Unlocking milk thistle's anti-psoriatic potential in mice: Targeting PI3K/AKT/mTOR and KEAP1/NRF2/NF-κB pathways to modulate inflammation and oxidative stress.

Silybum marianum, known as milk thistle (MT), is traditionally used to manage liver diseases. This study aimed to investigate the role of MT extract topical application as a potential treatment for imiquimod (IMQ)-induced psoriatic lesions in mice with particular emphasis on phosphoinositol-3 Kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and Kelch-like ECH-associated protein 1 (KEAP1)/ nuclear factor erythroid-2-related factor (NRF2)/ nuclear factor-kappa B (NF-κB) molecular cascades involvement. To address this aim, forty male Swiss albino mice were subdivided into four groups (n = 10 mice/group): control, IMQ model, standard group where mice were treated topically with IMQ, then the anti-psoriatic mometasone cream, and MT extract-treated group where mice were treated topically with IMQ followed by MT extract. In most measured parameters, MT extract, rich in silymarin, exhibited potent anti-psoriatic activity comparable to the standard cortisone treatment. MT extract mitigated dorsal skin erythema, scaling, and epidermal thickening, reflected by lowering the Psoriasis Area Severity Index (PASI) score. Moreover, it alleviated IMQ-induced splenomegaly. Mechanistically, the PI3K/AKT/mTOR pathway was the main functional pathway behind such improvements, where it was significantly inhibited by MT extract application. This led to NRF2 activation via KEAP1 downregulation with subsequent anti-inflammatory effect proven by reducing NF-κB, interleukin (IL)-23, and IL-17A and antioxidant ability proven by boosting the antioxidant glutathione and heme oxygenase-1. Such improvements were confirmed by alleviating the histopathological alteration. Thus, MT extract could be a promising therapeutic agent for psoriasis treatment by inhibiting PI3K/AKT/mTOR cascade, along with NRF2 signaling activation.

Exploring the multi-faceted potential: Synthesized ZnO nanostructure - Characterization, photocatalysis, and crucial biomedical applications.

This research describes the methodology for synthesizing zinc oxide nanoparticles (ZnO-NPs). It demonstrates a unique, cost-effective, and non-toxic chemical technique for producing ZnO-NPs using the precipitation method with NaOH as reducing and capping agents. The formed nanoparticles have been characterized and analyzed using numerous techniques such as; Fluorescence emission spectroscopy (FL), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray Spectroscopy (EDX), ultraviolet-visible optical absorption (UV-Vis), Fourier transform infrared spectroscopy (FTIR), and Thermal gravimetric analysis (TGA). Also, the analytical technique X-ray diffraction studies has been used which showed that the ZnO-NPs had a Wurtzite hexagonal crystal structure with an average crystallite size of 34.27 nm. The form and the size of the synthesized ZnO-NPs have been seen in SEM and TEM photographs. Using J-image, particle size has been obtained at 13.33 nm, and the grain boundaries were all approximately spherical. Peaks in the FT-IR spectrum of the NPs indicate the presence of carboxylate (COO) and hydroxyl (O-H) functional groups. According to these findings, Zn interstitial defects are responsible for the 380 nm emission peak. Since EDX could not identify any impurities below the detection threshold, we may be sure that Zn and O are the principal components of the synthesized sample. ZnO-NPs cause an absorption band at 350.34 nm in the UV-Vis spectrum and a band gap of 3.24 eV. The catalytic activity of the synthesized ZnO nanoparticles (NPs) was evaluated by investigating their effectiveness in degrading crystal violet (CV) and methylene blue (MB) dyes, along with assessing the degradation rates. The results demonstrated a high degradation efficiency, with ZnO NPs achieving approximately 96.72 % degradation for CV and 97.169 % for MB dyes, underscoring their remarkable efficacy in the degradation process. As for antimicrobial activity assessment, the results revealed that the ZnO-NPs had negligible impact on Gram-negative bacteria, whereas they exhibited a discernible effect on Gram-positive bacteria. Additionally, it showed anti-cancer potential against colon (SW480), breast (MDA-231), and cervix (HELA) lines cells as seen by (MTT) assay. Hence, due to its simplified processes and cheaper chemicals, our synthesis technique may use in industrial settings for various applications.

Acetylsalicylic Acid with Ascorbate: A Promising Combination Therapy for Solid Tumors.

BACKGROUND AND OBJECTIVE: Cancer is a deadly disease with high mortality rates in developing countries. A recent preclinical study found promising results in treating hepatocellular carcinoma (HCC) by combining acetylsalicylic acid (ASA) and ascorbate (AS), which might offer a safer alternative to expensive clinical chemotherapeutics; however, the impact of this combination on other tumors remains unexplored. Therefore, this study aims to investigate the effectiveness of combining ASA and AS in treating Ehrlich solid tumors. METHODS: Eighty female Swiss albino mice were divided into eight groups (10 mice/group): four healthy groups (healthy, AS, ASA, and AS+ASA) and four groups with carcinoma (Ehrlich ascites carcinoma [EAC], EAC+AS, EAC+ASA, and EAC+AS+ASA). AS was injected intraperitoneally (4 g/kg) daily for 10 days, whereas ASA was ingested orally at 60 mg/kg/day for 10 days. Carcinoma was induced by subcutaneous injection of 1×106 EAC cells/mouse once. Treatment of carcinoma started after 10 days of tumor inoculation. Blood, livers, and tumors were obtained, and tumor weights, volumes, and levels of hemoglobin, aminotransferases, albumin, bilirubin, urea, creatinine, lipid profile, malondialdehyde, nitric oxide, glutathione, catalase, total antioxidant capacity, lactate dehydrogenase, and creatine kinase were estimated. The percentage increase in lifespan was also assessed. RESULTS: Tumor treatment alleviated tumor burden. Tumor size was reduced, lifespan increased, organs (liver, kidney, and heart) functions adjusted, hemoglobin, lipid profile improved, and oxidative stress decreased. Combining ASA with AS showed more effective antitumor effects than only ASA or AS alone. CONCLUSION: After more validation research, combining ASA with AS may provide benefit in cancer treatment.

Phytoconstituents with cardioprotective properties: A pharmacological overview on their efficacy against myocardial infarction.

Myocardial infarction (MI) is considered one of the most common cardiac diseases and major cause of death worldwide. The prevalence of MI and MI-associated mortality have been increasing in recent years due to poor lifestyle habits viz. residency, obesity, stress, and pollution. Synthetic drugs for the treatment of MI provide good chance of survival; however, the demand to search more safe, effective, and natural drugs is increasing. Plants provide fruitful sources for powerful antioxidant and anti-inflammatory agents for prevention and/or treatment of MI. However, many plant extracts lack exact information about their possible dosage, toxicity and drug interactions which may hinder their usefulness as potential treatment options. Phytoconstituents play cardioprotective role by either acting as a prophylactic or adjuvant therapy to the concurrently used synthetic drugs to decrease the dosage or relief the side effects of such drugs. This review highlights the role of different herbal formulations, examples of plant extracts and types of several isolated phytoconstituents (phenolic acids, flavonoids, stilbenes, alkaloids, phenyl propanoids) in the prevention of MI with reported activities. Moreover, their possible mechanisms of action are also discussed to guide future research for the development of safer substitutes to manage MI.

Design, synthesis, and anticancer evaluation of novel coumarin/thiazole congeners as potential CDK2 inhibitors with molecular dynamics.

A series of novel coumarin-thiazoles was designed and synthesized as a possible CDK2 inhibitor with anticancer activity with low toxicity. The design relied on having hydrazine thiazole or its open-form thioamide to form H-bonds with the ATP binding site while coumarin maintained the crucial hydrophobic interactions for proper fitting. The biological evaluation revealed that the hydroxycoumarin-thiazole derivative 6c demonstrated the best inhibition with HepG2 and HCT116 IC50 2.6 and 3.5 µM, respectively. Similarly, its open thioamide chain congener 5c exhibited potent inhibition on MCF-7 and HepG2 with IC50 of 4.5 and 5.4 µM, respectively. Molecular docking simulations supported the assumption of inhibiting CDK2 by preserving the crucial interaction pattern with the hinge ATP site and the surrounding hydrophobic (HPO) side chains. Furthermore, molecular dynamics simulations of 5c and 6c established satisfactory stability and affinity within the CDK2 active site.

Consumers' Perceptions about Edible Insects' Nutritional Value and Health Effects: Study Involving 14 Countries.

Insects have been consumed for time immemorial in many regions of the globe. However, in other parts, they are not traditionally eaten. Because they are a more sustainable source of animal protein and provide valuable nutrients as well as bioactive compounds with beneficial effects on the human body, their consumption is encouraged. Knowledge can serve as a tool for better acceptance of insects as food. In this context, the present work investigated the knowledge about the nutritional value and health effects of edible insects in different countries. Data were collected by employing a questionnaire survey translated into the different languages of all participating countries and were treated using statistical tools. A total of 7222 responses were obtained. The results indicated that for many issues, the participants manifested a neutral opinion (neither agree nor disagree), but the participants who manifested agreement/disagreement were generally well informed. They were also able to identify untrue facts and answer accordingly by disagreeing. Factor analysis showed four groups of questions: nutritive value, negative perception and risks, safety and benefits of insects and contamination and harmful components. Finally, significant differences were observed according to the sociodemographic variables studies (sex, age, education, living environment and country), with age and country being the most influential of the sociodemographic factors on knowledge. Therefore, increasing knowledge is envisaged as an essential factor in augmenting the recognition of edible insects as a nutritional food, presenting health benefits apart from being a more sustainable source of animal protein when compared with beef or pork meats.

Beyond urinalysis: evaluation of various clinical and laboratory reflex criteria to warrant urine culture collection in the emergency department.

BACKGROUND: Clinical criteria are essential for diagnosing urinary tract infections (UTIs) followed by urine testing, including urinalysis (UA). No study has evaluated the potential related factors that may guide the appropriate collection of urine cultures. Therefore, we aimed to assess the factors that may guide the appropriate collection of urine cultures. METHODS: This was a case-control study of patients for whom a urine culture and a UA were ordered in the emergency department (ED) between February 2018 and December 2022. The cases included patients with positive cultures, whereas the controls included patients without growth. Patients were excluded if they were pregnant, underwent any urological procedure, received antibiotics within 3 days before ED presentation, or before culture collection. RESULTS: Of the 263 patients, 123 had growth and 140 did not have growth in urine cultures. In the univariate analysis, female gender, urinary symptoms, urinary white blood cell (WBC) count > 5 cells/hpf, and nitrite in urine were significantly associated with growth (P < 0.05). However, only female gender (aOR, 1.86; 95% CI, 1.06-3.24), urinary WBC count > 5 cells/hpf (aOR, 4.60; 95% CI, 2.21-9.59), and positive nitrite in urine (aOR, 21.90; 95% CI, 2.80-171.00) remained significant in the multivariable analysis. These factors also remained significant in the subgroup of patients with urinary symptoms, except for the female gender. CONCLUSION: A high urinary WBC count and positive nitrite in UA should be utilized as a guide to collect urine culture, particularly in female patients, to limit the unnecessary ordering of urine culture in the ED. These factors can be used as evidence-based UA reflex criteria as an antimicrobial stewardship intervention.

Attitudes toward colorectal cancer and colonoscopy in Palestine: a questionnaire-based study.

Colorectal cancer (CRC) is a frequent cause of cancer-related mortality in the Palestinian population. This cross-sectional study was conducted from July 2019 to March 2020 and examined attitudes toward CRC and colonoscopy, as well as the interplay between both. Participants were recruited using convenience sampling from public spaces, governmental hospitals, and primary healthcare centers across 11 governorates in Palestine. Displaying a positive attitude was defined as agreeing on at least the median number of questions related to CRC (5 of 11 questions) or colonoscopy (6 of 10 questions). A total of 4623 participants were included. Most participants agreed that 'early detection of CRC increases the possibility of more effective treatment' (n = 4161, 89.7%). Similarly, the majority of participants agreed on 'preferring a physician with a gender similar to the participants to perform the colonoscopy' (n = 3738, 80.9%) and 'willingness to have colonoscopy even if the participant had to pay for it' (n = 3727, 80.6%). Furthermore, 3115 participants (67.4%) demonstrated positive attitudes toward CRC, while 2540 participants (55.0%) displayed similar attitudes toward colonoscopy. Participants from the West Bank and Jerusalem were more likely than those from the Gaza Strip to display positive attitudes toward colonoscopy (59.2% vs. 48.9%). Participants with positive attitudes toward CRC were more likely to also display positive attitudes toward colonoscopy and vice versa. About two thirds of study participants exhibited positive attitudes toward CRC, and 55.0% displayed positive attitudes toward colonoscopy. There was a reciprocal relationship between having positive attitudes toward CRC and colonoscopy.

Differences in colorectal cancer awareness between screening eligible vs. ineligible Palestinians: a national cross-sectional study.

BACKGROUND: This study aimed to compare colorectal cancer (CRC) awareness between screening-eligible and ineligible individuals in Palestine. METHODS: Convenience sampling was utilized to recruit Palestinian adults from diverse settings, including hospitals, primary healthcare centers and public spaces across 11 governorates. The evaluation of CRC awareness in terms of signs/symptoms, risk factors and causation myths was conducted using Arabic-translated, modified versions of the validated instruments, the Bowel Cancer Awareness Measure and the Cancer Awareness Measure-Mythical Causes Scale. RESULTS: The final analysis included 2698 participants, with 2158 (80.9%) eligible for CRC screening and 540 (19.1%) ineligible for it. The most recognized CRC sign/symptom was 'lump in the abdomen' in both screening-eligible (n = 386, 71.5%) and ineligible (n = 1582, 73.3%) groups. 'Lack of physical activity' was the most recognized risk factor in both groups (eligible: n = 451, 83.5%; ineligible: n = 1766, 81.8%). The most reported causation myth in both groups was 'having a physical trauma' (eligible: n = 340, 63.0%; ineligible: n = 1353, 62.7%). In the screening-eligible group, only 210 participants (38.9%) demonstrated high awareness of CRC signs/symptoms, 213 participants (39.4%) showed high awareness of CRC risk factors and only 46 participants (8.5%) displayed high awareness of CRC causation myths. There were no significant associations between being eligible for screening colonoscopy and the awareness levels of CRC signs/symptoms, risk factors and causation myths. CONCLUSION: Overall, awareness levels of CRC signs/symptoms, risk factors and causation myths were notably low among screening-eligible participants. There were no differences in awareness levels between individuals eligible for colonoscopy and those who were not.

Evaluation of the Effects of Whey Protein and Moringa Oleifera Leaves Extract Mixture on Osseointegration in Rabbits.

Background: Osteogenic, antioxidant and anti-inflammatory effects of Whey protein and M. oleifera gel prompted us to evaluate their role alone or in combination on osseointegration in rabbits. Methods: In this study, 24 titanium implants were inserted in the femurs of six rabbits. One implant was placed without treatment, and another one was coated with a mixture of whey protein and M. oleifera gel for each side. The animals were divided into two groups of 2- and 6-week intervals and evaluated using histopathological and immunohistochemical techniques. Results: Histological evaluation revealed a significant difference between the experimental and the control groups after two weeks in osteoblast and osteocyte counts. The experimental group had mature bone development after six weeks of implantation, while the control group had a woven bone. Immunohistochemical results showed that the experimental group, compared to the control group, exhibited early positive expression of osteoblast cells at two weeks after the experiment. Based on histopathological observations, the experimental group showed a tiny area of collagenous fiber in 6th week after the implantation. Conclusion: A mixture of whey protein and M. oleifera could accelerate osseointegration and healing processes.

Synthesis, characterization and adsorption optimization of bimetallic La-Zn metal organic framework for removal of 2,4-dichlorophenylacetic acid.

To eliminate the hazardous pesticide 2,4-dichlorophenylacetic acid (2,4-D) through aqueous solutions, stacked nanorods known as hetero bimetallic organic frameworks (MOFs) of 2-methyl imidazole based on lanthanum and zinc are created. The research's convincing discoveries displayed that La/Zn-MOF is an actual adsorbent for the removal of 2,4-D through aqueous solutions. The La/Zn-MOF was investigated using a variability of techniques, with scanning electron microscope (SEM), powered X-ray diffraction (PXRD), and Brunauer-Emmett-Teller (BET) investigation. La/Zn-MOF has a significant pore capacity of 1.04 cm³/g and a comparatively large surface area of 897.69 m2/g. Our findings, which are quite intriguing, demonstrate that adsorption behavior is pointedly wedged by variations in pH. A pH 6 dose of 0.02 g was shown to be the optimal setting for the greatest capacity for adsorption. Because adsorption is an endothermic process, temperature variations affect its capability. The adsorption method was fit both isothermally and kinetically using the Langmuir isotherm classical. It was created that the entire process made use of a chemisorption mechanism. Solution pH, temperature, adsorbent dosage, and time were all improved using the Box-Behnken design (BBD) and Response Surface Methodology (RSM). We were able to accurately calculate the values of ΔHo, ΔSo, and ΔGo for 2,4-D by following the guidelines. These results demonstrated the spontaneous and endothermic character of the adsorption procedure employing La/Zn-MOF as an adsorbent. Adsorption-desorption cycles can be carried out up to five times. With the synthesized La/Zn-MOF adsorbent due to its exceptional reusability. Many processes, such π-π interaction, pore filling, H-bonding, or electrostatic contact, were postulated to explain the connection between La/Zn-MOF and 2,4-D after extra research to appreciate well the link was conducted. This is the first study to demonstrate the effectiveness of utilizing La/Zn-MOF as an adsorbent to eliminate 2,4-D from wastewater models. The results display that a pH of 6 is required to achieve the maximal 2,4-D adsorption capability on La/Zn-MOF, which is 307.5 mg/g.

A comprehensive study on changes in coastal hydrodynamics associated with cyclonic activity.

A Mediterranean cyclone is a weather phenomenon capable of producing extremely severe conditions, including heavy rainfall and strong winds. Between March 24 and 26, 2023, a cyclone passed along the western Egyptian Mediterranean coast, spanning three days. This paper aims to investigate the cyclone's impact on wave characteristics, focusing particularly on simulating changes in the energy transported from wind to waves during its passage, which constitutes the core objective of this study. The research methodology involved collecting meteorological and hydrodynamic data over five days from March 23 to 27, 2023, utilizing databases of the Bologna Limited Area Model (BOLAM) and the General Bathymetric Chart of the Oceans (GEBCO). This data, combined with field data for model calibration and validation, was analyzed using the Simulating the WAves Nearshore (SWAN) model packaged within the Delft 3D hydrodynamical model, integrated with other data manipulation tools. (SWAN) demonstrated the ability to simulate energy transport during extreme weather events along the coastal area with high resolution, up to 500 m. The results indicate a significant increase in significant wave height, reaching up to 2.5 m, and disturbances in wind direction, with velocities exceeding 10 m per second. These conditions pose risks to the infrastructure in some cities along the study area and have severe impacts on coastal communities. A notable finding from the simulations is the excess energy transport, which reached up to 12,000 watts per meter over the sea surface during the cyclone. Furthermore, calibration and validation results affirm the (SWAN) model's capability to accurately study wave characteristics.

Designing Green Synthesis-Based Silver Nanoparticles for Antimicrobial Theranostics and Cancer Invasion Prevention.

Introduction: Researchers are increasingly favouring the use of biological resources in the synthesis of metallic nanoparticles. This synthesis process is quick and affordable. The current study examined the antibacterial and anticancer effects of silver nanoparticles (AgNPs) derived from the Neurada procumbens plant. Biomolecules derived from natural sources can be used to coat AgNPs to make them biocompatible. Methods: UV-Vis spectroscopy was used to verify the synthesis of AgNPs from Neurada procumbens plant extract, while transmission electron microscopy (TEM), photoluminescence (PL) spectroscopy, dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR) were used to characterize their morphology, crystalline structure, stability, and coating. Results: UV-visible spectrum of AgNPs shows an absorption peak at 422 nm, indicating the isotropic nature of these nanoparticles. As a result of the emergence of a transmission peak at 804.53 and 615.95 cm-1 in the spectrum of the infrared light emitted by atoms in a sample, FTIR spectroscopy demonstrated that the Ag stretching vibration mode is metal-oxygen (M-O). Electron dispersive X-ray (EDX) spectral analysis shows that elementary silver has a peak at 3 keV. Irradiating the silver surface with electrons, photons, or laser beams triggers the illumination. The emission peak locations have been found between 300 and 550 nm. As a result of DLS analysis, suspended particles showed a bimodal size distribution, with their Z-average particle size being 93.38 nm. Conclusion: The findings showed that the antibacterial action of AgNPs was substantially (p≤0.05) more evident against Gramme-positive strains (S. aureus and B. cereus) than E. coli. The biosynthesis of AgNPs is an environmentally friendly method for making nanostructures that have antimicrobial and anticancer properties.

Electronic and Molecular Adsorption Properties of Pt-Doped BC6N: An Ab-Initio Investigation.

In the last two decades, significant efforts have been particularly invested in two-dimensional (2D) hexagonal boron carbon nitride h-BxCyNz because of its unique physical and chemical characteristics. The presence of the carbon atoms lowers the large gap of its cousin structure, boron nitride (BN), making it more suitable for various applications. Here, we use density functional theory to study the structural, electronic, and magnetic properties of Pt-doped BC6N (Pt-BC6N, as well as its adsorption potential of small molecular gases (NO, NO2, CO2, NH3). We consider all distinct locations of the Pt atom in the supercell (B, N, and two C sites). Different adsorption locations are also considered for the pristine and Pt-doped systems. The formation energies of all Pt-doped structures are close to those of the pristine system, reflecting their stability. The pristine BC6N is semiconducting, so doping with Pt at the B and N sites gives a diluted magnetic semiconductor while doping at the C1 and C2 sites results in a smaller gap semiconductor. We find that all doped structures exhibit direct band gaps. The studied molecules are very weakly physisorbed on the pristine structure. Pt doping leads to much stronger interactions, where NO, NO2, and NH3 chemisorb on the doped systems, and CO2 physiorb, illustrating the doped systems' potential for gas purification applications. We also find that the adsorption changes the electronic and magnetic properties of the doped systems, inviting their consideration for spintronics and gas sensing.

Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers' Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway.

Cadmium (Cd) is a serious environmental pollutant affecting various tissues/organs in broilers and compromising their immunological function and productivity. Therefore, the current study aimed to investigate Cd-induced immunotoxicity and potential immunoprotective effect of rutin nanoparticles (RNPs) in the bursal tissue of broilers. A total number of 150 chicks from the Hubbard breed were randomly divided into 5 groups. Group I was fed on standard basal diet (SD) with normal drinking water (DW), Group II received SD containing RNPs (50 mg/kg feed) with DW, Group III fed on SD and DW containing Cd (150 mg/L), Group IV co-treated with rutin-enforced SD (50 mg/kg diet) and DW containing Cd (150 mg/L), and finally, Group V co-supplemented with RNP-enhanced SD (50 mg/kg diet) DW containing Cd (150 mg/L). Productive performance, economic efficiency, oxidative biomarkers, histopathological changes, and the expression level of TLR-4, HSP-70, caspase 3, NF-κB, Bcl-2, and Bax were assessed in the BF tissue. Cd led to severe production and economic losses in exposed birds with a marked surge of oxidative biomarkers, pro-inflammatory cytokines, and histopathological changes in the bursal tissue which could be explained through upregulation of the Hsp70/TLR4/NF-κB molecular pathway in the BF tissue. Meanwhile, RNPs could alleviate most of these changes and prevail optimistic immunomodulatory properties which subsequently could enhance broilers' productivity when incorporated in their diets.

Insight on novel oxindole conjugates adopting different anti-inflammatory investigations and quantitative evaluation.

Background: A dual COX/5-LOX strategy was adopted to develop new oxindole derivatives with superior anti-inflammatory activity. Methods: Three series of oxindoles - esters 4a-p, 6a-l and imines 7a-o - were synthesized and evaluated for their anti-inflammatory and analgesic activities. Molecular docking and predicted pharmacokinetic parameters were done for the most active compounds. A new LC-MS/MS method was developed and validated for the quantification of 4h in rat plasma. Results: Compounds 4h, 6d, 6f, 6j and 7m revealed % edema inhibition up to 100.00%; also, 4l and 7j showed 100.00% writhing protection. Compound 4h showed dual inhibitory activity with IC50 = 0.0533 and 0.4195 µM for COX-2 and 5-LOX, respectively. Molecular docking rationalized the obtained biological activity. The pharmacokinetic parameters of 4h from rat plasma were obtained.

[Box: see text].

Exploring of novel oxazolones and imidazolones as anti-inflammatory and analgesic candidates with cyclooxygenase inhibitory action.

Aim: Over the last few decades, therapeutic needs have led to a search for safer COX-2 inhibitors with potential anti-inflammatory and analgesic activity. Materials & methods: A new series of oxazolone and imidazolone derivatives 3a-c and 4a-r were synthesized and evaluated as anti-inflammatory and analgesic agents. COX-1/COX-2 isozyme selectivity testing and molecular docking were performed. Results: All compounds showed good activities comparable to those of the reference, celecoxib. The most active compounds 3a, 4a, 4c, 4e and 4f showed promising gastric tolerability with an ulcer index lower than that of celecoxib. The molecular docking of p-methoxyphenyl derivative 4c showed alkyl interaction with the side pocket His75 of COX-2 and achieved the best anti-inflammatory activity, with a COX-2 selectivity index better than that of celecoxib.

[Box: see text].

Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Background and Objectives: Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Methods: Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. Results: 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Conclusion: Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Association Between Type 1 Diabetes Mellitus and Eating Disorders: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous meta-analyses have shown mixed results regarding the association between eating disorders (EDs) and type 1 diabetes mellitus (T1DM). Our paper aimed to analyse different EDs and disordered eating behaviours that may be practiced by patients with T1DM. METHODS: A literature search of PubMed, Scopus and Web of Science was conducted on 17 January 2023, using the key terms "T1DM," "Eating Disorders" and "Bulimia." Only observational controlled studies were included. The Revman software (version 5.4) was used for the analysis. RESULTS: T1DM was associated with increased risk of ED compared with nondiabetic individuals (RR = 2.47, 95% CI = 1.84-3.32, p-value < 0.00001), especially bulimia nervosa (RR = 2.80, 95% CI = 1.18-6.65, p-value = 0.02) and binge eating (RR = 1.53, 95% CI = 1.18-1.98, p-value = 0.001). Our analysis has shown that increased risk of ED among T1DM persisted regardless of the questionnaire used to diagnose ED; DM-validated questionnaires (RR = 2.80, 95% CI = 1.91-4.12, p-value < 0.00001) and generic questionnaires (RR = 2.03, 95% CI = 1.27-3.23, p-value = 0.003). Prevalence of insulin omission/misuse was 10.3%; diabetic females demonstrated a significantly higher risk of insulin omission and insulin misuse than diabetic males. CONCLUSION: Our study establishes a significant and clear connection between EDs and T1DM, particularly bulimia and binge eating, with T1DM. Moreover, female diabetics are at higher risk of insulin misuse/omission. Early proactive screening is essential and tailored; comprehensive interventions combining diabetes and ED components are recommended for this population, with referral to a specialised psychiatrist.