Development of topical silver nano gel formulation of Bixin: Characterization, and evaluation of anticancer activity.

Objective: Skin cancer refers to the pathological condition characterized by the proliferation of atypical skin cells in an uncontrolled manner. Plant-based products such as bixin although show promising anticancer properties, but maintaining their stability in a formulation is a difficult task. The objective of the research is to formulate a silver nanoparticle gel preparation of bixin and evaluate its anticancer properties. Methods: The extract from Bixa orellana seed was prepared by hot extraction technique to isolate the active ingredient, bixin. A green synthesis approach was utilized for preparing the silver nanoparticle gel of bixin (BOAgNPs). Characterization of silver nanoparticles was done using FTIR, scanning electron microscopy, compatibility study, homogeneity testing, pH evaluation, and drug content determination. The in-vitro anticancer activity was performed using cell lines (B16F10) and in-vivo by chemical carcinogen (7,12-dimethylbenz (a) anthracene) in mice. Results: The BOAgNPs-loaded topical gel was found to be homogeneous (clear orange color) and pH-compatible (pH ≈ 6.66) with the skin. The characterization studies indicated the presence of all functional groups in the formulation. An optimized batch of bixin-nano gel showed about 60% inhibitory effects on B16F10 cell lines (in-vitro activity) when equated with a reference drug, 5-fluorouracil. The in-vivo anticancer study suggested suppression of tumorigenesis and promotion of the healing process with bixin-nano gel application on the skin. Conclusion: The results suggested the promising anticancer property of bixin when formulated in silver nanoparticle gel. The preparation of silver particles nano gel with bixin might provide an effective alternative option for treating skin cancers, provided more research complements the findings of the present study.

From diagnosis to therapy: The critical role of lncRNAs in hepatoblastoma.

According to findings, long non-coding RNAs (lncRNAs) serves an integral part in growth and development of a variety of human malignancies, including Hepatoblastoma (HB). HB is a rare kind of carcinoma of the liver that mostly affects kids and babies under the age of three. Its manifestations include digestive swelling, abdominal discomfort, and losing weight. This thorough investigation digs into the many roles that lncRNAs serve in HB, giving views into their varied activities as well as possible therapeutic consequences. The function of lncRNAs in HB cell proliferation, apoptosis, migratory and penetrating capacities, epithelial-mesenchymal transition, and therapy tolerance is discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell processes such as angiogenesis, apoptosis, immunity, and growth. Circulating lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. In addition to their diagnostic utility, lncRNAs provide curative opportunities as locations and actors, contributing to the expanding landscape of cancer research. Several HB-linked lncRNAs have been demonstrated to exhibit abnormal expression and are involved in tumor-like characteristics via DNA, RNA, or protein binding or encoding short peptides. As a result, a better knowledge of lncRNA instability might bring fresh perspectives into HB etiology as well as innovative strategies for HB early diagnosis and therapy. We describe the abnormalities of lncRNA expression in HB and their tumor-suppressive or carcinogenic activities during HB carcinogenesis in this study. Furthermore, we explore lncRNAs' diagnostic and therapeutic possibilities in HB.

Computational investigation of 2, 4-Di Tert Butyl Phenol as alpha amylase inhibitor isolated from Coccinia grandis (L.) Voigt using molecular docking, and ADMET parameters.

INTRODUCTION: Diabetes Mellitus is the metabolic disorder most prevalent globally, accounting for a substantial morbidity rate. The conventional drugs available for the management of diabetes are either expensive or lack the required efficacy. The purpose of this research is to isolate and characterize an active phytoconstituent from Coccinia grandis and assess its anti-diabetic properties. METHODS AND MATERIALS: Stems of Coccinia grandis are subjected to successive extraction and isolation. The isolated compound by column chromatography was characterized by FTIR (fourier-transform infrared), 1 H NMR (proton nuclear magnetic resonance), and Mass spectroscopy. The antidiabetic potential of the isolated compound was evaluated by in-vitro alpha-amylase inhibitory activity. Further, the compound was subjected to molecular docking studies to study its interaction with the human pancreatic alpha-amylase (Molegro Virtual Docker) as well to determine the pharmacokinetic and toxicity profile using computational techniques (OSIRIS property explorer, Swiss ADME, pkCSM, and PreADMET). RESULTS: The characterization of the compound suggests the structure to be 2,4-ditertiary butyl phenol. The in-vitro alpha-amylase inhibitory study indicated a concentration-dependent inhibition and the IC50 (median lethal dose) value of the isolated compound was found to be 64.36 µg/ml. The docking study with the A chain of receptor 5EMY yielded a favorable docking score of -81.48 Kcal mol-1, suggesting that the compound binds to the receptor with high affinity through electrostatic, hydrophobic, and hydrogen bonds. Furthermore, the silico ADME analysis of the compound revealed improved metabolism, a skin permeability of -3.87 cm/s, gastrointestinal absorption of 95.48 %, and a total clearance of 0.984 log ml min-1 kg-1. In silico toxicity analysis also predicted cutaneous irritations but no carcinogenicity, mutagenicity, or hepatotoxicity. CONCLUSION: The data suggested that the isolated compound (2, 4-tertiary butyl phenol) has the potential to inhibit the alpha-amylase activity and possess optimal ADME properties as well as tolerable side effects.

Depression in persons with disabilities: a scoping review.

Individuals with disabilities are more vulnerable to depression development than the general population. This study sought to map the evidence on current knowledge of depression, intervention strategies, and assessment tools among people with disabilities. This review was conducted following Arksey and O'Malley's scoping review methodology framework. An electronic search was performed on four English databases: PubMed, Cochrane Library, PsycINFO, and Web of Science. The original search returned 1802 results, with 1,116 from Web of Science, 626 from PubMed, 25 from Cochrane, and 35 from PsycINFO. After removing duplicates, 786 articles were chosen for the title and abstract screening processes. Finally, 112 full-text publications were deemed eligible, with 41 papers being included in this scoping review for analysis. A large proportion (32; 78.04%) of the studies chosen were cross-sectional, 14 (34.14%) of them reported general disability, 12 (29.26%) used a patient health questionnaire (PHQ-9) to measure depression, and 14 (34.14%) had interventions, including cognitive behavioral therapy, psychological counseling, social support, and physical activity. All interventions successfully reduced the severity of the depression. Cognitive behavioral therapies and psychological counseling were widely used interventions that had a significant impact on reducing depression. More randomized controlled trials are required, and they should focus on individuals with specific disabilities to provide disability-specific care that can improve the quality of life for disabled individuals.

LncRNAs: Emerging biomarkers and therapeutic targets in rectal cancer.

According to findings, long non-coding RNAs (lncRNAs) have an important function in the onset and growth of various cancers, including rectal cancer (RC). RC offers unique issues in terms of diagnosis, treatment, and results, needing a full understanding of the cellular mechanisms that cause it to develop. This thorough study digs into the various functions that lncRNAs perform in RC, giving views into their multiple roles as well as possible therapeutic consequences. The function of lncRNAs in RC cell proliferation, apoptosis, migratory and infiltrating capacities, epithelial-mesenchymal shift, and therapy tolerance are discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell functions such as angiogenesis, death, immunity, and growth. Systemic lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. Besides adding to their diagnostic utility, lncRNAs offer therapeutic opportunities as actors, contributing to the expanding landscape of cancer research. Moreover, the investigation looks into the assessment and predictive utility of lncRNAs as RC markers. The article also offers insight into lncRNAs as chemoresistance and drug resistance facilitators in the setting of RC.

Deciphering the correlation of depression, quality of life, and COVID-19 challenges in people with disability: A Saudi Arabian perspective.

BACKGROUND: Disability is a serious health issue that can have a significant impact on both physical and mental health. This study attempted to investigate the relationship between depression, quality of life (QOL), and COVID-19 challenges faced by people with disabilities (PwD) from Saudi Arabia. METHODS: A structured interview questionnaire to measure QOL (WHOQOL-BREF) and depression (PHQ-9) was used to conduct a cross-sectional study among PwDs in Saudi Arabia. Binary regression analysis was done using SPSS-IBM and predictors for depression, quality of life and COVID-19 challenges were determined. RESULTS: Of the 111 study samples, two-thirds were male (67.6%), with only one-third employed (34.2%). Most of them (70%) reported moderate to severe disability-related difficulties. Only 28.8% of the samples were satisfied with the physical health domain of the quality of life, whereas 31.5%, 44.1%, and 50.5% were satisfied with the psychological, social, and environmental health domains, respectively. Approximately 62% of the participants had been diagnosed with depression. A significantly higher percentage of participants who had not received COVID-19 vaccination were depressed (P = 0.011), whereas the depression rate was lower among those who received three or four doses of vaccination (P = 0.006). Depression is 4.1 times more likely in people with comorbidities, and disability with increased difficulty (OR: 4.266). Furthermore, vaccinated people had a 5.3-fold higher chance of developing satisfactory QOL. CONCLUSION: Regardless of the type, cause, or duration of disability, the degree of difficulty is a strong predictor of depression and a decrease in quality of life. A multidisciplinary approach is needed to improve the well-being of people with disabilities.

Use of potentially inappropriate medication for elderly patients in tertiary care hospital of Riyadh, Saudi Arabia.

Background and objectives: The elderly population is affected by chronic diseases and lifelong medication. The American Geriatrics Society (AGS) Beers Criteria is a comprehensive approach to medication usage in the older population to reduce potentially inappropriate medication (PIM) use. The purpose of this study was to assess the usage of PIMs in elderly patients upon discharge from tertiary care hospital settings in Riyadh, Saudi Arabia, using the AGS Beers Criteria 2019. Methods: The data was obtained from the medical records of 1237 patients (>65 years) who were discharged from medical or surgical wards at two hospitals affiliated with King Abdulaziz Medical City. The data was analyzed to determine the prevalence of PIM prescription, and the proportional odds of the independent factors influencing outcomes were estimated using ordinal regression analysis for criteria 1 and 2, while Binary regression analysis was conducted for criterion 3. Results: There were approximately equal numbers of male and female participants in our study (male: 50.8 % vs. female: 49.2 %). One-third of the patients were above the age of 80 years, with 41 % being between the ages of 70 and 80 years. Moreover, almost 70 % of the samples had chronic illnesses. The overall prevalence of PIMs was 29.2 %, with 11 % of PIMs to be avoided in elderly patients and 17 % to be used with caution in the elderly, while disease-specific PIMs were identified in 1.2 % of the patients. The most common PIM class was proton pump inhibitors (44.41 %), and patients discharged from the surgical unit were more likely to be prescribed PIMs. Proton pump inhibitors (44.41 %) were the most inappropriately prescribed drug class, and patients discharged from the surgical unit were more likely to be prescribed PIMs. Conclusion: The study noticed that male gender, the presence of multiple diseases, and obesity are associated with more than one PIM prescription. There is a need to streamline the surgical department's prescription procedure to eliminate prescription disparities. Prescription monitoring is recommended to avoid medication errors, particularly in patients who are taking multiple medications.

An exploration of factors influencing the selection of generic and innovator medicines in Saudi Arabia using an observational cross-sectional study.

Background and objectives: Generic medications are cost-effective without compromising therapeutic outcomes. Therefore, the goal of this study was to investigate, using a cross-sectional study design, the factors influencing Saudi Arabian consumers' preferences between innovator and generic medications. Methods: This cross-sectional study was carried out in Saudi Arabia using a Google survey form. For data collection, a simple random sampling strategy was used. The recruited participants were surveyed using a validated questionnaire that focused on six influencing domains: physician, pharmacist, perceived effectiveness, price, information availability, and confidence based on prior experience. The obtained data was used to analyze factors that have an association with any of the six domains using multinomial regression analysis. A correlation analysis was performed to examine the relationship between domains. Results: The 317 participants included 64.4 % females, 52 % aged ≥ 26, and a large proportion of Saudi nationals (82.6 %) and university graduates (78.9 %). Being employed (OR:3.029; P = 0.006; CI: 6.715-1.366), a healthcare providers (OR:2.298; P = 0.043; CI: 5.151-1.025), and having insurance coverage (OR:1.908; P = 0.017; CI: 3.245-1.122) had a greater influence on medication selection. Participants with linguistic and business educational backgrounds (OR:3.443; P = 0.022; CI: 9.950-1.191), those living in the northern region of Saudi Arabia (OR:3.174; P = 0.009; CI: 7.585-1.328), having chronic ailments (OR:3.863; P = 0.013; CI: 11.274-1.324), and possess insurance (OR:1.748; P = 0.039; CI: 2.971-1.028) get readily influenced by pharmacist. People who were married and lived in Saudi Arabia's southern region were influenced by perceived effectiveness when choosing medicine. Participants from the northern region were found to be influenced by the price of the medicines, information about the medicines, and confidence based on previous experience. The price of medicines has a significant impact on those suffering from chronic diseases. At a significant level of P = 0.01, all six influencing domains were found to be positively correlated with each other. Conclusion: The study shows that healthcare providers, drug prices, perceived efficacy, and information availability all have a big influence on the Saudi Arabian population's choice of medications. Educational background, location, and chronic disease status are associated with several influencing domains. Aside from public awareness campaigns, healthcare professionals should be involved in the implementation of the generic medication policy.

Beyond the genome: MALAT1's role in advancing urologic cancer care.

Urologic cancers (UCs), which include bladder, kidney, and prostate tumors, account for almost a quarter of all malignancies. Long non-coding RNAs (lncRNAs) are tissue-specific RNAs that influence cell growth, death, and division. LncRNAs are dysregulated in UCs, and their abnormal expression may allow them to be used in cancer detection, outlook, and therapy. With the identification of several novel lncRNAs and significant exploration of their functions in various illnesses, particularly cancer, the study of lncRNAs has evolved into a new obsession. MALAT1 is a flexible tumor regulator implicated in an array of biological activities and disorders, resulting in an important research issue. MALAT1 appears as a hotspot, having been linked to the dysregulation of cell communication, and is intimately linked to cancer genesis, advancement, and response to treatment. MALAT1 additionally operates as a competitive endogenous RNA, binding to microRNAs and resuming downstream mRNA transcription and operation. This regulatory system influences cell growth, apoptosis, motility, penetration, and cell cycle pausing. MALAT1's evaluation and prognosis significance are highlighted, with a thorough review of its manifestation levels in several UC situations and its association with clinicopathological markers. The investigation highlights MALAT1's adaptability as a possible treatment target, providing fresh ways for therapy in UCs as we integrate existing information The article not only gathers current knowledge on MALAT1's activities but also lays the groundwork for revolutionary advances in the treatment of UCs.

Overcoming chemoresistance and radio resistance in prostate cancer: The emergent role of non-coding RNAs.

Prostate cancer (PCa) continues to be a major health concern worldwide, with its resistance to chemotherapy and radiation therapy presenting major hurdles in successful treatment. While patients with localized prostate cancer generally have a good survival rate, those with metastatic prostate cancer often face a grim prognosis, even with aggressive treatments using various methods. The high mortality rate in severe cases is largely due to the lack of treatment options that can offer lasting results, especially considering the significant genetic diversity found in tumors at the genomic level. This comprehensive review examines the intricate molecular mechanisms governing resistance in PCa, emphasising the pivotal contributions of non-coding RNAs (ncRNAs). We delve into the diverse roles of microRNAs, long ncRNAs, and other non-coding elements as critical regulators of key cellular processes involved in CR & RR. The review emphasizes the diagnostic potential of ncRNAs as predictive biomarkers for treatment response, offering insights into patient stratification and personalized therapeutic approaches. Additionally, we explore the therapeutic implications of targeting ncRNAs to overcome CR & RR, highlighting innovative strategies to restore treatment sensitivity. By synthesizing current knowledge, this review not only provides a comprehension of the chemical basis of resistance in PCa but also identifies gaps in knowledge, paving the way for future research directions. Ultimately, this exploration of ncRNA perspectives offers a roadmap for advancing precision medicine in PCa, potentially transforming therapeutic paradigms and improving outcomes for patients facing the challenges of treatment resistance.

Unveiling the silent threat: Heavy metal toxicity devastating impact on aquatic organisms and DNA damage.

Heavy metal pollution has significant impacts on aquatic fauna and flora. It accumulates in marine organisms, both plants and animals, which are then consumed by humans. This can lead to various health problems, such as organ damage and the development of cancer. Additionally, this pollution causes biological magnification, where the toxicity concentration gradually increases as aquatic organisms continuously accumulate metals. This process results in apoptotic mechanisms, antioxidant defence, and inflammation, which are reflected at the gene expression level. However, there is limited research on specific heavy metals and their effects on fish organs. The concentration of metal contamination and accumulation in different tropical environments is a concern due to their toxicity to living organisms. Therefore, this review focuses on determining the influences of metals on fish and their effects on specific organs, including DNA alterations.

Genetic variants associated with dengue hemorrhagic fever. A systematic review and meta-analysis.

Dengue hemorrhagic fever (DHF) is a severe condition resulting from the dengue virus, with four serotypes known as DEN-1, DEN-2, DEN-3, and DEN-4. Genetic variations play a crucial role in influencing susceptibility to DHF. Therefore, this investigation conducted a meta-analysis to uncover genetic changes that might have remained undetected in individual studies due to small sample sizes or methodological differences. Among 2212 initially identified studies, 23 were deemed suitable for analysis based on PRISMA guidelines. Toll-like receptors (TLR) and CD209 showed significant association with DHF (odds ratios: TLR=0.56, CD209 =0.55), indicating protective effects. However, tumor necrosis factor (TNF) and human leukocyte antigen (HLA) did not exhibit a statistically significant relationship with DHF. This study emphasizes the relevance of TLR and CD209 in DHF susceptibility and resistance across diverse geographical locations.

Beyond traditional medications: exploring novel and potential inhibitors of trypanothione reductase (LmTr) of Leishmania parasites.

The trypanothione reductase enzyme, which neutralizes the reactive oxygen species produced inside the macrophages to kill the parasites, is one of the evasion strategies Leishmania uses to survive inside the cells. The vitality of the parasite depends on Leishmania major trypanothione reductase (LmTr), a NADPH-dependent flavoprotein oxidoreductase essential for thiol metabolism. Since this enzyme is distinct and lacking in humans, we focused on it in our study to screen for new inhibitors to combat leishmaniasis. Using the I-TASSER server, a three-dimensional model of LmTr was generated. The Autodock vina program was used in high-throughput virtual screening of the ZINC database. The top seven molecules were ranked according to their binding affinity. The compounds with the highest binding affinities and the right number of hydrogen bonds were chosen. These compounds may be effective at inhibiting the target enzyme's (LmTr) activity, making them new leishmaniasis treatments. These compounds may serve as a useful starting point for a hit-to-lead approach in the quest for new anti-Leishmania drugs that are more efficient and less cytotoxic. The average node degree is 5.09, the average local clustering coefficient is 0.868, and the PPI enrichment p-value is 8.9e-06, indicating that it is sufficiently connected to regulate the network. TRYR (LmTr protein) also interacts physically with ten additional proteins in the pathogenesis network. The findings of the study indicated that successfully suppressing the LmTr protein in vitro and in vivo may finally result in regulating the L. major pathogenesis.Communicated by Ramaswamy H. Sarma.

Antidiabetic and antioxidant potential of Crocin in high-fat diet plus streptozotocin-induced type-2 diabetic rats.

OBJECTIVES: Crocin, the principal water-soluble active constituent of saffron, possesses numerous pharmacological activities. The present investigation examined the potential antidiabetic and antioxidant characteristics of Crocin in rats with type-2 diabetes by administering it orally and intraperitoneally (i.p.). METHODS: After 2 weeks of a high-fat diet, streptozotocin (STZ) (i.p., 40 mg/kg) was administered to male adult rats to induce type-2 diabetes mellitus. Body weight and fasting blood glucose (FBG) were measured on days zero, weeks 1, and 2. At the end of 2 weeks of drug administration in their respective groups, fasting insulin and glucose levels were estimated, and insulin resistance (HOMA-IR) was determined. Intraperitoneal glucose (IPGTT) and insulin tolerance tests (ITT) were carried out. Histopathological investigation and biochemical parameters were estimated in pancreatic tissues. RESULTS: The Crocin (100 mg/kg) treatment has significantly improved body weight, abatement of FBG, fasting insulin, and HOMA-IR. Likewise, Crocin treatment significantly improved the glucose and insulin challenges. We observed a significantly marked elevation in endogenous antioxidant enzymes in Crocin-treated groups. Similarly, Crocin treatment reversed the histopathological changes and restored the normal integrity and function of the pancreas. CONCLUSION: The overall finding indicates that intraperitoneal administration of Crocin demonstrated better control of glycemic level and body weight. Further, it has improved insulin levels in the serum and potentiated antioxidant properties.

Protective effects of vanillic acid on letrozole-induced polycystic ovarian syndrome: A comprehensive study in female wistar rats.

Background: Polycystic ovarian syndrome (PCOS) is one of the known causes of anovulatory fertility in the world. Previous research has linked oxidative stress could contribute to PCOS, and vanillic acid has shown antioxidant potential. Hence, the present study evaluated the effect of vanillic acid on letrozole-induced polycystic ovarian syndrome in female rats. Materials and methods: PCOS was induced in Wistar female rats with letrozole (1 mg/kg, orally) in carboxymethoxycellulose (1 % w/v), administered for 21 days. After induction, the standard group received clomiphene citrate (1 mg/kg, orally) while other treatment groups were administered with vanillic acid at doses 25, 50, and 100 mg/kg, orally for 15 days, and without treatment was considered a negative control group. Different parameters studied were body weight, ovary weight, blood glucose, lipid profile, hormonal levels [luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone], markers for oxidative stress (superoxide dismutase, reduced glutathione, catalase, and malonaldehyde), and histopathology of the ovary. Statistical analysis was done for the results and p < 0.05 was considered to indicate the significance. Results: Vanillic acid-treated animals showed a concentration-dependent activity on the tested parameters. The highest tested dose (100 mg/kg) produced a more prominent effect in significantly (P < 0.001) decreasing the body weight, and ovary weight and improving the hormonal imbalance. Also, vanillic acid significantly (P < 0.01) reduced elevated blood sugar and lipid levels. Additionally, vanillic acid reduced oxidative stress significantly (P < 0.001) in the ovaries of female rats. Histopathological reports showed a reduction in cystic follicles and appearance of normal healthy follicles at different stages of development after the administration of vanillic acid. Furthermore, these effects were observed to be comparable with those recorded for standard drug, clomiphene. Conclusion: The current study data suggests that vanillic acid has protected the letrozole-induced polycystic ovarian syndrome. In the event of several side effects associated with conventional treatments used for PCOS, the findings of this study suggest the promising role of vanillic acid. More research in this direction might identify the true potency of vanillic acid in the treatment of PCOS.

Novel ibuprofen prodrug: A possible promising agent for the management of complications of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer's properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet's test, p < 0.05 was considered to indicate the significance. Results: The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. Conclusion: The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Association of cholesterol with hepatorenal markers and quality of life in diabetic patients before and after magnesium and potassium supplements.

Background: Magnesium and potassium are two critical minerals that have been linked to the treatment of diabetes and its consequences. A lack of magnesium has been linked to insulin resistance and diabetes, whereas potassium has been found to promote insulin sensitivity and glucose metabolism. The study aimed to determine the relationship between cholesterol, liver and kidney markers, and quality of life in diabetic patients before and after magnesium and potassium supplementation. Methods: It was a single-blind randomized controlled study at Lahore Garrison University and Lahore Medical Research Centre (LMRC). The study included 200 diabetes participants. Four groups were made based on supplements. Blood samples of all diabetes patients were obtained to assess their quality of life before and after using Mg + and K + supplements, as well as the association between cholesterol, liver, and kidney markers. Results: The participants' average age was 51.0 ± 11.08. 139 (69.5 %) of the 200 participants were female, whereas 26 (30.5 %) were male. There was no correlation between the quality of life measure and the patients' cholesterol levels before and after the magnesium and potassium supplementation. Furthermore, the kidney and liver indicators were not dependent on the diabetes individuals' cholesterol levels. Conclusions: The study concluded that none of the four groups noticed a significant effect of magnesium and potassium therapies on the patient's quality of life or cholesterol levels. However, more research is needed to determine if liver and kidney problems are linked to cholesterol levels before and after medication, as the current study found no significant correlation between the two parameters.

Comparison of medical documentation between pharmacist-led anticoagulation clinics and physician-led anticoagulation clinics: A retrospective study.

Background and objectives: High-quality documentation is critical in medical settings for providing safe patient care. This study was done with the objective of assessing the standard of medical records in anticoagulation clinics and investigating the distinctions between notes written by pharmacists and physicians. Methods: A retrospective cross-sectional analysis of data from electronic health records (EHRs) was performed on patients who received anticoagulation and were observed at anticoagulation clinics from October to December 2020. Patients were monitored in two anticoagulation clinics, one administered by pharmacists and the other by physicians. The quality of the documentation was assessed using a score, and the note was assigned one of five categories according to its score: very good, good, average, poor, and very poor. The data was analyzed using Stata/SE 13.1. P value<0.05 was considered significant in all analytical tests. Results: A total of 331 patients were included. While 160 patients (48.3%) were followed by the physician-led clinic, 171 (51.6%) were by the pharmacist-led clinic. The average age of the patients was 54 ± 15. 60.73% of them were female, and 90.3% of them were Saudi nationals. Warfarin was the most widely used anticoagulant (70%), followed by rivaroxaban (15.7%). Compared to physicians, pharmacists demonstrated very strong documentation (54% vs. 18%). The examination of the variables considered in the study revealed that physicians had significantly less drug-drug interaction documentation (17 vs. 71 times) or drug-food interaction documentation (23 vs. 71 times) than pharmacists. In terms of follow-up frequency, pharmacists were found to adhere to the clinic protocol (150 times) more frequently than physicians (104 times). However, there was no significant difference in therapeutic plan documentation between the two groups. (p = 0.416). Conclusion: Pharmacists were more comprehensive in their documentation than physicians in anticoagulation clinics. Unified clinic documentation can ensure consistent documentation within EHRs across all disciplines.

In-vitro and computational analysis of Urolithin-A for anti-inflammatory activity on Cyclooxygenase 2 (COX-2).

Cyclooxygenase 2 (COX-2) participates in the inflammation process by converting arachidonic acid into prostaglandin G2 which increases inflammation, pain and fever. COX-2 has an active site and a heme pocket and blocking these sites stops the inflammation. Urolithin A is metabolite of ellagitannin produced from humans and animals gut microbes. In the current study, Urolithin A showed good pharmacokinetic properties. Molecular docking of the complex of Urolithin A and COX-2 revealed the ligand affinity of -7.97 kcal/mol with the ligand binding sites at TYR355, PHE518, ILE517 and GLN192 with the 4-H bonds at a distance of 2.8 Å, 2.3 Å, 2.5 Å and 1.9 Å. The RMSD plot for Urolithin A and COX-2 complex was observed to be constant throughout the duration of dynamics. A total of 3 pair of hydrogen bonds was largely observed on average of 3 simulation positions for dynamics duration of 500 ns. The MMPBSA analysis showed that active site amino acids had a binding energy of -22.0368 kJ/mol indicating that throughout the simulation the protein of target was bounded by Urolithin A. In-silico results were validated by biological assays. Urolithin A strongly revealed to exhibit anti-inflammatory effect on COX-2 with an IC50 value of 44.04 µg/mL. The anti-inflammatory capability was also depicted through reduction of protein denaturation that showed 37.6 ± 0.1 % and 43.2 ± 0.07 % reduction of protein denaturation for BSA and egg albumin respectively at 500 µg/mL. The present study, suggests Urolithin A to be an effective anti-inflammatory compound for therapeutic use.

Resveratrol-Laden Nano-Systems in the Cancer Environment: Views and Reviews.

The genesis of cancer is a precisely organized process in which normal cells undergo genetic alterations that cause the cells to multiply abnormally, colonize, and metastasize to other organs such as the liver, lungs, colon, and brain. Potential drugs that could modify these carcinogenic pathways are the ones that will be used in clinical trials as anti-cancer drugs. Resveratrol (RES) is a polyphenolic natural antitoxin that has been utilized for the treatment of several diseases, owing to its ability to scavenge free radicals, control the expression and activity of antioxidant enzymes, and have effects on inflammation, cancer, aging, diabetes, and cardioprotection. Although RES has a variety of pharmacological uses and shows promising applications in natural medicine, its unpredictable pharmacokinetics compromise its therapeutic efficacy and prevent its use in clinical settings. RES has been encapsulated into various nanocarriers, such as liposomes, polymeric nanoparticles, lipidic nanocarriers, and inorganic nanoparticles, to address these issues. These nanocarriers can modulate drug release, increase bioavailability, and reach therapeutically relevant plasma concentrations. Studies on resveratrol-rich nano-formulations in various cancer types are compiled in the current article. Studies relating to enhanced drug stability, increased therapeutic potential in terms of pharmacokinetics and pharmacodynamics, and reduced toxicity to cells and tissues are the main topics of this research. To keep the readers informed about the current state of resveratrol nano-formulations from an industrial perspective, some recent and significant patent literature has also been provided. Here, the prospects for nano-formulations are briefly discussed, along with machine learning and pharmacometrics methods for resolving resveratrol's pharmacokinetic concerns.