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Abstract Background Premenstrual syndrome (PMS) is a commonly underestimated disorder that negatively impacts a woman’s life. Medical workers, who live a more stressful life, may report an increased rate of PMS. Studies on the relationship between PMS and work-related quality of life for medical professionals are scarce, particularly in the Arab world. This study aimed to compare the frequency of PMS among medical versus non-medical workers at Zagazig University and to assess the association between PMS and their work-related quality of life. Methods A comparative cross-sectional study was conducted. The sample population consisted of 48 medical and 48 non-medical female workers aged 18–45 years from Zagazig University. The two groups filled out a questionnaire with 3 parts: sociodemographic and occupational data, the Premenstrual Symptoms Screening Tool (PSST), and the Work-Related Quality of Life Scale (WRQL). Results Severe PMS was reported in 45.8% of medical workers versus 20.8% of non-medical workers with a statistically significant difference between both groups (p = 0.009). Binary logistic regression showed that being a medical worker, clinical specialty, ≥ 8 years of work, ≥ 24 working hours per week, and having a non-set hourly schedule were predictors for severe PMS. PMS was found to be a statistically significant predictor of poor WRQL (p

Abstract The escalating threat posed by the Monkeypox virus (MPXV) to global health necessitates the urgent discovery of effective antiviral agents, as there are currently no specific drugs available for its treatment, and existing inhibitors are hindered by toxicity and poor pharmacokinetic profiles. This study aimed to identify potent MPXV inhibitors by screening a diverse library of small molecule compounds derived from marine fungi, focusing on the viral protein VP39, a key methyltransferase involved in viral replication. An extensive virtual screening process identified four promising compounds—CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569—alongside a control molecule. Rigorous evaluations, including re-docking, molecular dynamics (MD) simulations, and hydrogen bond analysis, were conducted to assess their inhibitory potential against MPXV VP39. CMNPD15724 and CMNPD30883, in particular, demonstrated a superior binding affinity and stable interactions within the target protein's active site throughout the MD simulations, suggesting a capacity to overcome the limitations associated with sinefungin. The stability of these VP39-compound complexes, corroborated by MD simulations, provided crucial insights into the dynamic behavior of these interactions. Furthermore, Principal Component Analysis (PCA) based free energy landscape assessments offered a detailed understanding of the dynamic conformational changes and energetic profiles underlying these compounds' functional disruption of VP39. These findings establish CMNPD15724, CMNPD28811, CMNPD30883, and CMNPD18569 as promising MPXV inhibitors and highlight marine fungi as a valuable source of novel antiviral agents. These compounds represent potential candidates for further experimental validation, advancing the development of safer and more effective therapeutic options to combat this emerging viral infection.

Abstract Background Currently, tap water consumption is not highly preferred in Egypt and around the world. People prefer to consume bottled water because they believe that it is much safer and tastes better than tap water. Unfortunately, this preference can create an economic burden for many people, especially in developing countries. Clay pots can be used to provide cool, alkaline drinking water because of their porous micro-texture, which traps pollutants. This study aimed to investigate the use of clay pots to store tap water and its impact on the requirements for drinking water quality. This is done with the intent to decrease the need for bottled water as a means of offering a more sustainable and economical option. Methods In this study, the efficiency of clay pots as sustainable storage containers for drinking water was tested by measuring physicochemical parameters (pH, TDS, EC, turbidity, DO, ammonia, chloride, total hardness, Ca hardness, Mg hardness, chlorine, Zn, and CaCO3) and biological parameters (TPC and Legionella). Results After 7 days of storage, the quality of the water stored in clay pots met the standards set by the Egyptian law with a significant difference (p

Abstract Natural-based materials represent green choices for biomedical applications. In this study, resin pulp capping restoration enclosing strengthening silica and bioactive portlandite nanofillers were prepared from industrial wastes. Silica nanoparticles were isolated from rice husk by heat treatment, followed by dissolution/precipitation treatment. Portlandite nanoparticles were prepared by calcination of carbonated lime waste followed by ultrasonic treatment. Both were characterized using x-ray diffraction, energy dispersive x-ray, and transmission electron microscopy. For preparing pulp capping restoration, silica (after silanization) and/or portlandite nanoparticles were mixed with 40/60 weight ratio of bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate. Groups A, B, and C enclosing 50 wt.% silica, 25 wt.% silica + 25 wt.% portlandite, and 50 wt.% portlandite, respectively, were prepared. All groups underwent microhardness, compressive strength, calcium release, pH, and apatite forming ability inspection in comparison to mineral trioxide aggregate (MTA) positive control. In comparison to MTA, all experimental groups showed significantly higher compressive strength, group B showed comparable microhardness, and group C showed significantly higher calcium release. Groups B and C showed prominent hydroxyapatite formation. Thus, the preparation of economic, silica-fortified, bioactive pulp capping material from under-utilized agricultural residues (rice husk) and zero-value industrial waste (carbonated lime from sugar industry) could be achieved.

Abstract In the modern era, with the rapid growth of various industries, the issues of energy crisis and environmental pollution have garnered increasing attention. One significant source of industrial pollution is printing and dyeing wastewater. This wastewater often contains dyes that have aromatic structures and azo groups, such as Methyl orange (MO), which are both toxic and difficult to degrade. If these dyes are released into the wastewater stream without any treatment, they can have adverse effects on ecological balance and human health. Therefore, it is crucial to identify suitable treatment strategies to efficiently remove dyes from wastewater systems before discharge. In this study, the Methyl orange (MO) azo dye has been removed from dyes-contaminated wastewater, for the first time, using a novel amino-ethyl carboxymethyl cellulose crosslinked ampholyte hydrogel (AECMC). Different characterization methods, including FTIR, TGA, and DSC were used to characterize the generated AECMC compounds. The water absorption and cationic exchange capacities were assessed. Factors affecting the MO anions adsorption including MO concentration, adsorption pH, temperature, time, adsorbent dose, and agitation speed have been investigated. Moreover, the kinetics of the adsorption process was assessed by the use of three models: pseudo-first-order, Pseudo-second-order, and Elovich. Moreover, the mechanism of the adsorption process was monitored using the Intraparticle diffusion and Boyd models. Additionally, the adsorption isotherm was examined using established models such as Langmuir, Freundlich, and Temkin isotherms. The thermodynamic characteristics of the MO adsorption process have been investigated at various adsorption temperatures using the Van't Hoff model. The results obtained from the study indicate that the process of MO adsorption adhered to the Pseudo-second-order kinetic model, the Langmuir isotherm model was found to be applicable, and spontaneous and exhibited an endothermic character. In conclusion, the developed novel amino-ethyl carboxymethyl cellulose crosslinked ampholyte hydrogels (AECMC) have successive in the removal of the MO anionic dye from contaminated wastewater.

Abstract Background Addressing microbial resistance urgently calls for alternative treatment options. This study investigates the impact of a bimetallic formulation containing colistin, silver, and copper oxide on a pandrug-resistant, highly virulent Pseudomonas aeruginosa (P. aeruginosa) isolate from a cancer patient at the National Cancer Institute, Cairo University, Egypt. Methods Silver nanoparticles (Ag NPs), copper oxide nanoparticles (CuO NPs), and bimetallic silver-copper oxide nanoparticles (Ag-CuO NPs) were synthesized using gamma rays, combined with colistin (Col), and characterized by various analytical methods. The antimicrobial activity of Col-Ag NPs, Col-CuO NPs, and bimetallic Col-Ag-CuO NPs against P. aeruginosa was evaluated using the agar well diffusion method, and their minimum inhibitory concentration (MIC) was determined using broth microdilution. Virulence factors such as pyocyanin production, swarming motility, and biofilm formation were assessed before and after treatment with bimetallic Col-Ag-CuO NPs. The in vivo efficacy was evaluated using the Galleria mellonella model, and antibacterial mechanism were examined through membrane leakage assay. Results The optimal synthesis of Ag NPs occurred at a gamma ray dose of 15.0 kGy, with the highest optical density (OD) of 2.4 at 375 nm. Similarly, CuO NPs had an optimal dose of 15.0 kGy, with an OD of 1.5 at 330 nm. Bimetallic Ag-CuO NPs were most potent at 15.0 kGy, yielding an OD of 1.9 at 425 nm. The MIC of colistin was significantly reduced when combined with nanoparticles: 8 µg/mL for colistin alone, 0.046 µg/mL for Col-Ag NPs, and 0.0117 µg/mL for Col-Ag-CuO NPs. Bimetallic Col-Ag-CuO NPs reduced the MIC four-fold compared to Col-Ag NPs. Increasing the sub-inhibitory concentration of bimetallic nanoparticles from 0.29 × 10-2 to 0.58 × 10-2 µg/mL reduced P. aeruginosa swarming by 32–64% and twitching motility by 34–97%. At these concentrations, pyocyanin production decreased by 39–58%, and biofilm formation was inhibited by 33–48%. The nanoparticles were non-toxic to Galleria mellonella, showing 100% survival by day 3, similar to the saline-treated group. Conclusions The synthesis of bimetallic Ag-CuO NPs conjugated with colistin presents a promising alternative treatment for combating the challenging P. aeruginosa pathogen in hospital settings. Further research is needed to explore and elucidate the mechanisms underlying the inhibitory effects of colistin-bimetallic Ag-CuO NPs on microbial persistence and dissemination.

Abstract Background While tuberculosis (TB) remains a significant global health threat, data on mortality in critically ill TB patients and those with drug-resistant TB (DR-TB) is limited. This study explores hematological profiles of critically ill TB patients and those with DR-TB, investigating associations with in-hospital and short-term mortality. Methods A longitudinal study of 269 patients with confirmed TB evaluated baseline blood cell counts and indices from medical records. We calculated in-hospital mortality and short-term prognosis, followed by analysis to identify predictors of mortality using hematological parameters. Results One-third of TB patients were critically ill (35.32%) and required intensive care unit (ICU) admission, while 14.5% had DR-TB, more common in females and smokers. Critically ill patients were older and tended to be non-smokers. DR-TB patients exhibited elevated lymphocyte and monocyte counts but lower neutrophil count and blood indices. Critically ill DS-TB patients had lower hemoglobin (Hb) and platelet (PLT) but higher total leucocytes count (TLC) and mean platelet volume (MPV). In-hospital mortality rate was 29.37%, significantly higher in critically ill DS-TB patients (74.74%). In-hospital mortality was 14-fold higher in critically ill DS-TB patients, 11-fold higher in stable DR-TB patients, and 6-fold higher in patients with comorbidities. Decreased Hb, monocyte level, and neutrophil to lymphocyte ratio (NLR) were significantly associated with in-hospital mortality. Predictors of short-term mortality included critical illness and comorbidities. However, the effect of DR-TB on short-term mortality disappeared. Decreasing Hb and TLC, especially neutrophils were significantly linked to short-term mortality. The utility of Hb in discriminating in-hospital and short-term mortality was very good, with AUC values of 78% and 79%, respectively. Cutoff values of less than 10 mg/dL and 9.75 mg/dL showed sensitivity ranging from 71 to 80% and specificity ranging from 75 to 80%, respectively. Conclusion This study provides valuable insights into patients with DR-TB and DS-TB with critically illness. We observed elevated lymphocyte and monocyte counts in DR-TB patients, as well as significant alterations in blood indices in critically ill patients. Importantly, the in-hospital mortality was notably higher in critically ill DS-TB patients, highlighting the importance of early recognition and aggressive management in this subgroup. Specifically, certain blood parameters such as hemoglobin, monocytes, neutrophils, and the NLR were associated with an increased risk of both in-hospital and short-term mortality. Furthermore, our findings underscore the prognostic significance of hematological parameters, particularly in resource-limited settings.

Abstract Background Apical surgery with standard retrograde maneuvers may be challenging in certain cases. Simplifying apical surgery to reduce operating time and streamline retrograde manipulation is an emerging need in clinical endodontics. Aim of the study The aim of the study was to compare the bacterial sealing ability of a calcium silicate-based sealer with the single cone technique combined with root end resection only, and calcium silicate-based sealer as a retrograde filling versus MTA retrofilling, and to analyze bacterial viability using confocal laser scanning microscope (CLSM). Materials and methods In this in vitro experimental study, 50 extracted human maxillary incisor teeth were instrumented and randomly divided into five groups: three experimental groups, a positive control group, and a negative control group (n = 10/group). In the experimental groups, the roots were obturated using the single cone technique (SCT) and a calcium silicate-based sealer. In group 1, the roots were resected 3 mm from the apex with no further retrograde preparation or filling. In groups 2 and 3, the roots were resected, retroprepared, and retrofilled with either a calcium silicate-based sealer or MTA, respectively. Group 4 (positive control) was filled with a single gutta-percha cone without any sealer. In group 5 (negative control), the canals were left empty, and the roots were sealed with wax and nail varnish. A bacterial leakage model using Enterococcus faecalis was employed to assess the sealing ability over a 30-day period, checking for turbidity and analyzing colony forming units (CFUs) per milliliter. Five specimens from each group were examined using CLSM for bacterial viability. Data for the bacterial sealing ability were statistically analyzed using chi-squared and Kruskal-Wallis tests. Results The three experimental groups did not show significant differences in terms of bacterial leakage, or bacterial counts (CFUs) (P > 0.05). However, significant differences were observed when comparing the experimental groups to the positive control group. Notably, the calcium silicate-based sealer, when used as a retrofilling, yielded the best sealing ability. CLSM imaging revealed viable bacterial penetration in all the positive control group specimens while for the experimental groups, dead bacteria was the prominent feature seen. Conclusion Within the limitations of this study, it could be concluded that the bacterial sealing ability of calcium silicate-based sealer with the single cone technique combined with root end resection only and calcium silicate-based sealer as a retrograde filling were comparable with MTA retrofilling during endodontic surgical procedures.

Abstract Two rapid, precise, and sensitive stability-indicating high performance chromatographic methods for the measurement of Teriflunomide in its degradation products’ existence were developed. These were RP-HPLC and HPTLC using UV detector. HPLC separation was accomplished utilizing Thermo BDS hypercil C18 column (250 × 4.6 mm, 5 μm) and acetonitrile: 0.03 M potassium dihydrogen phosphate: triethylamine (50:50:0.1%, by volume) as mobile phase at flow rate of 1mL/min. The separated peaks were detected at 250.0 nm. The densitometric approach was conducted utilizing HPTLC 60 F254 silica gel plates, and a developing system of benzene: ethanol: acetic acid (7.5:1:0.25, by volume) and detection was done at 250.0 nm. The developed approaches were evaluated regarding the International Conference on Harmonization (ICH) instructions. The calibration curves of both techniques were constructed with linearity ranges of (5-100) µg/mL and (2–10) µg /band, for HPLC and densitometric determination, consecutively. Teriflunomide was exposed to base and acid hydrolysis, oxidation using H2O2 and finally, thermal degradation as stated in ICH guidelines. The degradation product structures’ elucidation was achieved through LC-MS.

Abstract Background The DNA-dependent protein kinase (DNA-PK) complex comprises a catalytic (PRKDC) and two requisite DNA-binding (Ku70/Ku80) subunits. The role of the complex in repairing double-stranded DNA breaks (DSBs) is established, but its role in inflammation, as a complex or individual subunits, remains elusive. While only ~ 1% of PRKDC is necessary for DNA repair, we reported that partial inhibition blocks asthma in mice without causing SCID. Methods We investigated the central role of PRKDC in inflammation and its potential association with DNA repair. We also elucidated the relationship between inflammatory cytokines (e.g., TNF-α) and PRKDC by analyzing its connections to inflammatory kinases. Human cell lines, primary human endothelial cells, and mouse fibroblasts were used to conduct the in vitro studies. For animal studies, LPS- and oxazolone-induced mouse models of acute lung injury (ALI) and delayed-type hypersensitivity (DHT) were used. Wild-type, PRKDC+/−, or Ku70+/− mice used in this study. Results A ~ 50% reduction in PRKDC markedly blocked TNF-α-induced expression of inflammatory factors (e.g., ICAM-1/VCAM-1). PRKDC regulates Th1-mediated inflammation, such as DHT and ALI, and its role is highly sensitive to inhibition achieved by gene heterozygosity or pharmacologically. In endothelial or epithelial cells, TNF-α promoted rapid PRKDC phosphorylation in a fashion resembling that induced by, but independent of, DSBs. Ku70 heterozygosity exerted little to no effect on ALI in mice, and whatever effect it had was associated with a specific increase in MCP-1 in the lungs and systemically. While Ku70 knockout blocked VP-16-induced PRKDC phosphorylation, it did not prevent TNF-α − induced phosphorylation of the kinase, suggesting Ku70 dispensability. Immunoprecipitation studies revealed that PRKDC transiently interacts with p38MAPK. Inhibition of p38MAPK blocked TNF-α-induced PRKDC phosphorylation. Direct phosphorylation of PRKDC by p38MAPK was demonstrated using a cell-free system. Conclusions This study presents compelling evidence that PRKDC functions independently of the DNA-PK complex, emphasizing its central role in Th1-mediated inflammation. The distinct functionality of PRKDC as an individual enzyme, its remarkable sensitivity to inhibition, and its phosphorylation by p38MAPK offer promising therapeutic opportunities to mitigate inflammation while sparing DNA repair processes. These findings expand our understanding of PRKDC biology and open new avenues for targeted anti-inflammatory interventions.

Abstract Background Vortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration. Methods The experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue. Results Interestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group. Conclusion Thus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

Abstract Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Abstract Background Spondyloarthritis is a well-known chronic inflammatory disorder; despite recent advances, its genetic basis remains poorly understood. Recently, long non-coding RNA (H19) was identified to be associated with various human cancers and studied in some autoimmune diseases. Musculoskeletal ultrasound has been shown to have good sensitivity and specificity in detecting enthesitis. The Belgrade Ultrasound Enthesitis Score (BUSES) has recently been proposed as a comprehensive ultrasound enthesitis scoring system for differentiating between individuals with enthesitis associated with spondyloarthritis and those without spondyloarthritis. Aim The current work aimed to study the role of long non-coding RNA (H19) as a potential biomarker in axial spondyloarthritis and its relationship with the different disease parameters (clinical and laboratory), disease activity, and functional status as well as the relation between long non-coding RNA (H19) and articular manifestations using ultrasonographic assessment of enthesitis. Results Long non-coding RNA (H19) expression was statistically higher in axial spondyloarthritis patients than controls; there are no statistically significant correlations between long non-coding RNA (H19) relative expression and any of the listed parameters (ESR, CRP, ASDAS-CRP, BASDAI, BASFI, BASMI, BUSES, SPARCC index, mSASSS). As regards the Spearman correlation of Belgrade Ultrasound Enthesitis Score, it showed a statistically significant positive correlation with ASDAS-CRP, BASDAI, and BASMI (p value: 0.002, 0.02, and 0.046, respectively). Conclusion Both long non-coding RNA (H19) and Belgrade Ultrasound Enthesitis Score have good discriminative ability between patients with axial spondyloarthritis and normal population; this suggests a possible role in early diagnosis for patients with axial spondyloarthritis who do not fulfill ASAS classification criteria. Their role to monitor the disease activity still needs further studies to be established. Musculoskeletal ultrasound is much more accurate in the assessment of enthesis than clinical examination. Further studies are needed to study the correlation between ultrasonographic entheseal scores and activity markers either clinically or laboratory.

Alzheimer's disease (AZD) has emerged as a catastrophic world health concern in tandem with the phenomenon of worldwide aging. The purpose of this study was to examine the curative effects of bone marrow stem cell-derived exosomes (BMSCDEXO) to overcome sodium azide (NaN3)-induced AZD in a rat model. The animals were classified into two main groups: the first group (8 rats) was kept as a control; the second group (24 rats) received intraperitoneal treatment with NaN3 (12.5 mg/kg for the first five days and 10 mg/kg for the next nine days). Morris Water Maze (MWM) and Y maze tests were carried out to evaluate the Alzheimer's disease induction. Then, the animals were classified into three equal subgroups as follows: the AZD group, the AZD+ donepezil (DNP) group, in which animals orally received 5 mg/kg of DNP daily for four weeks, and the AZD+ BMSCDEXO group, in which animals were injected with a single dose of BMSCDEXO (intravenously, 100 µL). The results indicated that BMSCDEXO attenuated the behavioral signs in MWM and Y maze in the AZD group, which correlated with improvements in amyloid-beta precursor protein (AβPP), amyloid beta (Aβ) accumulation, and tau protein phosphorylation through mechanisms that involved the prevention of stress-related biochemical redox. Furthermore, it enhances the levels of antioxidant activities, mitochondrial functions, and cytochrome c oxidase (COX-IV). Finally, we conclude that BMSCDEXO modulates cognitive impairment through inhibition of amyloidogenesis and mitoprotection in NaN3-induced AZD in comparison with the therapeutic drug donepezil.