Search Results (61)

Introduction: NEDD8 Ultimate Buster 1 (NUB1) is a regulator of the cell cycle and a prognostic marker in cancer patients. However, its role in breast cancer (BC) and its response to 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) treatment remain unclear. This study investigated NUB1’s predictive value in FEC treatment and its mechanistic interaction with the oestrogen receptor (ER) in BC. Methods: MDA-MB-231 and MCF-7 cells were treated with FEC and analysed via flow cytometry for cell cycle distribution. Western blotting assessed NUB1 and ERα expression, while immunohistochemistry was conducted on a retrospective cohort (n = 85) from Malaysian hospitals to evaluate the clinical significance of NUB1 expression. Results: FEC treatment induced S and G2 phase cell cycle arrest in MDA-MB-231 cells (p = 0.04 and p = 0.02, respectively), accompanied by NUB1 upregulation. In MCF-7 cells, G2/M arrest was observed (p = 0.01), with reduced ERα expression and increased NUB1 levels in both cell lines. Lower cytoplasmic NUB1 expression was associated with poorer overall survival (OS) (HR = 0.60; 95% CI = 0.32–1.11; p = 0.10). Patients with low NUB1 and low ER expression showed the worst OS outcomes. Discussion: NUB1 upregulation following FEC treatment led to cell cycle arrest in ER-negative cells, whereas ERα suppression failed to induce S-phase arrest in ER-positive cells. Low NUB1 expression predicted poorer OS and increased BC recurrence. Conclusions: By integrating in vitro and clinical data, this study suggests that NUB1 may serve as a predictive biomarker in FEC-treated breast cancer. Larger studies are needed to validate and establish NUB1’s predictive role in FEC-treated patients. Full article

Background/Objectives: Dry eye disease (DED), also known as “keratoconjunctivitis sicca”, is a common chronic ocular surface disease accompanied by inflammation and diminished tear production. Bovine Lactoferrin (BLF), a multi-functional iron-binding glycoprotein found in tears, decreased significantly in patients with DED, used for the treatment of dry eye, conjunctivitis, and ocular inflammation. BLF has limited therapeutic efficacy due to poor ocular bioavailability. Methods: This study developed and optimized a BLF-loaded nanosuspension (BLF-NS) using the Box–Behnken Design (BBD). Optimized BLF-NS was then incorporated with polyvinyl pyrrolidone (PVP) and hydroxypropyl methyl cellulose (HPMC) dissolving microneedles (MNs). The formulations were characterized by Scanning and transmission microscopy, DSC, FTIR, ex vivo studies in corneal tissue from sheep and tested for its antibacterial and antifungal efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Aspergillus niger, respectively. Moreover, they were tested for their Benzalkonium chloride (BCL) dry eye in a rabbit model. Results: The optimized nanosuspension showed a vesicle size of (215 ± 0.45) nm, a Z.P (zeta potential) of (−28 ± 0.34) mV, and an Entrapment Efficiency (EE%) of (90 ± 0.66) %. The MNs were fabricated using a ratio of biodegradable polymers, PVP/HPMC. The resulting BLF-NS-MNs exhibited sharp pyramidal geometry with high mechanical strength, ensuring ocular insertion. In vitro release showed 95% lactoferrin release over 24 h, while ex vivo permeation achieved 93% trans-corneal delivery. In vivo, BLF-NS-MNs significantly reduced pro-inflammatory cytokines (TNF-α, IL-6, MMP-9, IL-1β, MCP-1) and upregulated antioxidant and anti-inflammatory genes (PPARA, SOD 1), restoring their levels to near-normal (p < 0.001). Conclusions: The nanosuspension combined with MNs has shown higher ocular tolerance against DED ensured by the Draize and Schirmer Tear Test. Full article

Background and Objectives: Bacterial infections amongst COVID-19 patients could be associated with worsened outcomes. This study aimed to investigate the efficacy of colistin antibiotic in multidrug-resistant (MDR) Gram-negative (-ve) secondary bacterial infections among hospitalized COVID-19 patients. Materials and Methods: In this multicentered retrospective study, we analyzed data from the medical records of 116 patients diagnosed with COVID-19 infection and secondary Gram-negative MDR bacterial respiratory infections. Results: We compared those assigned to colistin versus non-colistin-based antimicrobial therapy. The two arms of the study were similar in baseline clinical features, demographics, and Gram-negative pathogens’ distribution. Acinetobacter baumannii (51.7%) was the major pathogen, followed by Klebsiella pneumonia (26.7%). Patients who received colistin-based antimicrobial regimen showed a non-significant difference compared to non-colistin antimicrobial (NCA) therapy (p > 0.05) in the main outcomes. Nephrotoxicity was significantly higher in the IV colistin group, compared to the control (34.1% and 15.3%, p = 0.018). There were substantial differences observed in the levels of serum creatinine and urea among the study arms (p = 0.029 and <0.001, respectively). Conclusions: The combination of colistin with other antimicrobial agents showed comparable results to that of NCA regimens in hospitalized COVID-19 patients with superinfections with multidrug-resistant bacterial isolates; however, there was a notably elevated incidence of nephrotoxicity with colistin antimicrobial therapy. Further randomized controlled trials are needed to assess the therapeutic benefits and tolerability of colistin antimicrobial therapy. Full article

Background/Objectives: Diabetic mouth ulcers are a pathological condition of the oral mucosa leading to increases in susceptibility to infection and prolonged wound healing time. Still, there is a lack of natural formulations for treating this condition. Our principal objective was to formulate solid lipid nanoparticles (SLNs) that contained Althaea officinalis (marshmallow) (M.) extract with clove oil (CO.), subsequently integrated into a collagen sponge for enhancing stability, solubility, sustained release, antimicrobial efficacy, and healing power when targeting diabetic oral ulcers. Methods: A factorial design of 34 trials was established to evaluate the influence of lipid concentration (A), SAA concentration (B), lipid type (C), and SAA type (D). The optimized M-CO-SLNs was selected using Design Expert^®, the based Poly dispersibility index (Y2), zeta potential (MV) (Y3), and encapsulation efficiency (%) (Y4). The optimized SLNs were integrated into a collagen sponge matrix and tested for their antibacterial and antifungal efficacy against Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, respectively. Moreover, they were tested for their wound healing power in a diabetic mouth ulcer model. Results: The optimized formula (Run 16: 5% lipid concentration, 4% SAA concentration, capric acid) demonstrated P.S (110 ± 0.76 nm), ZP (−24 ± 0.32 mV), PDI (0.18 ± 0.05), and EE% (90 ± 0.65%.). The optimized M-CO-SLNs formula was incorporated into a cross-linked collagen sponge and showed superior antimicrobial efficacy, an increased swelling ratio, and was effective in an in vivo oral ulcer study, as evidenced by ELISA biomarkers, gene expression analysis, and histological analysis. Conclusions: M-CO-SLNs embedded in collagen sponges is a promising therapeutic formula for clinical application against diabetic mouth ulcers. Full article

Background and Objectives: Epilepsy is a common neurological disrupt that involves recurring seizures. α-Synuclein (α-Syn), one of the most abundant proteins in the nervous system, is implicated in both neurodegenerative conditions and epilepsy. This study aimed to assess serum α-Syn levels in children with drug-resistant epilepsy (DRE) and explore the relationship with diagnosis and clinical severity. Materials and Methods: This cross-sectional study was carried out at the Pediatric Neurology Outpatient Clinic of Beni-Suef University Hospital. It involved 30 children with DRE, 30 with drug-responsive epilepsy, and 30 age- and sex-matched healthy controls. Serum α-Syn levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Results: Serum α-Syn levels were significantly higher in children with epilepsy compared to healthy controls (p < 0.001), with significantly high levels observed in drug-resistant cases versus drug-responsive ones (p < 0.001). Receiver operating characteristic (ROC) investigation confirmed that α-Syn effectively distinguished epilepsy patients from healthy controls, yielding an area under the curve (AUC) of 0.773. It also successfully differentiated between drug-responsive and drug-resistant epilepsy, with an AUC of 0.858. Further analysis revealed significant positive correlations between serum α-Syn levels and the frequency of hospitalizations due to seizures, the number of anti-epileptic drugs (AEDs) prescribed, and monthly seizure frequency (p = 0.018, 0.009, and <0.001, respectively). In contrast, α-Syn levels were negatively associated with the time since the last seizure and the age at seizure onset (p = 0.001 and 0.016, respectively). Conclusions: Serum α-Syn levels are elevated in epilepsy patients, particularly those with drug-resistant epilepsy, suggesting its potential role as a biomarker for disease severity and treatment resistance. Full article

Background and Objectives: Ovarian cancer is a highly lethal gynecological malignancy and the fifth leading cause of cancer-related deaths. Diagnosis mainly involves gynecological examination and transvaginal ultrasonography. To evaluate the diagnostic performance of the Gynecology Imaging Reporting and Data System (GI-RADS) with regard to its ability to evaluate adnexal masses preoperatively, considering a definitive histopathological diagnosis. Materials and Methods: This study was approved by the ethics committee, and informed consent was obtained from all the patients. This research was conducted at Beni-suef University Hospital between June 2021 and January 2023 on 100 women who experienced pelvic pain due to an adnexal mass. Results: Our study results revealed that the combination of IV-V GI-RADS had high specificity (92.2%), sensitivity (87%), and a negative predictive value (95.9%), but moderate other diagnostic characteristics for predicting adnexal mass malignancy. Conclusions: The GI-RADS classification system is a reliable method for reporting ovarian masses, with high diagnostic accuracy for predicting malignancy. It aids in patient triage and clinical decision making. To optimize care, it is essential to inform referring clinicians about the objectives of the GI-RADS before its implementation in a treatment plan. Full article

Background/Objectives: Hesperidin (HSP) is a potent phytochemical antioxidant and anti-inflammatory agent that protects against otitis media. However, due to its low solubility and bioavailability, a suitable delivery method is needed to overcome these problems. A hydrogel is a promising nanocarrier for controlled drug delivery in response to external stimuli, such as pH variations. Methods: Graphene oxide (GO)-based nanocarriers that encapsulate hesperidin (HSP) were further coated with a polylactic-co-glycolic acid/alginate (PLGA-Alg) hydrogel before being integrated into a green neem oil (N.O.) double emulsion to produce a synergistic effect and then characterized by different assays. Results: The nanocarriers exhibited a substantial particle size (168 ± 0.32 nm), with high encapsulation (89.86 ± 0.23%) and a zeta potential of 37 ± 0.43 mV. In vitro release studies conducted over 96 h indicated a sustained HSP release of 82% at pH 5.4 and 65% at pH 7.4. The GO-HSP-loaded neem oil double emulsion formulation exhibits substantial antibacterial activity, as evidenced by inhibition zones of 39 ± 0.02 mm against Staphylococcus epidermidis, and considerable antifungal activity against Candida albicans, with an inhibition zone of 43 ± 0.13 mm, along with biofilm inhibition activity. The formulation demonstrated antioxidant activity (5.21 µg/mL) and increased cell viability (90–95%) while maintaining low cytotoxicity in HSE-2 cells. A histopathological analysis confirmed that treatment with the nanocarriers reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, TLR4, IL-6) and raised the levels of antioxidant markers (Nrf-2, SOD) in an in vivo rat model of otitis media. Conclusions: GO-based nanocarriers integrated into a neem oil double emulsion and coated with PLGA-Alg hydrogel deliver hesperidin with sustained release and enhanced antibacterial, antifungal, and antioxidant properties. This formulation may be used to treat otitis media and other oxidative stress diseases. Full article

A dangerous infection contracted in hospitals, ventilator-associated pneumonia is frequently caused by bacteria that are resistant to several drugs. It is one of the main reasons why patients in intensive care units become ill or die. This research aimed to determine the most effective empirical therapy of antibiotics for better ventilator-associated pneumonia control and to improve patient outcomes by using the minimal inhibitory concentration method and the Ameri–Ziaei double antibiotic synergism test and by observing the clinical responses to both single and combination therapies. Patients between the ages of one month and twelve who had been diagnosed with ventilator-associated pneumonia and had been on mechanical ventilation for more than 48 h were included in the study, which was carried out in the Pediatric Intensive Care Unit at Cairo University’s Hospital. When ventilator-associated pneumonia is suspected, it is critical to start appropriate antibiotic therapy as soon as possible. This is especially important in cases where multidrug-resistant Gram-negative infections may develop. Although using Polymyxins alone or in combination is effective, it is important to closely monitor their administration to prevent resistance from increasing. The combination therapy that showed the greatest improvement was a mix of aminoglycosides, quinolones, and β-lactams. A combination of aminoglycosides and dual β-lactams came next. Although the optimal duration of antibiotic treatment for ventilator-associated pneumonia is still unknown, treatments longer than seven days are usually required to eradicate MDR P. aeruginosa or A. baumannii completely. Full article

Background: FAT10 is a member of the ubiquitin-like modifier family. Similar to ubiquitin, FAT10 has a distinct enzyme cascade consisting of E1-activating, E2-conjugating, and possibly several E3-ligating enzymes, which will covalently link FAT10 to substrate proteins in order to target them directly for proteasomal degradation. FAT10 was reported to be phosphorylated by IKKβ during infection with influenza A virus. Methods: To assess the difference between the FAT10-dependent degradation of phosphorylated FAT10 and the non-phosphorylated FAT10 wild type (FAT10 WT), a mutated FAT10 that mimicked phosphorylation (FAT10 D) was constructed by replacing several serine residues and one threonine residue with aspartic or glutamic acid. The FAT10 degradation or conjugation was compared between the phospho-mimetic FAT10 and the wild-type FAT10 with respect to the dependence of the E3 ligase TRIM25, the UBL-UBA protein NUB1L, and the proteasomal ubiquitin receptor RPN10. Results: The phospho-mimetic FAT10 was more efficiently conjugated to substrate proteins as compared to the wild-type FAT10, particularly if TRIM25 was co-expressed. Additionally, the phospho-mimetic FAT10 was not bound by NUB1L. However, this did not affect FAT10 D or FAT10 WT degradation. No differences were found in the binding affinity of phospho-mimetic FAT10 to RPN10. Conclusions: In brief, the phospho-mimetic FAT10 shows enhanced conjugation efficiency, but phosphorylation does not alter its degradation by the proteasome. This reveals that phosphorylation may fine-tune FAT10’s interactions with specific interaction partners without disrupting its core function of proteasomal degradation. Full article

Background/Objectives: Hemophilia A is an X-linked recessive illness produced by a deficiency of coagulation factor VIII. This study aimed to evaluate serum vitamin D in hemophilic pediatric patients and its correlation with joint health and quality of life. Methods: This case-control study was performed on ninety children under the age of 18 years old and separated into two groups: study group of 45 children with hemophilia A and control group of 45 healthy children at an outpatient pediatric hematology clinic at the Beni-Suef University hospitals. Results: Serum vitamin D levels were significantly lower in hemophilia A patients than in controls (p < 0.001). The level of serum vitamin D was deficient in 38 (84.4%), insufficient in 4 (8.8%) and sufficient in 3 (6.6%) in the study group while deficient in 8 (17.7%), insufficient in 16 (35.5%) and sufficient in 21 (46.6%) in the control group. Total hemophilia joint health score (HJHS) had a significant negative correlation with serum total calcium (R = −0.31, p = 0.038) and serum vitamin D level (R = −0.974, p < 0.001) while also positively correlated with alkaline phosphatase (R = 0.834, p < 0.001). A quality-of-life index that is specific to total hemophilia (Haemo-Qol/Haem-A-QoL) had a significant positive correlation with total hemophilia joint health score (HJHS) (R = 0.934, p < 0.001) and negatively correlated with serum vitamin D level (R = −0.924, p-value lower than 0.001), alkaline phosphatase (R = 0.842, p < 0.001), and severity of hemophilia (R = 0.67, p < 0.001). Conclusions: patients with hemophilia A had lower vitamin D levels than healthy controls. The severity of vitamin D deficiency is related positively to (HJHS) hemophilia and quality of life hemophilia cases according to Haemo-QoL. Full article

To address road accident losses, there is a need to prioritize safety factors, especially in high-risk locations on the road network, toward assuring a sustainable transport system. This paper proposes an approach for quantitative risk assessments of safety factors in hazardous road locations and involves the integration of the Fuzzy logic model, the Analytic Hierarchy Process (FAHP) and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). This new innovative method offers a way to prioritize and select safety factors associated with hazardous locations using a hierarchical structure. To demonstrate the applicability of this method, a case study was conducted in Egypt. The assessment process involved active participation by professionals through multiple expert meetings. This collaborative approach ensures that the assessment incorporates valuable real-world knowledge and experiences. It analyzed road safety hazardous conditions across various sections, including intersections, non-intersection sections, narrow bridge sections, and curve sections. The application of FAHP-TOPSIS enables the determination of weights for safety factors within each section, facilitating the evaluation of safety indices between them and ranking the safety hazard sections. The achieved analysis revealed that the hazard safety factor index is comparatively higher in curved sections compared to other types of sections. Light utility poles and road barriers significantly affected the hazard index. By utilizing this approach, governments may make informed decisions regarding the allocation of resources and the implementation of safety measures at hazardous road locations. Full article

Background and Objectives: Patients with cirrhosis who seem normal during physical examinations may still have abnormalities in their electroencephalogram (EEG) or show pathological results in neuropsychological tests. This study aimed to investigate the progression of minimal hepatic encephalopathy, its effects on quality of life, its prognostic value, and its significance for daily functioning. Materials and Methods: This study involved 50 patients with confirmed cirrhosis (28 Child A, 12 Child B, 10 Child C) who were assessed for psychological symptoms and underwent several tests: the Minimal Mental State Examination (MMSE), the Letter Cancellation Test, the Digit Symbol Coding Test, and EEG. Results: showed that 40% of patients exhibited neuropsychiatric symptoms, with somatization being the most common at 96%. The MMSE revealed cognitive impairment in 48% of patients. In the Letter Cancellation Test (LCT) (total error), 80% of patients had organic disorders, and 24% showed affections with (LCT) (completion time). The Digit Symbol Coding Test results showed affection in 28% of patients. Significant EEG changes were observed in patients with Child C cirrhosis. Patients with portal hypertension (including varices and variceal bleeding), liver cell failure symptoms (such as ascites, lower limb edema, and bleeding tendency), as well as those who smoke, or obese, or have hyperlipidemia, all displayed notable EEG and psychological test abnormalities, making them more likely to develop hepatic encephalopathy. Conclusions: psychological testing and EEG changes are effective in detecting minimal hepatic encephalopathy, with a higher incidence in Child C patients compared to those in Child A and B. Full article

Background and Objectives: Pregnant women face an increased risk of experiencing negative consequences due to COVID-19 infection. Our study aimed to identify outcomes for both mothers and fetuses associated with COVID-19 during each trimester, as well as to identify post-COVID symptoms in this population. Materials and Methods: Among the total population, 14 females were infected during the first trimester, 25 during the second, and 66 during the third trimester. Weekly follow-ups were conducted until delivery. Seventy-five females (71.4%; 95% CI:26.9–115.9%) were admitted to the hospital secondary to COVID-19 infection. Maternal hospitalization was independently associated with COVID-19 severity (adjusted odds ratio (aOR) = 3.9; 95% CI: 1.6–9.2 at p = 0.002 relative to the reference group (mild infection)) and the presence of dyspnea at initial assessment (aOR = 6.9; 95% CI: 1.7–28.2 at p = 0.007 relative to nondyspneic patients). Results: The duration of hospitalization (mean ± SD) was higher in the third trimester than the first and second trimesters (10.1 ± 0.8 vs. 4.0 ± 1.2 days and 10.1 ± 0.8 vs. 6.2 ± 1.4 days, respectively, at p < 0.05). The number of maternal deaths in the third trimester was higher than in the first and second trimesters (16 (24.2%) vs. no deaths and 16 (24.2%) vs. 1 (4%) deaths, respectively, at p < 0.05). In terms of fetal outcomes, a good fetal condition was more likely if the mother was infected during the first trimester (92.9%) than the second (80%) or third trimesters (66.7%), but the difference was not significant. The percentage of preterm deliveries was insignificantly higher in the second trimester (16%) than the first (7.1%) and third (4.5%) trimesters. Conclusions: The most common post-COVID symptoms included persistent loss of smell, dry eyes, post-partum depression, knee pain, and myalgia. Post-COVID symptoms were more prevalent in patients infected during the third trimester. The adverse outcomes of COVID-19 infection for both mother and fetus were more severe in cases where the infection occurred during the third trimester compared to the second and first trimesters. Therefore, it is crucial to adhere to precautionary measures against COVID-19, prioritize vaccination, and provide comprehensive care for pregnant mothers. Full article

Background and Objectives: Elevated levels of pro-inflammatory cytokines have been linked to increased mortality in COVID-19 patients. Infliximab, a tumor necrosis factor inhibitor, has been reported to improve outcomes in COVID-19 patients by targeting the hyperinflammatory response. Our objective was to evaluate the effectiveness of incorporating Infliximab into standard care guidelines for the management of COVID-19. Materials and Methods: A retrospective analysis was conducted on 111 participants who were moderate to severe COVID-19 patients admitted to the hospital. Among them, 74 individuals received solely standard treatment, while 37 received standard therapy plus Infliximab. The primary outcomes of the study centered around the changes in laboratory test parameters. The secondary clinical findings included clinical recovery defined as improvement in patient oxygenation, time till recovery, and assessing necessity for ICU admission, and mortality rates. Results: There was no statistical difference observed in the inflammatory markers including, LDH, Ferritin, CRP, neutrophil to lymphocyte ratio (NLR), and P/F ratio between both groups and in the clinical outcomes including clinical recovery (p = 1.0), time to improvement (p = 0.436), and mortality rate (p = 0.601). However, there was a significant increase in secondary infection (45.9%, 20.3%; p = 0.005), and in liver enzymes, ALT (79.5, 50.0 IU/L; p = 0.02) and AST (57.5, 38.0 IU/L; p = 0.019) in the Infliximab group and the standard care group, respectively. Conclusions: Infliximab therapy did not demonstrate significant benefits compared to standard of care in moderate to severe hospitalized COVID-19 patients. Full article

Background and Objectives: It is well known that depression, anxiety, and impulsiveness are interrelated; however, studies that have assessed their association with the coronavirus outbreak are scarce. Hence, our study aimed to evaluate the impulsivity incidence and its correlation with anxiety and depression following COVID-19 infection between November 2022 and June 2023. Materials and Methods: The 201 participants completed the Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HAM-A), Sheehan Disability Scale (SDS), and short UPPS-P scales (urgency, premeditation, perseverance, sensation seeking, and positive urgency) to allow us to determine their anxiety and depression symptoms, functional impairment, and impulsivity, respectively. Results: Among our respondents, 22%, and 26.7% had moderate to severe anxiety and depression. The short UPPS-P scale significantly correlated with the HAM-A and HDRS scales. Participants with positive COVID-19 infection showed significantly higher functional impairment scores, especially in the work/study domain (mean (SD): 3.12 (2.2) vs. 2.43 (2.3); p = 0.037). COVID-19-related disruption significantly correlated with negative and positive urgency, HAM-A, HDRS, and the SDS total and subscales. Conclusions: Our findings showed a notable increase in anxiety, depression, and functional impairment among the population following COVID-19 infection. Our research highlights the correlation between impulsivity and the psychological distress experienced following the pandemic. Full article