A systematic review of thromboembolic complications and outcomes in hospitalised COVID-19 patients.

Thromboembolic (TE) complications [myocardial infarction (MI), stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE)] are common causes of mortality in hospitalised COVID-19 patients. Therefore, this review was undertaken to explore the incidence of TE complications and mortality associated with TE complications in hospitalised COVID-19 patients from different studies. A literature search was performed using ScienceDirect and PubMed databases using the MeSH term search strategy of "COVID-19", "thromboembolic complication", "venous thromboembolism", "arterial thromboembolism", "deep vein thrombosis", "pulmonary embolism", "myocardial infarction", "stroke", and "mortality". There were 33 studies included in this review. Studies have revealed that COVID-19 patients tend to develop venous thromboembolism (PE:1.0-40.0% and DVT:0.4-84%) compared to arterial thromboembolism (stroke:0.5-15.2% and MI:0.8-8.7%). Lastly, the all-cause mortality of COVID-19 patients ranged from 4.8 to 63%, whereas the incidence of mortality associated with TE complications was between 5% and 48%. A wide range of incidences of TE complications and mortality associated with TE complications can be seen among hospitalized COVID-19 patients. Therefore, every patient should be assessed for the risk of thromboembolic complications and provided with an appropriate thromboprophylaxis management plan tailored to their individual needs.

A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors.

AIM: We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients. METHODS: This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA). RESULTS: The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p < 0.001, partial η2 = 0.333). The Nuvastatic™ group significantly reduced VAS-F fatigue (F (2, 210) = 9.534, p < 0.001, partial η2 = 0.083), improved quality of life (QoL) (F (1.2, 127.48) = 34.07, p < 0.001, partial η2 = 0.243), and lowered urinary F2-IsoP concentrations (mean difference (95% CI) = 55.57 (24.84, 86.30)), t (55) = 3.624, p < 0.001, Cohen's d (95% CI) = 0.48 (0.20, 0.75)). Reported adverse events were vomiting (0.9%), fever (5.4%), and headache (2.7%). CONCLUSION: Nuvastatic™ is potentially an effective adjuvant for CRF management in solid tumor patients and worthy of further investigation in larger trials. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT04546607. Study registration date (first submitted): 11-05-2020.

Development of a novel direct compressible co-processed excipient and its application for formulation of Mirtazapine orally disintegrating tablets.

INTRODUCTION: Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouthfeel suitable for direct compression is limited. OBJECTIVE: This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs. METHODS: A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation. RESULTS: The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% microcrystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min. CONCLUSION: Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications.

Flumazenil Pretreatment Reduces Mefenamic Acid-Induced Central Nervous System Toxicity in Mice.

BACKGROUND: Mefenamic acid (MFA), a common analgesic, causes central nervous system (CNS) toxicity at high doses with a proposed activity on the Gamma-aminobutyric acid (GABA) system. However, it remains unknown whether flumazenil (FMZ), a GABA type A receptor (GABAAR) antagonist, can reverse MFA toxicity. METHODS: The behavioral and neurophysiological effects of MFA were investigated in mice with and without FMZ pre-treatment. The elevated zero maze (EZM) and marble burying tests were used to assess anxiety-like behaviors and burying activities, respectively. The standard bar test was used to evaluate catalepsy, while the actophotometer test was used to measure locomotor activity. Seizure intensity was scored, and fatalities were counted. RESULTS: Without FMZ pre-treatment, MFA induced behavioral and neurophysiological effects in a dose-dependent manner as follows: At a dose of 20 mg/kg, i.p, MFA-treated mice exhibited anxiety-like behaviors, which was determined by a significant increase in the time spent in the closed areas and a significant decrease in the number of entries to the open areas of the EZM apparatus. These mice also showed a significant decrease in the burying activity, manifested as a significant decrease in the number of buried marbles. At 40 mg/kg, i.p., MFA-treated mice showed catalepsy that was associated with a significant decrease in locomotor activity. At a dose of 80 mg/kg, i.p., mice developed fatal tonic-clonic seizures (seizure score = 4). Pre-treatment with FMZ (5 mg/kg, i.p.) significantly reversed the anxiety-like behaviors and restored marble-burying activity. Additionally, FMZ prevented catalepsy, significantly restored locomotor activity, reduced seizure intensity (seizure score = 0.3) and significantly reduced mortalities. CONCLUSIONS: The present study's findings indicate that activation of the GABAAR is involved in the CNS toxicity of MFA, and FMZ reverses MFA toxicity by interfering with this receptor.

Challenges of having a child with thalassemia in Pakistan: A phenomenological study.

BACKGROUND: Thalassemia is a persistent hemolytic disease and has debilitating effects on patients and their parents. Parents of these children experience pain and suffer from additional emotional strain as they provide daily and lifetime care and are mostly concerned about the health and future of their children. AIM: The study aimed to understand the experiences of parents of children with thalassemia related to their family, financial, social, treatment, and psychological issues in Pakistan. METHODS: This descriptive phenomenological study recruited 21 parents of children with thalassemia through purposive sampling until data saturation was achieved. Analysis of transcribed interviews was performed through Colaizzi's method and themes and subthemes revolving around diagnosis, challenges, and treatment issues were extracted. FINDINGS: A total of 21 Pakistani parents participated in this study. Most of the participants were females (n = 16, 76.19%), housewives/stay-at-home moms (n = 13 (61.90%), and were uneducated (n = 6, 28.57%). Regarding genetic traits, only three (14.28%) parents declared that they had genetic traits of thalassemia. The findings of our study revealed that thalassemia is enormously influenced by psychosocial and economic problems because of this disease in their families. CONCLUSION: Our findings indicated that parents of these children face multi-faceted challenges, such as physical, socio-emotional, financial, and familial. These findings may lead to an adequate understanding of their individual needs and efficient utilization of supportive and care programs. PRACTICE IMPLICATIONS: An understanding of such experiences, involving those distinctive to Pakistani culture, is especially vital to inform the care of these children and enhance their quality of life.

Meta-Analysis and Systematic Review of HLA DQ2/DQ8 in Adults with Celiac Disease.

Although people with human leukocyte antigens (HLA) DQ2 and/or DQ8 are more likely to develop celiac disease (CD), the condition cannot be fully explained by this genetic predisposition alone. Multiple, as yet unidentified, factors contribute to the genesis of CD, including genetics, the environment, and the immune system. In order to provide insight into a prospective possibility and an expanded screening technique, we aim to undertake a comprehensive and meta-analytical study of the assessment and distribution of HLA class II (HLA-DQ2/DQ8) in adult CD patients. A systematic review was conducted using an electronic search of databases (PubMed, Google Scholar, Embase, and Direct Science) from January 2004 to February 2022. DQ2/DQ2 homozygotes have the highest risk of developing CD. DQ2/DQ8 typing is an effective test to exclude CD from the differential diagnosis of a patient with CD symptoms. Although other non-HLA genes have been associated with CD, they are rarely considered at diagnosis because they account for only a small proportion of the heritability of CD. This finding, together with the information gathered previously, may be useful in considering widely available and economically feasible screening options for celiac disease in young people.

A Comprehensive Review of the Pharmacological Properties and Bioactive Components of Retama monosperma.

Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), known locally as "R'tam", is a spontaneous and annual herb that belongs to the Fabaceae family. It is native to the Mediterranean regions, specifically in the desert areas and across the Middle Atlas in Morocco. This plant has been extensively used in folk medicine and it is rich in bioactive compounds, including polyphenols, flavonoids, and alkaloids. Current research efforts are focusing on the development of novel natural drugs as alternatives to various organic and non-organic chemical products from Retama monosperma. In addition, extract, and isolated compounds obtained from different parts of the chosen plant have been described to exhibit multiple biological and pharmacological properties such as antioxidant, anti-aging, anti-inflammatory, antihypertensive, anti-helminthic, disinfectant, diuretic, and hypoglycemic effects. The plant-derived extract also acts as an antimicrobial agent, which is highly efficient in the treatment of bacterial, viral, and fungal infections. Its antiproliferative effects are associated with some mechanisms, such as the inhibition of cell cycle arrest and apoptosis. In light of these assessments, we critically highlight the beneficial effects of the flowers, stems, seeds extracts, and isolated compounds from R. monosperma (L.) Boiss in human health care, industrial, and other applications, as well as the possible ways to be employed as a potential natural source for future drug discovery.

Determination of Chemical Composition and Investigation of Biological Activities of Ocimum basilicum L.

This study aimed to determine the chemical composition of the essential oils (EOs) of Ocimum basilicum L., as well as to evaluate the antibacterial, antidiabetic, dermatoprotective, and anti-inflammatory properties, and the EOs and aqueous extracts of O. basilicum. The antibacterial activity was evaluated against bacterial strains, Gram-positive and Gram-negative, using the well diffusion and microdilution methods, whereas the antidiabetic activity was assessed in vitro using two enzymes involved in carbohydrate digestion, α-amylase and α-glucosidase. On the other hand, the dermatoprotective and anti-inflammatory activities were studied by testing tyrosinase and lipoxygenase inhibition activity, respectively. The results showed that the chemical composition of O. basilicum EO (OBEO) is dominated by methyl chavicol (86%) and trans-anethol (8%). OBEO exhibited significant antibacterial effects against Gram-negative and Gram-positive strains, demonstrated by considerable diameters of the inhibition zones and lower MIC and MBC values. In addition, OBEO exhibited significant inhibition of α-amylase (IC50 = 50.51 ± 0.32 µg/mL) and α-glucosidase (IC50 = 39.84 ± 1.2 µg/mL). Concerning the anti-inflammatory activity, OBEO significantly inhibited lipoxygenase activity (IC50 = 18.28 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 24.8 ± 0.01 µg/mL). Moreover, tyrosinase was considerably inhibited by OBEO (IC50 = 68.58 ± 0.03 µg/mL) compared to the aqueous extract (IC50 = 118.37 ± 0.05 µg/mL). The toxicological investigations revealed the safety of O. basilicum in acute and chronic toxicity. The finding of in silico analysis showed that methyl chavicol and trans-anethole (main compounds of OBEO) validate the pharmacokinetics of these compounds and decipher some antibacterial targets.

A Concise Review of Extraction and Characterization of Chondroitin Sulphate from Fish and Fish Wastes for Pharmacological Application.

Chondroitin sulphate (CS) is one of the most predominant glycosaminoglycans (GAGs) available in the extracellular matrix of tissues. It has many health benefits, including relief from osteoarthritis, antiviral properties, tissue engineering applications, and use in skin care, which have increased its commercial demand in recent years. The quest for CS sources exponentially increased due to several shortcomings of porcine, bovine, and other animal sources. Fish and fish wastes (i.e., fins, scales, skeleton, bone, and cartilage) are suitable sources of CS as they are low cost, easy to handle, and readily available. However, the lack of a standard isolation and characterization technique makes CS production challenging, particularly concerning the yield of pure GAGs. Many studies imply that enzyme-based extraction is more effective than chemical extraction. Critical evaluation of the existing extraction, isolation, and characterization techniques is crucial for establishing an optimized protocol of CS production from fish sources. The current techniques depend on tissue hydrolysis, protein removal, and purification. Therefore, this study critically evaluated and discussed the extraction, isolation, and characterization methods of CS from fish or fish wastes. Biosynthesis and pharmacological applications of CS were also critically reviewed and discussed. Our assessment suggests that CS could be a potential drug candidate; however, clinical studies should be conducted to warrant its effectiveness.

Improvement of lipid profile and hepatic oxidative stress in high-fat-diet induced hyperlipidemic Swiss albino rats by Piper betle juice: evidences from in vivo and in silico studies.

Piper betle L. leaves are very popular and traditionally used to chew with betel nut in many Asian countries. In this study, P. betle leaves juice (PBJ) was subjected to evaluation for its antihyperlipidemic activity in the high-fat-diet-induced hyperlipidemic rats model. Swiss albino rats were allowed to high-fat- diet for one month, followed by concurrent administration of PBJ for another month. The rats were then sacrificed and collected blood, tissues and organs. Pharmacokinetic, toxicological studies and molecular docking studies were performed using SwissADME, admetSAR and schrodinger suit-2017. Our investigation showed a promising effect of PBJ on body weight, lipid profile, oxidative and antioxidative enzymes, and the principle enzyme responsible for the synthesis of cholesterol. PBJ at 0.5 - 3.0 mL/rat significantly reduced body weight of hyperlipidemic rats compared to control. PBJ at the doses of 1.0, 1.5, 2.0, and 3.0 mL/rat significantly (p<0.05, p<0.01, p<0.001) improved the levels of TC, LDL-c, TG, HDL-c and VLDL-c. Similarly, PBJ doses starting from 1.0 mL/rat to 3.0 mL/rat reduced the oxidative biomarkers AST, ALT, ALP, and creatinine. The level of HMG-CoA was significantly reduced by PBJ doses 1.5, 2, and 3 ml/rat. A number of compounds have been found to have good pharmacokinetic profile and safety and 4-coumaroylquinic acid exerted the best docking score among them. Thus our findings clearly demonstrated the potential lipid-lowering activities of PBJ both in vivo and in silico studies. PBJ can be a good candidate for the development of antihyperlipidemic medication or as an alternative medicine.

Strategies for using topical corticosteroids in children and adults with eczema.

BACKGROUND: Eczema is a common skin condition. Although topical corticosteroids have been a first-line treatment for eczema for decades, there are uncertainties over their optimal use. OBJECTIVES: To establish the effectiveness and safety of different ways of using topical corticosteroids for treating eczema. SEARCH METHODS: We searched databases to January 2021 (Cochrane Skin Specialised Register; CENTRAL; MEDLINE; Embase; GREAT) and five clinical trials registers. We checked bibliographies from included trials to identify further trials. SELECTION CRITERIA: Randomised controlled trials in adults and children with eczema that compared at least two strategies of topical corticosteroid use. We excluded placebo comparisons, other than for trials that evaluated proactive versus reactive treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, with GRADE certainty of evidence for key findings. Primary outcomes were changes in clinician-reported signs and relevant local adverse events. Secondary outcomes were patient-reported symptoms and relevant systemic adverse events. For local adverse events, we prioritised abnormal skin thinning as a key area of concern for healthcare professionals and patients. MAIN RESULTS: We included 104 trials (8443 participants). Most trials were conducted in high-income countries (81/104), most likely in outpatient or other hospital settings. We judged only one trial to be low risk of bias across all domains. Fifty-five trials had high risk of bias in at least one domain, mostly due to lack of blinding or missing outcome data. Stronger-potency versus weaker-potency topical corticosteroids Sixty-three trials compared different potencies of topical corticosteroids: 12 moderate versus mild, 22 potent versus mild, 25 potent versus moderate, and 6 very potent versus potent. Trials were usually in children with moderate or severe eczema, where specified, lasting one to five weeks. The most reported outcome was Investigator Global Assessment (IGA) of clinician-reported signs of eczema. We pooled four trials that compared moderate- versus mild-potency topical corticosteroids (420 participants). Moderate-potency topical corticosteroids probably result in more participants achieving treatment success, defined as cleared or marked improvement on IGA (52% versus 34%; odds ratio (OR) 2.07, 95% confidence interval (CI) 1.41 to 3.04; moderate-certainty evidence). We pooled nine trials that compared potent versus mild-potency topical corticosteroids (392 participants). Potent topical corticosteroids probably result in a large increase in number achieving treatment success (70% versus 39%; OR 3.71, 95% CI 2.04 to 6.72; moderate-certainty evidence). We pooled 15 trials that compared potent versus moderate-potency topical corticosteroids (1053 participants). There was insufficient evidence of a benefit of potent topical corticosteroids compared to moderate topical corticosteroids (OR 1.33, 95% CI 0.93 to 1.89; moderate-certainty evidence). We pooled three trials that compared very potent versus potent topical corticosteroids (216 participants). The evidence is uncertain with a wide confidence interval (OR 0.53, 95% CI 0.13 to 2.09; low-certainty evidence). Twice daily or more versus once daily application We pooled 15 of 25 trials in this comparison (1821 participants, all reported IGA). The trials usually assessed adults and children with moderate or severe eczema, where specified, using potent topical corticosteroids, lasting two to six weeks. Applying potent topical corticosteroids only once a day probably does not decrease the number achieving treatment success compared to twice daily application (OR 0.97, 95% CI 0.68 to 1.38; 15 trials, 1821 participants; moderate-certainty evidence). Local adverse events Within the trials that tested 'treating eczema flare-up' strategies, we identified only 26 cases of abnormal skin thinning from 2266 participants (1% across 22 trials). Most cases were from the use of higher-potency topical corticosteroids (16 with very potent, 6 with potent, 2 with moderate and 2 with mild). We assessed this evidence as low certainty, except for very potent versus potent topical corticosteroids, which was very low-certainty evidence.  Longer versus shorter-term duration of application for induction of remission No trials were identified. Twice weekly application (weekend, or 'proactive therapy') to prevent relapse (flare-ups) versus no topical corticosteroids/reactive application Nine trials assessed this comparison, generally lasting 16 to 20 weeks. We pooled seven trials that compared weekend (proactive) topical corticosteroids therapy versus no topical corticosteroids (1179 participants, children and adults with a range of eczema severities, though mainly moderate or severe). Weekend (proactive) therapy probably results in a large decrease in likelihood of a relapse from 58% to 25% (risk ratio (RR) 0.43, 95% CI 0.32 to 0.57; 7 trials, 1149 participants; moderate-certainty evidence). Local adverse events We did not identify any cases of abnormal skin thinning in seven trials that assessed skin thinning (1050 participants) at the end of treatment. We assessed this evidence as low certainty. Other comparisons  Other comparisons included newer versus older preparations of topical corticosteroids (15 trials), cream versus ointment (7 trials), topical corticosteroids with wet wrap versus no wet wrap (6 trials), number of days per week applied (4 trials), different concentrations of the same topical corticosteroids (2 trials), time of day applied (2 trials), topical corticosteroids alternating with topical calcineurin inhibitors versus topical corticosteroids alone (1 trial), application to wet versus dry skin (1 trial) and application before versus after emollient (1 trial). No trials compared branded versus generic topical corticosteroids and time between application of emollient and topical corticosteroids. AUTHORS' CONCLUSIONS: Potent and moderate topical corticosteroids are probably more effective than mild topical corticosteroids, primarily in moderate or severe eczema; however, there is uncertain evidence to support any advantage of very potent over potent topical corticosteroids. Effectiveness is similar between once daily and twice daily (or more) frequent use of potent topical corticosteroids to treat eczema flare-ups, and topical corticosteroids weekend (proactive) therapy is probably better than no topical corticosteroids/reactive use to prevent eczema relapse (flare-ups). Adverse events were not well reported and came largely from low- or very low-certainty, short-term trials. In trials that reported abnormal skin thinning, frequency was low overall and increased with increasing potency. We found no trials on the optimum duration of treatment of a flare, branded versus generic topical corticosteroids, and time to leave between application of topical corticosteroids and emollient. There is a need for longer-term trials, in people with mild eczema.

Carrageenophyte Kappaphycus malesianus Inhibits Microglia-Mediated Neuroinflammation via Suppression of AKT/NF-κB and ERK Signaling Pathways.

Neuroinflammation is an inflammatory response in any part of the central nervous system triggered by the activation of microglia and astrocytes to produce proinflammatory cytokines in the brain. However, overproduction of proinflammatory cytokines further contributes to the development of neurodegenerative disorders. Red seaweed, Kappaphycus malesianus, is a predominant carrageenophyte commercially cultivated in Semporna, Sabah, Malaysia. It is an important source of raw material for kappa-carrageenan productions in the food, pharmaceutical and cosmetics industries. However, no studies have been conducted focusing on the antineuroinflammatory effects of K. malesianus. The aim of the present study was to investigate the effect of the antineuroinflammatory activity of K. malesianus extracts (ethyl acetate, ethanol and methanol) on lipopolysaccharide-stimulated BV2 microglia and the underlying mechanisms involved in the regulation of neuroinflammatory pathways. Extract with the most promising antineuroinflammatory activity was analyzed using liquid chromatography-mass spectrometry (LC-MS). Our results show that methanol extract has a convincing antineuroinflammatory effect by suppressing both AKT/NF-κB and ERK signaling pathways to inhibit the expression of all proinflammatory cytokines without causing a cytotoxicity effect. LC-MS analysis of methanol extract revealed two compounds: prosopinine and eplerenone. Our findings indicated that metabolites of K. malesianus are potent antineuroinflammatory agents with respect to prevention of neurological disorders.

Situational judgment using ethical reasoning in Saudi undergraduate pharmacy students.

INTRODUCTION: There is a paramount need for moral development for pharmacists and pharmacy students to practice the patient-centered profession. We aimed to explore the current situational judgment utilizing ethical reasoning among undergraduate pharmacy students. METHODS: A set of ten ethical dilemmas, representing potential real-life situations that the students come across in the university and may face in the future as a pharmacist were developed by a team of students, academic staff, and stakeholders. These ethical dilemmas were validated, checked for accuracy, and piloted. An online questionnaire was created consisting of these ten scenarios as open-ended questions and administered to fourth year and fifth year PharmD students in a public university located at the city of Mecca, Saudi Arabia, asking them how they would react in that situation. Responses of the participants were analyzed using thematic analysis independently by four researchers and inter-rater agreement were achieved through consensus. RESULTS: Out of 205, 186 students completed the questionnaire with a response rate of 90.7%. Analysis and resulted in the generation of 32 codes, which were then categorized into seven overarching themes: student engagement, social and professional responsibility, academic integrity, legal obligation, moral obligation, signposting, and moral engagement and patient safety. CONCLUSIONS: Undergraduate pharmacy students experience complex state of mind in connection with ethical reasoning. The participants' situational judgment were driven by cultural norm, authority, and responsibility. Student engagement is also affected by the state of mind and feelings of mutual trust, perceived cultural influence and peer pressure. The students were prone to seek help from university administrators or teachers when faced with situations in which they were helpless.

Targeting Immune Senescence in Atherosclerosis.

Atherosclerosis is one of the main underlying causes of cardiovascular diseases (CVD). It is associated with chronic inflammation and intimal thickening as well as the involvement of multiple cell types including immune cells. The engagement of innate or adaptive immune response has either athero-protective or atherogenic properties in exacerbating or alleviating atherosclerosis. In atherosclerosis, the mechanism of action of immune cells, particularly monocytes, macrophages, dendritic cells, and B- and T-lymphocytes have been discussed. Immuno-senescence is associated with aging, viral infections, genetic predispositions, and hyperlipidemia, which contribute to atherosclerosis. Immune senescent cells secrete SASP that delays or accelerates atherosclerosis plaque growth and associated pathologies such as aneurysms and coronary artery disease. Senescent cells undergo cell cycle arrest, morphological changes, and phenotypic changes in terms of their abundances and secretome profile including cytokines, chemokines, matrix metalloproteases (MMPs) and Toll-like receptors (TLRs) expressions. The senescence markers are used in therapeutics and currently, senolytics represent one of the emerging treatments where specific targets and clearance of senescent cells are being considered as therapy targets for the prevention or treatment of atherosclerosis.

Cosmeceutical Therapy: Engaging the Repercussions of UVR Photoaging on the Skin's Circadian Rhythm.

Sunlight is an important factor in regulating the central circadian rhythm, including the modulation of our sleep/wake cycles. Sunlight had also been discovered to have a prominent influence on our skin's circadian rhythm. Overexposure or prolonged exposure to the sun can cause skin photodamage, such as the formation of irregular pigmentation, collagen degradation, DNA damage, and even skin cancer. Hence, this review will be looking into the detrimental effects of sunlight on our skin, not only at the aspect of photoaging but also at its impact on the skin's circadian rhythm. The growing market trend of natural-product-based cosmeceuticals as also caused us to question their potential to modulate the skin's circadian rhythm. Questions about how the skin's circadian rhythm could counteract photodamage and how best to maximize its biopotential will be discussed in this article. These discoveries regarding the skin's circadian rhythm have opened up a completely new level of understanding of our skin's molecular mechanism and may very well aid cosmeceutical companies, in the near future, to develop better products that not only suppress photoaging but remain effective and relevant throughout the day.

Fast Melt Cocoa Butter Tablet: Effect of Waxes, Starch, and PEG 6000 on Physical Properties of the Preparation.

A fast melt tablet (FMT) is well regarded as an alternative delivery system that might help resolve a patient's non-compliance issue. The main objective of this study was to develop a cocoa butter-based FMT. Additives, namely 5-15% of PEG 6000, beeswax, paraffin wax, and corn starch, were incorporated into the cocoa butter-based FMT to study the effects of these additives with the physical characteristic of a cocoa butter FMT. An optimum-based formulation was chosen according to the desired hardness and disintegration time and the taste masking property achieved with the model drug-dapoxetine. The analysis demonstrated that incorporating beeswax (15%) and paraffin wax (15%) could prolong the disintegration time by at least two-fold. On the contrary, the presence of corn starch was found to cause an increase in the hardness and reduction of the disintegration time. The disintegration mechanism might be presumed due to the synergistic effect of starch swelling and cocoa butter melting. The hardness value and in vitro disintegration time of the optimum formulation were recorded at 2.93 ± 0.22 kg and 151.67 ± 6.98 s. In terms of dissolution, 80% of dapoxetine was released within 30 min and the dissolution profile was comparable to the innovator product. The formulation was palatable and stable for at least 1 year. The exposure of the FMT formulation at 30 °C for 12 months was reported to be stable. Along with the sound palatability profile and high drug load capacity, the current formulation possesses the desired characteristics to be scaled up and marketed.

In Silico Analysis of PORD Mutations on the 3D Structure of P450 Oxidoreductase.

Cytochrome P450 oxidoreductase (POR) is a membrane-bound flavoprotein that helps in transferring electrons from its NADPH domain to all cytochrome P450 (CYP450) enzymes. Mutations in the POR gene could severely affect the metabolism of steroid hormones and the development of skeletal muscles, a condition known as Cytochrome P450 oxidoreductase deficiency (PORD). PORD is associated with clinical presentations of disorders of sex development, Antley and Bixler's syndrome (ABS), as well as an abnormal steroid hormone profile. We have performed an in silico analysis of POR 3D X-ray protein crystal structure to study the effects of reported mutations on the POR enzyme structure. A total of 32 missense mutations were identified, from 170 PORD patients, and mapped on the 3D crystal structure of the POR enzyme. In addition, five of the missense mutations (R457H, A287P, D210G, Y181D and Y607C) were further selected for an in-depth in silico analysis to correlate the observed changes in POR protein structure with the clinical phenotypes observed in PORD patients. Overall, missense mutations found in the binding sites of POR cofactors could lead to a severe form of PORD, emphasizing the importance of POR cofactor binding domains in transferring electrons to the CYP450 enzyme family.

Formulation Development of Mirtazapine Liquisolid Compacts: Optimization Using Central Composite Design.

Mirtazapine is a tetracyclic anti-depressant with poor water solubility. The aim of this study was to improve the dissolution rate of mirtazapine by delivering the drug as a liquisolid compact. Central composite design (CCD) was employed for the preparation of mirtazapine liquisolid compacts. In this, the impacts of two independent factors, i.e., excipient ratio (carrier:coating) and different drug concentration on the response of liquisolid system were optimized. Liquisolid compacts were prepared using propylene glycol as a solvent, microcrystalline cellulose as a carrier, and silicon dioxide (Aerosil) as the coating material. The crystallinity of the formulated drug and the interactions between the excipients were examined using X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR), respectively. The dissolution study for the liquisolid compact was carried out as per FDA guidelines. The results showed loss of crystallinity of the mirtazapine in the formulation and was completely solubilized in non-volatile solvent and equally dispersed throughout the powder system. Moreover, drug dissolution was found to be higher in liquisolid compacts than the direct compressed conventional tablets (of mirtazapine). The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like mirtazapine.

In Vitro Influence of ZnO, CrZnO, RuZnO, and BaZnO Nanomaterials on Bacterial Growth.

In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria's growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings.

Influence of the Extraction Method on the Quality and Chemical Composition of Walnut (Juglans regia L.) Oil.

The present study investigated and compared the quality and chemical composition of Moroccan walnut (Juglans regia L.) oil. This study used three extraction techniques: cold pressing (CP), soxhlet extraction (SE), and ultrasonic extraction (UE). The findings showed that soxhlet extraction gave a significantly higher oil yield compared to the other techniques used in this work (65.10% with p < 0.05), while cold pressing and ultrasonic extraction gave similar yields: 54.51% and 56.66%, respectively (p > 0.05). Chemical composition analysis was carried out by GC−MS and allowed 11 compounds to be identified, of which the major compound was linoleic acid (C18:2), with a similar percentage (between 57.08% and 57.84%) for the three extractions (p > 0.05). Regarding the carotenoid pigment, the extraction technique significantly affected its content (p < 0.05) with values between 10.11 mg/kg and 14.83 mg/kg. The chlorophyll pigment presented a similar content in both oils extracted by SE and UE (p > 0.05), 0.20 mg/kg and 0.16 mg/kg, respectively, while the lowest content was recorded in the cold-pressed oil with 0.13 mg/kg. Moreover, the analysis of phytosterols in walnut oil revealed significantly different contents (p < 0.05) for the three extraction techniques (between 1168.55 mg/kg and 1306.03 mg/kg). In addition, the analyses of tocopherol composition revealed that γ-tocopherol represented the main tocopherol isomer in all studied oils and the CP technique provided the highest content of total tocopherol with 857.65 mg/kg, followed by SE and UE with contents of 454.97 mg/kg and 146.31 mg/kg, respectively, which were significantly different (p < 0.05). This study presents essential information for producers of nutritional oils and, in particular, walnut oil; this information helps to select the appropriate method to produce walnut oil with the targeted quality properties and chemical compositions for the desired purpose. It also helps to form a scientific basis for further research on this plant in order to provide a vision for the possibility of exploiting these oils in the pharmaceutical, cosmetic, and food fields.