Characterization of Candida species isolated from clinical specimens: insights into virulence traits, antifungal resistance and molecular profiles.

BACKGROUND: Candida species have emerged as a significant cause of opportunistic infections. Alongside the expression of various virulence factors, the rise of antifungal resistance among Candida species presents a considerable clinical challenge. AIM: This study aimed to identify different Candida species isolated from clinical specimens, evaluate their antifungal sensitivity patterns, identify key genes regulating virulence mechanisms using multiplex PCR and to assess any correlation between their virulence profiles and antifungal resistance patterns. METHOD: A total of 100 Candida spp. was isolated from 630 different clinical specimens and identified to the species level. Their antifungal susceptibility was phenotypically evaluated in accordance with CLSI guidelines using the Vitek-2 Compact System. Virulence markers, including biofilm formation capacity, protease production, melanin production, coagulase production and hemolysin production, were also phenotypically detected. The genetic determinants for biofilm formation and extracellular hydrolytic enzymes were assessed using a multiplex PCR assay. RESULTS: The prevalence of Candida spp. was 15.9%, with C. albicans (48%) and C. glabrata (16%) being the most common. C. albicans showed the highest virulence, with strong biofilm formation, and high proteinase and melanin production. Multiplex PCR revealed Hlp in 22.0%, Hwp in 80.0%, Als in 56.0%, and Sap genes in 56.0% of isolates. Virulence genes were more common in C. albicans than in non-albicans Candida (NAC). Resistance patterns significantly correlated with virulence profiles, with notable associations between flucytosine resistance and the presence of Hlp and Hwp genes. CONCLUSION: The significant correlation between virulent markers such as germination, coagulase, hemolysin production and resistance patterns among different Candida isolates is crucial for predicting the severity and outcomes of Candida infections. This understanding aids in guiding tailored treatment strategies.

Corticosteroids for the Management of Uveitic Macular Edema: A Comprehensive Review.

Uveitis, which refers to the inflammation of the uveal tract and surrounding structures in the eye, poses a significant risk of vision impairment, with macular edema (UME) being a prevalent complication. The current statement reviews UME's prevalence, pathogenesis, diagnosis, and management strategies, focusing on the utility of systemic and local corticosteroid therapy. Corticosteroids, with their multifaceted effects on inflammatory pathways, serve as the cornerstone of UME treatment. Various administration routes, including topical, periocular, intraocular, and systemic, are employed based on the anatomical type and severity of inflammation. The efficacy of different corticosteroid formulations, such as difluprednate, triamcinolone acetonide, dexamethasone implant, and fluocinolone acetonide implant, is evaluated through clinical trials and retrospective studies. Additionally, the role of corticosteroid-sparing treatments, including antimetabolites like methotrexate and mycophenolate mofetil, is explored. Emerging techniques, such as suprachoroidal space triamcinolone acetonide administration, offer promising alternatives for managing UME. Through a thorough examination of current evidence, this review provides valuable insights into optimizing the management of UME and improving visual outcomes in patients with uveitis.

The Untold Story: Early and Mid-Term Results of Subintimal Angioplasty in Superficial Femoral Artery Versus Popliteal Artery Chronic Total Occlusion.

OBJECTIVES: This study aims to compare the immediate and mid-term outcomes of subintimal angioplasty (SIA) of chronic total occlusions (CTOs) of superficial femoral artery (SFA) versus popliteal artery (PA) and to identify possible predictors of loss of limb-based patency (LBP). METHODS: This is a retrospective analysis of chronic lower-limb ischemia (CLI) patients (Rutherford classes 3-6) presenting with CTO of SFA or PA treated by SIA and selective stenting in the period 2018 to 2021. Immediate outcomes were compared between the SFA and PA groups, including technical success, perioperative complications, and 30-day major amputation and mortality rates. Mid-term outcomes for technically successful procedures included limb-based patency (LBP), wound healing rate, amputation-free survival (AFS), and major adverse limb events (MALEs). RESULTS: A total of 450 CLI patients underwent SIA of CTO at the SFA (n=260, 57.8%) and the PA (n=190, 42.2%). The indication for revascularization was chronic limb-threatening ischemia in 80.8% of SFA group and 84.2% of PA group. Technical success rate was higher in the PA group compared to the SFA group (96.3% vs 91.2%; p=0.03). The 30-day amputation rates were comparable between the SFA and PA groups (7.7% vs 6.8%, p=0.7, respectively). No perioperative mortality or systemic major complications occurred in the present study. Kaplan-Meier estimate of the 1-year rates were significantly better for SFA group regarding LBP (82% for SFA group vs 43% for PA group, p=0.006), AFS (88% vs 64%, p=0.02), and wound healing (79% vs 58%, p=0.027), respectively. The number of runoff vessels was the only factor associated with loss of LBP (hazard ratio [HR], 0.055; 95% confidence interval [CI]: 0.001-3.020, p=0.039). CONCLUSIONS: Subintimal angioplasty is an effective and safe endovascular treatment option of CTO at SFA and PA with satisfactory immediate outcomes. The mid-term outcomes, however, are better for SFA lesions in terms of improved LBP, AFS, and wound healing rates. CLINICAL IMPACT: Subintimal angioplasty is a valuable tool in the armamentarium of endovascular surgeons, as re-entry devices aren't always widely accessible. This study aims to assess the technical outcomes of peripheral vascular interventions for infrainguinal chronic total occlusions and identify possible predictors for successful subintimal angioplasty .Subintimal angioplasty is an effective treatment option for infrainguinal CTO with difference in result of immediate outcomes in popliteal lesions and SFA lesions.

Nifedipine Improves the Ketogenic Diet Effect on Insulin-Resistance-Induced Cognitive Dysfunction in Rats.

Insulin resistance, induced by high fructose consumption, affects cognitive function negatively. Nifedipine may be suggested for neurological disorders. This study aimed to assess the effect of nifedipine with either a normal diet (ND) or a ketogenic diet (KD) in cognitive dysfunction. Male Wistar rats received 10% fructose in drinking water for 8 weeks to induce insulin resistance. Rats received nifedipine (5.2 mg/kg/day; p.o.) later with ND or KD for an additional five weeks. One and two-way ANOVAs were used in analyzing the data. Reversion to the ND improved insulin resistance and lipid profile, besides brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3 beta (GSK3ß), and insulin-degrading enzyme (IDE) levels. Rats fed KD alone and those that received nifedipine with KD did not show similar improvement in the previously mentioned parameters as the ND group. However, nifedipine-ND rats showed improvement in cognitive behavior and insulin resistance. Treatment with nifedipine-KD ameliorated GSK3ß, amyloid ß (Aß), and tau protein levels. As the nifedipine-KD combination succeeded in diminishing the accumulated Aß and tau protein, KD may be used for a while due to its side effects, then nifedipine treatment could be continued with an ND. This conclusion is based on the finding that this combination mitigated insulin resistance with the associated improved behavior.

Development and Validation of Eyes Care Bundle for Mechanically Ventilated Patients.

Lack of proper eye care (EC) for mechanically ventilated patients can lead to serious ocular complications. Objective of this study is to develop and validate eyes care bundle for mechanically ventilated patients. A Delphi design study was conducted between March and May 2021. The Content Validity Index (CVI) was used to calculate the degree of agreement among the experts to analyze the bundle. Content validity was determined by 5 experts using a 4-point Likert scale. They evaluated the items in terms of the following: 1 = "irrelevant," 2 = "somewhat relevant if the phrasing is profoundly adjusted," 3 = "relevant with some adjustment," and 4 = "very relevant." The CVI was applied, and the accepted value was ≥0.50. The validation of EC bundle was conducted through 3 rounds after developed it based on the evaluated research evidence. The items were reviewed for content and face validity. The bundle was validated with 5 items with a total CVI of 0.96, a face validity of 1, and a Scale-Level Content Validity Index/Universal Agreement calculation method value of 0.8. This bundle can help critical care nurses, doctors, academics, and students assess and provide standard EC for mechanically ventilated patients.

Human Wharton's jelly-derived mesenchymal stromal stem cells preconditioned with valproic acid promote cell migration and reduce renal inflammation in ischemia/reperfusion injury by activating the AKT/P13K and SDF1/CXCR4 pathways.

OBJECTIVE: To determine whether WJ-MSCs pretreated with VPA would enhance their migration to improve functional recovery of renal IRI in rats. METHODS: 150 Sprague-Dawley rats were distributed into 5 groups; Sham, IRI, WJ-MSC, VPA, and WJ-MSCs + VPA. 10 rats were sacrificed after 3, 5, and 7 days. Role of WJ-MSCs pretreated with VPA was evaluated by assessment of renal function, antioxidant enzymes together with renal histopathological and immunohistopathological analyses and finally by molecular studies. RESULTS: WJ-MSCs and VPA significantly improved renal function and increased antioxidants compared to IRI group. Regarding gene expression, WJ-MSCs and VPA decreased BAX and TGF-ß1, up-regulated Akt, PI3K, BCL2, SDF1α, and CXCR4 related to IRI. Additionally, WJ-MSCs pretreated with VPA improved the measured parameters more than either treatment alone. CONCLUSION: WJ-MSCs isolated from the umbilical cord and pretreated with VPA defended the kidney against IRI by more easily homing to the site of injury.

Lipid nanoparticles of quercetin (QU-Lip) alleviated pancreatic microenvironment in diabetic male rats: The interplay between oxidative stress - unfolded protein response (UPR) - autophagy, and their regulatory miRNA.

BACKGROUND: Autophagy is a well-preserved mechanism essential in minimizing endoplasmic reticulum stress (ER)-related cell death. Defects in ß-cell autophagy have been linked to type 1 diabetes, particularly deficits in the secretion of insulin, boosting ER stress sensitivity and possibly promoting pancreatic ß-cell death. Quercetin (QU) is a potent antioxidant and anti-diabetic flavonoid with low bioavailability, and the precise mechanism of its anti-diabetic activity is still unknown. Aim This study aimed to design an improved bioavailable form of QU (liposomes) and examine the impact of its treatment on the alleviation of type 1 diabetes induced by STZ in rats. METHODS: Seventy SD rats were allocated into seven equal groups 10 rats of each: control, STZ, STZ + 3-MA, STZ + QU-Lip, and STZ + 3-MA + QU-Lip. Fasting blood glucose, insulin, c-peptide, serum IL-6, TNF-α, pancreatic oxidative stress, TRAF-6, autophagy, endoplasmic reticulum stress (ER stress) markers expression and their regulatory microRNA (miRNA) were performed. As well as, docking analysis for the quercetin, ER stress, and autophagy were done. Finally, the histopathological and immunohistochemical analysis were conducted. SIGNIFICANCE: QU-Lip significantly decreased glucose levels, oxidative, and inflammatory markers in the pancreas. It also significantly downregulated the expression of ER stress and upregulated autophagic-related markers. Furthermore, QU-Lip significantly ameliorated the expression of several MicroRNAs, which both control autophagy and ER stress signaling pathways. However, the improvement of STZ-diabetic rats was abolished upon combination with an autophagy inhibitor (3-MA). The findings suggest that QU-Lip has therapeutic promise in treating type 1 diabetes by modulating ER stress and autophagy via an epigenetic mechanism.

Can cross-sectional imaging replace diagnostic venography in pelvic venous disorder (PeVD)?

OBJECTIVE: The primary etiology of pelvic venous disorder is multifactorial and challengeable in vascular surgery as it mandates multidisciplinary team cooperation for its evaluation and management. METHODS: All patients investigated for pelvic venous disorder in a high-volume, tertiary referral university hospital were identified and analyzed retrospectively during the period (March 2021 through September 2022). Demographic and medical data were scored. Agreement between the noninvasive modalities (computed tomographic venography [CTV] or magnetic resonance venography [MRV]) and diagnostic venography in detecting the refluxing pelvic veins was analyzed. Sensitivity, specificity, and diagnostic accuracy are also measured. No patients' treatments were reported in this study as the treatment is scheduled in other sessions in some cases and is out of the scope of this article. All patients had a diagnostic venogram regardless of the axial imaging modality. The main goal was to compare cross-sectional imaging with diagnostic venography. RESULTS: The total number of patients was 120 with a mean age of 34.4 ± 7.1 years; 86.7% were multiparous. All patients presented chronic pelvic pain with vulvoperineal and/or atypical lower limb varicosities. Then patients were divided into two groups: those with CTV and those with MRV. Sensitivity, specificity, and diagnostic accuracy of CTV were 50%, 33%, and 47% for the detection of incompetent ovarian veins, 83%, 33%, and 53% for the detection of incompetent internal iliac veins, and 50%, 40%, and 47% for the detection of incompetent pelvic plexus veins, respectively, whereas time-resolved MRV achieved sensitivity, specificity, and diagnostic accuracy of 73%, 25%, and 60% for the detection of incompetent ovarian veins, 75%, 46%, and 53% for the detection of incompetent internal iliac veins, and 67%, 33% and 60% for detection of incompetent pelvic plexus veins, respectively. CONCLUSIONS: The desire to avoid the drawbacks of diagnostic venography led to an increase in the use of noninvasive imaging modalities. Our results achieved acceptable sensitivity, specificity, and diagnostic accuracy outcomes for cross-sectional imaging with the superiority of MRV over CTV in diagnosing PCS.

The Utilization of Protamine during Peripheral Vascular Interventions in the VQI.

BACKGROUND: Protamine administration was shown to reduce bleeding after carotid surgery but the role of protamine during peripheral vascular interventions (PVIs) remains unknown. This study evaluates the trend and outcomes of protamine use in the Vascular Quality Initiative (VQI). Our hypothesis is that the use of protamine is associated with decreased bleeding after PVI. METHODS: Patients undergoing elective PVI in the VQI (2016-2020) for peripheral arterial disease were reviewed and the utilization trend for protamine was described. The characteristics of patients undergoing PVI with and without protamine use were compared. After propensity score matching based on the patient's comorbidities, access site, and procedural characteristics, the perioperative outcomes of both groups were compared using multivariable Poisson regression to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (95% CIs). RESULTS: The total number of patients was 131,618 and patients who received protamine constituted 29.8% of the sample (N = 38,191). After propensity matching, the total number of patients was 94,582, and patients who received protamine constituted 28.8% of the sample (N = 27,275). Protamine use significantly increased during the study period from 5.2 to 22.9%. Before propensity score matching, patients who received protamine were more likely to be white (79% vs. 76.8, P ≤ 0.001), smokers (80.5% vs. 78.5%, P ≤ 0.001), with medical comorbidities including hypertension (88.9% vs. 88.5%, P = 0.074), congestive heart failure (20.5% vs. 19.8%, P = 0.006), and chronic obstructive pulmonary disease (28.2% vs. 26.5%). They were also more likely to be on perioperative medications such as P2Y12 inhibitors (44.3% vs. 45, P = 0.013%) and statin (77.4% vs. 76.5%, P = 0.001) compared to patients who did not receive protamine. After propensity matching, there were no significant differences between the 2 groups. There was a significant decrease in bleeding during procedures where protamine was administered compared to no protamine (2.0% vs. 2.2%) (aRR, 0.89 [95% CI 0.80, 0.98]). Protamine was more likely to be given in procedures complicated by perforation (0.8% vs. 0.5%) (aRR, 1.48 [95% CI 1.24, 1.76]) and less likely to be given during procedures with distal embolization (0.4% vs. 0.7%) (aRR, 0.59 [95% CI 0.49, 0.73]). However, patients receiving protamine had significantly higher cardiac complications (1.4% vs. 1.1%) (aRR, 1.27 [95% CI 1.12, 1.43]). There was no significant difference in mortality between the 2 groups. CONCLUSIONS: Protamine use is associated with decreased perioperative bleeding but increased cardiac complications. Protamine should be selectively administered to patients at high risk of bleeding during PVI.

Protective Effect of Topiramate against Diabetic Retinopathy and Computational Approach Recognizing the Role of NLRP3/IL-1ß/TNF-α Signaling.

The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach to investigate the possible protective effect of topiramate on experimental DREN and explore its impact on NLRP3/interlukin-1ß signaling and brain-derived neurotrophic factor (BDNF) expression. Male albino mice were distributed to four experimental groups and assigned the following categorizations: (i) saline, (ii) diabetic, (iii) diabetic + topiramate 10 mg/kg and (iv) diabetic + topiramate 30 mg/kg. We observed shrinkage of total retinal thickness and elevation in retinal glutamate, malondialdehyde, NLRP3 and interlukin-1ß but decreased glutathione (GSH) levels in the diabetic mice. Additionally, retinal ultra-structures in the diabetic group showed abnormalities and vacuolations in the pigmented epithelium, the photoreceptor segment, the outer nuclear layer, the inner nuclear layer and the ganglion cell layer (GCL). Mice treated with topiramate 10 or 30 mg/kg showed downregulation in retinal malondialdehyde, NLRP3 and interlukin-1ß levels; improvements in the retinal pathologies; enhanced immunostaining for BDNF and improved ultra-structures in different retinal layers. Overall, the current results suggest topiramate as a neuroprotective agent for DREN, and future studies are warranted to further elucidate the mechanism of its protective action.

Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population.

Introduction: The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results: The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784-52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673-81.249), both p < 0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p < 0.001). Conclusion: ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.

Proximal tubular transport of Metallothionein-Mercury complexes and protection against nephrotoxicity.

Mercury (Hg) is an important environmental toxicant to which humans are exposed on a regular basis. Mercuric ions within biological systems do not exist as free ions. Rather, they are bound to free sulfhydryl groups (thiols) on biological molecules. Metallothionein (MT) is a cysteine-rich, metal-binding protein that has been shown to bind to heavy metals and reduce their toxic effects in target cells and organs. Little is known about the effect of MT on the handing and disposition of Hg. Therefore, the current study was designed to test the hypothesis that overexpression of MT alters the corporal disposition of Hg and reduces its nephrotoxicity. Furthermore, the current study examined the transport of Hg-MT complexes in isolated proximal tubules. Rats were treated with saline or Zn followed by injection with a non-nephrotoxic (0.5 µmol kg-1), moderately nephrotoxic (1.5 µmol kg-1), or significantly nephrotoxic (2.25 µmol kg-1) dose of HgCl2 (containing radioactive Hg). Pretreatment with Zn increased mRNA expression of MT and enhanced accumulation of Hg in the renal cortex of male and female rats. In addition, injection with Zn also protected animals from Hg-induced nephrotoxicity. Studies using isolated proximal tubules from rabbit kidney demonstrated that Hg-MT is taken up rapidly at the apical and basolateral membranes. The current findings suggest that at least part of this uptake occurs through an endocytic process. This study is the first to examine the uptake of Hg-MT complexes in isolated proximal tubules. Overall, the findings of this study suggest that supplementation with Zn may be a viable strategy for reducing the risk of Hg intoxication in at-risk populations.

Balloon rupture with eversion during innominate vein angioplasty requiring surgical retrieval.

Balloon rupture during angioplasty can with calcified or recalcitrant lesions. A 61-year-old woman presented with worsening arm and facial swelling. She had a history of left upper extremity thrombolysis and stenting of the innominate vein 6 years prior. Venography showed severe in-stent stenosis. After crossing the lesion, a 12-mm balloon was inflated, which ruptured at nominal pressure. The balloon became stuck and could not be moved over the wire even after retraction of the sheath. A limited surgical cutdown was performed, and the balloon and the wire were removed together. The ruptured balloon part was found to be everted and circumferentially wrapped around the wire, preventing the wire exchange. After cutting the everted portion of the balloon, the catheter was removed without losing wire access. A high-pressure balloon was subsequently used to treat the lesion successfully. Her symptoms had resolved on follow-up, and the stent remained patent after 6 months.

How level of understanding and type of used sources relate to adherence to COVID-19 public health measures in Canada.

Previous studies have highlighted the importance of promoting health literacy and minimizing misinformation to encourage higher adherence to key public health measures during the COVID-19 pandemic. This study explores how one's self-reported understanding of information and types of sources used to get information regarding COVID-19 can hinder adherence to public health measures implemented by the Canadian government. Data was collected following a longitudinal design of 11 time points for April 2020 to April 2021. The sub-sample used for this study included 2659 Canadians who completed the survey for at least four time points. Using Latent Class Growth Analysis, we modelled typical trajectories of adherence to three key public health measures: staying home, social distancing and mask wearing. Overall, a lower level of understanding was associated with lower adherence trajectories to public health measures, and vice-versa. Adjusted odds ratio (AOR) showed that the higher the level of understanding, the higher were the chances of following a high adherence trajectory. The type of used sources also showed a significant statistical association with adherence trajectories for social distancing and staying home (AOR: between 1.1 and 3.4). These results are discussed considering future policy implications.

Revealing how phenytoin triggers liver damage and the potential protective effects of Balanites Aegyptiaca fruit extracts: Exploring Nrf2/MAPK/ Beclin-1 signaling pathways.

Phenytoin-induced liver injury (PHT ILII) is a serious condition that may necessitate discontinuation of the drug. This study investigates the mechanisms of PHT ILII and evaluates the protective effects of Balanites Aegyptiaca (BA) fruit extracts on the liver. We focus on the Nrf2/MAPK/NF-κB/Beclin-1 signaling pathways involved in oxidative stress and inflammation from drug-induced liver injury. Phytochemical analyses of BA fruit extracts (Bu-F and EA-F) are conducted. Molecular docking techniques explore the interaction between phenytoin (PHT) and the Nrf2/MAPK/NF-κB/Beclin-1 pathways. Thirty-six male rats are divided into Control, Bu-F, EA-F, PHT, Bu-F/PHT, and EA-F/PHT groups, and they are observed for 45 days. EA-F extract is rich in phenolics/flavonoids, while Bu-F extract mainly contains saponins.PHT ILII causes histological damage in liver tissues and affects Nrf-2, MAPK, TNF-α, IL-1ß, Mcp-1, Beclin-1, iNOS expression, and liver function markers (ALT, AST, ALP). However, EA-F/Bu-F extracts effectively improve the histological structure and significantly reduce biochemical/immunohistochemical parameters, restoring them to near-normal levels. EA-F extract is particularly effective.In conclusion, the Nrf2/MAPK /Beclin-1 pathways play a critical role in the development of PHT ILII. BA fruit extracts show promise as hepato-protective agents, with the EA-F extract demonstrating superior efficacy. These results lay the groundwork for new treatments for PHT ILII and drug-induced liver injuries.

Flexible Electrode Based on PES/GO Mixed Matrix Woven Membrane for Efficient Photoelectrochemical Water Splitting Application.

We introduced, for the first time, a membrane composed of nanostructured self-polyether sulphone (PES) filled with graphene oxide (GO) applied to photoelectrochemical (PEC) water splitting. This membrane was fabricated through the phase inversion method. A variety of characteristics analysis of GO and its composite with PES including FTIR, XRD, SEM, and optical properties was studied. Its morphology was completely modified from macro voids for bare PES into uniform layers with a random distribution of GO structure which facilitated the movement of electrons between these layers for hydrogen production. The composite membrane photocathode brought a distinct photocurrent generation (5.7 mA/cm2 at 1.6 V vs. RHE). The optimized GO ratio in the membrane was investigated to be PG2 (0.008 wt.% GO). The conversion efficiencies of PEC were assessed for this membrane. Its incident photon-to-current efficiency (IPCE) was calculated to be 14.4% at λ = 390 nm beside the applied bias photon-to-current conversion efficiency (ABPE) that was estimated to be 7.1% at -0.4 V vs. RHE. The stability of the PG2 membrane after six cycles was attributed to high thermal and mechanical stability and excellent ionic conductivity. The number of hydrogen moles was calculated quantitively to be 0.7 mmol h-1 cm-2. Finally, we designed an effective cost membrane with high performance for hydrogen generation.

Fabrication of PES Modified by TiO2/Na2Ti3O7 Nanocomposite Mixed-Matrix Woven Membrane for Enhanced Performance of Forward Osmosis: Influence of Membrane Orientation and Feed Solutions.

Water treatment is regarded as one of the essential elements of sustainability. To lower the cost of treatment, the wastewater volume is reduced via the osmotic process. Here, mixed-matrix woven forward osmosis (MMWFO) PES membranes modified by a TiO2/Na2Ti3O7 (TNT) nanocomposite were fabricated for treating water from different sources. Various techniques were used to characterize the TNT nanocomposite. The crystal structure of TNT is a mix of monoclinic Na2Ti3O7 and anorthic TiO2 with a preferred orientation of (2-11). The SEM image shows that the surface morphology of the TNT nanocomposite is a forked nano-fur with varying sizes regularly distributed throughout the sample. The impact of TNT wt.% on membrane surface morphologies, functional groups, hydrophilicity, and performance was investigated. Additionally, using distilled water (DW) as the feed solution (FS), the effects of various NaCl concentrations, draw solutions, and membrane orientations on the performance of the mixed-matrix membranes were tested. Different water samples obtained from various sources were treated as the FS using the optimized PES/TNT (0.01 wt.%) MMWFO membrane. Using textile effluent as the FS, the impact of various NaCl DS concentrations on the permeated water volume was investigated. The results show that the MMWFO membrane generated with the TNT nanocomposite at a 0.01 wt.% ratio performed better in FO mode. After 30 min of use with 1 M NaCl and various sources of water as the FS, the optimized MMWFO membrane provided a steady water flow and exhibited antifouling behavior. DW performed better than other water types whenever it was used owing to its greater flow (136 LMH) and volume reduction (52%). Tap water (TW), textile industrial wastewater (TIWW), gray water (GW), and municipal wastewater (MW) showed volume reductions of 41%, 34%, 33%, and 31.9%, respectively. Additionally, when utilizing NaCl as the DS and TIWW as the FS, 1 M NaCl resulted in more permeated water than 0.25 M and 0.5 M, yet a higher volume reduction of 41% was obtained.

Camptothecin Sensitizes Hepatocellular Carcinoma Cells to Sorafenib- Induced Ferroptosis Via Suppression of Nrf2.

Sorafenib is a potent inducer of ferroptosis used to manage hepatocellular carcinoma (HCC). The ferroptosis induced by sorafenib activates the p62-Keap1-Nrf2 pathway. Abnormal activation of Nrf2 reduces sorafenib's efficiency and ferroptosis action and induces sorafenib's resistance. Consequently, our study tried to study the effect of a novel combination of sorafenib and Camptothecin (CPT, Nrf2 inhibitor) to improve sorafenib's ferroptosis action and reduce sorafenib resistance in the treatment of HCC. We evaluated the efficacy of sorafenib and/or CPT using HepG2 and Huh7 cell lines. MTT assay evaluated the anti-proliferation effects. The combination index (CI) and dose reduction index (DRI) were calculated using Isobologram analysis. Malondialdehyde (MDA), total antioxidant capacity (TAC), iron concentration, glutathione peroxidase (GPX4), and glutathione reductase (GR) activity assays were used to determine the ferroptosis action of drugs. Western blot was used to investigate the expression of the implicated proteins. Bioinformatics tools were used to determine the correlation between these proteins. Finally, the HPLC technique is used to measure cellular drug uptake. Our results revealed a strong synergism between sorafenib and CPT. The synergetic combination significantly increases lipid peroxidation and iron concentration, decreases TAC, GPX4 and GR activity, and reduces the expression of both Nrf2 and SLC7A11. The downregulation of Nrf2 expression has a vital role in the reduction of resistance mediators to sorafenib against HCC cells like (p62, MT1G, and ABCG2) and improves the cellular uptake of sorafenib. The current study provided evidence that Nrf2 inhibition by CPT improves sorafenib's sensitivity and reduces sorafenib's resistance via the augmentation of sorafenib's ferroptosis action.

Enhanced Wound Healing Potential of Spirulina platensis Nanophytosomes: Metabolomic Profiling, Molecular Networking, and Modulation of HMGB-1 in an Excisional Wound Rat Model.

Excisional wounds are considered one of the most common physical injuries. This study aims to test the effect of a nanophytosomal formulation loaded with a dried hydroalcoholic extract of S. platensis on promoting excisional wound healing. The Spirulina platensis nanophytosomal formulation (SPNP) containing 100 mg PC and 50 mg CH exhibited optimum physicochemical characteristics regarding particle size (598.40 ± 9.68 nm), zeta potential (-19.8 ± 0.49 mV), entrapment efficiency (62.76 ± 1.75%), and Q6h (74.00 ± 1.90%). It was selected to prepare an HPMC gel (SPNP-gel). Through metabolomic profiling of the algal extract, thirteen compounds were identified. Molecular docking of the identified compounds on the active site of the HMGB-1 protein revealed that 12,13-DiHome had the highest docking score of -7.130 kcal/mol. SPNP-gel showed higher wound closure potential and enhanced histopathological alterations as compared to standard (MEBO® ointment) and S. platensis gel in wounded Sprague-Dawley rats. Collectively, NPS promoted the wound healing process by enhancing the autophagy process (LC3B/Beclin-1) and the NRF-2/HO-1antioxidant pathway and halting the inflammatory (TNF-, NF-κB, TlR-4 and VEGF), apoptotic processes (AIF, Caspase-3), and the downregulation of HGMB-1 protein expression. The present study's findings suggest that the topical application of SPNP-gel possesses a potential therapeutic effect in excisional wound healing, chiefly by downregulating HGMB-1 protein expression.

Carbon dioxide angiography during peripheral vascular interventions is associated with decreased cardiac and renal complications in patients with chronic kidney disease.

OBJECTIVE: Patients with chronic kidney disease (CKD) who undergo peripheral vascular interventions (PVI) with iodinated contrast are at higher risk of post-contrast acute kidney injury (PC-AKI). Carbon dioxide (CO2) angiography can reduce iodinated contrast volume usage in this patient population, but its impact on PC-AKI has not been studied. We hypothesize that CO2 angiography is associated with a decrease in PC-AKI in patients with advanced CKD. METHODS: The Vascular Quality Initiative PVI dataset from 2010 to 2021 was reviewed. Only patients with advanced CKD (estimated glomular filtration rate <45 ml/min/1.73 m2) treated for peripheral arterial disease were included. Propensity matching and multivariate logistic regression based on demographics, comorbidities, CKD stage, and indications were used to compare the outcomes of patients treated with and without CO2. RESULTS: There were 20,706 PVIs performed in patients with advanced CKD, and only 22% utilized CO2 angiography. Compared with patients treated without CO2, patients who underwent CO2 angiography were younger and less likely to be women or White, and more likely to have poor renal function, diabetes, cardiac comorbidities, and present with tissue loss. Propensity matching yielded well-matched groups with 4472 patients in each group. The procedural details after matching demonstrated 50% reduction in the volume of contrast used (32±33 vs 65±48 mL; P < .01). PVI with CO2 angiography was associated with lower rates of PC-AKI (3.9% vs 4.8%; P = .03) and cardiac complications (2.1% vs 2.9%; P = .03) without a significant difference in technical failure or major/minor amputations. Low contrast volumes (≤50 mL for CKD3, ≤20 mL for CKD4, and ≤9 mL for CKD5) are associated with reduced risk of PC-AKI (hazard ratio, 0.59; P < .01). CONCLUSIONS: CO2 angiography reduces iodinated contrast volume usage during PVI and is associated with decreased cardiac complications and PC-AKI. CO2 angiography is underutilized and should be considered for patients with advanced CKD who require endovascular therapy.