Integrating sustainability into higher education challenges and opportunities for universities worldwide.

This paper undertakes a comprehensive investigation into incorporating sustainability within higher education, aligning with the United Nations' Sustainable Development Goals (SDGs). Utilizing quantitative and qualitative research methods, our study delves into the status quo, methodologies, and impacts of sustainability education across a spectrum of international and local settings, with a specific lens on the United Arab Emirates. Our analysis spans various topics, from best practices in sustainability integration and educational frameworks to the influence of global initiatives like the Impact Ranking on promoting SDG-aligned transformations within academic institutions. Highlighting case studies from the UAE, we provide concrete evidence of successful sustainability strategies and interventions. These are juxtaposed with a global overview that uncovers the varying challenges and opportunities present in implementing sustainability education worldwide. Among our key findings is the essential role of interdisciplinary approaches and the critical need for active faculty involvement in fostering sustainability education. Drawing from a rich compilation of data and narratives, the paper presents a set of strategic recommendations designed to enhance the efficacy and reach of sustainability education. These recommendations are informed by the challenges observed and the success stories identified during our investigation. Ultimately, our research underscores the indispensable role that higher education plays in preparing future generations to navigate and address the complexities of sustainability challenges effectively.

Potent neutralization by a receptor binding domain monoclonal antibody with broad specificity for SARS-CoV-2 JN.1 and other variants.

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. While increasing herd immunity, current vaccines, and therapeutics have improved outcomes for some; prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed. Using a rationally designed SARS-CoV-2 Receptor Binding Domain (RBD) - ACE2 fusion protein and differential selection process with native Omicron RBD protein, we developed a recombinant human monoclonal antibody (hmAb) from a convalescent individual following SARS-CoV-2 Omicron infection. The resulting hmAb, 1301B7 potently neutralized a wide range of SARS-CoV-2 variants including the original Wuhan and more recent Omicron JN.1 strain, as well as SARS-CoV. Structure determination of the SARS-CoV-2 EG5.1 Spike/1301B7 Fab complex by cryo-electron microscopy at 3.1Å resolution demonstrates 1301B7 contacts the ACE2 binding site of RBD exclusively through its VH1-69 heavy chain, making contacts using CDRs1-3, as well as framework region 3 (FR3). Broad specificity is achieved through 1301B7 binding to many conserved residues of Omicron variants including Y501 and H505. Consistent with its extensive binding epitope, 1301B7 is able to potently diminish viral burden in the upper and lower respiratory tract and protect mice from challenge with Omicron XBB1.5 and Omicron JN.1 viruses. These results suggest 1301B7 has broad potential to prevent or treat clinical SARS-CoV-2 infections and to guide development of RBD-based universal SARS-CoV-2 prophylactic vaccines and therapeutic approaches.

Optimization of isotropic MoS2/PES membranes for efficient treatment of industrial oily wastewater.

Elimination of tiny oil droplets nearly miscible with wastewater can be realized using membrane technology through ultrafiltration. The novelty of this work was to blend different phases of molybdenum disulfide (MoS2) in isotropic polyethersulfone (PES). We prepared isotropic PES membranes by optimizing nonsolvent vapour-induced phase separation (VIPS). Membranes were blended with MoS2 nanosheets of different phases to promote separation performance and antifouling resistance. FE-SEM revealed the flower-like surface morphology of MoS2 nanosheets. HR-TEM of MoS2 revealed 2H domains in the monolayer, flakes of a few layers and a d-spacing of 0.22 nm. Raman spectroscopy could be used to distinguish mixed-phase MoS2 from single-phase MoS2. Isotropic PES membranes modified with 70% 1T/2H MoS2 had a significantly high permeance to pure water (6911 kg m-2 h bar). The same membrane possessed a high efficiency of oil rejection of 98.78%, 97.85%, 99.83% for emulsions of industrial crude oil at 100, 1000 and 10 000 mg L-1, respectively. Removal of oil droplets from wastewater was dominated by a mechanism based on size exclusion. Isotropic PES modified with 2H MoS2 possessed superior oleophilicity, which resulted in low rejection of crude oil. Modified membranes showed excellent fouling resistance for three successive filtration cycles, as evidenced by enhanced antifouling parameters. Our study reveals how the phase composition of MoS2 nanosheets can significantly affect the performance of isotropic PES membranes during the ultrafiltration of oily wastewater.

Loss of GIPR in LEPR cells impairs glucose control by GIP and GIP:GLP-1 co-agonism without affecting body weight and food intake in mice.

OBJECTIVE: The glucose-dependent insulinotropic polypeptide (GIP) decreases body weight via central GIP receptor (GIPR) signaling, but the underlying mechanisms remain largely unknown. Here, we assessed whether GIP regulates body weight and glucose control via GIPR signaling in cells that express the leptin receptor (Lepr). METHODS: Hypothalamic, hindbrain, and pancreatic co-expression of Gipr and Lepr was assessed using single cell RNAseq analysis. Mice with deletion of Gipr in Lepr cells were generated and metabolically characterized for alterations in diet-induced obesity (DIO), glucose control and leptin sensitivity. Long-acting single- and dual-agonists at GIPR and GLP-1R were further used to assess drug effects on energy and glucose metabolism in DIO wildtype (WT) and Lepr-Gipr knock-out (KO) mice. RESULTS: Gipr and Lepr show strong co-expression in the pancreas, but not in the hypothalamus and hindbrain. DIO Lepr-Gipr KO mice are indistinguishable from WT controls related to body weight, food intake and diet-induced leptin resistance. Acyl-GIP and the GIPR:GLP-1R co-agonist MAR709 remain fully efficacious to decrease body weight and food intake in DIO Lepr-Gipr KO mice. Consistent with the demonstration that Gipr and Lepr highly co-localize in the endocrine pancreas, including the ß-cells, we find the superior glycemic effect of GIPR:GLP-1R co-agonism over single GLP-1R agonism to vanish in Lepr-Gipr KO mice. CONCLUSIONS: GIPR signaling in cells/neurons that express the leptin receptor is not implicated in the control of body weight or food intake, but is of crucial importance for the superior glycemic effects of GIPR:GLP-1R co-agonism relative to single GLP-1R agonism.

Parliamentary question: Insights from the Federal National Council in the UAE.

This paper highlights the paramount role of parliamentary questioning as a control mechanism exercised by the Federal National Council (FNC) in the United Arab Emirates (UAE). The surge in its utilization, attributed to heightened awareness among FNC members and ministers, has significantly enhanced the Council's control capabilities, especially in the absence of alternative parliamentary control instruments such as interpellations. The paper underscores the simplicity and adaptability of parliamentary questioning, which spans diverse topics and addresses everyday state matters, rectifies errors, monitors law implementation, and fills legislative gaps. The structure of the paper comprises two sections: the first scrutinizes procedural requirements within the UAE's Constitution and the FNC's Bylaw, while the second section explores practical examples, offering insights into the distinctive nature of the FNC's parliamentary questioning compared to regional practices.

Outcomes of Percutaneous Image-Guided and Laparoscopic Cholecystostomies in High-Risk Patients With Acute Calculus Cholecystitis: A Five-Year District General Hospital Experience.

Introduction Acute cholecystitis (AC), inflammation of the gall bladder, is one of the most common emergency surgical presentations. In the UK, approximately 15% of the population is estimated to have gallstones, and approximately 20% of them can develop AC. Laparoscopic cholecystectomy (LC) is considered the definitive management of AC. However, cholecystectomy carries a very high risk of morbidity and mortality in high-risk frail patients with multiple comorbidities who are deemed unfit for surgery. Percutaneous cholecystostomy (PC), both image-guided and laparoscopic, is generally acknowledged as an interim treatment measure before definitive management, which is the LC. Materials and methods This is a retrospective study from the Royal Albert Edward Infirmary, a district general hospital (DGH) based in Wigan, UK. The medical records of all the patients who were admitted to the surgical department and underwent PC between January 2017 and December 2022 were analyzed. Patients with previous hepato-pancreato-biliary (HPB) malignancy, who underwent open cholecystostomy, or those with abdominal ascites were excluded from the study. Information was collected regarding the age, gender, American Society of Anaesthesiologists (ASA) grades, success rates of both procedures as temporary or definitive management, duration of hospital stay, 30-day and 1-year mortality after the procedure, timing of the procedure, and long-term complications after the procedure, particularly those related to cholecystostomy tube dislodgment or blockage. Results Twenty-seven patients who underwent PC were divided into two groups: group A, consisting of 10 patients who underwent laparoscopic cholecystostomies, and group B, consisting of 17 patients who had ultrasound (US)-guided cholecystostomies. The mean age of the patients in group A was 66.7 as compared to 75.1 in group B. Most of the patients were in ASA groups III (14) and IV (10). About 74% of patients had procedures done during the day and 26% had PC at night time. The mean hospital stay was 13.5 days. About 55% of patients had planned elective LC as a definitive management. Following the treatment, two patients died within 30 days, and eight patients passed away within a year. About 40% of the patients had complications related to the tube dislodgment and blockage. Conclusion This study concludes that PC, using both laparoscopic and US-guided techniques, can serve as an interim as well as a definitive measure, particularly in patients who are at high risk for anesthesia and the procedure itself and have multiple comorbidities.

Recent advances in functional micro/nanomaterials for removal of crude oil via thermal effects.

Crude oil is one of the most widely used energy and industrial raw materials that is crucial to the world economy, and is used to produce various petroleum products. However, crude oil often spills during extraction, transportation and use, causing negative impacts on the environment. Thus, there is a high demand for products to remediate leaked crude oil. Among them, oleophilic and hydrophobic adsorbents can absorb crude oil through thermal effects and are research hotspots. In this review, we first present an overview of wettability theory, the heating principles of various thermal effects, and the theory of reducing crude oil viscosity by heating. Then we discuss adsorbents based on different heating methods including the photothermal effect, Joule heating effect, alternating magnetic field heating effect, and composite heating effect. Preparation methods and oil adsorption performance of adsorbents are summarized. Finally, the advantages and disadvantages of various heating methods are briefly summarized, as well as the prospects for future research.

Exploring the impact of diet and nutrition on vitiligo: A systematic review of dietary factors and nutritional interventions.

BACKGROUND: Vitiligo, an autoimmune skin disorder linked to hormonal and genetic factors, results in reduced pigmentation due to a gradual decline in melanocyte activity. This systematic review delves into the role of dietary intervention and nutrition in managing vitiligo. METHODS: A comprehensive search on PubMed, Google Scholar, and European PMC identified 214 studies, with 14 meeting inclusion criteria post-screening. The selected studies primarily explored the impact of dietary supplements on disease activity. RESULTS: Heavy metal exposure, specifically Cd, Pb, and Hg, indicated potential links to heightened reactive oxygen species and vitiligo development. Conflicting evidence emerged regarding the role of trace minerals (Zn and Cu), with some studies suggesting deficiencies and others proposing excesses in vitiligo patients. Vitamins with anti-inflammatory properties like vitamin C, D, and B12, along with antioxidants, were investigated for their potential in repigmentation strategies. Additionally, polyunsaturated fatty acids (PUFAs), especially in varying types of fat consumption, were implicated. Emphasizing the need to reduce reliance on pharmacological and phototherapy interventions, the review uncovers novel roles for dietary supplements as adjuncts or flare reducers. CONCLUSION: While dietary interventions cannot be thought of as a standalone therapy, they still make a case for being used as adjuncts. Large scale clinical trials are warranted to establish strong evidence and protocols, and might also help reduce the dependency on pharmacological methods, which come with their adverse effect profiles.

Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1.

Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the host via hijacking essential host cell machinery components to evade the provoked antiviral innate immunity against the invading pathogen. Respiratory viral infections are usually acute with the ability to activate pattern recognition receptors (PRRs) in/on host cells, resulting in the production and release of interferons (IFNs), proinflammatory cytokines, chemokines, and IFN-stimulated genes (ISGs) to reduce virus fitness and mitigate infection. Nevertheless, the game between viruses and the host is a complicated and dynamic process, in which they restrict each other via specific factors to maintain their own advantages and win this game. The primary role of the non-structural protein 1 (NS1 and Nsp1) of influenza A viruses (IAV) and the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively, is to control antiviral host-induced innate immune responses. This review provides a comprehensive overview of the genesis, spatial structure, viral and cellular interactors, and the mechanisms underlying the unique biological functions of IAV NS1 and SARS-CoV-2 Nsp1 in infected host cells. We also highlight the role of both non-structural proteins in modulating viral replication and pathogenicity. Eventually, and because of their important role during viral infection, we also describe their promising potential as targets for antiviral therapy and the development of live attenuated vaccines (LAV). Conclusively, both IAV NS1 and SARS-CoV-2 Nsp1 play an important role in virus-host interactions, viral replication, and pathogenesis, and pave the way to develop novel prophylactic and/or therapeutic interventions for the treatment of these important human respiratory viral pathogens.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Compared with Warfarin in Patients with Low Bodyweight who have Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: oral anticoagulant (DOAC) agents are becoming the anticoagulation strategy of choice for most clinical risks for which they are indicated. However, residual uncertainty remains regarding their use in preventing stroke in patients with low bodyweight [< 60 kg or body mass index (BMI) < 18 kg/m2]. We have carried out pooled systematic analyses of published studies to determine the efficacy and safety of these agents compared with warfarin in stroke prevention in patients with low bodyweight. METHODS: We carried out a comprehensive search of electronic databases from inception to June 2023 for eligible studies reporting on the efficacy and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. These include PubMed, EMBASE, the Cochrane Database of Systematic Reviews, the Science Citation Index, and the Database of Abstracts of Reviews of Effectiveness. Using the random effects model, derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes in patient cohorts exposed to direct oral anticoagulants versus warfarin in patients with atrial fibrillation who had low bodyweight. RESULTS: Nine studies (n = 159,514 patients) were included in our meta-analysis. DOAC analogs were associated with lower stroke recurrence compared with warfarin [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.49-0.9]; however, there was no significant difference in the composite outcome (OR 0.81, 95% CI 0.59-1.09) and mortality (OR 0.82, 95% CI 0.48-1.41). Additionally, DOAC analogs showed a significant reduction in major bleeding events by 30% compared with warfarin (OR 0.70, 95% CI 0.62-0.80). CONCLUSION: In this pooled meta-analytical synthesis of studies comprising both real-world and randomized controlled data, the use of DOAC analogs in patients with atrial fibrillation and low bodyweight (< 60 kg or BMI < 18 kg/m2) was associated with a significant reduction in risks of stroke and major bleeding compared with patient cohorts stabilized on warfarin-based therapy. There was uncertainty regarding the composite outcome and mortality point estimate between these two anticoagulation strategies. This finding helps to resolve the uncertainty associated with the use of DOACs in this cohort. Additionally, it suggests the need for confirmatory non-inferiority randomized controlled trials evaluating DOACs versus warfarin in this cohort of patients.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

INTRODUCTION: Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. METHODS: We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. RESULTS: Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). DISCUSSION: In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

Anti-rheumatic colchicine phytochemical exhibits potent antiviral activities against avian and seasonal Influenza A viruses (IAVs) via targeting different stages of IAV replication cycle.

BACKGROUND: The continuous evolution of drug-resistant influenza viruses highlights the necessity for repurposing naturally-derived and safe phytochemicals with anti-influenza activity as novel broad-spectrum anti-influenza medications. METHODS: In this study, nitrogenous alkaloids were tested for their viral inhibitory activity against influenza A/H1N1 and A/H5N1 viruses. The cytotoxicity of tested alkaloids on MDCK showed a high safety range (CC50 > 200 µg/ml), permitting the screening for their anti-influenza potential. RESULTS: Herein, atropine sulphate, pilocarpine hydrochloride and colchicine displayed anti-H5N1 activities with IC50 values of 2.300, 0.210 and 0.111 µg/ml, respectively. Validation of the IC50 values was further depicted by testing the three highly effective alkaloids, based on their potent IC50 values against seasonal influenza A/H1N1 virus, showing comparable IC50 values of 0.204, 0.637 and 0.326 µg/ml, respectively. Further investigation suggests that colchicine could suppress viral infection by primarily interfering with IAV replication and inhibiting viral adsorption, while atropine sulphate and pilocarpine hydrochloride could directly affect the virus in a cell-free virucidal effect. Interestingly, the in silico molecular docking studies suggest the abilities of atropine, pilocarpine, and colchicine to bind correctly inside the active sites of the neuraminidases of both influenza A/H1N1 and A/H5N1 viruses. The three alkaloids exhibited good binding energies as well as excellent binding modes that were similar to the co-crystallized ligands. On the other hand, consistent with in vitro results, only colchicine could bind correctly against the M2-proton channel of influenza A viruses (IAVs). This might explicate the in vitro antiviral activity of colchicine at the replication stage of the virus replication cycle. CONCLUSION: This study highlighted the anti-influenza efficacy of biologically active alkaloids including colchicine. Therefore, these alkaloids should be further characterized in vivo (preclinical and clinical studies) to be developed as anti-IAV agents.

Bimetallic bis-Aroyldihydrazone-Isatin Complexes of High O=V(IV) and Low Cu(II) Valent Ions as Effective Biological Reagents for Antimicrobial and Anticancer Assays.

Due to the versatile bioreactivity of aroyldihydrazone complexes as cost-effective alternatives with different transition metals, two novel bimetallic homo-complexes (VOLph and CuLph) were prepared via the coordination of a terephthalic dihydrazone diisatin ligand (H2Lph) with VO2+ and Cu2+ ions, respectively. The structure elucidation was confirmed by alternative spectral methods. Biologically, the H2Lph ligand and its MLph complexes (M2+ = VO2+ or Cu2+) were investigated as antimicrobial and anticancer agents. Their biochemical activities towards ctDNA (calf thymus DNA) were estimated using measurable titration viscometrically and spectrophotometrically, as well as the gel electrophoresis technique. The growth inhibition of both VOLph and CuLph complexes against microbial and cancer cells was measured, and the inhibition action, MIC, and IC50 were compared to the inhibition action of the free H2Lph ligand. Both VOLph and CuLph showed remarkable interactive binding with ctDNA compared to the free ligand H2Lph, based on Kb = 16.31, 16.04 and 12.41 × 107 mol-1 dm3 and ΔGb≠ = 47.11, -46.89, and -44.05 kJ mol-1 for VOLph, CuLph, and H2Lph, respectively, due to the central metal ion (VIVO and CuII ions). VOLph (with a higher oxidation state of the V4+ ion and oxo-ligand) exhibited enhanced interaction with the ctDNA molecule compared to CuLph, demonstrating the role and type of the central metal ion within the performed electronegative and electrophilic characters.

Rethinking HDL-C: An In-Depth Narrative Review of Its Role in Cardiovascular Health.

The interplay between HDL-C and LDL levels are closely intertwined with the cardiovascular system. High-Density Lipoprotein Cholesterol (HDL-C) is a well-known biomarker traditionally being interpreted as higher the HDL-C levels, minimal the risk of adverse cardiovascular disease (CVD) outcomes. However, recent research has unveiled a more complex relationship between HDL-C levels and cardiovascular outcomes, including genetic influences and potential risks associated with extremely high HDL-C levels. Intriguingly, extremely high HDL-C levels have been linked to unexpected cardiovascular risks. Up To date research suggests that individuals with genetically linked ultra-high HDL-C levels may depict an increased susceptibility to CVD, challenging the conventional realm that higher HDL-C is always beneficial. The mechanisms underlying this mystery are not fully understood but may involve HDL particle functionality and composition. In a nutshell, the relationship between HDL-C levels and cardiovascular outcomes is multifactorial. While low HDL-C remains a recognized risk factor for CVD, the genetic determinants of HDL-C levels add complexity to this association. Furthermore, extremely high HDL-C levels may not exhibit the expected protective benefits and may even pose unprecedented cardiovascular risks. A comprehensive understanding of these dynamics is essential for advancing our knowledge of CVD risk assessment and developing targeted therapeutic interventions. Further studies are needed to unravel the intricacies of HDL-C's role in cardiovascular health and disease.

Tailored horseshoe-shaped nicotinonitrile scaffold as dual promising c-Met and Pim-1 inhibitors: Design, synthesis, SAR and in silico study.

For the horseshoe tactic to succeed in inhibiting c-Met and Pim-1, the nicotinonitrile derivatives (2a-n) were produced in high quantities by coupling acetyl phenylpyrazole (1) with the proper aldehydes and ethyl cyanoacetate under basic conditions. Consistent basic and spectroscopic data (NMR, IR, Mass, and HPLC) supported the new products' structural findings. With IC50 potency in nanomolar ranges, these compounds had effectively repressed them, particularly compounds 2d and 2 h, with IC50 values below 200 nM. The most potent compounds (2d and 2 h) were tested for their antitumor effects against prostate (PC-3), colon (HCT-116), and breast (MDA-MB-231) and were evaluated in comparison to the anticancer drug tivantinib using the MTT assay. Similar to tivantinib, these compounds showed good antiproliferative properties against the HCT-116 tumor cells while having low cytotoxicity towards healthy fetal colon (FHC) cells. In the HCT-116 cell line, their ability to trigger the apoptotic cascade was also investigated by looking at the level of Bax and Bcl-2 as well as the activation of the proteolytic caspase cascade. When HCT-116 cells were exposed to compounds 2d and 2 h in comparison to the control, active caspase-3 levels increased. The HCT-116 cell line also upregulated Bcl-2 protein levels and downregulated Bax levels. Additionally, when treated with compound 2d, the HCT-116 cell cycle was primarily stopped at the S phase. Compared to the control, compound 2d treatment significantly inhibited the protein expression levels of c-Met and Pim-1 kinases in the treated HCT-116 cells. Thorough molecular modeling analyses, such as molecular docking and dynamic simulation, were performed to ascertain the binding mechanism and stability of the target compounds.

Identification of 3-(5-cyano-6-oxo-pyridin-2-yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity.

New 5-cyano-6-oxo-pyridine-based sulfonamides (6a-m and 8a-d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D. anderson metastasis breast cancer cell line cells. Then, the possible CA inhibition against the human CA isoforms I, II, and IX was investigated, together with the EGFR inhibitory activity, with the most powerful derivatives. The neighboring methoxy group may have had a steric effect on the target sulfonamides, which prevented them from effectively inhibiting the CA isoforms while effectively inhibiting the EGFR. The effects of the 5-cyanopyridine derivatives 6e and 6l on cell-cycle disruption and the apoptotic potential were then investigated. To investigate the binding mechanism and stability of the target molecules, thorough molecular modeling assessments, including docking and dynamic simulation, were performed.

Polysaccharides from Spirulina platensis (PSP): promising biostimulants for the green synthesis of silver nanoparticles and their potential application in the treatment of cancer tumors.

Photosynthetic cyanobacterial components are gaining great economic importance as prospective low-cost biostimulants for the green synthesis of metal nanoparticles with valuable medical and industrial applications. The current study comprises the biological synthesis of silver nanoparticles (Ag-NPs) using soluble polysaccharides isolated from Spirulina platensis (PSP) as reducing and capping agents. FTIR spectra showed major functional groups of PSP and biogenic silver nanoparticles including O-H, C-H (CH2), C-H (CH3), C=O, amide, and COO- groups. The UV/Vis spectroscopy scan analyses of the extracted PSP showed absorption spectra in the range of 200-400 nm, whereas the biogenic Ag-NPs showed a maximum spectrum at 285 nm. Transmission electron microscopy (TEM) analysis of the synthesized Ag-NPs showed spherical nanoparticles with mean size between 12 and 15.3 nm. The extracted PSP and Ag-NPs exhibited effective cytotoxic activity against Hep-G2 (human hepatocellular carcinoma). The IC50 for PSP and Ag-NPs were 65.4 and 24.5 µg/mL, respectively. Moreover, cell apoptosis assays for PSP and Ag-NPs against the growth of Hep-G2 cells revealed superior growth inhibitory effects of the green synthesized Ag-NPs that encouraged tracing the apoptotic signalling pathway. In conclusion, the current study demonstrated an unprecedented approach for the green synthesis of silver nanoparticles (NPs), using the polysaccharide of Spirulina platensis as reducing and capping agents, with superior anticancer activity against a hepatocellular carcinoma cell line.

The use of integrin binding domain loaded hydrogel (RGD) with minimally invasive surgical technique in treatment of periodontal intrabony defect: a randomized clinical and biochemical study.

BACKGROUND: Periodontal regeneration faces multiple challenges, the most important being cellular insufficiency. In an attempt to improve defect cellularity, we aimed to demonstrate enhancing cellular attraction using arginine-glycine-aspartic acid (RGD) adhesion molecule legend blended hydrogel within the intrabony defects. METHODOLOGY: Forty-five intrabony defects were selected from patients with stage III or IV - grade A or B periodontitis and divided randomly into three equal groups of 15 each: group1 (G1): received minimally invasive surgical technique (MIST) alone, group2 (G2): received MIST and placebo hydrogel injection, and group3 (G3): were treated with MIST and RGD hydrogel injection. Primary outcomes 6 months following therapy were; defect base fill (DBF) and defect width measurement (DW); secondary outcomes were clinical attachment level (CAL), pocket depth (PD), plaque index (PI), gingival index (GI), and biochemical analysis of bone morphogenetic protein (BMP-2) evaluated at 1,7,14 and 21 days following therapy. RESULTS: Significant improvements in DBF, CAL, and PD were observed in the three studied groups 6 months following therapy compared to baseline (p<0.05). A significant improvement in DBF was reported in G3 compared to G1 and 2 (p=0.005). Additionally, a significantly higher CAL gain was reported in G3 compared to that of G1 (p=0.02). Group 3 was associated with a significantly higher level of BMP-2 compared to G1 and G2 in all reported periods. CONCLUSION: RGD peptide carried on a hydrogel delivery agent and contained with a minimally invasive flap could be a reliable option in improving the outcomes of periodontal therapy.