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Refractory naphthenic acids (NAs) are among the primary toxic compounds in oil sands process water (OSPW), a matrix with a complex chemical composition that poses challenges to its remediation. This study evaluated the effectiveness of calcium peroxide (CaO2) combined with solar radiation (solar/CaO2) as an advanced water treatment process for degrading model NAs (1,2,3,4-tetrahydronaphthalene-2-carboxylic acid, pentanoic acid, and diphenylacetic acid) in synthetic water (STW) and provide preliminary insights in treating real OSPW. Solar light and CaO2 acted synergistically to degrade target NAs in STW (>67 of synergistic factor) following a pseudo-first-order kinetic (R2 ≥ 0.95), with an optimal CaO2 dosage of 0.1 g L-1. Inorganic ions and dissolved organic matter were found to hinder the degradation of NAs by solar/CaO2 treatment; however, the complete degradation of NAs was reached in 6.7 h of treatment. The main degradation mechanism involved the generation of hydroxyl radicals (â¢OH), which contributed â¼90% to the apparent degradation rate constant (K), followed by H2O2 (4-5%) and 1O2 (0-5%). The tentative transformation pathways of three NAs were proposed, confirming an open-ring reaction and resulting in short-chain fatty acid ions as final products. Furthermore, a reduction in acute microbial toxicity and genotoxic effect was observed in the treated samples, suggesting that solar/CaO2 treatment exhibits high environmental compatibility. Furthermore, the solar/CaO2 system was successfully applied as a preliminary step for real-world applications to remove natural NAs, fluorophore organic compounds, and inorganic components from OSPW, demonstrating the potential use of this technology in the advanced treatment of oil-tailing-derived NAs.
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Nuclear receptor binding SET domain protein 2 (NSD2) significantly contributes to the development of cancer, making it a promising target for cancer drug discovery. This research explores natural compounds as potential selective inhibitors for NSD2 in cancer treatment. Employing a comprehensive in silico approach, the study utilized pharmacophore modeling, molecular docking, pharmacokinetic profiling, and molecular dynamics simulations. An e-pharmacophore model-based screening using the first selective and potent ligand bound to NSD2 identified 49,248 natural compounds from the SuperNatural 3.0 database (containing 449,008 molecules) with acceptable alignment with the developed pharmacophore hypotheses. Subsequently, molecular docking was executed to assess the standout compounds which led to the selection of ten candidates that surpassed the reference inhibitor in accordance w the binding affinity expressed as a G score. Ligand-residue interaction analyses of the top three hits (SN0450102, SN0410255, and SN0142336) revealed diverse crucial interactions with the NSD2 active site, including hydrogen bonds, pi-pi stacking, and hydrophobic contacts with key amino acid residues in the NSD2-PWWP1 domain. Pharmacokinetic profiling confirmed the drug-likability for the refined hits, indicating good cellular permeability and minimal blood-brain barrier penetration. Molecular dynamics simulations for 200 nanoseconds affirmed the stability of protein-ligand complexes, with minimal fluctuations in root mean square deviation and root mean square fluctuation analyses. Overall, this study identified promising natural compounds as potential pharmaceutical agents in the treatment of NSD2-associated cancers.
Subject(s)
Histone-Lysine N-Methyltransferase , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals , Humans , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Histone-Lysine N-Methyltransferase/metabolism , Histone-Lysine N-Methyltransferase/chemistry , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/metabolism , Ligands , Neoplasms/drug therapy , Neoplasms/metabolism , Repressor Proteins/chemistry , Repressor Proteins/metabolism , Repressor Proteins/antagonists & inhibitors , Protein Binding , Hydrogen Bonding , Drug Discovery , PharmacophoreABSTRACT
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.
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Arctium lappa (Burdock) root is used in various culinary applications especially in Asian Cuisine. Arctigenin (ARC) is a polyphenolic compound abundant in the roots of the burdock plant from which it derives its name. The emergence of bacterial resistance is a growing global worry, specifically due to the declining availability of new antibiotics. Screening for the antibacterial candidates among the safe natural products is a promising approach. The present study was aimed to assess the antibacterial activity of ARC against Pseudomonas aeruginosa exploring its effect on the bacterial cell membrane. Furthermore, the anti-virulence activities and anti-quorum sensing (QS) activities of ARC were in vitro, in vivo and in silico assessed against P. aeruginosa. The current results showed the ARC antibacterial activity was owed to its disruption effect of the cell membrane. ARC at sub-MIC significantly decreased the formation of biofilm, motility, production of extracellular enzymes and in vivo protected mice against P. aeruginosa. These anti-virulence activities of ARC are owed to its interference with bacterial QS and its expression. Furthermore, ARC showed mild effect on mammalian erythrocytes, low probability to induce resistance and synergistically combined with antibiotics. In summary, the promising anti-virulence properties of ARC indicate its potential as an effective supplement to conventional antibiotics for treating severe P. aeruginosa infections.
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Cardiac amyloidosis, characterized by amyloid fibril deposition in the myocardium, leads to restrictive cardiomyopathy and heart failure. This review explores recent advancements in imaging techniques for diagnosing and managing cardiac amyloidosis, highlighting their clinical applications, strengths, and limitations. Echocardiography remains a primary, non-invasive imaging modality but lacks specificity. Cardiac MRI (CMR), with Late Gadolinium Enhancement (LGE) and T1 mapping, offers superior tissue characterization, though at higher costs and limited availability. Scintigraphy with Tc-99m-PYP reliably diagnoses transthyretin (TTR) amyloidosis but is less effective for light chain (AL) amyloidosis, necessitating complementary diagnostics. Amyloid-specific PET tracers, such as florbetapir and flutemetamol, provide precise imaging and quantitative assessment for both TTR and AL amyloidosis. Challenges include differentiating between TTR and AL amyloidosis, early disease detection, and standardizing imaging protocols. Future research should focus on developing novel tracers, integrating multimodality imaging, and leveraging AI to enhance diagnostic accuracy and personalized treatment. Advancements in imaging have improved cardiac amyloidosis management. A multimodal approach, incorporating echocardiography, CMR, scintigraphy, and PET tracers, offers comprehensive assessment. Continued innovation in tracers and AI applications promises further enhancements in diagnosis, early detection, and patient outcomes.
Subject(s)
Amyloidosis , Cardiomyopathies , Humans , Cardiomyopathies/diagnosis , Cardiomyopathies/diagnostic imaging , Amyloidosis/diagnosis , Amyloidosis/diagnostic imaging , Positron-Emission Tomography/methods , Echocardiography/methods , Multimodal Imaging/methodsABSTRACT
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.
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Nitrogen-doped carbon materials, characterized by abundant microporous and nitrogen functionalities, exhibit significant potential for carbon dioxide capture and supercapacitors. In this study, a class of porous organic polymer (POP) were successfully synthesized by linking Cr-TPA-4BZ-Br4 and tetraethynylpyrene (Py-T). The model benzoxazine monomers of Cr-TPA-4BZ and Cr-TPA-4BZ-Br4 were synthesized using the traditional three-step method [involving CHâN formation, reduction by NaBH4, and Mannich condensation]. Subsequently, the Sonogashira coupling reaction connected the Cr-TPA-4BZ-Br4 and Py-T monomers, forming Cr-TPA-4BZ-Py-POP. The successful synthesis of Cr-TPA-4BZ-Br4 and Cr-TPA-4BZ-Py-POP was confirmed through various analytical techniques. After verifying the successful synthesis of Cr-TPA-4BZ-Py-POP, carbonization and KOH activation procedures were conducted. These crucial steps led to the formation of poly(Cr-TPA-4BZ-Py-POP)-800, a carbon material with a structure akin to graphite. In practical applications, poly(Cr-TPA-4BZ-Py-POP)-800 exhibited a noteworthy CO2 adsorption capacity of 4.4 mmol/g, along with specific capacitance values of 397.2 and 159.2 F g-1 at 0.5 A g-1 (measured in a three-electrode cell) and 1 A g-1 (measured in a symmetric coin cell), respectively. These exceptional dual capabilities stem from the optimal ratio of heteroatom doping. The outstanding performance of poly(Cr-TPA-4BZ-Py-POP)-800 microporous carbon holds significant promise for addressing contemporary energy and environmental challenges, making substantial contributions to both sectors.
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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.
Subject(s)
1-Naphthylisothiocyanate , Cholestasis , Glycogen Synthase Kinase 3 beta , NF-kappa B , Pyridones , Receptors, Cytoplasmic and Nuclear , Tumor Necrosis Factor-alpha , Wnt Signaling Pathway , Animals , Pyridones/pharmacology , NF-kappa B/metabolism , Wnt Signaling Pathway/drug effects , Male , 1-Naphthylisothiocyanate/toxicity , Mice , Receptors, Cytoplasmic and Nuclear/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cholestasis/chemically induced , Cholestasis/metabolism , Cholestasis/drug therapy , Cholestasis/pathology , Glycogen Synthase Kinase 3 beta/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/prevention & control , Mice, Inbred C57BL , beta Catenin/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathologyABSTRACT
BACKGROUND: Oral mucositis (OM) is a prevalent side effect of chemotherapy that negatively impacts patient quality of life (QoL). Educational guidelines may provide strategies to mitigate these effects. OBJECTIVE: To evaluate the effectiveness of educational guidelines on the severity of OM and QoL in oncology patients undergoing chemotherapy. METHODS: A quasi-experimental study was conducted. Patients (n = 108) were randomly assigned to an intervention group receiving educational guidelines or a control group receiving routine care. Outcomes were assessed at baseline and at one and three months post-intervention. Data were collected using a structured interview including assessments of personal characteristics, clinical data, chemotherapy side effects, OM severity, and QoL. RESULTS: Baseline QoL scores were comparable between groups. Post-intervention, the intervention group experienced significant improvements in QoL (p ≤ 0.05), while the control group showed a decline. OM severity was significantly reduced in the intervention group compared to the control group at both time points (p ≤ 0.05). CONCLUSION: Educational guidelines are an effective intervention for reducing OM severity and improving QoL in oncology patients receiving chemotherapy. Implementation of these guidelines can enhance patient well-being and support optimal treatment outcomes.
Subject(s)
Antineoplastic Agents , Neoplasms , Quality of Life , Stomatitis , Humans , Female , Male , Stomatitis/chemically induced , Neoplasms/drug therapy , Middle Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Patient Education as Topic , Follow-Up Studies , Adult , Prognosis , Severity of Illness Index , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Case-Control Studies , AgedABSTRACT
Intrahepatic cholestasis is a common clinical form of hepatobiliary injury characterized by the intrahepatic accumulation of toxic bile acids. Besides its antidiabetic activity, the dipeptidyl peptidase IV inhibitor sitagliptin (SG) has been recently assigned diverse pharmacological activities and therapeutic potential against different disorders owing to its emerging antioxidant and anti-inflammatory properties. The current study explored the potential hepatoprotective effect of SG on α-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and investigate its possible targeted signaling pathways. Mice received SG (10 and 20â¯mg/kg) for four consecutive days, two days before and after a single oral administration of ANIT (75â¯mg/kg). Our results revealed that SG administration remarkably prevented ANIT-induced histopathological lesions in the liver and maintained hepatic functions and oxidative/antioxidant balance. Ultimately, SG counteracted the inflammatory response in the liver, as indicated by the marked suppression of hepatic expression of NF-κB, TNF-α, and IL-6. Moreover, it inhibited the endoplasmic reticulum (ER) stress response in the liver. These beneï¬cial effects of SG were accompanied by upregulation of SIRT1, p-AMPK, and Nrf2 expressions while downregulating keap1 expression in the liver. In conclusion, this study is the first to demonstrate the ability of SG to protect against ANIT-induced CLI through modulating multiple signaling cascades, including SIRT1/AMPK, Nrf2/keap1, and NF-кB, which resulted in enhanced antioxidant capacity and repressed inflammatory and ER stress responses in the liver.
Subject(s)
1-Naphthylisothiocyanate , AMP-Activated Protein Kinases , Endoplasmic Reticulum Stress , NF-E2-Related Factor 2 , NF-kappa B , Oxidative Stress , Sirtuin 1 , Sitagliptin Phosphate , Animals , Sirtuin 1/metabolism , Oxidative Stress/drug effects , NF-E2-Related Factor 2/metabolism , Sitagliptin Phosphate/pharmacology , Endoplasmic Reticulum Stress/drug effects , Male , Mice , AMP-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , 1-Naphthylisothiocyanate/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/drug therapy , Signal Transduction/drug effects , Inflammation/prevention & control , Inflammation/metabolism , Cholestasis, Intrahepatic/chemically induced , Cholestasis, Intrahepatic/drug therapy , Cholestasis, Intrahepatic/prevention & control , Liver/drug effects , Liver/metabolism , Liver/pathologyABSTRACT
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.
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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.
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STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To compare the effect of posterolateral fusion (PLF) and posterior lumbar interbody fusion (PLIF) on sagittal radiographic parameters in patients with low-grade isthmic spondylolisthesis. Additionally, to explore the correlation between changes in these parameters and clinical outcomes. METHODS: Forty-six consecutive patients with single-level low-grade isthmic spondylolisthesis were initially enrolled. They were randomly assigned to undergo either PLF or PLIF. Patients were followed up for at least 24 months. Radiographic outcomes included pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, sagittal vertical axis, T1 pelvic angle, slip angle, slip degree and disc height. Clinical outcomes were assessed by the Oswestry Disability Index (ODI) and visual analogue scale (VAS). RESULTS: Four participants were lost to follow-up. Of the remaining 42 patients, 29 were female. The mean age was 40.23 ± 10.25 years in the PLF group and 35.81 ± 10.58 years in the PLIF group. There was a statistically significant greater correction of all radiographic parameters in the PLIF group. The ODI and VAS improved significantly in both groups, with no significant differences between the two groups. Changes in the ODI and VAS were significantly correlated with changes in disc height, slip angle and lumbar lordosis. CONCLUSIONS: In patients with low-grade isthmic spondylolisthesis, PLIF demonstrates superior efficacy compared to PLF in correcting sagittal radiographic parameters. Nevertheless, this distinction does not seem to influence short-term clinical results. Restoring disc height, correcting the slip angle, and reestablishing normal lumbar lordosis are crucial steps in the surgical management of isthmic spondylolisthesis.
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Introduction: Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression. Methods: This is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances. Results: During ten years follow-up (2011-2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions (p = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence (p = 0.006), size (p = 0.016) and number (p = 0.005) of CMBs. Conclusion: PRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.
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Universities and colleges play a pivotal role in the pursuit of a future that is sustainable through their pedagogical efforts and the execution of state-of-the-art research endeavors aimed at mitigating the effects of climate change. Higher Education Institutions (HEIs) serve as crucial catalysts in advancing sustainable development. HEIs are increasingly embracing precise measures to reduce their carbon footprint (CF) while also educating students on global sustainability. These nano-methods provide a quantitative framework for assessing a campus's sustainability efforts in line with Green Campus (GC) initiatives to lower carbon emissions align with GC goals. This study employs K-means clustering to analyze the integration of green and low-carbon principles in higher education political and ideological studies. Its goal is to identify patterns, assess teaching effectiveness, and improve sustainability education, aligning with Green Campus initiatives to enhance institutional contributions to sustainable growth through informed pedagogical strategies. Input data includes curriculum content, teaching methods, student engagement, and institutional goals related to sustainability. Seeking to improve sustainability education align with Green Campus initiatives, higher education can strategically enhance their contributions to long-term sustainability and growth through effective pedagogical approaches. Cluster 3 has the lowest WCSS value of 1200, indicating tighter cohesion and less variability within this cluster compared to Cluster 1 (1500) and Cluster 2 (1800). Cluster 3 stands out with the highest silhouette score of 0.7, suggesting well-defined and distinct clusters, while Cluster 2 has the lowest score of 0.4, indicating some overlap or ambiguity in data points. Cluster 1 has the lowest Davies-Bouldin Index of 0.4, implying better separation between clusters compared to Cluster 2 (0.6) and Cluster 3 (0.5). Cluster 3 is well-defined and cohesive, showing strong integration of green practices. Cluster 1 displays good separation and cohesion, while Cluster 2 requires refinement due to potential overlap in sustainability integration.
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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.
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APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG (Kaempferol-3-sophoroside-7-glucoside) is a kaempferol derivative that was separated from plant species belonging to different genera. This study explored the protective effects of KSG on ALI (acute liver injury) caused by APAP overdose in mice and elucidated its possible mechanisms. The results showed that KSG pretreatment alleviated APAP-induced hepatic damage as it reduced hepatic pathological lesions as well as the serum parameters of liver injury. Moreover, KSG opposed APAP-associated oxidative stress and augmented hepatic antioxidants. KSG suppressed the inflammatory response as it decreased the genetic and protein expression as well as the levels of inflammatory cytokines. Meanwhile, KSG enhanced the mRNA expression and level of anti-inflammatory cytokine, IL-10 (interleukin-10). KSG repressed the activation of NF-κB (nuclear-factor kappa-B), besides it promoted the activation of Nrf2 signaling. Additionally, KSG markedly hindered the elevation of ASK-1 (apoptosis-signal regulating-kinase-1) and JNK (c-Jun-N-terminal kinase). Furthermore, KSG suppressed APAP-induced apoptosis as it decreased the level and expression of Bax (BCL2-associated X-protein), and caspase-3 concurrent with an enhancement of anti-apoptotic protein, Bcl2 in the liver. More thoroughly, Computational studies reveal indispensable binding affinities between KSG and Keap1 (Kelch-like ECH-associated protein-1), ASK1 (apoptosis signal-regulating kinase-1), and JNK1 (c-Jun N-terminal protein kinase-1) with distinctive tendencies for selective inhibition. Taken together, our data showed the hepatoprotective capacity of KSG against APAP-produced ALI via modulation of Nrf2/NF-κB and JNK/ASK-1/caspase-3 signaling. Henceforth, KSG could be a promising hepatoprotective candidate for ALI.
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Common bile duct (CBD) stones are a common biliary tract disease. For asymptomatic CBD stones, stone removal by endoscopic retrograde cholangiopancreatography (ERCP) is recommended in available guidelines. Because asymptomatic CBD stones is a benign disease with no noticeable symptoms, the risk vs benefit strategy should be thoroughly considered before performing ERCP in these patients. Clinical care review, technical aspects of the procedure, and patient preferences should also be considered.
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Malathion (MAL) is one of the highly toxic organophosphorus (OP) compounds that induces hepatotoxicity. Echinops. ritro leaves extract (ERLE) is traditionally used in the treatment of bacterial/fungal infections. This study's goal was to investigate the potential of extracts from ERLE against hepatotoxicity induced by MAL in male albino rats. Four equal groups of forty mature male albino rats were created: The rats in the first group used as a control. The second group of rats received ERLE orally. The third group received MAL. ERLE and MAL were administered to the fourth group of rats. Six-week treatment groups were conducted. Using lipid peroxidation indicators [malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)], apoptotic markers [Bcl-2 & caspase-3] and tumor necrosis factor alpha (TNF-α). Rats treated with MAL underwent a significant increase on MDA, ALT, AST, caspase-3 and TNF-α marker with a significant decrease in antioxidant markers [CAT, SOD, GPx] and Bcl-2. Histologically, MAL-treated group's liver sections displayed damaged hepatocytes with collapsed portions, pyknotic nuclei, vacuolated cytoplasm, and congested central veins. Ultra structurally, rat livers treated with MAL showed dilated cisternae of endoplasmic reticulum, swollen mitochondria with disrupted cristae, nuclei with disrupted chromatin content, multiple lysosomes, multiple vacuolations and a disrupted blood sinusoid. With rats treated with ERLE, these alterations were essentially non-existent. It is possible to conclude that ERLE protects against MAL hepatotoxicity, and that this protection is related, at least in part, to its antioxidant activities.