Glucosamine-Mediated Hexosamine Biosynthesis Pathway Activation Uses ATF4 to Promote "Exercise-Like" Angiogenesis and Perfusion Recovery in PAD.

BACKGROUND: Endothelial cells (ECs) use glycolysis to produce energy. In preclinical models of peripheral arterial disease, further activation of EC glycolysis was ineffective or deleterious in promoting hypoxia-dependent angiogenesis, whereas pentose phosphate pathway activation was effective. Hexosamine biosynthesis pathway, pentose phosphate pathway, and glycolysis are closely linked. Glucosamine directly activates hexosamine biosynthesis pathway. METHODS: Hind-limb ischemia in endothelial nitric oxide synthase knockout (eNOS-/-) and BALB/c mice was used. Glucosamine (600 µg/g per day) was injected intraperitoneally. Blood flow recovery was assessed using laser Doppler perfusion imaging and angiogenesis was studied by CD31 immunostaining. In vitro, human umbilical vein ECs and mouse microvascular ECs with glucosamine, L-glucose, or vascular endothelial growth factor (VEGF165a) were tested under hypoxia and serum starvation. Cell Counting Kit-8, tube formation, intracellular reactive oxygen species, electric cell-substrate impedance sensing, and fluorescein isothiocyanate dextran permeability were assessed. Glycolysis and oxidative phosphorylation were assessed by seahorse assay. Gene expression was assessed using RNA sequencing, real-time quantitative polymerase chain reaction, and Western blot. Human muscle biopsies from patients with peripheral arterial disease were assessed for EC O-GlcNAcylation before and after supervised exercise versus standard medical care. RESULTS: On day 3 after hind-limb ischemia, glucosamine-treated versus control eNOS-/- mice had less necrosis (n=4 or 5 per group). Beginning on day 7 after hind-limb ischemia, glucosamine-treated versus control BALB/c mice had higher blood flow, which persisted to day 21, when ischemic muscles showed greater CD31 staining per muscle fiber (n=8 per group). In vitro, glucosamine versus L-glucose ECs showed improved survival (n=6 per group) and tube formation (n=6 per group). RNA sequencing of glucosamine versus L-glucose ECs showed increased amino acid metabolism (n=3 per group). That resulted in increased oxidative phosphorylation (n=8-12 per group) and serine biosynthesis pathway without an increase in glycolysis or pentose phosphate pathway genes (n=6 per group). This was associated with better barrier function (n=6-8 per group) and less reactive oxygen species (n=7 or 8 per group) compared with activating glycolysis by VEGF165a. These effects were mediated by activating transcription factor 4, a driver of exercise-induced angiogenesis. In muscle biopsies from humans with peripheral arterial disease, EC/O-GlcNAcylation was increased by 12 weeks of supervised exercise versus standard medical care (n=6 per group). CONCLUSION: In cells, mice, and humans, activation of hexosamine biosynthesis pathway by glucosamine in peripheral arterial disease induces an "exercise-like" angiogenesis and offers a promising novel therapeutic pathway to treat this challenging disorder.

A very rare case of the right middle lobe torsion postlower lobectomy due to chronic lung abscess.

Middle lobe torsion (MLT) is an unusual complication in lung surgery that is usually associated with upper lobe lobectomy and rarely develops postlower lobectomy. In the case of MLT, urgent surgical intervention is required to decrease the risk of mortality and morbidity, and diagnosis is challenging due to the nonspecific symptoms of MLT. In this article, we present a case of a recurring lung abscess treated by the right lower lobectomy, complicated by the right MLT and to our knowledge MLT consider rarest complication postright lower lobectomy.

Advancing the Frontier: Neuroimaging Techniques in the Early Detection and Management of Neurodegenerative Diseases.

Alzheimer's and Parkinson's diseases are among the most prevalent neurodegenerative conditions affecting aging populations globally, presenting significant challenges in early diagnosis and management. This narrative review explores the pivotal role of advanced neuroimaging techniques in detecting and managing these diseases at early stages, potentially slowing their progression through timely interventions. Recent advancements in MRI, such as ultra-high-field systems and functional MRI, have enhanced the sensitivity for detecting subtle structural and functional changes. Additionally, the development of novel amyloid-beta tracers and other emerging modalities like optical imaging and transcranial ultrasonography have improved the diagnostic accuracy and capability of existing methods. This review highlights the clinical applications of these technologies in Alzheimer's and Parkinson's diseases, where they have shown improved diagnostic performance, enabling earlier intervention and better prognostic outcomes. Moreover, the integration of artificial intelligence (AI) and longitudinal research is emerging as a promising enhancement to refine early detection strategies further. However, this review also addresses the technical, ethical, and accessibility challenges in the field, advocating for the more extensive use of advanced imaging technologies to overcome these barriers. Finally, we emphasize the need for a holistic approach that incorporates both neurological and psychiatric perspectives, which is crucial for optimizing patient care and outcomes in the management of neurodegenerative diseases.

Lung ultrasound in early prediction of bronchopulmonary dysplasia in pre-term babies.

PURPOSE: Bronchopulmonary dysplasia (BPD) is a respiratory morbidity related to prematurity. Early prediction of BPD allows the selection of patients who would benefit from new therapies. Lung ultrasound (LUS) is a non-invasive diagnostic tool that has proven to be reliable for many neonatal diseases recently. The study aimed to detect the role of LUS in predicting BPD at days 7 and 14 of life in preterm babies. METHODS: This was a prospective cohort study that included 95 preterm babies ≤ 34 weeks. Lung ultrasounds were performed on days 7 and 14 of life. RESULTS: The mean gestational age of the studied neonates was 30.25 ± 2.21 weeks. The mean birth weight was 1347.66 ± 432.14 gm. Patients who developed BPD had statistically significantly higher LUS scores on both days 7 and 14 of life. At first examination, a LUS score > 8 showed a sensitivity of 83.33% and a specificity of 60.87%, whereas at follow-up, a LUS score > 8 showed a sensitivity of 76.39% and a specificity of 82.61%. The multivariate logistic regression analysis shows that the most important factors associated with BPD were gestational age ≤ 30 weeks, LUS score at first examination > 8, platelets ≤ 245 × 109/L, segment neutrophils ≤ 42%, and CRP > 5 mg/l. CONCLUSIONS: The LUS score predicts BPD at 7 and 14 days of life. LUS scores increased with increasing BPD severity. LUS score > 8 was an independent factor in the prediction of BPD.

The Salutary Effects of Diminazene, Lisinopril or Valsartan on Cisplatin - Induced Acute Kidney Injury in Rats: A Comparative Study.

Nephrotoxicity as a cause of acute kidney injury (AKI) induced by cisplatin (CP), limits its usefulness as an anticancer agent. Diminazene, an angiotensin converting enzyme 2 activator, exhibited renoprotective properties on rat models of kidney diseases. This research aims to investigate the salutary effect of diminazene in comparison with lisinopril or valsartan in CP-induced AKI. The first and second groups of rats received oral vehicle (distilled water) for 9 days, and saline injection or intraperitoneal CP (6 mg/kg) on day 6, respectively. Third, fourth, and fifth groups received intraperitoneal injections of CP on day 6 and diminazene (15 mg/kg/day, orally), lisinopril (10 mg/kg/day, orally), or valsartan (30 mg/kg/day, orally), for 9 days, respectively. 24h after the last day of treatment, blood and kidneys were removed under anesthesia for biochemical and histopathological examination. Urine during the last 24 h before sacrificing the rats was also collected. CP significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin, calcium, phosphorus, and uric acid. It also increased urinary albumin/creatinine ratio, N-Acetyl-beta-D-Glucosaminidase/creatinine ratio, and reduced creatinine clearance, as well the plasma concentrations of inflammatory cytokines [plasma tumor necrosis factor-alpha, and interleukin-1beta], and significantly reduced antioxidant indices [catalase, glutathione reductase , and superoxide dismutase]. Histopathologically, CP treatment caused necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. Diminazine, lisinopril, and valsartan ameliorated CP-induced biochemical and histopathological changes to a similar extent. The salutary effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Keywords: Cisplatin, Diminazene, ACE2 activator, Lisinopril, Valsartan, Acute kidney injury.

Expression of concern: Cefotaxime incorporated bimetallic silver-selenium nanoparticles: promising antimicrobial synergism, antibiofilm activity, and bacterial membrane leakage reaction mechanism.

Expression of concern for 'Cefotaxime incorporated bimetallic silver-selenium nanoparticles: promising antimicrobial synergism, antibiofilm activity, and bacterial membrane leakage reaction mechanism' by Abdelrahman A. Elakraa et al., RSC Adv., 2022, 12, 26603-26619, https://doi.org/10.1039/D2RA04717A.

Extensive Type A Aortic Arterial Dissection Presenting With Stroke Symptoms: A Case Report.

Aortic dissection (AD) is a rare but often lethal condition if not properly and urgently treated. Most often, patients arrive with acute hemodynamic instability and ripping chest agony. The patient's life depends critically on a correct diagnosis made as soon as possible. We describe a 60-year-old man who arrived at the emergency room with symptoms of a brain stroke, including poor consciousness, left-sided weakness, and speech disturbance associated with hemodynamic instability, and chest pain. Thoracic aortic arch dissection was observed on CT angiography (CTA). In addition, CTA revealed that the dissection extends proximally into the left common carotid artery, left subclavian artery, brachiocephalic trunk, and right common carotid artery and distally to the left common iliac artery, coupled with significant stenosis of the left common iliac artery. Proper management of blood pressure (BP) parameters is life-saving for the patient. Since our hospital did not offer cardiothoracic surgery services, the patient was transferred to a different institution, where he received medical care immediately from an expert team and had surgery.

A Novel Epigenetic Strategy to Concurrently Block Immune Checkpoints PD-1/PD-L1 and CD155/TIGIT in Hepatocellular Carcinoma.

Tumor microenvironment is an intricate web of stromal and immune cells creating an immune suppressive cordon around the tumor. In hepatocellular carcinoma (HCC), Tumor microenvironment is a formidable barrier towards novel immune therapeutic approaches recently evading the oncology field. In this study, the main aim was to identify the intricate immune evasion tactics mediated by HCC cells and to study the epigenetic modulation of the immune checkpoints; Programmed death-1 (PD-1)/ Programmed death-Ligand 1 (PD-L1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT)/Cluster of Differentiation 155 (CD155) at the tumor-immune synapse. Thus, liver tissues, PBMCs and sera were collected from Hepatitis C Virus (HCV), HCC as well as healthy individuals. Screening was performed to PD-L1/PD-1 and CD155/TIGIT axes in HCC patients. PDL1, CD155, PD-1 and TIGIT were found to be significantly upregulated in liver tissues and peripheral blood mononuclear cells (PBMCs) of HCC patients. An array of long non-coding RNAs (lncRNAs) and microRNAs validated to regulate such immune checkpoints were screened. The lncRNAs; CCAT-1, H19, and MALAT-1 were all significantly upregulated in the sera, PBMCs, and tissues of HCC patients as compared to HCV patients and healthy controls. However, miR-944-5p, miR-105-5p, miR-486-5p, miR-506-5p, and miR-30a-5p were downregulated in the sera and liver tissues of HCC patients. On the tumor cell side, knocking down of lncRNAs-CCAT-1, MALAT-1, or H19-markedly repressed the co-expression of PD-L1 and CD155 and accordingly induced the cytotoxicity of co-cultured primary immune cells. On the immune side, ectopic expression of the under-expressed microRNAs; miR-486-5p, miR-506-5p, and miR-30a-5p significantly decreased the transcript levels of PD-1 in PBMCs with no effect on TIGIT. On the other hand, ectopic expression of miR-944-5p and miR-105-5p in PBMCs dramatically reduced the co-expression of PD-1 and TIGIT. Finally, all studied miRNAs enhanced the cytotoxic effects of PBMCs against Huh7 cells. However, miR-105-5p showed the highest augmentation for PBMCs cytotoxicity against HCC cells. In conclusion, this study highlights a novel co-targeting strategy using miR-105-5p mimics, MALAT-1, CCAT-1 and H19 siRNAs to efficiently hampers the immune checkpoints; PD-L1/PD-1 and CD155/TIGIT immune evasion properties in HCC.

Association of the interleukine-6 polymorphism with catheter-induced coronary artery spasm in Egyptians.

BACKGROUND: The role of coronary artery spasm (CAS) was extended beyond variant angina to ischemic heart disease in general, including effort angina, unstable angina, acute myocardial infarction (MI) and sudden death. It is difficult and cumbersome to examine CAS during coronary angiography. Risk factors for CAS include smoking and genetic polymorphisms. AIM: We aimed to investigate the association of the interleukin-6 (IL-6) polymorphism with catheter-induced CAS in Egyptian patients who undergo coronary angiography. METHODS: This is a case-control study. Two hundred patients with chronic coronary artery disease who underwent elective coronary angiography were included in the study. Patients were divided into two groups: the non-CAS group (100 patients) and the CAS group (100 patients). The subjects were genotyped to the -572 C>G (rs 1800796) polymorphism of the IL-6 gene by PCR-restriction fragment length polymorphism. RESULTS: We found that patients with CAS have more risk factors for atherosclerosis compared to those without CAS. Smoking, the IL-6 GG genotype, and the G allele were independent risk factors for CAS. CONCLUSION: We concluded that the GG genotype and G allele of the IL-6 gene are associated with CAS. Smoking, the GG genotype, and the G allele of the IL-6 gene are independent predictors of catheter-induced CAS.

A 3D scaling law for supravalvular aortic stenosis suited for stethoscopic auscultations.

In this study a frequency scaling law for 3D anatomically representative supravalvular aortic stenosis (SVAS) cases is proposed. The law is uncovered for stethoscopy's preferred auscultation range (70-120 Hz). LES simulations are performed on the CFD solver Fluent, leveraging Simulia's Living Heart Human Model (LHHM), modified to feature hourglass stenoses that range between 30 to 80 percent (mild to severe) in addition to the descending aorta. For physiological hemodynamic boundary conditions the Windkessel model is implemented via a UDF subroutine. The flow-generated acoustic signal is then extracted using the FW-H model and analyzed using FFT. A preferred receiver location that matches clinical practice is confirmed (right intercostal space) and a correlation between the degree of stenosis and a corresponding acoustic frequency is obtained. Five clinical auscultation signals are tested against the scaling law, with the findings interpreted in relation to the NHS classification of stenosis and to the assessments of experienced cardiologists. The scaling law is thus shown to succeed as a potential quantitative decision-support tool for clinicians, enabling them to reliably interpret stethoscopic auscultations for all degrees of stenosis, which is especially useful for moderate degrees of SVAS. Computational investigation of more complex stenotic cases would enhance the clinical relevance of this proposed scaling law, and will be explored in future research.

Molecular detection and characterization of Theileria annulata, Babesia bovis, and Babesia bigemina infecting cattle and buffalo in southern Egypt.

Tick-borne diseases have a major adverse effect on livestock worldwide, causing enormous economic losses in meat and milk production as well threatening animal and public health. In this study, we aimed to detect and characterize piroplasms isolated from cattle and buffalo in southern Egypt, using molecular techniques. Three hundred blood samples were collected from cattle and buffalo in two governorates in southern Egypt. All 300 samples (100%) were confirmed to contain DNA, as they exhibited bands of bovine ß-actin gene at the expected 227 bp for cattle and buffalo. The samples were analyzed by PCR for the presence of piroplasms, specifically Babesia bovis, Babesia bigemina, and Theileria annulata. Samples positive for the piroplasma 18S ribosomal RNA gene were further examined for two additional genes, spherical body protein 4 gene, to provide an enhanced degree of specificity for the identification of B. bovis and B. bigemina, and the major merozoite surface antigen gene for T. annulata. The infection rate for piroplasma spp. was 60/300 (20%). The positivity rates were 10.7% (32/300) for T. annulata, 5.3% (16/300) for B. bovis, and 4% (12/300) for B. bigemina. By host species, 42/150 (28%) cattle and 18/150 (12%) buffalo were positive for piroplasms. None of the isolates sequenced for the B. bovis isolates from buffalo in this study showed 100% identity with any sequence deposited in GenBank for the small subunit ribosomal RNA gene (maximum identity value = 99.74%). Similarly, no T. annulata small subunit ribosomal RNA gene sequence identified in this study exhibited 100% identity with any sequence deposited in GenBank (maximum identity value = 99.89%). The current study provides a partial sequence of the T. annulata merozoite-piroplasm surface antigen gene, as well as the B. bovis and B. bigemina spherical body protein 4 genes, in cattle and buffalo in southern Egypt, and is the first report on these piroplasma genes in cattle and buffalo in southern Egypt.

Maxillofacial trauma caused by e-scooters: a retrospective review prior to the extension of the UK scheme.

The nationwide extension of the electric scooter (e-scooter) scheme, which began in 2020, aimed to alleviate public transport congestion, to reduce pollution and peak-time road traffic. This retrospective study evaluates the range of e-scooter-related maxillofacial trauma before the recent scheme extension and compares the findings with existing literature on this topic. The Queen Elizabeth Hospital Birmingham, United Kingdom (UK) operates as a Level 1 Regional Major Trauma Centre and serves a population of four million. All patient records between September 2021 to September 2022 were analysed to establish the types of e-scooter-related maxillofacial trauma sustained. A Pearson's chi-squared test was used to assess for significant associations between variables recorded. Falls accounted for the majority of injuries (44.3%), and soft tissue lacerations were the most common maxillofacial injury (38%). Statistically significant results were measured in the following variables: gender and intoxication status (p = 0.007), helmet status and injuries sustained in maxillofacial and non-maxillofacial regions (p = 0.043), mechanism of injury and injuries sustained in both the maxillofacial and non-maxillofacial regions (p = 0.045). E-scooters are an emerging concern within the UK. Further studies across the UK are required to assess the frequency of e-scooter-related injuries. Such data may prove useful in determining the government's decision on e-scooter use on UK roads.

Diagnostic performance of spectral Doppler in acute appendicitis with an equivocal Alvarado score.

PURPOSE: This study aims to evaluate the added value of duplex Doppler examination to the routinely graded compression grayscale ultrasound (US) for patients with suspected acute appendicitis (AA) in correlation with surgical management outcomes. METHODS: The study lasted from January 2020 to March 2021. Throughout that period, patients who had suspected appendicitis were included with a visible appendix in the grayscale US. These patients were categorized clinically based on Alvarado's score. They underwent graded compression grayscale US of the appendix and duplex Doppler study. Subsequently, they were assigned for non-contrast multislice computed tomography (MSCT) according to Alvarado's score and underwent either emergency appendicectomy or conservative clinical management afterward. A Student's t-test was used to determine if there were significant differences in the mean values between the groups. The diagnostic performance of spectral Doppler US for the diagnosis of AA was depicted. RESULTS: Eighty-four patients with visualized color flow in the appendicular Doppler US were enrolled, with 60 (71.4%) having AA, and 24 (28.6%) not having appendicitis. Spectral Doppler criterion of PSV greater than 8.6 cm/s demonstrated a high sensitivity of 91.67% and specificity of 77.78% for patients with Alvarado score ranging from 4 to 7, and appendiceal MOD ranging from 6 to 8 mm, while a discriminatory criterion of RI greater than 0.51 had a high sensitivity of 100% and a relatively lower specificity of 66.67%. CONCLUSION: The patients with AA have significantly higher point PSV and point RI values than those without AA and are especially useful in equivocal patients whose MODs and Alvarado scores are in the diagnostically equivocal ranges of 6-8 mm and 4-7, respectively, with the point PSV and RI demonstrating negative predictive value 87.5% and 100%.

Novel phenylthiazoles with a tert-butyl moiety: promising antimicrobial activity against multidrug-resistant pathogens with enhanced ADME properties.

The structure-activity relationship of a new tert-butylphenylthiazole series, with a pyrimidine linker, was investigated. We wished to expand knowledge of this novel class of antibiotics by generating 21 new derivatives bearing ≥2 heteroatoms in their side chains. Their activity was examined against isolates of methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, Escherichia coli, Neisseria gonorrhoeae, and Candida albicans. Two compounds with 1,2-diaminocyclohexane as a nitrogenous side chain showed promising activity against the highly infectious MRSA USA300 strain, with a minimum inhibitory concentration (MIC) of 4 µg mL-1. One of these two compounds demonstrated potent activity against C. difficile, with a MIC of 4 µg mL-1. Moderate activities against a C. difficile strain with a MIC of 8 µg mL-1 were noted. Some new compounds possessed antifungal activity against a wild fluconazole-resistant C. albicans strain, with MIC values of 4-16 µg mL-1. ADME and metabolism-simulation studies were performed for the most promising compound and compared with lead compounds. Our results revealed that one compound possessed greater penetration of bacterial membranes and metabolic resistance, which aided a longer duration of action against MRSA.

Psychosexual dysfunction in male patients with cannabis dependence and synthetic cannabinoid dependence.

OBJECTIVE: There are contradicting reports regarding the relationship between cannabis use and male sexual functions with almost no data about synthetic cannabinoids (SC) and its effect on male sexual functions. This study investigates psychological concerns related to male sexual functions among cannabis and SC users. The research aims to assess different sexual functions and aspects of sexual psychopathology in cannabis and SCs dependent men compared to controls. METHOD: Thirty male patients with cannabis dependence, thirty male patients with SCs dependence and thirty matched controls from the outpatient clinic of Kasr Al Ainy hospital, Egypt, were assessed using Structured Clinical Interview for DSM-IV TR Axis I Disorders (SCID-I), International Index of Erectile Function (IIEF), and Sexuality scale. RESULTS: The means of IIEF questionnaire in the cannabis and SC group were significant lower than the means of the control group (P < .001) except the orgasmic function in cannabis group (P = .052). In the SCs group, sexual depression was higher and preoccupation lower than the cannabis (P < .020; P < .003, respectively) and control groups (P < .001; P < .001, respectively). The duration and dose of intake of cannabis and SCs correlated significant with sexual esteem, sexual preoccupation and all domains of IIEF. CONCLUSION: Cannabis and SC dependence were associated with lower erectile function, sexual desire, intercourse satisfaction and overall satisfaction, and lower orgasmic functions in the SC group than controls. Both groups showed higher sexual depression, lower sexual esteem and sexual preoccupation than controls. SC has a higher negative impact on male sexual functions and psychopathology than cannabis.

Long-Term Survival in Patients with Cancers: Surveillance, epidemiology and end results-based analysis.

Objectives: This study aimed to explore real-world data on the long-term survival of cancer patients using historical records from the Surveillance, Epidemiology, and End Results (SEER) Programme. Long-term survival is an important endpoint in the management of different malignancies. It is rarely assessed due to the unfeasibility of follow-up for a long duration of time. Besides reporting the five-year relative survival, the 10- and 20-year survival rates for different types of cancers were analysed. Additionally, survival trends as a function of time, age and tumour type were reviewed and reported. Methods: The study used SEER*Stat (Version 8.3.6.1) for data acquisition from the SEER 9 Regs (November 2019) database. Data from patients diagnosed with cancer between 1975 and 2014 were retrieved and included in the analysis. Results: For patients diagnosed with any malignant disease (N = 4,412,024), there was a significant increase in median overall survival over time (P <0.001). The 20-, 10-, and 5-year survival rates were higher in solid tumours compared to haematological malignancies (50.8% versus 38%; 57% versus 47.4%; and 62.2% versus 57.4%, respectively). The highest 20-year relative survival rates were observed in thyroid cancer (95.2%), germ cell and trophoblastic neoplasms (90.3%), melanoma (86.8%), Wilms' tumour (86.2%) and prostate cancer (83.5%). Conclusion: Long-term follow-up data were suggestive of high 20-year relative survival rates for most tumour types. Relative survival showed an improving trend over time, especially in solid tumours.

Dye removal membrane from electrospun nanofibers of blended polybutylenesuccinate and sulphonated expanded polystyrene waste.

Polystyrene (PS) is a thermoplastic polymer used in food packaging and the manufacture of trays and cups, among other applications. In this work, the preparation of a membrane by electrospinning blended sulphonated expanded PS waste and polybutylenesuccinate (PBS) is described. The fiber quality is controlled by selecting the right polymers' ratios and solvents. Investigation of the structure of the produced membranes by Fourier transform infrared spectroscopy-attenuated total reflectance confirmed the successful sulphonation of expanded PS and the appearance of characteristic (PBS) bands in the prepared blends. Morphology study of the electrospun membranes using a scanning electron microscope revealed that the quality of the fibers is improved significantly by increasing the amount of PBS in the blend solution. Moreover, continuous and more homogenous fibers are produced by increasing the ratio of PBS to 2%. The efficiency of the prepared membranes in dye removal was tested using methylene blue. The effects of different parameters such as, pH, contact time, temperature, and dye concentration have been studied. Also, kinetic and adsorption isotherm models as well as the durability of the prepared membranes were investigated. The membrane prepared from PSS/1% PBS demonstrated the highest dye uptake (846 mol) with good regeneration efficiency. The adsorption process was found to be endothermic and fits the Freundlich isotherm and pseudo-second-order kinetic model. The values of activation energy for the adsorption process are 36.98, 30.70, and 43.40 kJ/mol over PSS, PSS/1% PBS and PSS/2% PBS, respectively.

New thiazolidine-2,4-diones as effective anti-proliferative and anti-VEGFR-2 agents: Design, synthesis, in vitro, docking, MD simulations, DFT, ADMET, and toxicity studies.

Novel thiazolidine-2,4-dione derivatives, 11a-g, were designed, and synthesized targeting the VEGFR-2 protein. The in vitro studies indicated the abilities of the synthesized derivatives to inhibit VEGFR-2 and prevent the growth of two different cancer cell types, HepG2 and MCF-7. Compound 11 f exhibited the strongest anti-VEGFR-2 activity (IC50 = 0.053 µM). As well, compound 11 f showed impressive anti-proliferative activity against the mentioned cancer cell lines with IC50 values of 0.64 ± 0.01 and 0.53 ± 0.04 µM, respectively. Additionally, compound 11 f arrested the MCF-7 cell cycle at the S phase and increased the overall apoptosis percentage. Furthermore, cell migration assay revealed that compound 11 f has a significant ability to prevent migration and healing potentialities of MCF-7. Moreover, computational studies were used to conduct the molecular investigation of the VEGFR-2-11 f complex. The kinetic and structural features of the complex were examined using molecular dynamics simulations and molecular docking. Besides, Principal component analysis (PCA) was used to explain the dynamics of the VEGFR-2-11 f complex at various spatial scales. The DFT calculations also provided further clarity regarding compound 11 f's structural and electronic features. To evaluate how closely the developed compounds might look like drugs, ADMET and toxicity experiments were computed. To conclude, the presented study demonstrates the potential of compound 11 f as a viable anti-cancer drug, which can serve as a prototype for future structural modifications and further biological investigations.