the effective dose, the gender was also included in the fitting model. By utilising the information about the scan type, region and age, it becomes feasible to estimate the ASDE and effective dose using the models provided in this study.

Effects of Vitamin D and E Supplementation on Prevention of Bronchopulmonary Dysplasia (BPD) in Premature Neonates: A Systematic Review and Meta-Analysis.

BACKGROUND: Bronchopulmonary Dysplasia (BPD) has a multifactorial etiology. Vitamin E and vitamin D play an important role in lung development and can potentially be beneficial in the prevention of BPD. OBJECTIVE: The study aimed to compare the risk of BPD occurrence in preterm neonates supplemented with vitamin D or E versus those who did not get supplementation. METHODS: The literature search was conducted for this systematic review by searching the PubMed, Scopus, and Web of Science databases up to December 2022. Randomized controlled trials involved administering vitamin D or E to preterm neonates and examining the occurrence of BPD. We excluded non-English articles, and articles with non-relevant and insufficient data. We used the Critical Appraisal Skills Programme (CASP) checklist to assess the quality of the included studies. We used Egger's test to evaluate the risk of bias among the included studies. Heterogeneity was also assessed through Q-test and I2. We applied the random effect model for analysis. A P-value less than 0.05 was considered as significant. All the statistical analysis in the current study was performed using STATA 14. The Relative Risk (RR) was calculated as the effect size with 95% Confidence Interval (CI). RESULTS: Three eligible studies seeking the role of vitamin D in the prevention of BPD were analysed. Meta-analysis revealed that receiving vitamin D supplementation can significantly reduce the risk of BPD in preterm infants (RR = 0.357, 95% CI: 0.189-0.675, I2 = 0.0%; p = 0.002). Similarly, for assessing the role of Vitamin E in the prevention of BPD, three eligible studies were analysed. Vitamin E supplementation was not found to play a significant role in the reduction of BPD (RR = 0.659, 95%CI = 0.243-1.786, I2 = 38.7%; p = 0.412). CONCLUSION: Vitamin D supplementation could be beneficial in preventing BPD in preterm infants. However, evidence is not enough regarding vitamin E's role in reducing the incidence of BPD in preterm infants.

Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. METHODS: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. RESULTS: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. CONCLUSION: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Memory loss induced by lisdexamfetamine in the rat: A behavioral, electrophysiological, and histopathological Study.

Lisdexamfetamine (LDX) is one of the drugs commonly used to treat attention deficit hyperactivity disorder (ADHD). However, its neurological side effects, particularly on cognition, are not fully understood. The present study focused on memory in rats treated with four weeks of LDX injection. We compared LDX-treated rats with control ones, using several methods to evaluate the behavioral responses and electrophysiological, molecular, and histological properties in the hippocampus. Our findings demonstrated that subchronic administration of LDX impaired behavioral performance in all memory assessment tests (Y maze, Morris Water Maze, and Shuttle box). Although LDX did not alter population spike (PS) amplitude, it increased the field excitatory postsynaptic potential (fEPSP) slope of evoked potentials of LTP components. Also, in addition to an increase in expression of caspase-3 in the hippocampus, which indicates the susceptibility to apoptosis in LDX-treated rats, the number of microglia and astrocytes went up significantly in the LDX group. Moreover, Sholl's analysis showed an increase in the soma size and total process length in both hippocampal astrocytes and microglia. Overall, because of these destructive effects of LDX on the hippocampus, which is one of the critical memory-related areas of the brain, the findings of this investigation provide evidence to show the disruption of memory-related variables following the LDX. However, more research is needed to clarify it.

Exploring the therapeutic potential: Apelin-13's neuroprotective effects foster sustained functional motor recovery in a rat model of Huntington's disease.

Huntington's disease (HD) is a hereditary condition considered by the progressive degeneration of nerve cells in the brain, resultant in motor dysfunction and cognitive impairment. Despite current treatment modalities including pharmaceuticals and various therapies, a definitive cure remains elusive. Therefore, this study investigates the therapeutic potential effect of Apelin-13 in HD management. Thirty male Wistar rats were allocated into three groups: a control group, a group with HD, and a group with both HD and administered Apelin-13. Apelin-13 was administered continuously over a 28-day period at a dosage of around 30 mg/kg to mitigate inflammation in rats subjected to 3-NP injection within an experimental HD model. Behavioral tests, such as rotarod, electromyography (EMG), elevated plus maze, and open field assessments, demonstrated that Apelin-13 improved motor function and coordination in rats injected with 3-NP. Apelin-13 treatment significantly increased neuronal density and decreased glial cell counts compared to the control group. Immunohistochemistry analysis revealed reduced gliosis and expression of inflammatory factors in the treatment group. Moreover, Apelin-13 administration led to elevated levels of glutathione and reduced reactive oxygen species (ROS) level in the treated group. Apelin-13 demonstrates neuroprotective effects, leading to improved movement and reduced inflammatory and fibrotic factors in the HD model.

Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease.

Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.

Bromelain decreases oxidative stress and Neuroinflammation and improves motor function in adult male rats with cerebellar Ataxia induced by 3-acetylpyridine.

Bromelain is a plant-based molecule with antioxidant, antithrombotic, anticancer, and anti-inflammatory properties. Bromelain has been shown to reduce the release of inflammatory cytokines. This study aimed to determine whether bromelain can prevent ataxia in rats caused by 3-acetylpyridine (3-AP). Thirty-six albino rats were divided into the control, 3-AP, and 3-AP + Brom groups. In the 3-AP + Brom group, bromelain was injected intraperitoneally at 40 mg/kg daily for 30 days. Various techniques such as rotarod, electromyography (EMG), elevated plus maze, IHC, and Sholl analysis were used to evaluate the possible effects of bromelain on cerebellar neurons and glial cells. The results demonstrated significant improvements in most of the 3-AP + Brom, including motor coordination, neuromuscular response, anxiety, oxidative capacity, microgliosis, astrogliosis, cell death, and morphological variables compared to the 3-AP group. The mechanism of action of bromelain in restoring cerebellar ataxia needs further investigation, but it may be a candidate to help restore degeneration in animals with ataxia.

Chronic Administration of Lisdexamfetamine Induces Apoptosis and Inflammation and Reduces Sperm Quality in Adult Male Rats.

Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.