Pirfenidone ameliorates ANIT-induced cholestatic liver injury via modulation of FXR, NF-кB/TNF-α, and Wnt/GSK-3ß/ß-catenin signaling pathways.

Cholestasis is a hepatobiliary disorder characterized by the excessive accumulation of toxic bile acids in hepatocytes, leading to cholestatic liver injury (CLI) through multiple pathogenic inflammatory pathways. Currently, there are limited therapeutic options for the management of cholestasis and associated CLI; therefore, new options are urgently needed. Pirfenidone (PF), an oral bioavailable pyridone analog, is used for the treatment of idiopathic pulmonary fibrosis. PF has recently demonstrated diverse potential therapeutic activities against different pathologies. Accordingly, the present study adopted the α-naphthyl isothiocyanate (ANIT)-induced CLI model in mice to explore the potential protective impact of PF and investigate the underlying mechanisms of action. PF intervention markedly reduced the serum levels of ALT, AST, LDH, total bilirubin, and total bile acids, which was accompanied by a remarkable amelioration of histopathological lesions induced by ANIT. PF also protected the mice against ANIT-induced redox imbalance in the liver, represented by reduced MDA levels and elevated GSH and SOD activities. Mechanistically, PF inhibited ANIT-induced downregulated expressions of the farnesoid X receptor (FXR), as well as the bile salt export pump (BSEP) and the multidrug resistance-associated protein 2 (MRP2) bile acid efflux channels. PF further repressed ANIT-induced NF-κB activation and TNF-α and IL-6 production. These beneficial effects were associated with its ability to dose-dependently inhibit Wnt/GSK-3ß/ß-catenin/cyclin D1 signaling. Collectively, PF protects against ANIT-induced CLI in mice, demonstrating powerful antioxidant and anti-inflammatory activities as well as an ability to oppose BA homeostasis disorder. These protective effects are primarily mediated by modulating the interplay between FXR, NF-κB/TNF-α/IL-6, and Wnt/ß-catenin signaling pathways.

Linagliptin mitigates cisplatin-induced kidney impairment via mitophagy regulation in rats, with emphasis on SIRT-3/PGC-1α, PINK-1 and Parkin-2.

Cisplatin (CDDP) often leads to kidney impairment, limiting its effectiveness in cancer treatment. The lack of mitophagy in proximal tubules exacerbates this issue. Hence, targeting SIRT-3 and PGC1-α shows promise in mitigating CDDP-induced kidney damage. The potential renoprotective effects of linagliptin, however, remain poorly understood. This study represents the first exploration of linagliptin's impact on CDDP-induced kidney impairment in rats, emphasizing its potential role in mitophagic pathways. The experiment involved four rat groups: Group (I) received saline only, Group (II) received a single intraperitoneal injection of CDDP at 6 mg/kg. Groups (III) and (IV) received linagliptin at 6 and 10 mg/kg p.o., respectively, seven days before CDDP administration, continuing for an additional four days. Various parameters, including renal function tests, oxidative stress, TNF-α, IL-1ß, IL-6, PGC-1α, FOXO-3a, p-ERK1, and the gene expression of SIRT-3 and P62 in renal tissue, were assessed. Linagliptin improved renal function, increased antioxidant enzyme activity, and decreased IL-1ß, TNF-α, and IL-6 expression. Additionally, linagliptin significantly upregulated PGC-1α and PINK-1/Parkin-2 expression while downregulating P62 expression. Moreover, linagliptin activated FOXO-3a and SIRT-3, suggesting a potential enhancement of mitophagy. Linagliptin demonstrated a positive impact on various factors related to kidney health in the context of CDDP-induced impairment. These findings suggest a potential role for linagliptin in improving cancer treatment outcomes. Clinical trials are warranted to further investigate and validate its efficacy in a clinical setting.

Biofilm-mediated infections by multidrug-resistant microbes: a comprehensive exploration and forward perspectives.

A biofilm is a collection of microorganisms organized in a matrix of extracellular polymeric material. Biofilms consist of microbial cells that attach to both surfaces and each other, whether they are living or non-living. These microbial biofilms can lead to hospital-acquired infections and are generally detrimental. They possess the ability to resist the human immune system and antibiotics. The National Institute of Health (NIH) states that biofilm formation is associated with 65% of all microbial illnesses and 80% of chronic illnesses. Additionally, non-device-related microbial biofilm infections include conditions like cystic fibrosis, otitis media, infective endocarditis, and chronic inflammatory disorders. This review aims to provide an overview of research on chronic infections caused by microbial biofilms, methods used for biofilm detection, recent approaches to combat biofilms, and future perspectives, including the development of innovative antimicrobial strategies such as antimicrobial peptides, bacteriophages, and agents that disrupt biofilms.

Exploring the potential of Aspergillus wentii: secondary metabolites and biological properties.

Fungi are of considerable importance due to their capacity to biosynthesize various secondary metabolites with bioactive properties that draw high attention in new drug discovery with beneficial uses for improving human well-being and life quality. Aspergillus genus members are widespread and cosmopolitan species with varying economic significance in the fields of industry, medicine, and agriculture. Its species are renowned for their biosynthesis of secondary metabolites, characterized by both potent biological activity and structural novelty, making them a substantial reservoir for the development of new pharmaceuticals. The current work aimed at focusing on one species of this genus, Aspergillus wentii Wehmer, including its reported secondary metabolites in the period from 1951 to November 2023. A total of 97 compounds, including nitro-compounds, terpenoids, anthraquinones, xanthones, benzamides, and glucans. A summary of their bioactivities, as well as their biosynthesis was highlighted. Additionally, the reported applications of this fungus and its enzymes have been discussed. This review offers a useful reference that can direct future research into this fungus and its active metabolites, as well as their possible pharmacological and biotechnological applications.

Piceatannol: a renaissance in antibacterial innovation unveiling synergistic potency and virulence disruption against serious pathogens.

In the relentless battle against multi-drug resistant Gram-negative bacteria, piceatannol emerges as a beacon of hope, showcasing unparalleled antibacterial efficacy and a unique ability to disrupt virulence factors. Our study illuminates the multifaceted prowess of piceatannol against prominent pathogens-Proteus mirabilis, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Notably, piceatannol demonstrated a remarkable ability to inhibit biofilm formation, reduce bacterial mobility, and diminish extracellular enzyme synthesis.Mechanistic insights into piceatannol's activity unraveled its impact on membrane potential, proton motive force, and ATP production. Furthermore, our study delved into piceatannol's anti-quorum sensing (QS) activity, showcasing its potential to downregulate QS-encoding genes and affirming its affinity to critical QS receptors through molecular docking. Crucially, piceatannol exhibited a low propensity for resistance development, positioning it as a promising candidate for combating antibiotic-resistant strains. Its mild effect on red blood cells (RBCs) suggests safety even at higher concentrations, reinforcing its potential translational value. In an in vivo setting, piceatannol demonstrated protective capabilities, significantly reducing pathogenesis in mice infected with P. aeruginosa and P. mirabilis. This comprehensive analysis positions piceatannol as a renaissance in antibacterial innovation, offering a versatile and effective strategy to confront the evolving challenges posed by resilient Gram-negative pathogens.

Ustekinumab Drug Levels and Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Data regarding the utility of therapeutic drug monitoring with ustekinumab (UST) are sparse. Our aim was to determine the correlation of UST levels with outcomes in a cohort of patients with inflammatory bowel disease (IBD). METHODS: This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. The primary outcomes were the correlation of UST level with clinical remission (per physician global assessment), endoscopic healing [the absence of ulcers/erosions in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC)], and normal serum C-reactive protein (CRP) (≤5 mg/L). Secondary outcomes included defining optimal UST trough levels associated with favorable outcomes. RESULTS: A total of 71 patients (74.6% with CD; 57.7% female) were included. The median age was 39.5 years [interquartile range (IQR): 26 to 52] and 12.6% were on combination therapy with immunomodulators. Median UST trough levels were significantly higher in patients who achieved endoscopic healing at 5.4 µg/mL versus 3.5 µg/mL (P=0.035) and normal CRP at 5.5 µg/mL versus. 3.1 µg/mL (P=0.002). A cutoff UST level of 4.8 µg/mL yielded the highest area under the curve (AUC) of 0.73 (95% CI: 0.61-0.80) to predict a normal CRP followed by a cutoff of 3.5 µg/mL which yielded an AUC of 0.66 (95% CI: 0.52-0.81) to predict endoscopic healing. CONCLUSIONS: UST trough levels were significantly higher in patients who achieved a normal CRP and endoscopic healing. A cutoff UST level of 4.8 µg/mL reliably predicted CRP normalization.

Rates, Predictors, and Outcomes of Ustekinumab Dose Escalation in Inflammatory Bowel Disease.

OBJECTIVE: Ustekinumab (UST) is effective for the induction and maintenance of remission in inflammatory bowel disease (IBD). However, a significant proportion of patients will require UST dose escalation. We sought to determine the rates, predictors, and outcomes of UST dose escalation in patients with IBD. PATIENTS AND METHODS: This was a multicenter, retrospective study of all patients with IBD who received UST from January 1, 2014 to March 1, 2022. Primary outcomes were the rates and predictors of UST dose escalation. Secondary outcomes included steroid-free clinical remission, endoscopic healing, and normalization of serum c-reactive protein in patients who underwent UST dose escalation. RESULTS: A total of 198 patients were included (58% females and 76.7% with Crohn's disease). UST dose was escalated by 55.5% (n = 110). Mean baseline albumin was lower in the UST dose escalation group at 3.86 ± 0.47 versus 4.03 ± 0.45 g/dL (P = 0.044). The mean hemoglobin was lower in the UST dose escalation group at 12.1 ± 1.83 versus 12.7 ± 1.42 (P = 0.049). On multivariate analysis, male sex alone was associated with the need for dose escalation (odds ratio: 4.08, 95% CI: 1.20 - 13.90; P = 0.025). In the UST dose escalation group, 66.1% achieved steroid-free clinical remission, 55.8% had normalization of c-reactive protein, and 35.8% achieved endoscopic healing. CONCLUSIONS: UST dose escalation was needed in more than half of patients with IBD in this real-world cohort. UST dose escalation resulted in clinical remission in more than half of the cohort and endoscopic healing in one-third of patients.

Selective and Sensitive Detection of Fe3+ Ions Using a Red-Emissive Fluorescent Probe Based on Triphenylamine and Perylene-Linked Conjugated Microporous Polymer.

The Expansion of modern industry underscores the urgent need to address heavy metal pollution, which is a threat to human-health and environment. Efforts are underwent to develop precise technologies for detecting heavy metal ions (M+-ion). One promising approach involves the use of Conjugated Microporous Polymers (CMPs) modified with Triphenylamine (TPA) anderylene (Peryl), known as TPA-Peryl-CMP, which emits strong refluorescence. Various analytical techniques, such as Brunauer-Emmett-Teller analysis, Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and thermogravimetric analysis (TGA), are utilized to characterize the synthesized TPA-Peryl-CMP and understand its functional properties. In addition to its remarkable fluorescence behavior, TPA-Peryl-CMP shows promise as a sensor for Fe3+ ions using a turn-off strategy. Due to its exceptional stability and robust π-electron system, this platform demonstrates remarkable sensitivity and selectivity, significantly improving detection capabilities for specific analytes. Detailed procedures related to the mechanism for detecting Fe3+ ions are outlined for sensing Fe3+ ions, revealing a notably strong linear correlation within the concentration range of 0-3 µM, with a correlation coefficient of 0.9936 and the Limit of detection (LOD) 20 nM. It is anticipated that development of such a kind of TPA-Peryl-CMP will observe broader applications in detecting various analytes related to environmental and biological systems.

Utilizing nanotechnology and advanced machine learning for early detection of gastric cancer surgery.

Nanotechnology has emerged as a promising frontier in revolutionizing the early diagnosis and surgical management of gastric cancers. The primary factors influencing curative efficacy in GIC patients are drug inefficacy and high surgical and pharmacological therapy recurrence rates. Due to its unique optical features, good biocompatibility, surface effects, and small size effects, nanotechnology is a developing and advanced area of study for detecting and treating cancer. Considering the limitations of GIC MRI and endoscopy and the complexity of gastric surgery, the early diagnosis and prompt treatment of gastric illnesses by nanotechnology has been a promising development. Nanoparticles directly target tumor cells, allowing their detection and removal. It also can be engineered to carry specific payloads, such as drugs or contrast agents, and enhance the efficacy and precision of cancer treatment. In this research, the boosting technique of machine learning was utilized to capture nonlinear interactions between a large number of input variables and outputs by using XGBoost and RNN-CNN as a classification method. The research sample included 350 patients, comprising 200 males and 150 females. The patients' mean ± SD was 50.34 ± 13.04 with a mean age of 50.34 ± 13.04. High-risk behaviors (P = 0.070), age at diagnosis (P = 0.034), distant metastasis (P = 0.004), and tumor stage (P = 0.014) were shown to have a statistically significant link with GC patient survival. AUC was 93.54%, Accuracy 93.54%, F1-score 93.57%, Precision 93.65%, and Recall 93.87% when analyzing stomach pictures. Integrating nanotechnology with advanced machine learning techniques holds promise for improving the diagnosis and treatment of gastric cancer, providing new avenues for precision medicine and better patient outcomes.

Eco-friendly nanotechnology in rheumatoid arthritis: ANFIS-XGBoost enhanced layered nanomaterials.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation and pain in the joints, which can lead to joint damage and disability over time. Nanotechnology in RA treatment involves using nano-scale materials to improve drug delivery efficiency, specifically targeting inflamed tissues and minimizing side effects. The study aims to develop and optimize a new class of eco-friendly and highly effective layered nanomaterials for targeted drug delivery in the treatment of RA. The study's primary objective is to develop and optimize a new class of layered nanomaterials that are both eco-friendly and highly effective in the targeted delivery of medications for treating RA. Also, by employing a combination of Adaptive Neuron-Fuzzy Inference System (ANFIS) and Extreme Gradient Boosting (XGBoost) machine learning models, the study aims to precisely control nanomaterials synthesis, structural characteristics, and release mechanisms, ensuring delivery of anti-inflammatory drugs directly to the affected joints with minimal side effects. The in vitro evaluations demonstrated a sustained and controlled drug release, with an Encapsulation Efficiency (EE) of 85% and a Loading Capacity (LC) of 10%. In vivo studies in a murine arthritis model showed a 60% reduction in inflammation markers and a 50% improvement in mobility, with no significant toxicity observed in major organs. The machine learning models exhibited high predictive accuracy with a Root Mean Square Error (RMSE) of 0.667, a correlation coefficient (r) of 0.867, and an R2 value of 0.934. The nanomaterials also demonstrated a specificity rate of 87.443%, effectively targeting inflamed tissues with minimal off-target effects. These findings highlight the potential of this novel approach to significantly enhance RA treatment by improving drug delivery precision and minimizing systemic side effects.

The potential effects of N-Acyl homoserine lactones on aerobic sludge granulation during phenolic wastewater treatment.

The formation of aerobic granular sludge (AGS) is relatively difficult during the treatment of refractory wastewater, which generally shows small granular sizes and poor stability. The formation of AGS is regulated by N-Acyl homoserine lactones (AHLs)-mediated quorum sensing (QS). However, the potential role of AHLs in AGS formation under the toxic stress of refractory pollutants and the heterogeneity in the distribution and function of AHLs across different aggregates are not well understood. This study investigated the potential effects of AHLs on the formation of AGS during phenolic wastewater treatment. The distribution and succession of AHLs across varying granular sizes and development stages of AGS were investigated. Results showed that AGS was successfully formed in 13 days with an average granular size of 335 ± 39 µm and phenol removal efficiency of >99%. The levels of AHLs initially increased and then decreased. C4-HSL and 3-oxo-C10-HSL were enriched in large granules, suggesting they may play a pivotal role in regulating the concentration and composition of extracellular polymeric substances (EPS). The content of EPS constantly increased to 149.4 mg/gVSS, and protein (PN) was enriched in small and large granules. Luteococcus was the dominant genus constituting up to 62% after the granulation process, and exhibited a strong association with C4-HSL. AHLs might also regulate the bacterial community responsible for EPS production, and pollutant removal, and facilitate the proliferation of slow-growing microorganisms, thereby enhancing the formation of AGS. The synthesis and dynamics of AHLs were mainly governed by AHLs-producing bacterial strains of Rhodobacter and Pseudomonas, and AHLs-quenching strains of Flavobacterium and Comamonas. C4-HSL and 3-oxo-C10-HSL might be the major contributors to promoting sludge granulation under phenol stress and play critical roles in large granules. These findings enhance our understanding of the roles that AHLs play in sludge granulation under toxic conditions.

Emergency Decompression of Orbital Emphysema, a Sight-Saving Tool in a Patient With Precious Eye.

A woman, 19 years old, with a history of falling from a height with resulting zygomatico-maxillar complex fracture on the right side, a mandibular fracture on the left side for which she underwent repair with plate insertion, and traumatic optic atrophy in her right eye, presented 9 months later with eye facial swelling, proptosis, and acute rapid loss of vision in the left eye. The diagnosis was done immediately aided by radiology assistance and a decision was taken to admit the patient to undergo urgent decompression to save the vision and the patient did recover well. This case presented here and the associated literature review focus on severe orbital emphysema with compressive optic neuropathy and orbital compartment syndrome as a morbidity that can exist with delayed presentation after trauma and not elicited by sneezing or forced blowing, as well as the drastic importance of brisk intervention, to save vision and prevent visual complications if left untreated.

Gas Chromatography-Mass Spectrometry Chemical Profiling of Commiphora myrrha Resin Extracts and Evaluation of Larvicidal, Antioxidant, and Cytotoxic Activities.

Plant extracts and essential oils can be alternative environmentally friendly agents to combat pathogenic microbes and malaria vectors. Myrrh is an aromatic oligum resin that is extracted from the stem of Commiphora spp. It is used in medicine as an insecticide, cytotoxic, and aromatic. The current study assessed the effect of Commiphora myrrha resin extracts on the biological potency of the third larval stage of Aedes aegypti, as well as its antioxidant and cytotoxic properties against two types of tumor cells (HepG-2 and Hela cell lines). It also used GC-MS to determine the chemical composition of the C. myrrha resin extracts. Fifty components from the extracted plant were tentatively identified using the GC-MS method, with curzerene (33.57%) typically listed as the primary ingredient, but other compounds also make up a significant portion of the mixture, including 1-Methoxy-3,4,5,7-tetramethylnaphthalene (15.50%), ß-Elemene (5.80%), 2-Methoxyfuranodiene (5.42%), 2-Isopropyl-4,7-Dimethyl-1-Naphthol (4.71%), and germacrene B (4.35%). The resin extracts obtained from C. myrrha exhibited significant efficacy in DPPH antioxidant activity, as evidenced by an IC50 value of 26.86 mg/L and a radical scavenging activity percentage of 75.06%. The 50% methanol extract derived from C. myrrha resins exhibited heightened potential for anticancer activity. It demonstrated substantial cytotoxicity against HepG-2 and Hela cells, with IC50 values of 39.73 and 29.41 µg mL-1, respectively. Notably, the extract showed non-cytotoxic activity against WI-38 normal cells, with an IC50 value exceeding 100 µg mL-1. Moreover, the selectivity index for HepG-2 cancer cells (2.52) was lower compared to Hela cancer cells (3.40). Additionally, MeOH resin extracts were more efficient against the different growth stages of the mosquito A. aegypti, with lower LC50, LC90, and LC95 values of 251.83, 923.76, and 1293.35 mg/L, respectively. In comparison to untreated groups (1454 eggs/10 females), the average daily number of eggs deposited (424 eggs/L) decreases at higher doses (1000 mg/L). Finally, we advise continued study into the possible use of C. myrrha resins against additional pests that have medical and veterinary value, and novel chemicals from this extract should be isolated and purified for use in medicines.

Nurse managers' managerial innovation and it's relation to proactivity behavior and locus of control among intensive care nurses.

BACKGROUND: The nursing profession is undergoing rapid transformation, requiring innovation in management approaches and proactive behaviors among staff. Nurse Managers play a vital role through managerial innovation, but its impacts on intensive care nurses' proactivity and locus of control remain underexplored. OBJECTIVES: This study aimed to assess the levels of Nurse Managers' managerial innovation and relate it to proactivity behaviors and locus of control orientations among intensive care nurses. METHODS: A cross-sectional correlational design was adopted, recruiting 242 intensive care nurses from Tanta University Hospital, Egypt. Participants completed standardized questionnaires measuring perceived managerial innovation, proactivity behavior, and locus of control. RESULTS: Nurse Managers demonstrated moderately high innovation across all dimensions, especially in continuous learning and development (mean = 4.65) and advanced technology use (mean = 4.56). Nurses exhibited sound proactivity levels, particularly in adaptability (mean = 4.40) and planning (mean = 4.35). The majority of nurses showed an internal locus of control (64.5%). Managerial innovation had significant positive correlations with nurses' proactivity (r = 0.45, p < 0.001) and internal locus of control (r = 0.42, p < 0.001). Regression analysis revealed age, gender, experience, education, and ICU type as significant predictors of proactivity and locus of control. CONCLUSION: Innovative nursing leadership positively influences staff's proactivity levels and perceived control over their practice. This underscores the vital role of nurse managers in creating empowering environments in intensive care.

Role of finite element analysis for selection of single point fixation in zygomaticomaxillary complex fracture.

BACKGROUND: One-point fixation was superior to the two and three-points fixation in minimally displaced zygomaticomaxillary complex (ZMC) fracture regarding the cost, invasiveness, scaring, number of wounds, and operation time. Accordingly, this study aimed to predict which one-point fixation is the most stable in managing minimally displaced ZMC fracture. MATERIAL & METHODS: This study simulated the different one-point fixation approaches on three ZMC models after fracture reduction and application of all forces exerted on the fractured area. The findings were represented as stress impact on the ZMC fracture and plating system as well as the inter-fragments micro-motion. RESULTS: The von misses stresses of plates for the zygomaticofrontal, infra-orbital rim, and zygomaticomaxillary buttress model were (66.508, 1.285, and1.16 MPa) respectively. While the screws' von misses for the infraorbital rim, zygomaticofrontal, and zygomaticomaxillary buttress models were (13.8, 4.05, and 1.60 MPa) respectively. Whereas, the maximum principles stress at zygomaticofrontal, zygomaticomaxillary buttress, and infraorbital rim models were (37.03, 37.01, and 34.46 MPa) respectively. In addition, the inter-fragment micro-motion for zygomaticomaxillary buttress, infraorbital rim, and zygomaticofrontal models were (0.26, 0.25, and 0.15 mm) respectively. CONCLUSION: One-point fixation at zygomaticomaxillary buttress is the preferred point because it is exposed to low stresses, and the inter-fragment micro-motion is within the approved limit with the elements in the same direction of fixation which indicates the rigid fixation. In addition, it is less palpable and scarless. TRIAL REGISTRATION: clinical trial.gov (NCT05819372) at 19/04/2023.

Assessing the antibacterial potential of 6-gingerol: Combined experimental and computational approaches.

The rise of antibiotic resistance in bacteria is becoming a global concern, particularly due to the dwindling supply of new antibiotics. This situation mandates the discovery of new antimicrobial candidates. Plant-derived natural compounds have historically played a crucial role in the development of antibiotics, serving as a rich source of substances possessing antimicrobial properties. Numerous studies have supported the reputation of 6-gingerol, a prominent compound found in the ginger family, for its antibacterial properties. In this study, the antibacterial activities of 6-gingerol were evaluated against Gram-negative bacteria, Acinetobacter baumannii and Klebsiella pneumoniae, with a particular focus on the clinically significant Gram-negative Pseudomonas aeruginosa and Gram-positive bacteria Staphylococcus aureus. Furthermore, the anti-virulence activities were assessed in vitro, in vivo, and in silico. The current findings showed that 6-gingerol's antibacterial activity is due to its significant effect on the disruption of the bacterial cell membrane and efflux pumps, as it significantly decreased the efflux and disrupted the cell membrane of S. aureus and P. aeruginosa. Furthermore, 6-gingerol significantly decreased the biofilm formation and production of virulence factors in S. aureus and P. aeruginosa in concentrations below MICs. The anti-virulence properties of 6-gingerol could be attributed to its capacity to disrupt bacterial virulence-regulating systems; quorum sensing (QS). 6-Gingerol was found to interact with QS receptors and downregulate the genes responsible for QS. In addition, molecular docking, and molecular dynamics (MD) simulation results indicated that 6-gingerol showed a comparable binding affinity to the co-crystalized ligands of different P. aeruginosa QS targets as well as stable interactions during 100 ns MD simulations. These findings suggest that 6-gingerol holds promise as an anti-virulence agent that can be combined with antibiotics for the treatment of severe infections.

Protective effect of kaempferol glucoside against lipopolysaccharide-caused acute lung injury via targeting Nrf2/NF-κB/NLRP3/GSDMD: Integrating experimental and computational studies.

The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. KSG markedly increased the survival rate and alleviated lung pathological lesions induced by lipopolysaccharide (LPS). Furthermore, KSG attenuated differential and total cell counts in BALF (bronchoalveolar lavage fluid) and MPO (myeloperoxidase) activity. KSG counteracted the NF-κB (nuclear factor-κB) activation and significantly ameliorated the downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, KSG suppressed the over-expression of NLRP3 (NOD-like receptor protein 3), caspase-1, and pro-inflammatory cytokine interleukin IL-1ß (interleukine-1ß) and prohibited the elevation of the pyroptotic parameter GSDMD-N (N-terminal domain of gasdermin D) induced by LPS challenge. In addition, KSG significantly enhanced Nrf2 (nuclear-factor erythroid-2-related factor) and HO-1 (heme-oxygenase-1) expression. Meanwhile, KSG mitigated lipid peroxidative markers (malondialdehyde, protein carbonyl and 4-hydroxynonenal) and boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) in lung tissue. In silico analyses revealed that KSG disrupts Keap1-Nrf2 protein-protein interactions by binding to the KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior binding affinity of KSG to KEAP1 compared to the reference inhibitor, with docking scores of -9.576 and -6.633 Kcal/mol, respectively. Additionally, the MM-GBSA binding free energy of KSG (-67.25 Kcal/mol) surpassed that of the reference inhibitor (-56.36 Kcal/mol). Furthermore, MD simulation analysis revealed that the KSG-KEAP1 complex exhibits substantial and stable binding interactions with various amino acids over a duration of 100 ns. These findings showed the protective anti-inflammatory and anti-oxidative modulatory efficiencies of KSG that effectively counteracted LPS-induced ALI and encouraged future research and clinical applications of KSG as a protective strategy for ALI.

α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies.

Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol-3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy -5.33 and -4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds 1-7 demonstrated weak affinity to butyrylcholinesterase. Compounds 2 and 4 displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6 and 168.7 µM, respectively). Compound 4 exhibited moderate α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer's disease (AD) and mitigating hyperglycemia.

Consumption of aphrodisiac drugs without prescription among men in Saudi Arabia: cross-sectional study.

Background: The prevalence and patterns of aphrodisiac drug consumption without prescription among men in Saudi Arabia remain underexplored, with limited empirical evidence available. Given the potential health implications and societal considerations, a comprehensive investigation is warranted. Aim: Assess the Prevalence, pattern of use and the associated factors of Aphrodisiac drugs consumption without prescription among men at Najran City, Saudi Arabia. Methods: Employing a cross-sectional descriptive study, 500 participants were included through convenience sampling. The utilized questionnaires covered a range of data, including socio-demographic information, patterns of aphrodisiac use, knowledge about aphrodisiacs, lifestyle details, a sexual health inventory for men, and a perceived stress level scale. Results: The study reveals a significant prevalence of unsanctioned aphrodisiac drug use (31%) among men in Najran City, Saudi Arabia, with a majority (79.3%) consuming these substances four times monthly. Associated disparities in knowledge, lifestyle, stress, and sexual function underscore the urgent need for policy interventions and tailored health education initiatives for this demographic. Conclusion: Approximately one-third of the sampled population engaged in the unsanctioned use of aphrodisiac drugs, with the majority utilizing them four times monthly. Tablets emerged as the most prevalent form of consumption. Commonly cited motives and justifications included peer influence and the perceived safety of aphrodisiacs. Influential factors encompassed levels of knowledge, lifestyle, stress levels, erectile function, age, education, and the number of wives. Recommendations: Urgent policy interventions are warranted to regulate the acquisition and distribution of aphrodisiacs. Tailored health education initiatives should be implemented for married and prospective married men.

Organic-Inorganic Phenolic/POSS Hybrids Provide Highly Ordered Mesoporous Structures Templated by High Thermal Stability of PS-b-P4VP Diblock Copolymer.

Anionic living polymerization was used to prepare a diblock copolymer of poly(styrene-b-4-vinyl pyridine) (PS-b-P4VP), and a phenolic resin with a double-decker silsesquioxane (DDSQ) cage structure was used to form a phenolic/DDSQ hybrid (PDDSQ-30 with 30 wt.% DDSQ). Strong intermolecular hydrogen bonding could be confirmed through the hydroxyl (OH) groups of PDDSQ hybrid with the pyridine group of the P4VP block in PDDSQ-30/PS-b-P4VP blends based on Fourier transform infrared spectroscopy analyses, where increasing PDDSQ concentrations resulted in a higher proportion of hydrogen-bonded pyridine groups. After thermal polymerization at 180 °C, the self-assembled structures of these PDDSQ/PS-b-P4VP blends were revealed by data from small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), where the d-spacing increased with raising PDDSQ concentration. Because relatively higher thermal stability of the PDDSQ hybrid than pure phenolic resin and PS-b-P4VP template, we can obtain the long ranger order of mesoporous PDDSQ hybrids after removing the PS-b-P4VP template, which reveals the high surface area and high pore volume with cylindrical and spherical structures corresponding to the PDDSQ compositions that are rarely observed by using pure phenolic resin as the matrix and could be used in supercapacitor application.