•Recognition memory was impaired in a d-galactose/AlCl3 AD mouse model.•Melatonin improved recognition memory in AD mouse model.•Melatonin improved passive avoidance performance deficits in AD mouse ...model.•Resveratrol improved passive avoidance memory deficit in AD mouse model.•Melatonin improved AChE levels and BDNF/CREB1 expression in AD mice.
Alzheimer’s disease (AD) is the foremost cause of dementia among other neurodegenerative diseases, leading to memory loss and cognitive deficits. AD has gained extensive attention in research for exploring possible interventions. One promising field is natural substances and compounds that could provide a wide range of neuroprotection against AD. This study aimed to investigate the possible effects of melatonin (MEL) and resveratrol (RES) in improving memory deficits in a sporadic mouse model of AD. Memory deficit was induced using AlCl3 and d-galactose for generating an AD mouse model. Mice were randomly distributed into five groups (n = 13): control, AD, AD + MEL (AD mice treated with 80 mg/kg of MEL), AD + RES (AD mice treated with 40 mg/kg of RES), and AD + Combination)AD mice that received 80 mg/kg MEL and 40 mg/kg RES). A novel object recognition task (NORT) and passive avoidance task (PAT) were used for assessing memory. Moreover, acetylcholinesterase (AChE) level, brain-derived neurotrophic factor (BDNF), and cAMP-response element binding (CREB) protein expression were measured in the prefrontal cortex tissue. Our results showed that MEL significantly improved memory deficits in both the NORT and PAT of the AD model, while RES improved the PAT only in the AD model. Co-treatment with MEL and RES exerted beneficial additive effects on recognition memory impairment in the AD mouse model. Moreover, our results demonstrated that both MEL and RES enhanced the cholinergic system and BDNF and CREB signaling pathways in the prefrontal cortex in an AD mouse model.
Factor XIII (FXIII) is a transglutaminase enzyme that catalyses the formation of ε-(γ-glutamyl)lysyl isopeptide bonds into protein substrates. The plasma form, FXIIIA
B
, has an established function ...in haemostasis, with fibrin being its principal substrate. A deficiency in FXIII manifests as a severe bleeding diathesis emphasising its crucial role in this pathway. The FXIII-A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage. The cellular form, a homodimer of the A subunits denoted FXIII-A, was perceived to remain intracellular, due to the lack of a classical signal peptide for its release. It is now apparent that FXIII-A can be externalised from cells, by an as yet unknown mechanism. Thus, three pools of FXIII-A exist within the circulation: plasma where it circulates in complex with the inhibitory FXIII-B subunits, and the cellular form encased within platelets and monocytes/macrophages. The abundance of this transglutaminase in different forms and locations in the vasculature reflect the complex and crucial roles of this enzyme in physiological processes. Herein, we examine the significance of these pools of FXIII-A in different settings and the evidence to date to support their function in haemostasis and wound healing.
. This study provides a comprehensive analysis of the characteristics of clinical trials related to alcohol dependence that are registered on ClinicalTrials.gov.
. All ClinicalTrials.gov trials ...registered up to 1 January 2023 were examined, focusing on trials that involved alcohol dependence. All 1295 trials were summarized by presenting their characteristics and results and reviewed most intervention drugs used in the treatment of alcohol dependence.
. The study analysis identified a total of 1295 clinical trials registered on ClinicalTrials.gov that were focused on alcohol dependence. Of these, 766 trials had been completed, representing 59.15% of the total, while 230 trials were currently recruiting participants, accounting for 17.76% of the total. None of the trials had yet been approved for marketing. The majority of the studies included in this analysis were interventional studies (1145 trials, or 88.41%), which accounted for most of the patients enrolled in the trials. In contrast, observational studies represented only a small portion of the trials (150 studies, or 11.58%) and involved a smaller number of patients. In terms of geographic distribution, the majority of registered studies were located in North America (876 studies, or 67.64%), while only a small number of studies were registered in South America (7 studies, or 0.54%).
. The purpose of this review is to provide a basis for the treatment of alcohol dependence and prevention of its onset through an overview of clinical trials registered at ClinicalTrials.gov. It also offers essential information for future research to guide future studies.
: Numerous studies have indicated that antibiotics may adversely affect testicular and sperm function. As an alternative to penicillin, vancomycin is a glycopeptide antibiotic developed to treat ...resistant strains of Staphylococcus aureus. A few studies have suggested that vancomycin could cause testicular toxicity and apoptosis. Vancomycin, however, has not been investigated in terms of its mechanism of causing testicular toxicity.
An experiment was conducted to investigate the effects of resveratrol (20 mg/kg, oral gavage) against vancomycin (200 mg/kg, i.p.) on the testicular function of Wistar rats for one week (7 days). There were three subgroups of animals. First, saline (i.p.) was administered to the control group. Then, in the second group, vancomycin was administered. Finally, vancomycin and resveratrol were administered in combination in the third group.
After seven days of vancomycin treatment, testosterone levels, sperm counts, and sperm motility were significantly reduced, but resveratrol attenuated the effects of vancomycin and restored the testosterone levels, sperm counts, and sperm motility to normal. In the presence of resveratrol, the vancomycin effects were attenuated, and the luteinizing hormone and follicular hormone levels were normalized after seven days of treatment with vancomycin. Histologically, vancomycin administration for seven days caused damage to testicular tissues and reduced the thickness of the basal lamina. However, the resveratrol administration with vancomycin prevented vancomycin's toxic effects on testicular tissue.
Resveratrol showed potential protective effects against vancomycin-induced testicular toxicity in Wistar rats.
Human activity has led to a rise in the demand for water, prompting Saudi Arabia to search for alternative groundwater supplies. Wadi As-Sirhan is one area that has experienced extensive agricultural ...growth and the severe over-exploitation of its groundwater resources. The groundwater drawn from the wadi should be continuously monitored to determine the best management options for groundwater resources and economic growth. The most recent Gravity Recovery and Climate Experiment (GRACE) mission and outputs of land surface models were combined to estimate the depletion rate of the groundwater of the Wadi As-Sirhan drainage basin in the northern region of Saudi Arabia throughout the period of April 2002–December 2021. The findings are: (1) the average GRACE-derived terrestrial water storage variation (ΔTWS) was calculated at −13.82 ± 0.24 mm/yr; (2) the soil moisture storage variation was averaged at +0.008 ± 0.004 mm/yr; (3) the GRACE-derived groundwater depletion rate was estimated at −13.81 ± 0.24 mm/yr; (4) the annual precipitation data over the Wadi As-Sirhan was averaged at 60 mm/yr; (5) The wadi has a minimal recharge rate of +2.31 ± 0.24 mm/yr, which may partially compensate for a portion of the groundwater withdrawal; (6) the sediment thickness shows an increase from 0 m at the southern igneous and volcanic rocks to more than 3000 m close to the Saudi–Jordanian border; (7) The wadi’s eastern, southern, and western portions are the sources of its tributaries, which ultimately drain into its northwestern portion; (8) change detection from the Landsat photos reveals considerable agricultural expansions over recent decades. The integrated method is useful for analyzing changes to groundwater resources in large groundwater reservoirs and developing environmentally appropriate management programs for these resources.
The coronavirus diseases of 2019 (COVID-19) pandemic was classified as one of the worst pandemics in the 21st century. Its rapid transmission, unpredicted mortality rate, and the uncertainty ...surrounding its transmission method have evoked additional fear and anxiety. Nonetheless, to the best of our knowledge, no prior study has explored PTSD prevalence three months after the start of the quarantine procedures in Saudi Arabia nor has examined PTSD prevalence by three different methods.
This observational cross-sectional study aimed to identify the prevalence, severity, and influencing factors of PTSD in different regions of Saudi Arabia three months after the onset of the quarantine procedures related to the COVID-19 pandemic.
Through the month of June 2020, 1374 people (49.05% men and 50.95% women) completed a 35-item, 10-minute online. The prevalence of PTSD was measured using PCL-S (specific for COVID-19) that assesses the 17 symptoms of PTSD. Resilience was measured using 2-items Arabic version of the Connor-Davidson Resilience Scale 2 (CD-RISC 2).
We calculated the prevalence by three methods, namely, PTSD cut-off score, criteria, and combined, and the prevalence was 22.63%, 24.8%, and 19.6%, respectively. Female participants showed higher prevalence than male. As well, participants who were either tested positive or suspected of having been infected with COVID-19 showed higher PTSD prevalence. Higher resilience was associated with lower PTSD prevalence.
This was the first study to report PTSD prevalence by three differential methods three months after the onset of the quarantine procedures related to the COVID-19 pandemic in Saudi Arabia. We observed a significant impact of the COVID-19 pandemic in the Saudi population; therefore, great attention should be performed in implementing new procedures that deal with the highlighted risk factors, especially in vulnerable groups, to overcome the psychological impact of the COVID-19 pandemic.
Tapentadol is an analgesic compound that acts centrally to attenuate pain. Previous studies have shown that tapentadol has dual mechanisms of action as a mu-opioid receptor agonist and noradrenaline ...re-uptake inhibition. Therefore, tapentadol provides a great advantage over classic opioids in pain management from nociceptive to neuropathic. Cumulative evidence from in vitro data suggests that tapentadol effect of norepinephrine re-uptake could be a new target that overcomes other classic opioids in chronic neuropathic pain. Compared to tramadol and other opioids, tapentadol is associated with fewer adverse effects than tramadol. Tapentadol is a new alternative to treat acute, chronic, and neuropathic pain. Thus, this review article was focused on understanding the studies that led to the development of tapentadol as a novel analgesic drug and its advantages over conventional opioids. Thus, tapentadol is a good alternative with fewer adverse effects and is available for human use.
Complex regional pain syndrome (CRPS) is a chronic disease that affects a limb following an injury or trauma. The CRPS associated with symptoms, including severe pain, swelling, as well as changes in ...skin color and temperature. Treatment of CRPS requires a multidisciplinary approach, with a focus on personalized treatment plans and addressing psychological factors. This review provides an overview of updates in the diagnosis and treatment of CRPS. There are clinical criteria for diagnosing CRPS, including persistent pain and swelling. The CRPS can also be diagnosed with imaging and laboratory tests. Novel insights into treatment approaches for CRPS have been gained from advances in understanding its pathophysiology. Treatment of CRPS includes both pharmacological and non-pharmacological interventions. The latest guidelines for CRPS treatment emphasize the importance of early diagnosis and intervention, personalized treatment plans, and addressing psychological factors in managing CRPS.
Recently, machine learning (ML) and deep learning (DL) models based on artificial intelligence (AI) have emerged as fast and reliable tools for predicting water quality index (WQI) in various regions ...worldwide. In this study, we propose a novel stacking framework based on DL models for WQI prediction, employing a convolutional neural network (CNN) model. Additionally, we introduce explainable AI (XAI) through XGBoost-based SHAP (SHapley Additive exPlanations) values to gain valuable insights that can enhance decision-making strategies in water management. Our findings demonstrate that the stacking model achieves the highest accuracy in WQI prediction (R2: 0.99, MAPE: 15.99%), outperforming the CNN model (R2: 0.90, MAPE: 58.97%). Although the CNN model shows a relatively high R2 value, other statistical measures indicate that it is actually the worst-performing model among the five tested. This discrepancy may be attributed to the limited training data available for the CNN model. Furthermore, the application of explainable AI (XAI) techniques, specifically XGBoost-based SHAP values, allows us to gain deep insights into the models and extract valuable information for water management purposes. The SHAP values and interaction plot reveal that elevated levels of total dissolved solids (TDS), zinc, and electrical conductivity (EC) are the primary drivers of poor water quality. These parameters exhibit a nonlinear relationship with the water quality index, implying that even minor increases in their concentrations can significantly impact water quality. Overall, this study presents a comprehensive and integrated approach to water management, emphasizing the need for collaborative efforts among all stakeholders to mitigate pollution levels and uphold water quality. By leveraging AI and XAI, our proposed framework not only provides a powerful tool for accurate WQI prediction but also offers deep insights into the models, enabling informed decision-making in water management strategies.
Factor XIII (FXIII) is a transglutaminase that promotes thrombus stability by cross-linking fibrin. The cellular form, a homodimer of the A subunits, denoted FXIII-A, lacks a classical signal peptide ...for its release; however, we have shown that it is exposed on activated platelets. Here we addressed whether monocytes expose intracellular FXIII-A in response to stimuli. Using flow cytometry, we demonstrate that FXIII-A antigen and activity are up-regulated on human monocytes in response to stimulation by IL-4 and IL-10. Higher basal levels of the FXIII-A antigen were noted on the membrane of the monocytic cell line THP-1, but activity was significantly enhanced following stimulation with IL-4 and IL-10. In contrast, treatment with lipopolysaccharide did not upregulate exposure of FXIII-A in THP-1 cells. Quantification of the FXIII-A activity revealed a significant increase in THP-1 cells in total cell lysates following stimulation with IL-4 and IL-10. Following fractionation, the largest pool of FXIII-A was membrane associated. Monocytes were actively incorporated into the fibrin mesh of model thrombi. We found that stimulation of monocytes and THP-1 cells with IL-4 and IL-10 stabilized FXIII-depleted thrombi against fibrinolytic degradation, via a transglutaminase-dependent mechanism. Our data suggest that monocyte-derived FXIII-A externalized in response to stimuli participates in thrombus stabilization.
PDF
