Potential acetylcholinesterase inhibitors to treat Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is identified by neuropathological symptoms, and there is now no effective treatment for the condition. A lack of the brain neurotransmitter acetylcholine has been related to the etiology of Alzheimer's disease. Acetylcholinesterase is an enzyme that breaks down acetylcholine to an inactive form and causes the death of cholinergic neurons. Conventional treatments were used but had less effectiveness. Therefore, there is a crucial need to identify alternative compounds with potential anti-cholinesterase agents and minimal undesirable effects. MATERIALS AND METHODS: Fluoroquinolones and benzimidazole-benzothiazole derivatives offer antimicrobial, anti-inflammatory, anti-oxidant, anti-diabetic, and anti-Alzheimer activities. To enhance the chemical portfolio of cholinesterase inhibitors, a variety of fluoroquinolones and benzimidazole-benzothiazole compounds were evaluated against acetylcholinesterase (AChE) butyrylcholinesterase (BChE) enzymes. For this purpose, molecular docking and adsorption, distribution, metabolism, excretion, and toxicology ADMET models were used for in-silico studies for both AChE and BChE enzymes to investigate possible binding mechanisms and drug-likeness of the compounds. The inhibitory effect of docked heterocyclic compounds was also verified in vitro against AChE and BChE enzymes. Fluoroquinolones (Z, Z3, Z4, Z6, Z8, Z12, Z15, and Z9) and benzimidazole-benzothiazole compounds (TBIS-16, TBAF-1 to 9) passed through the AChE inhibition assay and their IC50 values were calculated. RESULTS: The compound 1-ethyl-6-fluoro-7-(4-(2-(4-nitrophenylamino)-2-oxoethyl)piperazin-1-yl) -4-oxo-1,4 di-hydroquinoline-3-carboxylic acid and 2-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(3-bromobenzyl)-4-hydroxy-2H-thiochromene-3-carbohydrazide 1,1-dioxide (Z-9 and TBAF-6) showed the lowest IC50 values against AChE/BChE (0.37±0.02/2.93±0.03 µM and 0.638±0.001/1.31±0.01 µM, respectively) than the standard drug, donepezil (3.9±0.01/4.9±0.05 µM). During the in-vivo investigation, behavioral trials were performed to analyze the neuroprotective impact of Z-9 and TBAF-6 compounds on AD mouse models. The groups treated with Z-9 and TBAF-6 compounds had better cognitive behavior than the standard drug. CONCLUSIONS: This study found that Z-9 (Fluoroquinolones) and TBAF-6 (benzimidazole-benzothiazole) compounds improve behavioral and biochemical parameters, thus treating neurodegenerative disorders effectively.

Effect of Nutrition and Behavior Modification Program (NBMP) on maternal and neonatal outcomes among hyperglycemic mothers.

OBJECTIVE: Hyperglycemic mothers and their offspring are at increased risk of various maternal and neonatal complications such as macrosomia, future type 2 diabetes, and metabolic abnormalities. Early diagnosis and individualized dietary management, exercise, and emotional well-being are expected to reduce these risks. The study aims to identify the effect of the Nutrition and Behavior Modification Program (NBMP) on maternal and neonatal outcomes of hyperglycemic mothers. PATIENTS AND METHODS: A pre-experimental study was performed among 89 hyperglycemic mothers. Glycemic control at 28 and 36 weeks, weight gain during pregnancy, pre-eclampsia, pregnancy-induced hypertension (PIH), mode of delivery, duration of exercise, emotional well-being, neonates' birth weight, incidence of hypoglycemia, and NICU admission were compared among the study and control groups. The intervention group received an individualized NBMP from their diagnosis of hyperglycemia until delivery. RESULTS: The results showed a significant difference in blood glucose between the study periods and groups at p<0.05 as per repeated ANOVA. Also, diet scores had a significant influence on BMI and glycemic control at p<0.05. Logistic regression models, adjusted for potential confounders including baseline blood glucose, age, economic status, previous GDM, family history of DM as well as baseline BMI, diet score, physical activity, and maternal well-being score, indicated that the NBMP reduced the blood glucose and BMI significantly at p<0.05 in the study group. NBMP also reduced the risk of SGA/LGA and preterm/post-mature birth, as well as increased the exercise duration and emotional well-being of mothers. CONCLUSIONS: The study's conclusions draw attention to the possible roles that maternal wellness, physical activity, and diet may have in reducing risks for both hyperglycemic mothers and their newborns. The NBMP resulted in higher adherence to lifestyle changes. Further research on a larger sample of hyperglycemic mothers is recommended to expand the generalizability of the findings.

The wake of the triple epidemic (Tripledemic): does it emphasizes the COVID-19 vaccine as a routine immunization for children? - A cross-sectional study.

OBJECTIVE: Many countries, including the USA, are currently confronting a triple epidemic in children as COVID-19 cases increase and new strains emerge which urge COVID-19 vaccination for children. The Advisory Committee on Immunization Practices (ACIP) for the CDC unanimously approved the inclusion of the COVID-19 vaccine (C19V) in the recommended immunizations. As healthcare professionals (HCPs) and parents are significant players in changing the trend of the triple epidemic by giving the C19V, the present study was done to determine awareness and perception of HCPs and parents on the tripledemic and the need for inclusion of C19V in vaccination schedules for children. PATIENTS AND METHODS: A cross-sectional study was conducted among 400 HCPs and 200 parents to assess their knowledge and perception of tripledemic and the need for the inclusion of C19V. RESULTS: Noticeably, half of the participants had either recent personal (36.2%) or family (21.8%) exposure to some of the tripledemic like RSV, Flu, or COVID-19. On perceived awareness, 42% were concerned about tripledemic, and 35% thought that regular C19V may prevent or reduce tripledemic. Ironically, 11% were not willing to give C19V to their children. The logistic regression model for positive perception of tripledemic and regular C19V identified significant relationships with education (OR 2.19, CI 1.48-3.81), gender (OR 0.9, CI 01.02-2.63), recent personal or family exposure to any of the tripledemic (OR 0.239, CI 0.87-1.63) and presence of children in the family (OR 0.71, CI 1.4-1.96). The reason for favorable perception was preventing self and family from tripledemic. CONCLUSIONS: The findings may give insight to the policymakers for a strategic plan to include C19V in the routine schedule to combat the pandemic and tripledemic by improving herd immunity.

The complexity of basophobia and aging: covariates and consequences.

OBJECTIVE: The study aim is to determine the drug-induced incidence of basophobia, falls, its' related variables and the consequences among older adults. PATIENTS AND METHODS: A descriptive, cross-sectional study was adopted with 210 older adult samples. The tool consisted of 6 sections: a standardized, semi-structured questionnaire and physical examination. Descriptive and inferential statistics were used to analyze the data. RESULTS: Among the study participants, 49% had falls or near falls and 51% had basophobia in the past 6 months. As per final simultaneous regression analysis model of the study, the covariates to activity avoidance were age (ß=-0.129, CI=-0.087 to -0.019), having >5 chronic diseases (ß=-0.086, CI=-1.41 to -1.182), depressive symptoms (ß=-0.09, CI=-0.089 to -0.189), vision impairment (ß=-0.075, CI=-1.28 to -1.56), basophobia (ß=-0.26, CI=-0.059 to -0.415), taking regular antihypertensives (ß=-0.096, CI= -1.21 to -1.56), oral hypoglycemics and insulin (ß=-0.17, CI=-0.442 to -0.971) and sedatives and tranquilizers (ß=-0.37, CI=-1.32 to -1.73). Use of antihypertensives (p<0.001), oral hypoglycemics and insulin (p<0.01), sedatives and tranquilizers (p<0.001) were strongly associated with fall related to activity avoidance. CONCLUSIONS: The result of this current study suggests that the falls, basophobia and its related activity avoidance among elderly may set in a "vicious cycle" of falls, basophobia, and the numerous negative outcomes such as functional impairment, a decrease in quality of life, and hospitalization. Preventive strategies such as tittering dosage, home- and community -based exercises, cognitive behavioral therapy, yoga, meditation and sleep hygiene may be the choice to break this vicious cycle.

Beneficial effects of Naringin against lopinavir/ ritonavir-induced hyperlipidemia and reproductive toxicity in male albino rats.

OBJECTIVE: This research work was planned to determine whether Naringin (NG) had any protective effects against lopinavir/ritonavir (LR)-induced alterations in blood lipid levels, hepatotoxicity, and testicular toxicity. MATERIALS AND METHODS: Four groups of six rats each were used for the study: Control (1% ethanol), naringin (80 mg/kg), lopinavir (80 mg/kg)/ritonavir (20 mg/kg), and lopinavir (80 mg/kg)/ritonavir (20 mg/kg) + naringin (80 mg/kg). The drug treatment was continued for 30 days. On the last day, the serum lipid fractions, liver biochemical parameters, testicular antioxidants (enzymatic and non-enzymatic), and the histopathology of the liver and testis tissue were assessed for all rats. RESULTS: Treatment with NG decreased significantly (p<0.05), the baseline serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C). But these parameters were significantly (p<0.05) increased in LR-treated animals. Naringin, co-administered with LR, restored the liver and testicular biochemical, morphological, and histological balance. CONCLUSIONS: This study shows that NG can be used as a treatment for LR-induced biochemical and histological changes in the liver and testes and changes in serum lipid levels.

Effect of COVID-19 vaccination on influenza-associated respiratory infection (IARI): benefit or backfire.

OBJECTIVE: Undoubtfully, COVID-19 vaccine (C19V) has significantly changed the pandemic's trajectory positively. At the same time, reports of transient local and systemic post-vaccination reactions leave a concern about its unknown impact on common ailments. Its effect on IARI is unclear because the present IARI epidemic began immediately after C19V in the previous season. PATIENTS AND METHODS: A retrospective observational cohort study among 250 Influenza-associated respiratory infection (IARI) patients by a structured interview questionnaire was conducted with the comparison between 3 groups with 1 dose, 2 doses and 2 doses plus booster dose of C19V. The p<0.05 was considered significant in this study. RESULTS: Among samples 21.2% received one dose of the C19V, only 3.6% got Flu vaccination, 30% had ≥2 comorbidities such as diabetes (22.8%), hypertension (28.4%) and ionically, 77.2% were on chronic medications. Significant differences (p<0.05) were found between groups with duration of illness, cough, headache, fatigue, shortness of breath and hospital visits. The logistic regression analysis shows that the extended IARI symptoms and hospital visits were significantly high among Group 3 (OR=9.17, 95% CI=3.01-29.0) and the same trend remained significant after adjusting the incidence of comorbidities among samples, the chronic conditions (OR=5.13, 95% CI=1.37-14.91) and flu vaccination status (O=4.96, 95% CI=1.41-16.2). Also, 66.4% of the patients were indecisive about getting vaccinated further. CONCLUSIONS: It has been challenging to reach any definitive conclusions regarding the effects of C19V on IARI, conducting extensive, substantial population-based studies that integrate clinical and virological data from more than one season is absolutely required, despite the fact that the majority of the reported effects were mild and temporary.

The perspective of pharmacist on pharmacovigilance and adverse drug reaction reporting in Asir region, Saudi Arabia.

OBJECTIVE: Adverse drug reactions (ADRs) are widespread worldwide, and their intervention is critical to patient safety and healthcare quality. Pharmacists are essential in monitoring and reporting ADRs, directly influencing patient care. This study aimed to examine the prevalence of ADRs among pharmacists and their knowledge regarding ADRs, including the factors affecting ADR reporting. SUBJECTS AND METHODS: From September 2021 to November 2021, a cross-sectional survey among pharmacists in the Asir area of Saudi Arabia was planned. This study involved contacting 97 pharmacists using a cluster sampling method. The study's goals were met using a 25-item self-administered questionnaire. Data analysis was done using SPSS version 25 (IBM Corp., Armonk, NY, USA). RESULTS: Ninety-seven pharmacists (male 53.6% and female 46.4%) completed the survey. More than three-fourths of the participants (78.4%) know the ADR reporting system. The survey was completed by 97 pharmacists (male 53.6% and female 46.4%). More than three-quarters of the participants (78.4%) were aware of the ADR reporting system, and the majority (70.8%) were aware that it is done using an online system. Still, only 56.7% knew that the Saudi FDA is the regulatory agency collecting ADR data in Saudi Arabia. Furthermore, 73.2% cited stress in the workplace as a critical deterrent to reporting. Most respondents (76.3%) had an unfavorable attitude about reporting ADRs. CONCLUSIONS: Pharmacists understand ADR reporting, but most lack the mentality to report the incidents. As a result, comprehensive and ongoing training for pharmacists is required to raise awareness of the need for ADR reporting.

General Public Knowledge of Coronavirus Disease 2019 (COVID-19) at Early Stages of the Pandemic: A Random Online Survey in Saudi Arabia.

BACKGROUND: A novel coronavirus was identified at the end of 2019 in Wuhan City, China. Later, it was named as coronavirus disease 2019 (COVID-19) and declared a pandemic in March 2020. Saudi and global health agencies have provided various COVID-19 knowledge tools and facts to the general public. Therefore, this study aims to assess COVID-19 knowledge among the general public in Saudi Arabia at the early stages of the pandemic. PARTICIPANTS AND METHODS: A cross-sectional study was conducted in March 2020 in Saudi Arabia. The study included 1006 participants who responded to a random online COVID-19 public knowledge questionnaire that included five sections: demographic characteristics, general knowledge, prevention practices, home quarantine measures, and knowledge of governmental restrictions. Three levels of knowledge were established: excellent, intermediate, and poor. Differences in the percentages of participants with different knowledge levels by the demographic variables were analyzed using the chi-square test. RESULTS: Regarding overall general knowledge of COVID-19, 75%, 24%, and 1% of the participants had excellent, intermediate, and poor knowledge levels, respectively. Knowledge levels were significantly different by nationality and age (P=0.027 and 0.008, respectively). Most participants (98.4%) reported excellent knowledge of prevention practices, with no statistically significant differences among groups (P>0.005). Older age groups reported higher knowledge of home quarantine measures (86.6% and 86.4% of the 51-60 and older than 60 age groups, respectively, P=0.001). CONCLUSION AND RECOMMENDATIONS: High levels of knowledge about the virus, including prevention practices, are essential. The provision of COVID-19 facts and knowledge tools should be focused on younger generations to enhance compliance with the governmental restrictions required to stop the spread of COVID-19.

Pectin co-functionalized dual layered solid lipid nanoparticle made by soluble curcumin for the targeted potential treatment of colorectal cancer.

The investigation is to increase the cytotoxicity of soluble curcumin (SC) by loading it onto pectin and skimmed milk powder (SMP) dual layered solid lipid nanoparticles (DL-SLN). The DL-SLN exhibited significantly higher encapsulation efficiency (83.94 ± 6.16), better stability (90 days), and sustained the drug release in different gastro intestional (GI) environments upto 72 h. Molecular docking revealed that the Vander Waals (57420.669 Kcal-mol-1) and electrostatic (-197.533) bonds were involved in the DL-SLN complex formation. The in vivo toxicity of DL-SLN was performed by the zebrafish model, the cell cycle arrest at G2/M phase (64.34 %) by flow cytometry, and western blot investigation was recognized molecular level cell death using SW480 cells. Pharmacokinetic (PK) evaluation (Cmax-5.78 ± 3.26 µg/mL; Tmax-24 h) and organ distribution studies confirmed that the co-functionalized pectin based SLN could efficiently improve the oral bioavailability (up to 72 h) of curcumin (CMN) on colon-targeted release.

Stoichiometrically Governed Curcumin Solid Dispersion and Its Cytotoxic Evaluation on Colorectal Adenocarcinoma Cells.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. Curcumin (CMN) is obtained from a natural source and has no toxicity, even at high doses (8,000 mg/kg body weight in 24 hours) and was determined to have anticancer potency on several kinds of carcinoma. However, its medical applications were limited because of its low solubility and poor bioavailability. MATERIALS AND METHODS: To improve the medical applications of CMN, various hydrophilic carriers such as poloxamer 407 (PMX-407), poloxamer 188 (PMX-188), Gelucire 50/13 (Gel-50/13), and mannitol (MNL) were used to prepare a binary complex solid dispersion (SD). These binary SDs were characterized for aqueous solubility in various solvents. Physical stability, thermal behaviors, and morphology were determined by Fourier transform infrared spectrophotometric analysis, powder X-ray diffraction analysis, thermogravimetric analysis, differential scanning calorimetric analysis, scanning electron microscopy, dynamic light scattering study, and the novel dyeing test. In vitro drug release was determined by dissolution study. Based on the characterization, the better SD complex was optimized using Box-Behnken design (BBD). The cytotoxicity and apoptosis study of prepared CMN (C-SD) were used to test for colorectal adenocarcinoma cell lines. RESULTS: These results showed that the solubility of CMN is greatly improved after complexation with PXM-407 in SD. CMN is practically insoluble in water at acidic and neutral pH; however, the SD of CMN with PXM-407 produced significant improvement in solubility (1.266±0.0242 mg/mL) and dissolution (91.36±0.431% at 30 minutes); similarly, these data fit with a phase solubility study and in silico molecular modeling. Moreover, the solid-state characterization revealed that the SD complex exhibits the intermolecular hydrogen bond with drug and carrier. Also, the complex does not undergo any chemical modification owing to the amorphous form, and the dye test showed better coloring impact indicating the solubility of CMN. The cell cycle arrest confirmed at G2/M phase from flow cytometry analysis, and Western blot investigation was recognized molecular level cell death and the complex induced more exploit DNA during apoptosis. CONCLUSION: This study confirmed that the ideal stoichiometric ratio of CMN with carrier to enhance its solubility was 1:1. This molecular complex of PXM-407 was found to be more effective against colorectal cancer (CRC) than pure CMN.

Understanding the genetic aspects of resistance to antidepressants treatment.

Major depression disorder (MDD) is an extremely prevalent disorder and is expected to be the second leading cause of disease burden by 2020 according to the World Health Organisation (WHO). Moreover, this disease burden is predicted to rise in the next 20 years. Antidepressant medications are vital in the therapy of major depression. However, approximately 30-60% of patients treated with current antidepressant drugs fail to attain remission of depressive symptoms leading to drug resistance. Such patients account for a disproportionately great burden of disease, as supported by cost, augmented disability, and suicidal incidents. Antidepressants resistance remains to challenge mental health care professionals, and more relevant research relating newer medications is necessitated to enhance the quality of life of patients with depression. Enhancement in response rates continues the major challenge in antidepressant research, thus a wealth of potentials still exists concerning the antidepressant resistance for the management of major depression. However, the mechanisms causing resistance to antidepressant treatment remain unknown. Hence, clinical and basic research in understanding the fundamental mechanism of antidepressant resistance should remain a key priority. One potential source accounting for these differences in treatment outcome is genetic variations. The pharmacological mechanisms behind antidepressant response are only partly known but genetic factors play a significant role. Future research of risk factors should assist to advance the understanding of the mechanisms underlying drug resistance in mood disorders and contribute to progress their therapeutic management. Thus, psychiatrists could rely on more effective approaches to treat depressive episodes, reducing the incidence of further drug resistance. This review critically summarises the author's view on many aspects of treatment resistance, specific genetic biomarkers, potential strategies and clinical relevance from both clinical and preclinical studies in drug resistance to antidepressant therapies. Finally, this will allow us to suggest possible recommendations and innovative treatment strategies to improve therapeutic outcomes in managing antidepressant resistance.

Efficacy of a novel herbal formulation for weight loss demonstrated in a 16-week randomized, double-blind, placebo-controlled clinical trial with healthy overweight adults.

AIM: To re-evaluate the weight loss efficacy of LI85008F in healthy overweight adults via a 16-week randomized, double-blind, placebo-controlled clinical study. MATERIALS AND METHODS: One hundred and forty overweight participants (body mass index [BMI] 27-29.9 kg/m2 , 29.3% male; ages 21-50 years) were randomized into placebo (n =70) and LI85008F (n =70) groups. The participants received either 900 mg/d of LI85008F in two divided doses or two identical placebo capsules. In addition, participants were counselled to follow an ~1800 kcal/d diet and to engage in walking for 30 min, 5 d/wk throughout the study. RESULTS: At the end of the trial period, the LI85008F supplemented group showed significant reductions in body weight (5.36 ± 1.769 vs. 0.87 ± 1.381 kg; P < 0.0001) and BMI (2.05 ± 0.693 vs. 0.34 ± 0.559 kg/m2 ; P < 0.0001), compared with placebo. Significant reductions in waist and hip circumferences, and a 2.08-fold reduction of waist/hip ratio, were noted in the LI85008F supplemented group. LI85008F supplementation also resulted in significant improvements in lipid profiles, compared with the placebo; low-density lipoprotein (LDL) cholesterol decreased, while high-density lipoprotein (HDL) cholesterol increased, resulting in a significantly improved LDL/HDL ratio. No major adverse events were reported by the participants during the study. CONCLUSIONS: The unique herbal extract blend LI85008F, combined with modest calorie restriction and physical activity, is well tolerated, safe, and effective for weight management in overweight men and women.

A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee.

INTRODUCTION: 5-Loxin is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin in the treatment of osteoarthritis (OA) of the knee. METHODS: Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin in OA patients. RESULTS: Seventy patients completed the study. At the end of the study, both doses of 5-Loxin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups. CONCLUSION: 5-Loxin reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients. TRIAL REGISTRATION: ( CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN05212803.).

Hypoglycemic effect of aqueous extract of Parthenium hysterophorus L. in normal and alloxan induced diabetic rats.

OBJECTIVES: To study the effects of Parthenium hysterophorus L. flower on serum glucose level in normal and alloxan induced diabetic rats. MATERIALS AND METHODS: Albino rats were divided into six groups of six animals each, three groups of normal animals receiving different treatments consisting of vehicle, aqueous extract of Parthenium hysterophorus L. flower (100 mg/kg) and the standard antidiabetic drug, glibenclamide (0.5 mg/kg). The same treatment was given to the other three groups comprising alloxan induced diabetic animals. Fasting blood glucose level was estimated using the glucose oxidase method in normal and alloxan induced diabetic rats, before and 2 h after the administration of drugs. RESULTS: Parthenium hysterophorus L. showed significant reduction in blood glucose level in the diabetic (P<0.01) rats. However, the reduction in blood glucose level with aqueous extract was less than with the standard drug glibenclamide. The extract showed less hypoglycemic effect in fasted normal rats, (P<0.05). CONCLUSION: The study reveals that the active fraction of Parthenium hysterophorus L. flower extract is very promising for developing standardized phytomedicine for diabetes mellitus.