Dementia and Multimorbidity Trends in Al-Baha, Saudi Arabia: An Analytical Retrospective Study Using Records-Based Data.

BACKGROUND: The prevalence of dementia is escalating significantly, posing a substantial societal burden. Currently, there exists a dearth of comprehensive health data about dementia patients in Saudi Arabia, particularly within Al-Baha City. METHODS: A retrospective case-series study was undertaken to ascertain the prevalence of dementia within the populace of the Al-Baha region, Kingdom of Saudi Arabia. This investigation utilized hospital-based records encompassing individuals exhibiting symptoms or diagnosed with dementia and its related forms across the Al-Baha region. Furthermore, the study aimed to evaluate the burden of comorbidities among dementia patients and document the pharmacological therapeutic interventions administered to manage dementia and its associated concurrent health conditions. RESULTS: Our investigation explored the prevalence rates of various forms of dementia and the accompanying comorbidities among affected individuals. The study spanned from August 2020 to August 2023. Our study encompassed 407 patients diagnosed with Alzheimer's disease (AD), Parkinson's disease, vascular dementia (VaD), or other forms of dementia who were either admitted to or attended tertiary hospitals in Al-Baha. Assessment of the comorbidity burden was conducted using the Charlson Comorbidity Index (CCI). Our findings revealed that among these patients, 13.3% presented with AD, 23.6% with VaD, 33.4% with Parkinson's disease, 15.75% with amnesia, and 14.0% with other types of dementia. The spectrum of comorbidities observed among dementia patients encompassed various conditions, with diabetes mellitus emerging as the predominant comorbidity (19.1%), followed by hypertension (16.4%). Additionally, manifestations of depression were noted in 14% of patients, while 9.82% suffered from paralysis. Chronic conditions such as cancer, chronic obstructive pulmonary disorder (COPD), and cervical spondylosis were also observed among individuals afflicted with dementia and its varied forms. Statistically significant correlations were established between gender, age, nationality, comorbidities, and the prevalence of dementia. Therapeutic interventions in the form of pharmacological treatments were prescribed for dementia patients with comorbidities. Commonly administered medications included Amlod (6.3%), Amlodipine (6.6%), Amlor (5.8%), Aspirin (10.5%), chemotherapeutic drugs (4.4%), Glipizide (8.5%), Lantus (11.3%), Levodopa (23.5%), Metformin (7.8%), acetylcholinesterase inhibitors (6.8%), and Pulmicort (7.86%). These medications aimed to alleviate symptoms associated with dementia and its accompanying comorbidities. CONCLUSIONS: Our investigation underscores the substantial burden of comorbidities experienced by dementia patients. These findings offer crucial insights into the overall health status of individuals grappling with dementia, serving as a catalyst for increased awareness among clinicians and policymakers. Such awareness can drive improvements in medical care and support frameworks tailored to the specific needs of dementia patients.

Discovery of 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea as a promising anticancer drug via synthesis, characterization, biological screening, and computational studies.

Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using flow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC50 = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored - 9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and - 7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.

Green Synthesis of Zinc Oxide Nanoparticles Using Cymbopogon citratus Extract and Its Antibacterial Activity.

Excessive use of antimicrobial medications including antibiotics has led to the emerging menace of antimicrobial resistance, which, as per the World Health Organization (WHO), is among the top ten public health threats facing humanity, globally. This necessitates that innovative technologies be sought that can aid in the elimination of pathogens and hamper the spread of infections. Zinc oxide (ZnO) has multifunctionality owing to its extraordinary physico-chemical properties and functionality in a range of applications. In this research, ZnO nanoparticles (NPs) were synthesized from zinc nitrate hexahydrate, by a green synthesis approach using Cymbopogon citratus extract followed by characterization of the NPs. The obtained X-ray diffraction peaks of ZnO NPs matched with the standard JCPDS card (no. 89-510). The particles had a size of 20-24 nm, a wurtzite structure with a high crystallinity, and hexagonal rod-like shape. UV-Vis spectroscopy revealed absorption peaks between 369 and 374 nm of ZnO NPs synthesized from C. citratus extract confirming the formation of ZnO. Fourier transform infrared confirmed the ZnO NPs as strong absorption bands were observed in the range of 381-403 cm-1 corresponding to Zn-O bond stretching. Negative values of the highest occupied molecular orbital-lowest unoccupied molecular orbital for ZnO NPs indicated the good potential to form a stable ligand-protein complex. Docking results indicated favorable binding interaction between ZnO and DNA gyrase subunit b with a binding energy of -2.93 kcal/mol. ZnO NPs at various concentrations inhibited the growth of Escherichia coli and Staphylococcus aureus. Minimum inhibitory concentration values of ZnO NPs against E. coli and S. aureus were found to be 92.07 ± 0.13 and 88.13 ± 0.35 µg/mL, respectively, at a concentration of 2 mg/mL. AO/EB staining and fluorescence microscopy revealed the ability of ZnO NPs to kill E. coli and S. aureus cells. Through the findings of this study, it has been shown that C. citratus extract can be used in a green synthesis approach to generate ZnO NPs, which can be employed as alternatives to antibiotics and a tool to eliminate drug-resistant microbes in the future.

Natural and synthetic drugs and formulations for intravaginal HPV clearance.

BACKGROUND: Except for a few preventative Human Papillomavirus (HPV) vaccines, there is currently no cure for HPV infection. There are a number of cutting-edge strategies and potent medications or herbal formulations that can be applied topically for early clearance of HPV infection before HPV DNA gets integrated into host cell genome. This is facilitated due to cervical cancer having distinct and well-recognized long precancerous stages. OBJECTIVES: This review aims to outline every possible medication and formulation, both natural and synthetic, that can be applied topically as intravaginal application to help remove HPV infection at an early precancerous stage. RESULTS: Several anti-HPV/HPV clearance compounds and formulations for high-grade lesions are undergoing clinical trials. However, the majority of compounds are still in the early stages of development and require additional research to become viable HPV clearance candidates. Synthetic drugs may be more promising because they may have a more targeted effect; however, they may also have significant adverse effects. On the other hand, natural medications are safer to use. They are less specific, but have minimal to no adverse effects. CONCLUSIONS: This article may serve as a valuable resource of information for managing and preventing precancerous carcinogenic HPV infections. Research could be directed toward developing candidate drugs to make evidence-based decisions about advancing them to clinical trials and, eventually, to the market for potential use in the prevention and control of cervical cancer, which is almost always preventable or even curable if detected early.

Novel insights on perils and promises of miRNA in understanding colon cancer metastasis and progression.

Colorectal cancer (CRC) is the third highest frequent malignancy and ultimate critical source of cancer-associated mortality around the world. Regardless of latest advances in molecular and surgical targeted medicines that have increased remedial effects in CRC patients, the 5-year mortality rate for CRC patients remains dismally low. Evidence suggests that microRNAs (miRNAs) execute an essential part in the development and spread of CRC. The miRNAs are a type of short non-coding RNA that exhibited to control the appearance of tumor suppressor genes and oncogenes. miRNA expression profiling is already being utilized in clinical practice as analytical and prognostic biomarkers to evaluate cancer patients' tumor genesis, advancement, and counteraction to drugs. By modulating their target genes, dysregulated miRNAs are linked to malignant characteristics (e.g., improved proliferative and invasive capabilities, cell cycle aberration, evasion of apoptosis, and promotion of angiogenesis). This review presents an updated summary of circulatory miRNAs, tumor-suppressive and oncogenic miRNAs, and the potential reasons for dysregulated miRNAs in CRC. Further we will explore the critical role of miRNAs in CRC drug resistance.

A Retrospective Study of Epidemiological Correlations of Food, Drug and Chemical Poisoning in Al-Baha, Western Saudi Arabia.

Poisoning is a common and severe problem worldwide. Due to significant growth in the agricultural, chemical, and pharmaceutical industries over the past few decades, poisoning risks have increased with the use of food, chemicals, and medicines everywhere in the world, especially in Saudi Arabia. Advanced information on acute poisoning patterns is critical for the effective management of poisoning events. This study aimed to examine the characteristics of patients with various patterns of acute poisoning, caused by food, drugs, and chemicals, that were reported to the Department of Toxicology and Poison Center at King Fahad Hospital and the Poison Center in Al-Baha Province, Saudi Arabia. The study also examined the relationship between demographic characteristics, including age, toxin type, and geographical distribution, and poisonings in Baha Province. This retrospective cross-sectional analysis included 622 poisoning cases. The data were collected from 2019 to 2022 and it was found that out of 622 instances, 159 had food poisoning, with more men than females sick (53.5% male and 46.5% female), 377 had drug poisoning (54.1% males and 45.9% females), and 86 had chemical poisoning (74.4% males and 25.6% females). This study found that the most prevalent agents implicated in acute poisoning were medicines, particularly analgesics and antipsychotic drugs. Food poisoning was the second most common acute poisoning, affecting largely males followed by female patients. Finally, chemical poisoning involved acute poisoning, with most cases involving methanol and household items including the strongest bleaches (chlorines) (Clorox®, Oakland, CA, USA). Insecticides and pesticides were also secondary sources of chemical poisoning. Additional research revealed that the incidence of food, chemical, and drug poisoning was highest in children aged 1-15 years (food poisoning, n = 105, 66%; drug poisoning, n = 120, 31.8%); patients aged 11-20 years had the highest incidence of chemical poisoning (n = 41, 47.7%). Most poisoning incidents among youngsters are caused by easy access to drugs at home. Implementing strategies to enhance public awareness and limit children's access to drugs would contribute considerably to decreasing the community's burden of this problem. The findings of this study suggest that Al-Baha should improve its education regarding the rational and safe use of drugs and chemicals.

Nanogel-based Transdermal Drug Delivery System: A Therapeutic Strategy with Under Discussed Potential.

The application of nanoparticles in medication delivery has revolutionized the field of therapeutic biology. To improve medical efficacy, currently, drug nanocarriers are employed to control the release and stability, expand its circulation time, or protect it from cell clearance or premature breakdown. A crosslinked polymeric framework is used to crosslink the hydrogel nanoparticle dispersions for safer and stable delivery on target sites. Nanogels have developed in the last two decades as potential biomaterials with a wide variety of applications. Later attributes of nanogels are mainly due to large surface areas, retention of molecules, size flexibility, and water-based formulations that have made them popular as drug delivery vehicles, as seen by several in vivo uses. The gel matrix containing the nanoparticle drug demonstrated a considerable increase in drug penetration in transdermal drug and topical delivery methods. This review aims to understand why and how nanogels are considered so innovative as a drug delivery method. It also examines their preparation methods and applications in the pharmaceutical and biomedical fields and discusses the benefits of nanogels, including swelling capacity and stimulus stimuli sensitivity. Nanogels, on the other hand, have recently been investigated for applications outside the field of biomedicine. Since there are many possible uses for nanogels, we have comprehensively reviewed the current state of the art for all feasible nanogel applications and manufacturing methods.

In silico epitope-based vaccine design against influenza a neuraminidase protein: Computational analysis established on B- and T-cell epitope predictions.

Objective: Influenza A virus belongs to the most studied virus and its mutant initiates epidemic and pandemics outbreaks. Inoculation is the significant foundation to diminish the risk of infection. To prevent an incidence of influenza from the transmission, various practical approaches require more advancement and progress. More efforts and research must take in front to enhance vaccine efficacy. Methods: The present research emphasizes the development and expansion of a universal vaccine for the influenza virus. Research focuses on vaccine design with high efficacy. In this study, numerous computational approaches were used, covering a wide range of elements and ideas in bioinformatics methodology. Various B and T-cell epitopic peptides derived from the Neuraminidase protein N1 are recognized by these approaches. With the implementation of numerous obtained databases and bioinformatics tools, the different immune framework methods of the conserved sequences of N1 neuraminidase were analyzed. NCBI databases were employed to retrieve amino acid sequences. The antigenic nature of the neuraminidase sequence was achieved by the VaxiJen server and Kolaskar and Tongaonkar method. After screening of various B and T cell epitopes, one efficient peptide each from B cell epitope and T cell epitopes was assessed for their antigenic determinant vaccine efficacy. Identical two B cell epitopes were recognized from the N1 protein when analyzed using B-cell epitope prediction servers. The detailed examination of amino acid sequences for interpretation of B and T cell epitopes was achieved with the help of the ABCPred and Immune Epitope Database. Results: Computational immunology via immunoinformatic study exhibited RPNDKTG as having its high conservancy efficiency and demonstrated as a good antigenic, accessible surface hydrophilic B-cell epitope. Among T cell epitope analysis, YVNISNTNF was selected for being a conserved epitope. T cell epitope was also analyzed for its allergenicity and cytotoxicity evaluation. YVNISNTNF epitope was found to be a non-allergen and not toxic for cells as well. This T-cell epitope with maximum world populace coverages was scrutinized for its association with the HLA-DRB1*0401 molecule. Results from docking simulation analyses showed YVNISNTNF having lower binding energy, the radius of gyration (Rg), RMSD values, and RMSE values which make the protein structure more stable and increase its ability to become an epitopic peptide for influenza virus vaccination. Conclusions: We propose that this epitope analysis may be successfully used as a measurement tool for the robustness of an antigen-antibody reaction between mutant strains in the annual design of the influenza vaccine.

Possible Interaction of Nonsteroidal Anti-inflammatory Drugs Against NF-κB- and COX-2-Mediated Inflammation: In Silico Probe.

In recent years, inflammatory mediators have been considered a possible key for nonsteroidal anti-inflammatory drugs (NSAID's). NSAID's have been known as most promising medication against inflammation and its mediated pain. Inflammation could be recognize as a systemic adaptive stimulation triggered by detrimental stimuli as pathogenic attack and endogenous signals mediated injury inside the cells. In addition, there has been an inflammatory key mechanism involved in disease state. NSAIDs have been compromisingly recommended for targeting specific proteins and/or inflammatory-mediated enzymes including cyclooxygenases (COX). This subsequently inhibits the prostaglandins at the site of inflammation. For the past decades, two forms of the COX enzyme have been implicated as COX-1 expressed in cells and tissues and other COX-2 selectively triggered via proinflammatory cytokines at the site of inflammation and/or injury. In addition, NSAID's have also been implicated for the inhibition of NF-κB pathways, and other relevant proteins considered potent candidates for these drugs. NF-κB has been identified a classical proinflammatory signaling pathway. It has been recognized as a primary target for novel anti-inflammatory drugs. In our results, reports are being confirmed via the probable effects of NSAID's on inflammatory-mediated switches. Several studies were considered to enquire the possible interactions of NSAID's and inflammatory hub. Nevertheless, the exact mechanism is still debatable. In our study, NSAID's and their targeted proteins or molecules caused a convincing pattern. For improvised perception, the binding affinity of NSAID's with inflammatory-mediated proteins was quantified using a molecular docking tool. In addition, we have depicted the complex juncture of hydrogen bonding in targeted proteins with NSAID's. Our in silico investigations have revealed NSAID's as the powerful armor against COX-2- and NF-κB-mediated inflammation.

Natural products against cancer: Review on phytochemicals from marine sources in preventing cancer.

Marine natural products have as of now been acknowledged as the most important source of bioactive substances and drug leads. Marine flora and fauna, such as algae, bacteria, sponges, fungi, seaweeds, corals, diatoms, ascidian etc. are important resources from oceans, accounting for more than 90% of the total oceanic biomass. They are taxonomically different with huge productive and are pharmacologically active novel chemical signatures and bid a tremendous opportunity for discovery of new anti-cancer molecules. The water bodies a rich source of potent molecules which improve existence suitability and serve as chemical shield against microbes and little or huge creatures. These molecules have exhibited a range of biological properties antioxidant, antibacterial, antitumour etc. In spite of huge resources enriched with exciting chemicals, the marine floras and faunas are largely unexplored for their anticancer properties. In recent past, numerous marine anticancer compounds have been isolated, characterized, identified and are under trials for human use. In this write up we have tried to compile about marine-derived compounds anticancer biological activities of diverse flora and fauna and their underlying mechanisms and the generous raise in these compounds examined for malignant growth treatment in the course of the most recent quite a long while.

Bisphenol A-Induced Endocrine Toxicity and Male Reprotoxicopathy are Modulated by the Dietary Iron Deficiency.

INTRODUCTION: Bisphenol A (BPA) is suspected to cause hormonal imbalance in humans. Dietary factors are known to bring changes in hormonal profile. In order to study chemico-biological interaction of iron deficiency on toxicity outcome of BPA exposure, we studied the modulatory effects of iron deficiency on the hormone levels in rats chronically-exposed to BPA. METHODS: Weanling rats maintained on normal and iron-deficient diets were exposed to low level of BPA at 0, 1, 5 and 10 ppm for six months through drinking water. The serum levels of thyroidstimulating hormone (TSH), testosterone, progesterone and estradiol were measured in the animals by enzyme-linked immunosorbent assay kit. Histopathology was performed to check the pathological changes in gonads. RESULTS: No significant change was observed in TSH, progesterone and estradiol levels at 1 and 5 ppm BPA. However, at 10 ppm BPA a significant increase in TSH level was observed in the animals maintained on an iron-deficient diet of either sex. BPA caused a significant change in testosterone level even at 5 and 10 ppm doses in animals of either sex. However, in male rats 1 ppm dose also showed a significant effect in the animals maintained on iron deficient diet. Changes in the histoarchitecture of the testes at high dose of BPA (10 ppm) were more remarkable in anemic rats. CONCLUSION: These results suggest that iron deficiency has no generalized effect on hormonal levels in BPA-treated animals and trends indicate a more remarkable effect in male animals at hormonal and tissue levels.

Bleomycin-induced pulmonary toxicopathological changes in rats and its prevention by walnut extract.

Oxidative stress-related inflammation and apoptosis are important pathogenic consequences, which result in acute pulmonary toxicity. Bleomycin (BLM) is used to treat various forms of cancers. However, its prolonged administration is associated with major toxicity to respiratory system. We studied the effect of walnut (Juglans regia) extract in a rat model of BLM-induced pulmonary toxicopathy. We also studied parameters of inflammation, apoptosis and oxidative stress in various groups of animals. Prophylactic treatment of total methanolic extract of walnut at the dose of 150mg/kg b.w. was given per os to Wistar rats for 14days prior to BLM exposure. A single intratracheal injection of BLM (10U/kg b.w.) was administered on the eleventh day of the treatment. There was a marked increase in the hydroxyproline level, lipid peroxidation, nitric oxide production, and in the activities of xanthine oxidase and myeloperoxidase in the lung tissue in BLM-treated animals when compared to control animals. BLM also decreased the activities of antioxidant enzymes such as glutathione reductase and catalase and increased the lung inflammation and apoptosis by upregulating the NF-κB signaling pathway and caspase-3 expression. Treatment with walnut extract attenuated these changes in a significant manner. Walnut extract significantly modulated the lung injury as measured by markers of cellular injury such as lactate dehydrogenase and alkaline phosphatase, total cell count, total protein and reduced glutathione in bronchoalveolar lavage fluid. Histological findings supported the protective effects of walnut extract against BLM-induced lung injury. Walnut which has been shown to have numerous medicinally valuable constituents including ellagic acid showed efficacy in preventing the various toxicopathological effects of BLM in rat lungs. Overall, walnut extract decreases BLM-induced oxidative stress and lung inflammation by modulating the alveolar macrophage inflammatory response in rats and thus protecting them from the pathological effect of BLM.

Mitochondrial dysfunction induced by Bisphenol A is a factor of its hepatotoxicity in rats.

Bisphenol A (BPA), an estrogenic and endocrine disrupting agent, is widely used in manufacturing of polycarbonate plastics and epoxy resins. BPA and other endocrine disrupting chemicals (EDCs) act via multiple mechanisms including interference with mitochondrial functions. Mitochondria are the hub of cellular energy pool and hence are the target of many EDCs. We studied perturbation of activities of mitochondrial enzymes by BPA and its possible role in hepatotoxicity in Wistar rats. Rats were exposed to BPA (150 mg/kg, 250 mg/kg, 500 mg/kg per os, for 14 days) and activities of enzymes of mitochondrial electron transport chain (ETC) were measured. Besides, other biochemical parameters such as superoxide generation, protein oxidation, and lipid peroxidation (LPO) were also measured. Our results indicated a significant decrease in the activities of enzymes of mitochondrial ETC complexes, i.e., complex I, II, III, IV, and V along with significant increase in LPO and protein oxidation. Additionally, a significant increase in mitochondrial superoxide generation was also observed. All these findings could be attributed to enhanced oxidative stress, decrease in reduced glutathione level, and decrease in the activity of superoxide dismutase in rat liver mitochondria isolated from BPA-treated rats. BPA treatment also caused a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase indicating its potential hepatotoxicity. Furthermore, histopathological findings revealed marked edema formation, hepatocellular degeneration, and necrosis of liver tissue in BPA-exposed rats. In conclusion, this study provides an evidence of impaired mitochondrial bioenergetics and liver toxicity after high-dose BPA exposure in rats. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1922-1934, 2016.