Evaluation of Pharmacology and Pathophysiology Knowledge of Epilepsy among Senior Pharmacy Students: A Single Center Experience.

Background and Objectives: Epilepsy is a chronic disease that causes substantial morbidity and mortality. Pharmacists represent an integral role in managing patients with epilepsy. The aim of this study was to evaluate the level of knowledge about the pharmacology and pathophysiology of epilepsy among senior pharmacy students. Materials and Methods: Cross-sectional study using a designed questionnaire to measure the pharmacological and physiological knowledge of senior pharmacy students regarding epilepsy who are studying at Umm Al-Qura University, Makkah, Saudi Arabia, from August to October 2022. Results: A total of 211 senior clinical pharmacy students responded to the questionnaire. The majority of the respondents were 4th year pharmacy students. The numbers of female and male participants were equal (106 and 105 students, respectively). The participants represented an acceptable level of knowledge about the pathophysiology aspects of epilepsy, with a mean total score of 6.22 ± 1.9 out of a maximum score of 10. The respondents reported that epilepsy could be due to genetic predisposition combined with environmental conditions (80.1%) or brain stroke (17.1%). Regarding the respondent knowledge about the pharmacology of epilepsy, the total score was 4.6 ± 2.1 (maximum attainable score: 9). Conclusions: The majority of pharmacy students had knowledge about the pathophysiology concept of the disease; however, low knowledge was shown by the respondents regarding the pharmacology of epilepsy. Thus, there is a need to identify better strategies to improve students' education.

Targeting inflammation and redox perturbations by lisinopril mitigates Freund's adjuvant-induced arthritis in rats: role of JAK-2/STAT-3/RANKL axis, MMPs, and VEGF.

BACKGROUND: Cardiovascular disorders are major complications of rheumatoid arthritis (RA). Hence, finding effective agents that can target RA progression and its cardiovascular consequences is demanding. The present work aimed to explore the potential of lisinopril, an angiotensin-converting enzyme inhibitor, to mitigate adjuvant's-induced arthritis with emphasis on the pro-inflammatory signals, articular degradation cues, and angiogenesis alongside JAK-2/STAT-3 and Nrf2/HO-1 pathways. METHODS: Lisinopril (10 mg/kg/day) was administered by oral gavage for 3 weeks and the target signals were examined by biochemical assays, ELISA, histopathology, immunoblotting, and immunohistochemistry. RESULTS: Lisinopril attenuated the progression of arthritis as proven by lowering paw edema, arthritic index, and gait scores alongside diminishing the immune-cell infiltration/aberrant histopathology in the dorsal pouch lining. These favorable actions were associated with curtailing the production of inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-17) and the pro-inflammatory angiotensin II alongside upregulating the anti-inflammatory angiotensin-(1-7) in the hind paw of arthritic rats. At the molecular level, lisinopril inhibited the upstream JAK-2/STAT-3 pathway by downregulating the protein expression of p-JAK-2/total JAK-2 and p-STAT-3/total STAT-3 ratio and the nuclear levels of NF-κBp65. Meanwhile, lisinopril curbed the downstream cartilage degradation signals matrix metalloproteinases (MMP-3 and MMP-9) and the bone erosion cue RANKL. Equally important, the protein expression of the angiogenesis signal VEGF was downregulated in the hind paw/dorsal lining. With respect to oxidative stress, lisinopril suppressed the paw lipid peroxides and boosted GSH and Nrf-2/HO-1 pathway. CONCLUSION: Lisinopril attenuated adjuvant-induced arthritis via inhibition of inflammation, articular degradation cues, and angiogenesis.

Wound Healing Metabolites from Peters' Elephant-Nose Fish Oil: An In Vivo Investigation Supported by In Vitro and In Silico Studies.

Gnathonemuspetersii (F. Mormyridae) commonly known as Peters' elephant-nose fish is a freshwater elephant fish native to West and Central African rivers. The present research aimed at metabolic profiling of its derived crude oil via GC-MS analysis. In addition, wound healing aptitude in adult male New Zealand Dutch strain albino rabbits along with isolated bioactive compounds in comparison with a commercial product (Mebo®). The molecular mechanism was studied through a number of in vitro investigations, i.e., radical scavenging and inhibition of COX enzymes, in addition to in silico molecular docking study. The results revealed a total of 35 identified (71.11%) compounds in the fish oil, belonging to fatty acids (59.57%), sterols (6.11%), and alkanes (5.43%). Phytochemical investigation of the crude oil afforded isolation of six compounds 1-6. Moreover, the crude oil showed significant in vitro hydrogen peroxide and superoxide radical scavenging activities. Furthermore, the crude oil along with one of its major components (compound 4) exhibited selective inhibitory activity towards COX-2 with IC50 values of 15.27 and 2.41 µM, respectively. Topical application of the crude oil on excision wounds showed a significant (p < 0.05) increase in the wound healing rate in comparison to the untreated and Mebo®-treated groups, where fish oil increased the TGF-ß1 expression, down-regulated TNF-α, and IL-1ß. Accordingly, Peters' elephant-nose fish oil may be a potential alternative medication helping wound healing owing to its antioxidant and anti-inflammatory activities.

The Effect of Melatonin Supplement on High Arterial Blood Pressure: An Overview from Clinicaltrials.gov.

Background: Melatonin is a hormone produced by the pineal gland primarily at night. It has been suggested that melatonin may possess various cardiovascular benefits, including the potential to lower blood pressure. For this reason, we sought to identify and provide evidence of the effectiveness of melatonin on high arterial blood pressure in clinical trials. Methods: Using the search term "melatonin and hypertension", a search of the ClinicalTrials.gov database was performed on October 10th, 2023. I defined the exclusion and inclusion criteria to isolate appropriate clinical trials. Inclusion criteria for the search included hypertension that utilized melatonin as a treatment supplement; all non-related trials were omitted from the search. The data extractions, including study title, study type, study status, and intervention and outcome details, were compiled. Results: Of the 13 clinical trials identified, only three focused on examining the effects of melatonin. The study titles, enrollment numbers, conditions, statuses, interventions, and outcome measures have been explained in depth. Information gathered from these clinical trials will assist us in identifying the possible risks and benefits of melatonin with respect to high arterial blood pressure. Conclusion: Melatonin has been shown to be an effective treatment for lowering blood pressure. More research is required to fully establish the potential benefits and risks and highlight the mechanisms through which melatonin may influence blood pressure regulation.

Propolis attenuates diabetes-induced testicular injury by protecting against DNA damage and suppressing cellular stress.

Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties-particularly its phenolic and flavonoid constituents-that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group's normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100 mg/kg, respectively, for 8 weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis.

Targeting inflammation in glioblastoma: An updated review from pathophysiology to novel therapeutic approaches.

Glioblastoma (GBM) is a highly aggressive primary malignant brain tumor with a dismal prognosis despite current treatment strategies. Inflammation plays an essential role in GBM pathophysiology, contributing to tumor growth, invasion, immunosuppression, and angiogenesis. As a result, pharmacological intervention with anti-inflammatory drugs has been used as a potential approach for the management of GBM. To provide an overview of the current understanding of GBM pathophysiology, potential therapeutic applications of anti-inflammatory drugs in GBM, conventional treatments of glioblastoma and emerging therapeutic approaches currently under investigation. A narrative review was carried out, scanning publications from 2000 to 2023 on PubMed and Google Scholar. The search was not guided by a set research question or a specific search method but rather focused on the area of interest. Conventional treatments such as surgery, radiotherapy, and chemotherapy have shown some benefits, but their effectiveness is limited by various factors such as tumor heterogeneity and resistance.

Understanding migraine in Saudi society: An assessment of public knowledge and attitudes: A cross-sectional study.

OBJECTIVE: This study aims to assess the knowledge and perceptions of the public toward migraine in Saudi Arabia. METHODS: This cross-sectional survey assessed the knowledge and perceptions of migraine among Saudi Arabian individuals. The study was conducted over three months in 2023 (1st of June 2023 to 31st of August 2023) using a prevalidated online questionnaire divided into four sections. RESULTS: A total of 1,975 adults aged between 18 and 64 completed the web-based survey. Of these, over half were male (n = 1,268; 64.2%). The main causes of migraine identified by the participants were genetic disease (n = 540, 27.3%), followed by physical disease (n = 341, 17.3%), head trauma (n = 274, 13.9%), and psychiatric disease (n = 157, 7.9%). The main symptoms identified by the participants were photophobia (21%), followed by inability to control urine (14.1%), vomiting and nausea (13.8%), and vision loss (8.3%). The majority of the participants in this study had a good knowledge of migraines, while 49% had poor knowledge. The migraine knowledge score was significantly associated with the participants' gender (p = 0.002), age (p = 0.0001), educational level (p = 0.001), employment status (p = 0.001), monthly income (p = 0.0001), region (p = 0.0001), and history of migraine (p = 0.0001). CONCLUSION: Although one-third of the participants exhibiting good knowledge, deficiencies existed in certain clinical aspects, emphasizing the need for targeted educational interventions to enhance public awareness and understanding of migraines.

Serum lncRNAs TUG1, H19, and NEAT1 and their target miR-29b/SLC3A1 axis as possible biomarkers of preeclampsia: Potential clinical insights.

To date, the epigenetic signature of preeclampsia (PE) is not completely deciphered. Oxidative stress-responsive long non-coding RNAs (lncRNAs) are deregulated in preeclamptic placenta; however, their circulating profiles and diagnostic abilities are still unexplored. We investigated serum redox-sensitive lncRNAs TUG1, H19, and NEAT1, and their target miR-29b/cystine/neutral/dibasic amino acids transporter solute carrier family 3, member 1 (SLC3A1) as potential non-invasive biomarkers of PE risk, onset, and severity. We recruited 82 patients with PE and 78 healthy pregnant women. We classified PE patients into early-onset (EOPE) and late-onset (LOPE) subgroups at a cut-off 34 gestational weeks and into severe and mild PE subgroups by blood pressure and proteinuria criteria. Bioinformatics analysis was employed to select lncRNAs/microRNA/target gene interactions. Serum H19, NEAT1, and SLC3A1 mRNA expression were reduced, meanwhile miR-29b levels were elevated, whereas there was no significant difference in TUG1 levels between PE patients and healthy pregnancies. Serum H19 levels were lower, whereas miR-29b levels were higher in EOPE versus LOPE. Serum miR-29b and H19 levels were higher in severe versus mild PE. ROC analysis identified serum H19, NEAT1, miR-29b, and SLC3A1 as potential diagnostic markers, with H19 (AUC = 0.818, 95%CI = 0.744-0.894) and miR-29b (AUC = 0.82, 95%CI = 0.755-0.885) were superior discriminators. Only H19 and miR-29b discriminated EOPE and severe PE cases. In multivariate logistic analysis, miR-29b and H19 were associated with EOPE, using maternal age and gestational age as covariates, while miR-29b was associated with severe PE, using maternal age as covariate. Studied markers were correlated with clinical and ultrasound data in the overall PE group. Serum H19 and TUG1 were negatively correlated with albuminuria in EOPE and LOPE, respectively. NEAT1 and SLC3A1 were correlated with ultrasound data in EOPE. Likewise, TUG1, miR-29b, and SLC3A1 showed significant correlations with ultrasound data in LOPE. Conclusively, this study configures SLC3A1 expression as a novel potential serum biomarker of PE and advocates serum H19 and miR-29b as biomarkers of EOPE and miR-29b as a biomarker of PE severity.

Repurposing ezetimibe as a neuroprotective agent in a rotenone-induced Parkinson's disease model in rats: Role of AMPK/SIRT-1/PGC-1α signaling and autophagy.

As a severe neurological disorder, Parkinson's disease (PD) is distinguished by dopaminergic neuronal degeneration in the substantia nigra (SN), culminating in motor impairments. Several studies have shown that activation of the AMPK/SIRT1/PGC1α pathway contributes to an increase in mitochondrial biogenesis and is a promising candidate for the management of PD. Furthermore, turning on the AMPK/SIRT1/PGC1α pathway causes autophagy activation, which is fundamental for maintaining neuronal homeostasis. Interestingly, ezetimibe is an antihyperlipidemic agent that was recently reported to possess pleiotropic properties in neurology by triggering the phosphorylation and activation of AMPK. Thus, our study aimed to investigate the neuroprotective potential of ezetimibe in rats with rotenone-induced PD by activating AMPK. Adult male Wistar rats received rotenone (1.5 mg/kg, s.c.) every other day for 21 days to induce experimental PD. Rats were treated with ezetimibe (5 mg/kg/day, i.p.) 1 h before rotenone. Ezetimibe ameliorated the motor impairments in open field, rotarod and grip strength tests, restored striatal dopamine and tyrosine hydroxylase in the SN, up-regulated p-AMPK, SIRT1, and PGC1α striatal expression, upsurged the expression of ULK1, beclin1, and LC3II/I, reduced Bax/Bcl2 ratio, and alleviated rotenone-induced histopathological changes in striatum and SN. Our findings also verified the contribution of AMPK activation to the neuroprotective effect of ezetimibe by using the AMPK inhibitor dorsomorphin. Together, this work revealed that ezetimibe exerts a neuroprotective impact in rotenone-induced PD by activating AMPK/SIRT-1/PGC-1α signaling, enhancing autophagy, and attenuating apoptosis. Thus, ezetimibe's activation of AMPK could hold significant therapeutic promise for PD management.

Targeting JAK2/STAT3, NLRP3/Caspase-1, and PK2/PKR2 Pathways with Arbutin Ameliorates Lead Acetate-Induced Testicular Injury in Rats.

The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen's damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.

Exploring Promising Therapies for Non-Alcoholic Fatty Liver Disease: A ClinicalTrials.gov Analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disease and has been increasing in recent years. To date, no FDA-approved drug specifically targets NAFLD. Methods: The terms "Non-alcoholic Fatty Liver Disease" and "NAFLD" were used in a search of ClinicalTrials.gov on August 24, 2023. Two evaluators independently examined the trials using predetermined eligibility criteria. Studies had to be interventional, NAFLD focused, in Phase IV, and completed to be eligible for this review. Results: The ClinicalTrials.gov database was searched for trials examining pharmacotherapeutics in NAFLD. The search revealed 1364 trials, with 31 meeting the inclusion criteria. Out of these, 19 were finalized for evaluation. The dominant intervention model was Parallel. The most prevalent studies were in Korea (26.3%) and China (21.1%). The most common intervention was metformin (12.1%), with others like Exenatide and Pioglitazone accounting for 9.1%. Conclusion: Therapeutics used to manage NAFLD are limited. However, various medications offer potential benefits. Further investigations are definitely warranted.

Activation of AMPK/mTOR-Driven Autophagy and Suppression of the HMGB1/TLR4 Pathway with Pentoxifylline Attenuates Doxorubicin-Induced Hepatic Injury in Rats.

Despite being an effective chemotherapeutic agent, the clinical use of doxorubicin (DOX) is limited by several organ toxicities including hepatic injury. Pentoxifylline (PTX) is a methylxanthine derivative with marked anti-inflammatory and anti-apoptotic features. It is unknown, however, whether PTX can mitigate DOX-evoked hepatotoxicity. This study aims to explore the potential hepatoprotective impact of PTX in DOX-induced hepatic injury and the underlying molecular mechanisms. Histopathology, immunohistochemistry, and ELISA were used to examine liver tissues. The current findings revealed that PTX administration to DOX-intoxicated rats mitigated the pathological manifestations of hepatic injury, reduced microscopical damage scores, and improved serum ALT and AST markers, revealing restored hepatic cellular integrity. These favorable effects were attributed to PTX's ability to mitigate inflammation by reducing hepatic IL-1ß and TNF-α levels and suppressing the pro-inflammatory HMGB1/TLR4/NF-κB axis. Moreover, PTX curtailed the hepatic apoptotic abnormalities by suppressing caspase 3 activity and lowering the Bax/Bcl-2 ratio. In tandem, PTX improved the defective autophagy events by lowering hepatic SQSTM-1/p62 accumulation and enhancing the AMPK/mTOR pathway, favoring autophagy and hepatic cell preservation. Together, for the first time, our findings demonstrate the ameliorative effect of PTX against DOX-evoked hepatotoxicity by dampening the hepatic HMGB1/TLR4/NF-κB pro-inflammatory axis and augmenting hepatic AMPK/mTOR-driven autophagy. Thus, PTX could be utilized as an adjunct agent with DOX regimens to mitigate DOX-induced hepatic injury.

Use of Vaping as a Smoking Cessation Aid: A Review of Clinical Trials.

Purpose: Smoking is a global public health concern, with a significant negative impact on human health and healthcare spending. Vaping, or the use of electronic cigarettes (e-cigarettes), has emerged as a popular alternative to traditional nicotine replacement therapies (NRTs) for smoking cessation. While considered less harmful than combustible cigarettes, the long-term health effects of e-cigarettes (vaping) are unknown. Therefore, this study aimed to identify and provide a comprehensive overview of the performance of vaping in clinical trials. Patients and Methods: A search was conducted in the ClinicalTrials.gov database on April 14th, 2023, using the search term "smoking cessation, e-cigarettes, NRTs, and vaping". Inclusion and exclusion criteria were defined to identify relevant clinical trials. Randomized controlled trials (RCTs) and non-randomized clinical trials that evaluated vaping as a therapeutic approach to smoking cessation were included. Results: A total of 87 clinical trials were identified, of which only seven were related to smoking cessation through vaping as a form of treatment. The primary endpoint was the effect of vaping as smoking cessation, and the secondary endpoints were patients' abstinence rate, withdrawal symptoms, and adverse events of e-cigarettes. Most of the trials used e-cigarettes as an intervention, with some trials including a combination of e-cigarettes and other NRTs. The trials lasted from 4 weeks to 12 months. The overall results of the trials indicated that vaping was effective in helping smokers to quit. It was also associated with a lower risk of adverse events than combustible cigarettes. Conclusion: Vaping appears to be an effective method for smoking cessation, and it is associated with a lower risk of adverse events than combustible cigarettes.

Efficacy and safety of ondansetron for morning sickness in pregnancy: a systematic review of clinical trials.

Background: Ondansetron is a selective antagonist of the serotonin 5-HT3 receptor that is commonly used to treat morning sickness. It is estimated that 70%-80% of pregnant women suffer from morning sickness, a condition characterized by nausea and vomiting. However, it is still controversial regarding its safety during pregnancy, and continued research will be necessary to fully understand the risks and benefits associated with its use. Therefore, we aimed to identify and provide details of the efficacy and safety of ondansetron in clinical trials. Methods: A search was conducted of the ClinicalTrials.gov database on 13 April 2023, using the search term "ondansetron and pregnancy." Inclusion and exclusion criteria were defined to identify relevant clinical trials. The inclusion criteria encompassed clinical trials related to pregnancy that utilized ondansetron as a treatment, while other clinical trials were excluded from consideration. All data extractions such as study title, study status, study type, intervention details, and outcome were collected. Results: A total of 18 clinical trials were identified, of which only 6 focused on studying the effects of ondansetron. Their respective study titles, statuses, conditions, interventions, outcome measures, and enrollment sizes have been written in detail. The information collected from these trials will contribute to our understanding of the potential benefits and risks of ondansetron in the context of pregnancy and its complications. Conclusion: Ondansetron has been shown to be an effective treatment for nausea and vomiting, including pregnancy-related morning sickness. Further research is needed to better understand the potential risks and benefits associated with its use in pregnant women. Systematic Review Registration: ClinicalTrials.gov, identifier.

The preventive effects of ondansetron on chemotherapy-induced nausea and vomiting in adult cancer patients: systematic review from ClinicalTrials.gov.

Purpose: Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of chemotherapy-induced nausea and vomiting (CINV) is of main concern. Ondansetron is a selective serotonin 5-HT3 receptor antagonist that has emerged as an essential medication against CINV in adult cancer patients. Ondansetron efficacy and tolerability have made it a primary medication in CINV prophylaxis and treatment regimens. The study aims to offer a detailed overview of ondansetron's effectiveness, safety, and impact on patients' lives, ultimately contributing to the ongoing research to enhance the quality of cancer care. Methods: On 4 September 2023, a search was conducted of the ClinicalTrials.gov database using the search terms "cancer," "ondansetron," and "Zofran." Inclusion and exclusion criteria were defined to select relevant clinical trials. Included trials were completed with results and interventional studies that assessed the preventive effects of ondansetron on CINV in adult cancer patients. Results: A total of 23 clinical trials were identified, with only 13 of them focusing on investigating the preventive effects of ondansetron on CINV in adult cancer patients. The collective findings from these trials showed an effective management of CINV using ondansetron. Conclusion: Through a comprehensive overview of clinical trials, the use of ondansetron in adult cancer patients represents a significant improvement in CINV management.

The Impact of Intermittent Fasting on Non-Alcoholic Fatty Liver Disease in Older Adults: A Review of Clinicaltrials.gov Registry.

Background: Non-alcoholic fatty liver disease (NAFLD) is a predominant health condition across the world due to its rising prevalence and association with various metabolic disorders. Intermittent fasting (IF) has attracted increasing attention as a dietary approach to addressing weight management and enhancing metabolic well-being, and its potential effects on NAFLD have been a topic of growing research interest. Aim: This review aims to critically evaluate the current evidence on IF's impact on NAFLD, including the mechanisms underlying the observed effects in older adults (65+). Methods: A comprehensive search of Clinicaltrials.gov was conducted to identify relevant studies that investigated the effects of IF on NAFLD in older adults (65+). Data on study design, sample size, intervention details, and outcomes related to NAFLD were extracted and analyzed. Results: As of April 12th, 2023, there were 1304 clinical trials on NAFLD. Most of these were interventional studies. The investigation focused on completed studies and found that limited clinical trials were identified with limited interventional measures. Only five out of the 1304 studies on NAFLD involved IF. Basic and advanced outcome measures were examined. Conclusion: Although some studies suggest that IF may have potential benefits for NAFLD, the evidence is still limited and inconclusive.

Neuroprotective Impact of Linagliptin against Cadmium-Induced Cognitive Impairment and Neuropathological Aberrations: Targeting SIRT1/Nrf2 Axis, Apoptosis, and Autophagy.

Cadmium is an environmental contaminant associated with marked neurotoxicity and cognitive impairment. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has demonstrated promising neuroprotection against cerebral ischemia and diabetic dementia. However, there has been no study of its effect on cadmium-induced cognitive deficits. In the present work, linagliptin's prospective neuroprotective effects against cadmium-evoked cognitive decline were examined in vivo in rats. The molecular pathways related to oxidative stress, apoptosis, and autophagy were investigated. Histology, immunohistochemistry, ELISA, and biochemical assays were performed on brain hippocampi after receiving linagliptin (5 mg/kg/day). The current findings revealed that cadmium-induced learning and memory impairment were improved by linagliptin as seen in the Morris water maze, Y-maze, and novel object recognition test. Moreover, linagliptin lowered hippocampal neurodegeneration as seen in histopathology. At the molecular level, linagliptin curtailed hippocampal DPP-4 and augmented GLP-1 levels, triggering dampening of the hippocampal neurotoxic signals Aß42 and p-tau in rats. Meanwhile, it enhanced hippocampal acetylcholine and GABA and diminished the glutamate spike. The behavioral recovery was associated with dampening of the hippocampal pro-oxidant response alongside SIRT1/Nrf2/HO-1 axis stimulation. Meanwhile, linagliptin counteracted hippocampal apoptosis markers and inhibited the pro-apoptotic kinase GSK-3ß. In tandem, linagliptin activated hippocampal autophagy by lowering SQSTM-1/p62 accumulation, upregulating Beclin 1, and stimulating AMPK/mTOR pathway. In conclusion, linagliptin's antioxidant, antiapoptotic, and pro-autophagic properties advocated its promising neuroprotective impact. Thus, linagliptin may serve as a management approach against cadmium-induced cognitive deficits.

Amphetamines in child medicine: a review of ClinicalTrials.gov.

Background: Globally, the use of amphetamines as therapeutic agents in pediatric medicine is a crucial area of concern, especially given the population's vulnerability. Methods: On 6 August 2023, a search was conducted on ClinicalTrials.gov using "amphetamine" as the keyword. Two independent examiners screened trials against set criteria, including a focus on amphetamine, completion status, an interventional approach, and included children. Ongoing or observational studies were excluded. Data extracted from the qualified trials encompassed primary objectives, participant counts, study duration, and outcomes, with the aim of analyzing children disorders treated by amphetamine. Results: On 6 August 2023, a search of the ClinicalTrials.gov database with the term "amphetamines" identified 179 clinical trials. After extensive exclusion criteria, 19 trials were ultimately selected for analysis. The predominant condition under investigation was attention deficit hyperactivity disorder (ADHD), present in 84.2% of studies. Key study characteristics included: phase 4 trials (36.8%), randomized allocation (63.2%), and the parallel intervention model (42.1%). Masking techniques varied, with no masking in 42.1% of studies, and double and quadruple masking both accounting for 21.1%. Geographically, 78.9% of the studies' participants were from the United States. Conclusion: This study highlights the notable therapeutic potential of amphetamines in pediatric ADHD populations and emphasizes the importance of recognizing potential side effects and addiction risks. As pharmacogenomics offers the prospect of personalized treatments, there is potential to increase therapeutic efficacy and decrease adverse reactions. It is vital to balance these benefits against the inherent risks, understanding the need for continued research to optimize the use of amphetamines in medicine.

Targeting Autophagy, Apoptosis, and Oxidative Perturbations with Dapagliflozin Mitigates Cadmium-Induced Cognitive Dysfunction in Rats.

Cognitive decline and Alzheimer-like neuropathology are common manifestations of cadmium toxicity. Thanks to its antioxidant/anti-apoptotic features, dapagliflozin has demonstrated promising neuroprotective actions. However, its effect on cadmium-induced neurotoxicity is lacking. The present work aimed to examine whether dapagliflozin could protect rats from cadmium-evoked cognitive decline. In this study, the behavioral disturbances and hippocampal biomolecular alterations were studied after receiving dapagliflozin. Herein, cadmium-induced memory/learning decline was rescued in the Morris water maze, novel object recognition task, and Y-shaped maze by dapagliflozin. Meanwhile, the hippocampal histopathological abnormalities were mitigated. The molecular mechanisms revealed that dapagliflozin lowered hippocampal expression of p-tau and Aß42 neurotoxic proteins while augmenting acetylcholine. The cognitive enhancement was triggered by hippocampal autophagy stimulation, as indicated by decreased SQSTM-1/p62 and Beclin 1 upregulation. Meanwhile, a decrease in p-mTOR/total mTOR and an increase in p-AMPK/total AMPK ratio were observed in response to dapagliflozin, reflecting AMPK/mTOR cascade stimulation. Dapagliflozin, on the other hand, dampened the pro-apoptotic processes in the hippocampus by downregulating Bax, upregulating Bcl-2, and inactivating GSK-3ß. The hippocampal oxidative insult was mitigated by dapagliflozin as seen by lipid peroxide lowering, antioxidants augmentation, and SIRT1/Nrf2/HO-1 pathway activation. In conclusion, dapagliflozin's promising neuroprotection was triggered by its pro-autophagic, anti-apoptotic, and antioxidant properties.

Stimulation of Autophagy by Dapagliflozin Mitigates Cadmium-Induced Testicular Dysfunction in Rats: The Role of AMPK/mTOR and SIRT1/Nrf2/HO-1 Pathways.

Cadmium (Cd) is a widespread environmental pollutant that triggers testicular dysfunction. Dapagliflozin is a selective sodium-glucose co-transporter-2 inhibitor with notable antioxidant and anti-apoptotic features. It has shown marked cardio-, reno-, hepato-, and neuroprotective effects. Yet, its effect on Cd-evoked testicular impairment has not been examined. Hence, the goal of the current study was to investigate the potential positive effect of dapagliflozin against Cd-induced testicular dysfunction in rats, with an emphasis on autophagy, apoptosis, and oxidative insult. Dapagliflozin (1 mg/kg/day) was given by oral gavage, and testicular dysfunction, impaired spermatogenesis, and biomolecular events were studied via immunohistochemistry, histopathology, and ELISA. The current findings demonstrated that dapagliflozin improved relative testicular weight, serum testosterone, and sperm count/motility and reduced sperm abnormalities, signifying mitigation of testicular impairment and spermatogenesis disruption. Moreover, dapagliflozin attenuated Cd-induced histological abnormalities and preserved testicular structure. The testicular function recovery was prompted by stimulating the cytoprotective SIRT1/Nrf2/HO-1 axis, lowering the testicular oxidative changes, and augmenting cellular antioxidants. As regards apoptosis, dapagliflozin counteracted the apoptotic machinery by downregulating the pro-apoptotic signals together with Bcl-2 upregulation. Meanwhile, dapagliflozin reactivated the impaired autophagy, as seen by a lowered accumulation of SQSTM-1/p62 and Beclin 1 upregulation. In the same context, the testicular AMPK/mTOR pathway was stimulated as evidenced by the increased p-AMPK (Ser487)/total AMPK ratio alongside the lowered p-mTOR (Ser2448)/total mTOR ratio. Together, the favorable mitigation of Cd-induced testicular impairment/disrupted spermatogenesis was driven by the antioxidant, anti-apoptotic, and pro-autophagic actions of dapagliflozin. Thus, it could serve as a tool for the management of Cd-evoked testicular dysfunction.