The Awareness, Prevalence, and Risk Factors of Chronic Kidney Disease Among Diabetes Mellitus and Hypertensive Patients in the Aseer Region, Saudi Arabia.

Background and objective Given its ever-increasing burden, chronic kidney disease (CKD) represents a significant public health threat. CKD is characterized by a gradual alteration in the kidney's normal glomerular filtration rate, which results in the progressive loss of kidney function over a period of time ranging from a few months to years. Diabetes mellitus (DM) and hypertension (HTN) are well-known risk factors for developing CKD and end-stage renal failure. In light of this, this study aimed to assess the awareness, prevalence, and risk factors of CKD in patients with diabetes and those with HTN in the Aseer region, the Kingdom of Saudi Arabia. Methods A correlational cross-sectional study was conducted among a sample of people across Saudi Arabia. The data collection was conducted via an online questionnaire circulated on social media platforms. The study questionnaire included socioeconomic and demographic information and medical history of DM, HTN, and CKD. Also, patients' awareness of and attitude towards CKD were assessed. Results A total of 301 diabetic or hypertensive patients fulfilling the inclusion criteria completed the study questionnaire. Of them, 174 (57.8%) were aged less than 55 years, while 127 (42.2%) were aged more than 55 years; 200 (66.4%) patients were males. A total of 94 (31.2%) study patients were diabetic, 64 (21.3%) were hypertensive, and 143 (47.5%) were both diabetic and hypertensive; 226 (75.1%) study patients had an overall good awareness of CKD while only 75 (24.9%) showed a poor awareness level. Higher awareness was associated with patients' age, education, and having CKD, DM, or HTN (p<0.05). Conclusion Our findings revealed that CKD was not common among study patients, and its prevalence was found to be less than estimated based on many studies in the literature. Also, diabetic and hypertensive patients showed a higher than satisfactory level of awareness of CKD, especially young patients with high levels of education.

Assessment of Primary Healthcare Providers' Knowledge and Practices in Addressing Asymptomatic Hyperuricemia and Gout in the Asir Region of Saudi Arabia.

Introduction and aim Gout, the most common form of inflammatory arthritis, arises from hyperuricemia, a condition where elevated levels of uric acid lead to the deposition of monosodium urate (MSU) crystals in the joints. Nevertheless, it's important to note that not all cases of hyperuricemia result in gout. Methodology This cross-sectional study was conducted in the Asir region of Saudi Arabia, targeting primary healthcare physicians (PHPs) specializing in family medicine and general practice. The study utilized a modified electronic questionnaire, inspired by similar studies and aligned with recent guidelines, to assess PHPs' knowledge and practices concerning asymptomatic hyperuricemia (AH) and gout. The questionnaire encompassed the PHPs' demographic data and their knowledge and practices for AH and gout management. Results Out of 201 participating PHPs, the majority were male (68.2%), predominantly aged 25-34 years (73.1%), and practicing as general practitioners (61.2%). A significant proportion of PHPs had less than five years of experience (63.7%). In terms of education, 36.8% attended continuing medical education (CME) on AH or gout, and 66.7% were aware of the related management guidelines. The study revealed that the total knowledge score among PHPs averaged 5.18 out of seven, indicating a moderate level of knowledge. However, their practice level was moderate, with a mean practice score of 6.75 out of 12. The study also found no significant differences in knowledge scores based on gender, age, or years of experience, but significant variations were noted based on medical specialty. Conclusion There is a moderate level of knowledge and practice among PHPs in managing AH and gout in the Asir region. Despite adequate knowledge levels, there appears to be a gap in implementing this knowledge into practice, particularly in long-term management strategies. The findings emphasize the need for ongoing medical education and specialized training programs to bridge these gaps. The study provides a valuable framework for identifying and addressing similar challenges in other regions and medical practices.

Cichorium intybus L. significantly alleviates cigarette smoke-induced acute lung injury by lowering NF-κB pathway activation and inflammatory mediators.

Background: Cigarette smoke (CS) is one of the primary causes of acute lung injury (ALI) via provoking pulmonary inflammation and oxidative stress. Despite substantial studies, no effective treatment for ALI is presently available. Purpose: New prospective treatment options for ALI are required. Thus, this project was designed to investigate the in vivo and in vitro protective effects of 70 % methanolic-aqueous crude extract of whole plant of Cichorium intybus (Ci.Mce) against CS-induced ALI. Study design: /methods: Initially, male Swiss albino mice were subjected to whole-body CS exposure for 10 continuous days to prepare CS-induced ALI models. Normal saline (10 mL/kg), Ci.Mce (100, 200, 300 mg/kg), and Dexamethasone (1 mg/kg) were orally administered to respective animal groups 1 h prior to CS-exposure. 24 hrs after the last CS-exposure, BALF and lungs were harvested to study the key characteristics of ALI. Next, HPLC analysis was done to explore the phytoconstituents. Results: Ci.Mce exhibited significant reductions in lung macrophage and neutrophil infiltration, lung weight coefficient, and albumin exudation. Additionally, it effectively ameliorated lung histopathological alterations and hypoxemia. Notably, Ci.Mce exerted inhibitory effects on the excessive generation of IL-6, IL-1ß, and KC in both CS-induced ALI murine models and CSE-stimulated RAW 264.7 macrophages. Noteworthy benefits included the attenuation of oxidative stress induced by CS, evidenced by decreased levels of MDA, TOS, and MPO, alongside enhanced TAC production. Furthermore, Ci.Mce demonstrated a marked reduction in CS-induced NF-κB expression, both in vivo and in vitro. Conclusion: Consequently, Cichorium intybus could be a therapeutic option for CS-induced ALI due to its ability to suppress inflammatory reactions, mitigate oxidative stress, and quell NF-κB p65 activation.

Barriers and Motivators toward Childhood COVID-19 Vaccination: A Cross-Sectional Study Conducted among Saudi Population.

Background and Objectives: In 2020, one of the most important steps that were made was to give priority to the development of a COVID-19 vaccine to prevent the rising incidence of COVID-19 from continuing to rise. However, globally, there is a variable acceptance of the level of the COVID-19 vaccine. This study aims to explore Saudi parents' willingness to vaccinate their children against COVID-19. Materials and Methods: This was a cross-sectional study; the online questionnaire was used to investigate the views of Saudi parents with children aged under 18 toward the immunization of their children against COVID-19. The data were gathered from 10 May 2022 to 31 October 2022. The data analysis uses SPSS version 20. A p-value of 0.05 or lower was regarded as statistically significant. Results: A total of 978 Saudi parents participated in this study. Most of the respondents were from the age group of 36-45 years with the educational qualification of high school and bachelor's degree. Overall, it was observed that the majority, 98.2% of the respondents, disclosed that they needed more information (p = 0.004) about COVID-19 vaccine safety among children so that they could decide whether to vaccinate their child. About 91.4% of parents mention that vaccination against COVID-19 is not necessary for children (p = 0.001). About 68.3% of respondents agreed that getting vaccinated against COVID-19 could help Saudi Arabia control COVID-19 (p = 0.007, RI = 0.76). In terms of negative attitudes toward COVID-19 vaccination, 71.3% think that there will be severe side effects (p = 0.019, RI = 0.75); 67.7% think that the vaccine's protection will only last for a short time (p = 0.055, RI = 0.72); 80.1% said they were afraid of getting vaccinated because of needle fear (p = 0.045, RI = 0.76), and 41.2% said lack of time was the main barrier to not vaccinating their child. Conclusions: Parents expressed concerns regarding the safety and efficacy of the COVID-19 vaccine, which might be some of the main factors influencing their decision to vaccinate their children. It is the need of the hour to take action to communicate, educate, and intervene with Saudi parents to enhance COVID-19 vaccination compliance rates across the board.

Guided Tissue and Bone Regeneration Membranes: A Review of Biomaterials and Techniques for Periodontal Treatments.

This comprehensive review provides an in-depth analysis of the use of biomaterials in the processes of guided tissue and bone regeneration, and their indispensable role in dental therapeutic interventions. These interventions serve the critical function of restoring both structural integrity and functionality to the dentition that has been lost or damaged. The basis for this review is laid through the exploration of various relevant scientific databases such as Scopus, PubMed, Web of science and MEDLINE. From a meticulous selection, relevant literature was chosen. This review commences by examining the different types of membranes used in guided bone regeneration procedures and the spectrum of biomaterials employed in these operations. It then explores the manufacturing technologies for the scaffold, delving into their significant impact on tissue and bone regenerations. At the core of this review is the method of guided bone regeneration, which is a crucial technique for counteracting bone loss induced by tooth extraction or periodontal disease. The discussion advances by underscoring the latest innovations and strategies in the field of tissue regeneration. One key observation is the critical role that membranes play in guided reconstruction; they serve as a barrier, preventing the entry of non-ossifying cells, thereby promoting the successful growth and regeneration of bone and tissue. By reviewing the existing literature on biomaterials, membranes, and scaffold manufacturing technologies, this paper illustrates the vast potential for innovation and growth within the field of dental therapeutic interventions, particularly in guided tissue and bone regeneration.

A Retrospective Cohort Study of the Association Between Calcium Serum Level and Hypertension in Older Adults.

INTRODUCTION:  One of the major global risk factors for cardiovascular morbidity and death is hypertension. Earlier research has been conducted on the connection between calcium consumption and blood pressure. OBJECTIVE: This study aims to investigate the association between calcium serum levels and hypertension in older hypertensive adults. METHODS:  A retrospective cohort study of 121 of hypertension patients was conducted in Prince Faisal Bin Khalid Cardiac Center. The data of all patients were collected by records, including lab, pathology, and medical review, in order to determine the effects on patients, providers, and institutions. Statistical analyses were performed using SPSS Statistics version 26.0. A p-value of <0.05 was considered statistically significant. RESULTS:  The study included 121 adult hypertensive patients with a mean of age 60.29 ± 13.92. The majority of included patients were male (81%). More than one-third of patients were obese (39.7%), about one-third (33.9%) were overweight, and 26.4% of patients were in normal weight. The majority of patients had co-morbidities (68.3%); about one-half of them had diabetes mellitus (52.1%). The calcium level mean was 5.07 ± 1.26. The creatine kinase (CK) (initial day) mean ± SD was 813.22 ± 1146.37 became 221.4 ± 330.67 on the last day. The CK-myocardial band (CK-MB) (initial day) was 65.43 ± 118.9 and became 24.38 ± 23.26 on the last day. Additionally, the troponin (initial day) mean was 23.49 ± 104.26 and became 1.65 ± 2.66 on the last day. The most common discharge medications were anti-platelets (95%), beta-blockers (78.5%), statins (70.2%), and proton-pump inhibitors (PPI) (64.5%). The hospital stay days ranged from 1 to 20 days with a mean of 4.83 ± 3.38. The ICU stay days ranged from 1 to 15 days with a mean of 3.57 ± 2.72. Most of the patients (90.9%) improved. CONCLUSION: There is no significant correlation between calcium levels in hypertensive patients and the demographic characteristics of patients, home or current medications, ECHO findings, or procedures done. However, there is a significant correlation between the calcium level and CK level among patients with hypertension. Further investigations are required to verify the relationship between CK and calcium levels in hypertensive patients.

Public Perception towards Vaccines as Preventive Measures against a Twindemic (Seasonal Influenza and COVID-19): A Cross-Sectional Study from the Aseer Region, Saudi Arabia.

This study aimed to evaluate Saudi Arabian public perceptions toward influenza and COVID-19 immunization during the flu season. A cross-sectional self-administered, structured, and closed-questionnaire online survey was conducted on the general public. A total of 422 people willingly participated in the survey using several social media platforms from 15 May to 15 July 2021. Residents of Saudi Arabia aged 18 or older (eligible for COVID-19 vaccination) were included in the study and willing to answer questionnaires. The 422 participants who agreed to participate in the study completed the questionnaire. Thirty-seven percent of the participants were youth (18-25 years). More than 80% of the participants in the study agreed or strongly agreed that flu and COVID-19 vaccines must be mandatory for all populations. At the same time, 42.4% considered that the COVID-19 vaccine might positively impact the public and the economy in the future. Participants confirmed to have had COVID-19 or the flu since the beginning of the outbreak totaled 21.3%. Of the participants, 54% had sufficient knowledge about vaccine types and safety. Most of our participants (54.9%) agreed that preventive measures were still required, even with the existence of vaccines. Our study provides an overview of COVID-19's influence on Saudi Arabia during the flu season. The Saudi Arabian government should consider preventive efforts to strengthen confidence in the health advantages offered by prospective immunization to prevent a twindemic of influenza and COVID-19.

In silico evaluation of molecular interactions between macrocyclic inhibitors with the HCV NS3 protease. Docking and identification of antiviral pharmacophore site.

An array of computational approaches DFT/QSAR/POM methods has been used for a better understanding of drug properties regarding 13 inhibitor derivatives containing either P2 cyclopentane P1 carboxylic acid moiety (1-9) or a P1 cyclopropyl acyl sulfonamide (10-13). To further recognize binding interactions and their activity trends, molecular docking studies were carried out with the use of HCV, which can be used to accurately predict the interactions of ligands with the receptor. The QSAR models are developed through the use of Multiple Linear Regression (MLR) together with Principal Component Analysis (PCA) methods. The statistical results indicate the multiple correlation coefficient R2 = 0.840, which shows favorable estimation stability, as well as showing a significant correlation between the HCV NS3 protease of the studied compounds and their electron-accepting ability. The POM analysis of the Physico-chemical properties of compounds 1-13, shows that they are bearing (O1, O2) and/or (O1, O2, O3) antiviral pockets, whereby all oxygen atoms are Osp2 and bearing negative charges. Similar to the reference ligand (F9K), the most active compound 10 was bound deeply into the binding cavity of NS3 protease making interactions with the residues Gly137, His57, Ala157, and His528. The anti-hepatitis pharmacophore site is similar to the anti-HIV pharmacophore site.Communicated by Ramaswamy H. Sarma.

Green Synthesis, Characterizations of Zinc Oxide Nanoparticles from Aqueous Leaf Extract of Tridax procumbens Linn. and Assessment of their Anti-Hyperglycemic Activity in Streptozoticin-Induced Diabetic Rats.

Herein, zinc oxide nanoparticles (ZnO NPs) were greenly synthesized from Tridax procumbens aqueous leaf extract (TPE) and characterized physically (e.g., Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM)) and biologically (test of their anti-diabetic activity). Anti-diabetic activities of TPE and TPE-derived ZnO NPs have been carried out in a streptozotocin (STZ)­induced diabetic rat model. Diabetes mellitus (DM) was induced with a single intraperitoneal dosage of the glucose analogue STZ (55 mg/Kg) known to be particularly toxic to pancreatic insulin-producing beta-cells. TPE and TPE-derived ZnO NPs were administered orally, once every day for 21 days in diabetic rats, at 100 and 200 mg/Kg, respectively. The standard antidiabetic medication, glibenclamide, was used as a control at a dose of 10 mg/Kg. Various parameters were investigated, including bodyweight (bw) variations, glycemia, lipidaemia, glycated hemoglobin (HbA1c), and histopathological alterations in the rat's liver and pancreas. The TPE-mediated NPs were small, spherical, stable, and uniform. Compared to TPE and, to a lesser extent, glibenclamide, TPE-derived ZnO NPs lowered blood glucose levels considerably (p < 0.05) and in a dose-dependent manner while preventing body weight loss. Further, positive benefits for both the lipid profile and glycated hemoglobin were also noticed with TPE-derived ZnO NPs. The histopathological assessment revealed that synthesized TPE-derived ZnO NPs are safe, non-toxic, and biocompatible. At 200 mg/Kg/day, TPE-derived ZnO NPs had a more substantial hypoglycemic response than at 100 mg/Kg/day. Thus, in this first reported experimental setting, ZnO NPs biosynthesized from the leaf extract of Tridax procumbens exert more potent anti-diabetic activity than TPE and glibenclamide. We conclude that such a greenly prepared nanomaterial may be a promising alternative or complementary (adjuvant) therapy, at least to the current Indian's traditional medicine system. Translational findings are prompted in human populations to determine the efficacy of these NPs.

Pharmacological effects (gastrointestinal, respiratory and vascular) of Calligonum polygonoides: Animal model based studies.

The aim of this study was to analyze gastrointestinal, respiratory and vascular pharmacological effects of 70% hydro-alcoholic extract of Calligonum polygonoides (Cp. Cr) in animal models. All the procedures were carried-out as per previous literature with slight modification where necessary. It was found that Cp. Cr affected significant relaxation of spontaneous and K+ (80 mM) induced contractions. The results showed a corresponding shift of calcium concentration response curves. Similarly Cp. Cr showed relaxant effect on trachea in carbachol (Cch) induced tracheal contractions. Moreover, contractions induced by phenylephrine (1µM) in quarantine rabbit aortic preparations causes Cp. Cr induced relaxation of aortal contractions. Verapamil was used as a standard calcium channel blocker. The findings of this study suggested vasodilator, bronchodilator and spasmolytic effects of Cp. Cr.

A novel approach for the quantification of paclitaxel loaded in ethyl cellulose/kollicoat and ethylcellulose/eudragit colloidal particles by UPLC-PDA.

An optimized rapid reversed phase ultra-performance liquid chromatography (UPLC-PDA) method has been developed and validated for precise and accurate quantification of paclitaxel in drug delivery systems. The chromatographic separation was attained on L1 (USP) column (2.1 ×50 mm, 1.7µm) with an isocratic mobile phase comprised of acetonitrile and water (1:1; flow rate 0.6 mL/min) and detection was executed at 227 nm by PDA detector. The proposed UPLC-PDA method is found to be rapid with retention time of 1.37 min, selective with homogenous peaks and sensitive with Limit of Detection (LOD) of 0.08µg/mL and Limit of Quantification (LOQ) of 2.6µg/mL. The method showed excellent linearity (R2>0.998) over the range of 0.1 to 0.4mg/mL and applied for the paclitaxel quantification in different formulations with no inference of excipients. Thus, the proposed approach has potential for rapid estimation of drug purity, assay and release profile from pharmaceutical preparations.

Attitude and Willingness to Get COVID-19 Vaccines by a Community Pharmacist in Saudi Arabia: A Cross-Sectional Study.

Introduction: Community pharmacists play a key role as vaccinators for COVID-19. They can reduce the burden of the disease worldwide. Objective: This study used a cross-sectional questionnaire to determine whether the Saudi Arabian public was willing to obtain the COVID-19 vaccine via community pharmacists. Results: The questionnaire focused on the satisfaction, concerns, and opinions towards providing vaccination by community pharmacists. The study featured 415 individuals aged 18 and older (eligible for the COVID-19 vaccine). Of the participants in this study, 58.1% were aged 18-25, with 55.4% female. Most participants (72.8%) have not been exposed to COVID-19 and are not aware of the approval of COVID-19 vaccination by community pharmacists. Of the 415 complete questionnaires, 45% believed that community pharmacists are not experienced in administering vaccines. However, 63% of participants are satisfied with getting the COVID-19 vaccination by a community pharmacist if no other option is available. More than 68% of the respondents agree that community pharmacies should expand their health care services to include vaccinations, prescriptions, checkups, and other forms of preventative medicine. Discussion: The availability of community pharmacist-administered vaccination in Saudi Arabia could be a significant factor in the success of the country's vaccination program. This study may serve as a model to expand the role of pharmacists in other countries' vaccination programs.

Formulation and Evaluation of Diclofenac Potassium Gel in Sports Injuries with and without Phonophoresis.

Background: Pain remains a global public heath priority. Phonophoresis, also known as sonophoresis or ultrasonophoresis, is when an ultrasound is used to maximize the effects of a topical drug. Purpose: The objective of this study was to test, in patients injured in sports or accidents (N = 200), the efficacy of diclofenac potassium (DK) 6%, 4%, and 2% formulated gels with and without phonophoresis in comparison with market available standard diclofenac sodium (DS or DN) gel. Methods: The patients were enrolled after informed consent. By using the lottery method, 100 patients were randomly segregated into five groups without phonophoresis and repeated similarly with phonophoresis at a frequency of 0.8 MHz, an intensity of about 1.5 W/cm2, and at continuous mode (2:1). Group-1 was treated with 6% DK gel, group-2 was treated with 4% DK gel, group-3 was treated with 2% DK gel, group-4 was treated with 4% DS gel and group-5 was given control gel three to four times a week for 4 weeks. The patients were screened by using NPRS and WOMAC scales. They were assessed on the baseline, 4th session, 8th session, 12th session, and 16th session. Results: Significant dose-dependently relief was observed in NPRS (Numeric Pain Rating Scale) and the WOMAC (Western Ontario McMaster Osteo-Arthritis) index for pain in disability and stiffness for each group treated with DK gel compared to DS gel. Phonophoresis increased these benefits significantly when used after topical application of DK gel or DS gel, and the dose-dependent effects of DK gel plus phonophoresis were stronger than the dose-dependent effects of DS gel plus phonophoresis. The faster and profounder relief was due to phonophoresis, which allows more penetration of the DK gel into the skin as compared to the direct application of DK gel in acute, uncomplicated soft tissue injury, such as plantar fasciitis, bursitis stress injuries, and tendinitis. In addition, DK gel with phonophoresis was well tolerated. Thus, in this personalized clinical setting, according to the degree of inflammation or injured-induced pain, disability, and stiffness, DK gel 6% with phonophoresis appeared more effective and thus more recommendable than DS gel 6% alone or DS gel 6% combined to phonophoresis.

Codon Usage is Influenced by Compositional Constraints in Genes Associated with Dementia.

Dementia is a clinical syndrome characterized by progressive cognitive decline, and the symptoms could be gradual, persistent, and progressive. In the present study, we investigated 47 genes that have been linked to dementia. Compositional, selectional, and mutational forces were seen to be involved. Nucleotide components that influenced A- and GC-affected codon usages bias at all three codon positions. The influence of these two compositional constraints on codon usage bias (CUB) was positive for nucleotide A and negative for GC. Nucleotide A also experienced the highest mutational force, and GC-ending codons were preferred over AT-ending codons. A high bias toward GC-ending codons enhances the gene expression level, evidenced by the positive association between CAI- and GC-ending codons. Unusual behavior of the TTG codon showing an inverse relationship with the GC-ending codon and negative influence of gene expression, behavior contrary to all other GC-ending codons, shows an operative selectional force. Furthermore, parity analysis, higher translational selection value, preference of GC-ending codons over AT-ending codons, and association of gene length with gene expression refer to the dominant role of selection pressure with compositional constraint and mutational force-shaping codon usage.

Pharmacokinetic profile of sarcin and thionin from Aspergillus giganteus and in vitro validation against human fungal pathogen.

Fungal infections are more predominant in agricultural and clinical fields. Aspergillosis caused by Aspergillus fumigatus leads to respiratory failure in patients along with various illnesses. Due to the limitation of antifungal therapy and antifungal drugs, there is an emergence to develop efficient antifungal compounds (AFCs) from natural sources to cure and prevent fungal infections. The present study deals with the investigation of the mechanism of the active compounds from Aspergillus giganteus against aspergillosis. Primarily, the bioavailability and toxicological properties of antifungal proteins such as, sarcin, thionin, chitinase and their derivatives have proved the efficiency of pharmacokinetic properties of selected compounds. Molecular interactions of selected compounds from A. giganteus with the virulence proteins of A. fumigatus (UDP-N-acetylglucosamine pyrophosphorylase, N-myristoyl transferase and Chitinase) have exhibited a good glide score and druggable nature of the AFCs. The antagonistic potential of AFCs on the pathogen was confirmed by SEM analysis where the shrunken and damaged spores of AFCs treated pathogen were observed. The integrity of A. fumigatus cell membrane and nuclear membrane treated with AFCs were analyzed by determining the release of cellular materials. The effective concentration of AFCs was found to be 250 µg/ml (P<0.0001). The GC-MS profiling has revealed the volatile bioactive metabolites present in A. giganteus. Further, interaction studies might provide more information on the synergism activity with the non-volatile metabolites which leads to the development of novel drugs for the treatment of aspergillosis.

Glycation-induced age-related illnesses, antiglycation and drug delivery strategies.

OBJECTIVES: Ageing is a major cause of multiple age-related diseases. Several mechanisms have been reported to contribute to these abnormalities including glycation, oxidative stress, the polyol pathway and osmotic stress. Glycation, unlike glycosylation, is an irregular biochemical reaction to the formation of active advanced glycation end-products (AGEs), which are considered to be one of the causes of these chronic diseases. This study provides a recent and comprehensive review on the possible causes, mechanisms, types, analytical techniques, diseases and treatments of the toxic glycation end products. KEY FINDINGS: Several mechanisms have been found to play a role in generating hyperglycaemia-induced oxidative stress including an increase in the levels of reactive oxygen species (ROS), increase in the levels of AGEs, binding of AGEs and their receptors (RAGE) and the polyol pathway and thus have been investigated as promising novel targets. SUMMARY: This review focuses on the key mechanisms attributed to cumulative increases of glycation and pathological RAGE expression as a significant cause of multiple age-related diseases, and reporting on different aspects of antiglycation therapy as a novel approach to managing/treating age-related diseases. Additionally, historical, current and possible future antiglycation approaches will be presented focussing on novel drug delivery methods.

Synthesis and In Vitro/Ex Vivo Characterizations of Ceftriaxone-Loaded Sodium Alginate/poly(vinyl alcohol) Clay Reinforced Nanocomposites: Possible Applications in Wound Healing.

(1) Background: Nanocomposite films are widely applied in the pharmaceutical industry (e.g., nanodrug delivery systems-NDDS). Indeed, these nanomaterials can be produced at a large industrial scale and display valuable properties (e.g., antibacterial, renewability, biodegradability, bioavailability, safety, tissue-specific targeting, and biocompatibility), which can enhance the activity of conventional marketed drugs. (2) Aim: To fabricate and investigate the in vitro properties of the antibiotic ceftriaxone sodium (CTX) once encapsulated into sodium alginate (SA)/poly(vinyl alcohol)PVA-clay reinforced nanocomposite films. (3) Methods: Different ratios of the polymers (i.e., SA, PVA) and CTX drug were used for the synthesis of nanocomposite films by solvent casting technique. Montmorillonite (MMT), modified organically, was added as a nanofiller to increase their thermal and mechanical strength. The prepared samples were physically characterized by thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electronic microscopy (SEM), and energy-dispersive X-ray analysis (EDX). The physicochemical behavior (i.e., swelling, erosion, dissolution/drug release behavior and rat skin permeation) was also assessed. Comparisons were made with the currently marketed free CTX dosage form. (4) Results: TGA of the nanoformulation showed increased thermostability. XRD revealed its semi-crystalline nature. SEM depicted a homogeneous drug-loaded SA/PVA nanocomposite with an average size ranging between 300 and 500 nm. EDX confirmed the elemental composition and uniform distribution of mixing components. The water entrapment efficiency study showed that the highest swelling and erosion ratio is encountered with the nanoformulations S100(3) and S100D15(3). Ex vivo permeation revealed a bi-step discharge mode with an early burst liberation chased by continued drug discharge of devised nanoparticles (NPs). The dissolution studies of the drug-loaded polymer nanocomposites elicited sustained pH-dependent drug release. The cumulative drug release was the highest (90.93%) with S100D15(3). (5) Conclusion: S100D15(3) was the finest formulation. To the best of our knowledge, we also pioneered the use of solvent casting for the preparation of such nanoformulations. Polymers and reinforcing agent, concentrations and pH were rate-deterring features for the preparation of the optimized formulation. Thus, CTX-loaded SA/PVA-MMT reinforced nanocomposite appeared as a promising nanodrug delivery system (NDDS) based on its in vitro physicochemical properties.

Cardioprotective Effect of Rumex vesicarius Linn. Leaf Extract against Catecholamine-Induced Cardiotoxicity.

Rumex vesicarius (L.) is a folklore medicinal herb that has been used for centuries to cure cardiovascular diseases. The present work was carefully designed to ascertain the pharmacological basis for R. vesicarius's therapeutic efficacy in cardiovascular diseases, as well as the underlying mechanism. In the ex vivo investigation, the aqueous-methanolic leaf extract of R. vesicarius was shown to have endothelium-dependent vasorelaxant effects in rabbit aorta tissue preparations, and its hypotensive responses were quantified by pressure and force transducers coupled to the Power Lab Data Acquisition System. Furthermore, when rabbits were subjected to adrenaline-induced myocardial infarction, R. vesicarius demonstrated cardioprotective characteristics. In contrast to the intoxicated group, the myocardial infarction model showed lower ALP, CK-MB, CRP, LDH, ALT, troponin, and AST levels (p > 0.005−0.000), as well as edema, necrosis, apoptosis, inflammatory cell enrolment, and necrosis. R. vesicarius exhibited significant antioxidant activity and delayed noradrenaline-induced platelet aggregation. Its cardioprotective, anticoagulant, and vasorelaxant properties in both investigations (in vivo and ex vivo) are mediated through partial endothelium-dependent, NO and calcium channel blockade mediated vasorelaxation. The minimizing of adrenaline, oxidative stress, and tissue damage demonstrate its therapeutic efficacy in cardiovascular diseases.

Strong Selectional Forces Fine-Tune CpG Content in Genes Involved in Neurological Disorders as Revealed by Codon Usage Patterns.

Neurodegenerative disorders cause irreversible damage to the neurons and adversely affect the quality of life. Protein misfolding and their aggregation in specific parts of the brain, mitochondrial dysfunction, calcium load, proteolytic stress, and oxidative stress are among the causes of neurodegenerative disorders. In addition, altered metabolism has been associated with neurodegeneration as evidenced by reductions in glutamine and alanine in transient global amnesia patients, higher homocysteine-cysteine disulfide, and lower methionine decline in serum urea have been observed in Alzheimer's disease patients. Neurodegeneration thus appears to be a culmination of altered metabolism. The study's objective is to analyze various attributes like composition, physical properties of the protein, and factors like selectional and mutational forces, influencing codon usage preferences in a panel of genes involved directly or indirectly in metabolism and contributing to neurodegeneration. Various parameters, including gene composition, dinucleotide analysis, Relative synonymous codon usage (RSCU), Codon adaptation index (CAI), neutrality and parity plots, and different protein indices, were computed and analyzed to determine the codon usage pattern and factors affecting it. The correlation of intrinsic protein properties such as the grand average of hydropathicity index (GRAVY), isoelectric point, hydrophobicity, and acidic, basic, and neutral amino acid content has been found to influence codon usage. In genes up to 800 amino acids long, the GC3 content was highly variable, while GC12 content was relatively constant. An optimum CpG content is present in genes to maintain a high expression level as required for genes involved in metabolism. Also observed was a low codon usage bias with a higher protein expression level. Compositional parameters and nucleotides at the second position of codons played essential roles in explaining the extent of bias. Overall analysis indicated that the dominance of selection pressure and compositional constraints and mutational forces shape codon usage.

Puberty Induction in Adolescent Males: Current Practice.

Puberty is a developmental stage characterized by the appearance of secondary sexual characteristics which leads to complete physical, psychosocial, and sexual maturation. The current practice of hormonal therapy to induce puberty in adolescent males is based on published consensus and expert opinion. Evidence-based guidelines on optimal timing and regimen in puberty induction in males are lacking, and this reflects some discrepancies in practice among endocrinologists. It is worth mentioning that the availability of various hormonal products in markets, their different routes of administration, and patients/parents' preference also have an impact on clinical decisions. This review outlines the current clinical approach to delayed puberty in boys with an emphasis on puberty induction.