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Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible for energy production and calcium regulation. This review offers an in-depth examination of the interplay between epilepsy, mitochondrial function, and aging. Many factors might account for the correlation between epilepsy and aging. Mitochondria, integral to cellular energy dynamics and neuronal excitability, perform a critical role in the pathophysiology of epilepsy. The mechanisms linking epilepsy and mitochondria are multifaceted, involving mitochondrial dysfunction, reactive oxygen species (ROS), and mitochondrial dynamics. Mitochondrial dysfunction can trigger seizures by compromising ATP production, increasing glutamate release, and altering ion channel function. ROS, natural byproducts of mitochondrial respiration, contribute to oxidative stress and neuroinflammation, critical factors in epileptogenesis. Mitochondrial dynamics govern fusion and fission processes, influence seizure threshold and calcium buffering, and impact seizure propagation. Energy demands during seizures highlight the critical role of mitochondrial ATP generation in maintaining neuronal membrane potential. Mitochondrial calcium handling dynamically modulates neuronal excitability, affecting synaptic transmission and action potential generation. Dysregulated mitochondrial calcium handling is a hallmark of epilepsy, contributing to excitotoxicity. Epigenetic modifications in epilepsy influence mitochondrial function through histone modifications, DNA methylation, and non-coding RNA expression. Potential therapeutic avenues targeting mitochondria in epilepsy include mitochondria-targeted antioxidants, ketogenic diets, and metabolic therapies. The review concludes by outlining future directions in epilepsy research, emphasizing integrative approaches, advancements in mitochondrial research, and ethical considerations. Mitochondria emerge as central players in the complex narrative of epilepsy, offering profound insights and therapeutic potential for this challenging neurological disorder.

Honeybees have been helpful insects since ancient centuries, and this benefit is not limited to being a honey producer only. After the bee stings a person, pain, and swelling occur in this place, due to the effects of bee venom (BV). This is not a poison in the total sense of the word because it has many benefits, and this is due to its composition being rich in proteins, peptides, enzymes, and other types of molecules in low concentrations that show promise in the treatment of numerous diseases and conditions. BV has also demonstrated positive effects against various cancers, antimicrobial activity, and wound healing versus the human immunodeficiency virus (HIV). Even though topical BV therapy is used to varying degrees among countries, localized swelling or itching are common side effects that may occur in some patients. This review provides an in-depth analysis of the complex chemical composition of BV, highlighting the diverse range of bioactive compounds and their therapeutic applications, which extend beyond the well-known anti-inflammatory and pain-relieving effects, showcasing the versatility of BV in modern medicine. A specific search strategy was followed across various databases; Web of sciences, Scopus, Medline, and Google Scholar including in vitro and in vivo clinical studies.to outline an overview of BV composition, methods to use, preparation requirements, and Individual consumption contraindications. Furthermore, this review addresses safety concerns and emerging approaches, such as the use of nanoparticles, to mitigate adverse effects, demonstrating a balanced and holistic perspective. Importantly, the review also incorporates historical context and traditional uses, as well as a unique focus on veterinary applications, setting it apart from previous works and providing a valuable resource for researchers and practitioners in the field.

Background Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol. Materials and Methods Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done. Results Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues. Conclusion Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Objectives: The present study examined the effect DHEA (dehydroepiandrosterone) on bone mineral content (BMC) and bone mineral density (BMD) and biomarkers of bone remodeling in orchidectomized male rats. Material and Methods: A total of 32 male rats were divided equally into four groups (n = 8): (i) control group (C), (ii) control treated with DHEA (Control + DHEA), (iii) orchidectomized (ORCH) group that underwent bilateral orchidectomy and (iv) orchidectomized (ORCH) rats treated with DHEA (ORCH+DHEA). DHEA treatment started 4 weeks after orchidectomy and continued for 12 weeks. After 12 weeks the bone mineral density (BMD) and bone mineral content (BMC) were assayed in the tibia and femur of the right hind limb of each rat. We also measured the serum levels of the bone turnover markers deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTx), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase 5b (TRAP-5b) and osteocalcin (OC) as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG). Results: Orchidectomy in rats caused significant reduction in BMD, BMC, serum levels of testosterone, PTH (parathyroid hormone), OPG, OC and ALP with significant rise in serum levels of TRAP-5B, RANK, Dpd and NTx1 (p < 0.05). On the other hand, DHEA therapy for 12 weeks caused significant improvement in all studied parameters except NTx1 (p < 0.05). Conclusions: DHEA corrected hypogonadism-induced osteoporosis in male rats probably via inhibiting osteoclastogenesis, stimulating the activity of osteoblasts and stimulating the secretion of PTH and testosterone.

ABSTRACT Mesenchymal stem cells‐derived exosomes (MSCs‐EXs) applications have brought a key breakthrough in treating type 1 diabetes mellitus (T1DM) and its diabetic complications. However, various recent strategies aimed to construct prominent engineered EXs with greater precision and higher efficiency for diabetes syndrome were conducted. In this research, we seek to enhance the medicinal potentialities of MSCs‐EXs on type 1 diabetic rats' hepatic complications, via loading with either selenium (Se) or nano selenium (NSe) particles. For consecutive 4‐weeks, rats were divided into 8 groups as; control, EXs, EXs + Se, EXs + NSe, STZ‐diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. The three diabetic‐treated groups manifested a significant reduction in hepatic contents of oxidative stress (OS) (MDA, NO, and H2O2) inflammatory (IL‐6, TNF‐α, and TGF‐β), and apoptotic (P53, BAX, caspase‐3, and Bcl2) markers, with marked elevation in hepatic antioxidant levels (GSH, GPX, SOD, and CAT). Such results were supported by the marked diminish in serum total proteins, liver function enzymes (AST, ALT, and bilirubin), and both serum and liver lipid profile fractions. In addition, hepatic histological examination showed marked improvement in liver architecture of all treated diabetic rats' groups, compared to diabetic untreated rats. Significantly, diabetic rats with EXs loaded with NSe exhibited the most therapeutic superiority. [ABSTRACT FROM AUTHOR]

Honeybees have been helpful insects since ancient centuries, and this benefit is not limited to being a honey producer only. After the bee stings a person, pain, and swelling occur in this place, due to the effects of bee venom (BV). This is not a poison in the total sense of the word because it has many benefits, and this is due to its composition being rich in proteins, peptides, enzymes, and other types of molecules in low concentrations that show promise in the treatment of numerous diseases and conditions. BV has also demonstrated positive effects against various cancers, antimicrobial activity, and wound healing versus the human immunodeficiency virus (HIV). Even though topical BV therapy is used to varying degrees among countries, localized swelling or itching are common side effects that may occur in some patients. This review provides an in-depth analysis of the complex chemical composition of BV, highlighting the diverse range of bioactive compounds and their therapeutic applications, which extend beyond the well-known anti-inflammatory and pain-relieving effects, showcasing the versatility of BV in modern medicine. A specific search strategy was followed across various databases; Web of sciences, Scopus, Medline, and Google Scholar including in vitro and in vivo clinical studies. to outline an overview of BV composition, methods to use, preparation requirements, and Individual consumption contraindications. Furthermore, this review addresses safety concerns and emerging approaches, such as the use of nanoparticles, to mitigate adverse effects, demonstrating a balanced and holistic perspective. Importantly, the review also incorporates historical context and traditional uses, as well as a unique focus on veterinary applications, setting it apart from previous works and providing a valuable resource for researchers and practitioners in the field. [ABSTRACT FROM AUTHOR]

Background: Parkinson’s disease (PD) is a neurological condition that typically shows up with aging. It is characterized by generalized slowness of movement, resting tremor or stiffness, and bradykinesia. PD patients’ brains mostly exhibit an increase in inflammatory mediators and microglial response. Nevertheless, a variety of non-steroidal anti-inflammatory medications (NSAIDS) offered neuroprotection in animal models and preclinical trials.Aim: The current systematic review and meta-analysis were designed to try to resolve the debate over the association of NSAID use with the development of PD because the results of several studies were somehow contradictory.Methods: An intense search was performed on Scopus, PubMed, and Web of Science databases for articles relating the incidence of PD to the use of NSAIDs. Statistical analysis of the included studies was carried out using Review Manager version 5.4.1 by random effect model. The outcome was identified as the development of PD in patients who were on NSAIDs, ibuprofen only, aspirin only, and non-aspirin NSAIDs. This was analyzed using pooled analysis of odds ratio (OR) at a significance level of ≤0.05 and a confidence level of 95%. A statistically significant decreased risk of PD was observed in patients taking NSAIDs, Ibuprofen, and non-aspirin NSAIDs.Results: The ORs of PD occurrence in patients who took NSAIDs, Ibuprofen, and non-aspirin NSAIDs were 0.88 [95% CI (0.8–0.97), p = 0.01], 0.73 [95% CI (0.53–1), p = 0.05] and 0.85 [95% CI (0.75–0.97), p = 0.01]. Meanwhile, the risk of PD in patients who took aspirin was not statistically significant.Conclusion: In conclusion, Ibuprofen, non-aspirin NSAIDs, and other types of NSAIDs could be associated with a reduction in PD risk. However, there was no association between aspirin intake and the development of PD.

BackgroundNeuroinflammation pathways have been associated with the development of major depressive disorders (MDD). The anti-inflammatory characteristics of statins have been demonstrated to have significance in the pathophysiology of depression.AimTo investigate the mechanistic pathways of high dose atorvastatin in MDD.Patients and methodsThis trial included 60 patients with MDD who met the eligibility requirements. Two groups of patients (n = 30) were recruited by selecting patients from the Psychiatry Department. Group 1 received 20 mg of fluoxetine plus a placebo once daily. Group 2 received fluoxetine and atorvastatin (80 mg) once daily. All patients were assessed by a psychiatrist using the Hamilton Depression Rating Scale (HDRS). A HDRS score of ≤7 indicates remission or partial remission [HDRS7]. Response was defined as ≥ 50% drop in the HDRS score. The serum concentrations of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP-3), interleukin-6 (IL-6), adenosine monophosphate activated protein kinase (AMPK), and signal transducer and activator of transcription factor-3 (STAT-3) were measured.ResultsThe atorvastatin group showed a significant reduction in the levels of all measured markers along with a statistical increase in the levels of AMPK when compared to the fluoxetine group. The atorvastatin group displayed a significant decrease in HDRS when compared to its baseline and the fluoxetine group. The response rate and partial remission were higher in the atorvastatin group than fluoxetine (p = 0.03, and p = 0.005), respectively.ConclusionThese results imply that atorvastatin at high doses may be a promising adjuvant therapy for MDD patients by altering the signaling pathways for AMPK/NLRP3 and IL-6/STAT-3.Clinical Trial Registrationclinicaltrials.gov, identifier NCT05792540.

Background and Objectives: Motor vehicle accidents (MVAs) are the leading cause of disability, particularly among young adults in Saudi Arabia. Persistent disabilities account for around 7% of all injuries attributed to MVAs in Saudi Arabia in the last twenty years. Limited studies on musculoskeletal disabilities following MVAs have been carried out in Saudi Arabia. This study aims to explore the epidemiology and prevalence of musculoskeletal disabilities in motor vehicle accident (MVA) patients in the Aljouf region, Saudi Arabia. Materials and Methods: This retrospective cross-sectional study evaluated all MVA victims treated in the Aljouf region, Saudi Arabia, from January 2020 to December 2022. A total of 3252 medical records were collected, with 731, 1197, and 1324 musculoskeletal injury cases per year, of which 88, 168, and 153 records from 2020, 2021, and 2022 were analysed, respectively. Results: The study found that patients aged 25–34 and 35–44 years were the most likely to experience disability following MVAs. The difference between age groups during a single year was statistically significant (p < 0.001). Most patients were male (89.8%, 82.7%, and 79.7%) during 2020, 2021, and 2022, respectively. The majority of injuries involved the upper extremities (38.6%, 36.9%, and 40.5%), followed by lower extremities (36.4%, 35.7%, and 34.6%), head and neck (21.6%, 26.2%, and 34.6%), thoracic region (20.5%, 24.4%, and 17%), and finally lumbosacral spine (6.8%, 5.4%, and 6.5%) during 2020, 2021, and 2022, respectively, with a significant difference for each year (p < 0.001). The study found a link between the likelihood of developing high disability grades and injury severity scores. The patients with very severe ISS ≥ 25 (OR: ∞ CI 95%: 39.81–∞; p < 0.001), severe ISS = 16–24 (OR: ∞ CI 95%: 20.90–∞; p < 0.001), and moderate ISS = 9–15 (OR: ∞ CI 95%: 1.2–∞; p = 0.02) were at greater risk of developing high grades of disability. Conclusions: This study highlighted the musculoskeletal disabilities in the Aljouf region following MVAs. Severe musculoskeletal disabilities were rare, but fractures were the most common following MVAs. More efforts should be directed towards education on early transportation and transfer to the nearest medical centres, seeking assistance immediately after MVAs for patient safety, and disability prevention.

Background and Objectives: Compared to other subjects, obese people have inferior trunk muscle endurance and balance. A modern method of neuro-muscular training called whole body vibration (WBV) may improve trunk muscle endurance and balance. This study evaluates the impact of a 4-week WBV program on trunk endurance and balance in obese female students. Materials and Methods: Sixty participants from 18 to 25 years of age and with BMI values ≥ 30 were randomly distributed into two equal groups: Group A (WBV group), who received 4 min of WBV, and Group B (sham WBV group), who received WBV with a turn-off device. The training was conducted two days/week for six weeks. Trunk endurance was evaluated using the Sorensen Test (ST) and Trunk Flexor Endurance Test (TFET). The Single-Leg Test (SLT) was used to assess static balance, while the Biodex Stability System measured dynamic balance. Results: The current study demonstrated no significant differences (p > 0.05) in pre-treatment variables between Groups A and B. Post-treatment, Group A showed a significantly higher duration of the Sorensen test, TFET and SLS than Group B (p < 0.001). Moreover, Group A showed significantly lower dynamic balance (p < 0.001) than Group B. Conclusions: WBV has a short-term effect on trunk endurance and balance in obese female students. WBV can be added to the rehabilitation program for obese subjects with deficits in trunk endurance and balance.