Exploring the potential use of melatonin as a modulator of tramadol-induced rewarding effects in rats.

Background: Melatonin is responsible for regulating the sleep-wake cycle and circadian rhythms in mammals. Tramadol, a synthetic opioid analgesic, is used to manage moderate to severe pain but has a high potential for abuse and dependence. Studies have shown that melatonin could be a potential modulator to reduce tramadol addiction. Methods: Male Wistar rats were used to investigate the effect of melatonin on tramadol-induced place preference. The rats were divided into four groups: control, tramadol, tramadol + melatonin (single dose), and tramadol + melatonin (repeated doses). Tramadol was administered intraperitoneally at 40 mg/kg, while melatonin was administered at 50 mg/kg for both the single dose and repeated-dose groups. The study consisted of two phases: habituation and acquisition. Results: Tramadol administration produced conditioned place preference (CPP) in rats, indicating rewarding effects. However, melatonin administration blocked tramadol-induced CPP. Surprisingly, repeated doses of melatonin were ineffective and did not reduce the expression of CPP compared to that of the single dose administration. Conclusion: The study suggests that melatonin may be a potential therapeutic option for treating tramadol addiction. The results indicate that melatonin attenuates the expression of tramadol-induced CPP, supporting its uses as an adjunct therapy for managing tramadol addiction. However, further studies are needed to investigate its effectiveness in humans.

The natural anticoagulant protein S; hemostatic functions and deficiency.

Protein S (PS) is a vital endogenous anticoagulant. It plays a crucial role in regulating coagulation by acting as a cofactor for the activated protein C (APC) and tissue factor pathway inhibitor (TFPI) pathways. Additionally, it possesses direct anticoagulant properties by impeding the intrinsic tenase and prothrombinase complexes. Protein S oversees the coagulation process in both the initiation and propagation stages through these roles. The significance of protein S in regulating blood clotting can be inferred from the significant correlation between deficits in protein S and an elevated susceptibility to venous thrombosis. This is likely because activated protein C and tissue factor pathway inhibitor exhibit low efficacy as anticoagulants when no cofactors exist. The precise biochemical mechanisms underlying the roles of protein S cofactors have yet to be fully elucidated. Nevertheless, recent scientific breakthroughs have significantly enhanced comprehension findings for these functions. The diagnosis of protein S deficiency, both from a technical and genetic standpoint, is still a subject of debate due to the complex structural characteristics of the condition. This paper will provide an in-depth review of the molecular structure of protein S and its hemostatic effects. Furthermore, we shall address the insufficiency of protein S and its methods of diagnosis and treatment.

What is the purpose of this summary? To provide an in-depth review of the molecular structure of protein S and its hemostatic effects.To address the deficiency of protein S and its methods of diagnosis and treatment.What is known? Protein S operates as an anticoagulant through its roles as a cofactor for APC, TFPI, and an inhibitor of FIXa.Protein S deficiency can be either inherited or acquired.What is new? Plasma protein S and platelet-derived protein S contribute to regulating coagulation and maintaining hemostasis. Protein S can be used as a potential promising treatment target for persons diagnosed with hemophilia.

Saudi Adults' Understanding and Views of Weight Management Practices and Obesity.

Background and Objective: The rising prevalence of overweight and obesity presents a significant global challenge. This study aimed to investigate the understanding and views of weight management practices and obesity among Saudi adults. Methodology: A cross-sectional online survey was conducted from October 2022 to January 2023 among adults residing in Saudi Arabia. Participants completed a self-administered 41-item questionnaire designed to assess their understanding and views regarding weight management practices and obesity. Results: A total of 1066 participants completed the survey. Gender distribution showed a majority of males (55.7%). Age-wise, the majority fell below 51 years, with 37.7% (young) between 18-24, 32.7% (young adult) between 25-33, and 21.3% (adult) between 34-51. Employment was reported by one-third (n = 315) of respondents, while 22.0% (n = 234) had a history of chronic diseases. Furthermore, 77.3% (n = 824) engaged in regular physical activity.The study results revealed that participants' mean score for understanding obesity was 3.28 ± 2.37 (range 0-6), while the average views score was 28.08 ± 8.79 (range 0-34). Furthermore, females displayed a higher level of understanding compared to males. Employment status also played a significant role, with employed individuals having a better understanding of obesity than those who were unemployed. Moreover, participants with higher qualifications demonstrated a more comprehensive understanding of obesity compared to those with lower qualifications. Additionally, individuals with higher monthly income levels displayed a greater understanding of obesity compared to those with lower incomes. Lastly, participants who engaged in regular physical activity exhibited a higher level of understanding compared to those who were physically inactive. Conclusion: The study indicates that factors such as being older, being female, being employed, having higher education and income, and engaging in regular physical activity are associated with increased understanding and favorable views regarding weight management practices and obesity.

The complex regional pain syndrome: Diagnosis and management strategies.

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.

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.

Community pharmacists' perspectives on cardiovascular disease pharmaceutical care in the United Arab Emirates: a questionnaire survey-based analysis.

Background: Community pharmacists play an intermediary role between prescribing physicians and patients in the United Arab Emirates (UAE) and thus are responsible for ensuring that patients receive optimal cardiovascular disease (CVD) pharmaceutical care. Methods: we used a cross-sectional design to assess the perceptions and practices of community pharmacists concerning pharmaceutical care for patients with CVD. A trained researcher visited randomly selected community pharmacies and used a structured questionnaire to conduct in-person interviews with pharmacists. The questionnaire collected demographic data and information on perceptions and practices regarding CVD pharmaceutical care. Results: Five hundred and fifty-one participants were recruited. The average participant age (mean ± SD) was 35 ± 2.7 years. The average perception score regarding CVD prevention and management was 75.6% (95% confidence interval [CI] 77.1%-74.2%), and the average practice score for CVD prevention and management was 87.1% (95% CI 76.5%-79.6%). Bivariate analysis revealed that gender (p = 0.001), education level (p < 0.001), pharmacy position (p = 0.004), work experience (p < 0.001), number of patients served per day (p < 0.001) and being trained on CVD prevention and management (p < 0.001) were significantly associated with perceptions about the prevention and management of CVD. Better practice scores were seen among older participants (OR 1.01; 95% CI 1-1.019), postgraduates (OR 1.77; 95% CI 1.66-1.89), workers at chain pharmacies (OR 1.24; 95% CI 1.11-1.39), pharmacists in charge (OR 1.22; 95% CI 1.01-1.47), pharmacists with >10 years of experience (OR 11.3; 95% CI 6.01-15.62), pharmacists with 6-10 years of experience (OR 4.42; 95% CI 3.90-5) and pharmacists trained on CVD prevention and management (OR 1.29; 95% CI 1.15-1.46). Conclusion: Pharmacy practitioners working in community pharmacies in the UAE actively engage in delivering pharmaceutical care to patients, playing a role in CVD management and prevention. However, they showed low levels of involvement in other healthcare services, specifically in screening and measuring patients' weight, glucose levels, and blood pressure, monitoring treatment responses, maintaining medical records, and reviewing medication refill histories. Activities such as educating patients, providing medication counseling, offering support for treatment adherence, and fostering collaborative relationships with other healthcare providers should be encouraged among UAE community pharmacists to ensure the provision of high-quality patient care.

Factors influencing community pharmacists' knowledge about women's issues in epilepsy.

Background: Previous studies have highlighted instances where pharmacists lacked knowledge regarding women's health issues related to epilepsy. Objectives: To assess UAE community pharmacists' knowledge, toward women's issues in epilepsy. Methods: a cross-sectional research method was employed. A team of seven pharmacy students in their final year visited a randomly selected sample of community pharmacies in the UAE and face-to-face interviews were conducted with the pharmacists using a structured questionnaire. The questionnaire includes two parts; Eight questions designed to elicit data about the demographics of the study participants and 12 questions eliciting insights into the participants' knowledge of women's issues in epilepsy. Results: A total of 412 community pharmacist were recruited in the study. The overall level of knowledge about women's issues in epilepsy was good and the average knowledge score was 81% with a 95% confidence interval (CI) [79.1, 82.7%]. The results of multivariate analysis showed higher knowledge scores in chain pharmacies (OR 1.37; 95% CI 1.12-1.67), Chief pharmacists (OR 1.44; 95% CI 1.01-2.06), Pharmacists in charge (OR 3.46; 95% CI 2.7-4.45), pharmacists with 1-5 Years of experience (OR 2.87; 95% CI 1.71-4.82), pharmacists with 6-10 Years (OR 2.63; 95% CI 1.58-4.38), pharmacists with >10 years (OR 3.13; 95% CI 2.03-4.83), graduation form regional universities (OR 1.37; 95% CI 1.12-1.67), graduation form international universities (OR 1.73; 95% CI 1.36-2.20) and receiving a training on epilepsy (OR 1.36; 95% CI 1.12-1.67). Conclusion: While the findings reveal an overall promising level of knowledge among community pharmacists regarding the issues faced by women with epilepsy, pinpointing which clinical and demographic factors have the most significant impact on this knowledge would permit the implementation of tailored educational interventions. Workshops and modules targeting the issues faced by women with epilepsy would further raise the knowledge and competence among community pharmacists in this area, ensuring better pharmaceutical care for this population.

Community pharmacists' skills and practice regarding dispensing fiscalized substances: a cross-sectional survey.

Background: The use of drugs containing fiscalized substances is essential in different medical areas, including pain management, obstetric emergencies, and the treatment of mental disorders. However, due to their potential for abuse and negative health effects, the dispensing of these substances demands pharmacists with the requisite skills and practice. Objective: This study assesses the skills and practices of pharmacy personnel in the United Arab Emirates (UAE) regarding the dispensing of tramadol, a medication containing fiscalized substances, in community pharmacies. Methodology: A cross-sectional study was conducted. Community Pharmacies were chosen via random sampling, and seven well-trained final year pharmacy students visited them and conducted face-to-face interviews. The survey tool covered items highlighting the demographic data of the subjects, and items on the practice and skills regarding dispensing the fiscalized substances. The content validity ratio values of all tool questions were more than 0.78, suggesting acceptable validity and the Cronbach's α of 0.75 showed as acceptable internal reliability. The primary outcome measures of interest were the skills and practice regarding dispensing Fiscalized substances. Results: A total of 612 pharmacists were recruited in the study. The average practice score was 80%. There was a statistically significant association (p < 0.05) between practices about dispensing fiscalized substances and gender, age group, pharmacy type, work experience, university of graduation, and receiving training on epilepsy and antiepileptic drugs. Conclusion: The results implied that competency and experience are vital factors for the dispensing of tramadol. Contextually, the majority of the pharmacists evidently have the requisite competencies to provide high-quality and proper medical care, with regards to dispensing tramadol, which will minimize drug abuse and medication errors, and assist outpatients to manage their drugs containing fiscalized substances.

Usage of Glucagon-Like Peptide-1 for Obesity in Children; Updated Review of Clinicaltrials.gov.

Background: Obesity in both adults and children is a primary health concern that can lead to many complications at a young age, including insulin resistance, type 2 diabetes, and other diseases. Glucagon-like peptide-1 receptor agonists (GLP-1) are drugs utilized to treat diabetes, but they are also approved as an adjunct to a low-calorie diet to reduce body weight and to enhance the metabolic profile readings for diabetic and non-diabetic patients. However, their efficacy and safety in children have not been extensively examined. Aim: To identify glucagon-like peptide-1 medications for obesity in pediatric participants (aged up to 17 years old). Methods: Analysis of all clinical trials registered on ClinicalTrials.gov for obesity using GLP-1 as a treatment for children. Results: As of January 26th, 2023, 10,828 clinical trials were found. The search included childhood obesity using GLP-1. The number of trials on the use of GLP-1 to treat childhood obesity is limited. The final number of analyzed trials was 19. GLP-1 has been shown to result in the effective management of body gain among children. Conclusion: Exenatide, semaglutide, and liraglutide were the only GLP-1 medications used as the pharmacotherapy option. It has been studied in many circumstances eg, to treat children with severe obesity, PCOS, hypothalamic obesity, glucose tolerance, and as a complementary treatment alongside behavior-lifestyle change and surgery for obesity.

A Review of the Characteristics of Clinical Trials and Potential Medications for Alcohol Dependence: Data Analysis from ClinicalTrials.gov.

Objective. This study provides a comprehensive analysis of the characteristics of clinical trials related to alcohol dependence that are registered on ClinicalTrials.gov. Methods. 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. Results. 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%). Conclusions. 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.

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.

Characterization of interventional clinical trials for monkeypox; systematic review of ClinicalTrials.gov database.

Background: Monkeypox (mpox), a zoonotic viral infection, poses a global threat that is being acknowledged at the national and international levels. This systematic review aims to identify and characterize interventional clinical trials for mpox. Method: All interventional clinical trials registered at ClinicalTrials.gov for mpox were searched up to January 6, 2023. We described the characteristics of interventional clinical trials, and drug interventions (including drugs and vaccines). Results: As of January 6, 2023, there were 10 clinical trials in the ClinicalTrials.gov registry that met our criteria. Most of the interventional clinical trials were focused on the treatment (N = 4, 40%) and prevention (N = 4, 40%) of mpox. From the 10 trials, 50% used random treatment allocation, and six (60%) chose the parallel assignment intervention model. All 10 studies were blinded, and six were open-label blinded. The largest proportion of the clinical trials (N = 4, 40%) were registered in Europe, followed by America (N = 3, 30%) and Africa and others (N = 3, 30%). The JYNNEOS vaccine (40%), followed by Tecovirimat (30%) were the most frequently studied drugs used against mpox. Conclusion: A limited number of clinical trials have been registered on ClinicalTrials.gov since the first case of mpox was reported. Therefore, there is an urgent need to conduct large-scale randomized clinical trials to assess the safety and efficacy of the drugs and vaccines being used against the mpox virus.

Resveratrol Ameliorates Vancomycin-Induced Testicular Dysfunction in Male Rats.

Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusion: Resveratrol showed potential protective effects against vancomycin-induced testicular toxicity in Wistar rats.

Tapentadol: A Review of Experimental Pharmacology Studies, Clinical Trials, and Recent Findings.

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.

Protective role of resveratrol against VCM-induced hepatotoxicity in male wistar rats.

Background: Vancomycin is a glycopeptide antibiotic with a high risk of acute liver injury. Resveratrol is believed to protect the liver against toxicity. Aim: To investigate the ability of resveratrol to attenuate vancomycin-induced liver toxicity in rats injected with vancomycin. Method: Twenty-four adult male Wistar rats were distributed into three groups. The control group received only a vehicle, while the treated group received either vancomycin 200 (mg/kg, i. p.) only or vancomycin (200 mg/kg, i. p.) with resveratrol (20 mg/kg, oral gavage). All groups received their dose once daily for 7 days. Hepatic damage was assessed by measuring biochemical parameter levels in serum, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Also, antioxidants and inflammation biomarkers such as Interleukin-6 (IL-6), malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH) were measured. Furthermore, the vancomycin-induced pathological changes in the liver were evaluated by histopathological studies. Results: In the vancomycin-treated group, hepatic serum biomarkers such as AST, ALT, ALP, IL-6, and MDA were elevated, while NO and GSH were depleted. However, resveratrol co-treatment with vancomycin prevented the elevation of AST, ALT, ALP, IL-6, and MDA and it protected the liver from NO and GSH depletion. Also, regarding vancomycin-induced degeneration of hepatocytes, resveratrol co-treatment with vancomycin prevented such degeneration and improved mononuclear cells in the liver. Conclusion: The results showed that oral administration of resveratrol has a significant hepatoprotective effect against vancomycin-induced hepatotoxicity.

Prevalence of Etiological Factors in Adult Patients With Epilepsy in a Tertiary Care Hospital in the Western Region of Saudi Arabia: A Cross-Sectional Study.

Background Epilepsy is a chronic neurologic condition with different risk factors and genetic predispositions. It is characterized by the occurrence of an epileptic seizure. To our knowledge, most studies have focused on revealing epilepsy prevalence in Saudi Arabia, but the etiological prevalence is still not well-studied in the region. Thus, this research aims to raise awareness and provide more insights into the etiological prevalence of this disorder. Methodology A cross-sectional study was performed among 431 adult patients diagnosed with epilepsy in the Neurology Department at King Abdulaziz Medical City in Jeddah, Saudi Arabia. Patients' data were retrospectively collected from electronic medical files covering the period between May 2016 and April 2021. Epilepsy etiologies were classified as suggested by the International League Against Epilepsy 2017. Results The most commonly identified seizures were generalized (25.3%) and focal (8.9%). However, 66.1% of seizure types were unidentifiable. The most common etiology was structural (42.9%), followed by genetic (7.2%), with strokes (24.3%) and tumors (23.8%) being the most prevalent structural etiologies. However, 47.6% of the patients were classified under unknown etiology. Conclusions This study suggested that epilepsy diagnosed as generalized was by far the most common seizure type in our cohort. Structural etiology was evident in most patients, with stroke being the highest presented etiology.

PLGA-Based Nanomedicine: History of Advancement and Development in Clinical Applications of Multiple Diseases.

Research on the use of biodegradable polymers for drug delivery has been ongoing since they were first used as bioresorbable surgical devices in the 1980s. For tissue engineering and drug delivery, biodegradable polymer poly-lactic-co-glycolic acid (PLGA) has shown enormous promise among all biomaterials. PLGA are a family of FDA-approved biodegradable polymers that are physically strong and highly biocompatible and have been extensively studied as delivery vehicles of drugs, proteins, and macromolecules such as DNA and RNA. PLGA has a wide range of erosion times and mechanical properties that can be modified. Many innovative platforms have been widely studied and created for the development of methods for the controlled delivery of PLGA. In this paper, the various manufacturing processes and characteristics that impact their breakdown and drug release are explored in depth. Besides different PLGA-based nanoparticles, preclinical and clinical applications for different diseases and the PLGA platform types and their scale-up issues will be discussed.

The Neuroprotective Propensity of Organic Extracts of Acacia stenophylla Bark and Their Effectiveness Against Scopolamine-/Diazepam-Induced Amnesia in Mice.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that is more prevalent in the elderly. There is extensive literature on using Acacia species against central nervous system disorders, although Acacia stenophylla has not been investigated for any neuroprotective potential. The purpose of the study was to elucidate the ameliorative effect of ethyl acetate (ASEE) and butanol (ASB) extracts from the bark of A. stenophylla on memory deficits and cognitive dysfunction in scopolamine- or diazepam-induced amnesia in mice. Methods: The phytochemical constituents of the extracts of A. stenophylla were determined by GC-MS and the in vitro anticholinesterase plus antioxidant activities were also evaluated. Anti-amnesic effects were determined employing the open field test, elevated plus maze (EPM), Morris water maze (MWM), and Y-maze paradigms. Results: The in vitro cholinesterase assays disclosed a concentration-dependent inhibition of both AChE and BuChE with IC50 values of 28.48 and 44.86 µg/mL for the ASEE extract and 32.04 and 50.26 µg/mL for the ASB extract against AChE and BuChE respectively. DPPH and H2O2 antioxidant assays revealed respective IC50 values for the ASEE extract of 28.04 and 59.84 µg/mL, plus 32.77 and 64.65 µg/mL for ASB extract. The findings revealed that both extracts possessed substantial antioxidant properties. Furthermore, these fractions restored scopolamine- and diazepam-induced memory deficits in a dose-dependent manner, as observed by a significant decrease in the transfer latency in EPM, reduction in escape latency, added time spent in the target quadrant in the MWM, and elevated spontaneous alternation behavior (SAB) in the Y-maze test. Conclusion: The ameliorative effect of A. stenophylla on scopolamine- and diazepam-induced amnesia can be attributed to antioxidant and anticholinesterase activity. Consequently, the use of A. stenophylla might be exploited in the alleviation of oxidative stress and the management of AD.

Efficacy and safety of delafloxacin, ceftaroline, ceftobiprole, and tigecycline for the empiric treatment of acute bacterial skin and skin structure infections: A network meta-analysis of randomized controlled trials.

Background: This review aimed to conduct an indirect comparison using a Bayesian network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of delafloxacin versus other single antibiotic regimens for the empiric treatment of Acute Bacterial Skin and Skin Structure Infections. Method: A systematic search with no start date restrictions was conducted. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs. Results: Of the 577 studies initially identified, nine RCTs were included in the review. The network meta-analysis showed that ceftaroline, ceftobiprole, delafloxacin and tigecycline had similar efficacy in the indirect comparisons [Ceftaroline Odds Ratio (OR) = 1.2, 95% Crl = 0.46-3.6), ceftobiprole (OR = 1.3, 95% Crl = 0.34-3.0) and tigecycline (OR = 0.96, 95% Crl = 0.30-2.9)]. However, the ranking plot for the intention to treat (ITT) population showed that delafloxacin had a probability of 80.8% to be ranked first followed by ceftobiprole (13.1%). The analysis of the overall adverse events showed that ceftaroline (OR = 0.88, 95% Crl = 0.65-1.2), ceftobiprole (OR = 1.1, 95% Crl = 0.69-2.0), delafloxacin (OR = 0.88, 95% Crl = 0.57-1.3) and tigecycline (OR = 1.4, 95% Crl = 0.88-2.2) had similar safety profiles. Conclusion: Delafloxacin did not show any statistically significant differences when compared to ceftaroline, ceftobiprole, and tigecycline in terms of efficacy and safety. However, the surface under the cumulative ranking curve (SUCRA) probability ranked delafloxacin as the first option for the ITT population.

Deciphering the Link Between ERUPR Signaling and MicroRNA in Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative proteinopathic disease. The deposits of misfolded Amyloid ß and Tau proteins in the brain of patients with AD suggest an imbalance in endoplasmic reticulum (ER) proteostasis. ER stress is due to accumulation of aberrant proteins in the ER lumen, which then leads to activation of three sensor protein pathways that ultimately evokes the adaptive mechanism of the unfolded protein response (UPR). The UPR mechanism operates via adaptive UPR and the apoptotic UPR. Adaptive UPR tries to restore imbalance in ER hemostasis by decreasing protein production, enhanced chaperone involvement to restore protein folding, misfolded protein decay by proteasome, and suppression of ribosomal translation ultimately relieving the excessive protein load in the ER. Subsequently, apoptotic UPR activated under severe ER stress conditions triggers cell death. MicroRNAs (miRNAs) are small non-coding protein causing dysregulated translational of mRNAs in a sequential manner. They are considered to be critical elements in the maintenance of numerous cellular activities, hemostasis, and developmental processes. Therefore, upregulation or downregulation of miRNA expression is implicated in several pathogenic processes. Evidence from scientific studies suggest a strong correlation between ERUPR signaling and miRNA dysregulation but the research done is still dormant. In this review, we summarized the cross-talk between ER stress, and the UPR signaling processes and their role in AD pathology by scrutinizing and collecting information from original research and review articles.