Search

Abstract Conditioned media (CM) is derived from mesenchymal stem cells (MSC) culture and contains biologically active components. CM is easy to handle and reduces inflammation while repairing injured joints. Combination therapy of the CM with cross-linked hyaluronic acid (HA) could ameliorate the beneficial effect of HA in treating degenerative changes of articulating surfaces associated with arthritic rats’ temporomandibular joints (TMJs). This study aimed to evaluate the therapeutic potential of HA hydrogel combined with bone marrow stem cells-conditioned medium (BMSCs-CM) on the articulating surfaces of TMJs associated with complete Freund’s adjuvant (CFA)-induced arthritis. Fifty female Sprague-Dawley rats were divided randomly into five equal groups. Rats of group I served as the negative controls and received intra-articular (IA) injections of 50 µl saline solution, whereas rats of group II were subjected to twice IA injections of 50 µg CFA in 50 µl; on day 1 of the experiment to induce persistent inflammation and on day 14 to induce arthritis. Rats of group III and IV were handled as group II and instead, they received an IA injection of 50 µl HA hydrogel and 50 µl of BMSCs-CM, respectively. Rats of group V were given combined IA injections of 50 µl HA hydrogel and BMSCs-CM. All rats were euthanized after the 4th week of inducing arthritis. The joints were processed for sectioning and histological staining using hematoxylin and eosin, Masson’s trichrome and toluidine blue special staining, and immunohistochemical staining for nuclear factor-kappa B (NF-κB). SPSS software was used to analyze the data and one-way analysis of variance followed by post-hoc Tukey statistical tests were used to test the statistical significance at 0.05 for alpha and 0.2 for beta. In the pooled BMSC-CM, 197.14 pg/ml of platelet-derived growth factor and 112.22 pg/ml of interleukin-10 were detected. Compared to TMJs of groups III and IV, TMJs of group V showed significant improvements (P = 0.001) in all parameters tested as the disc thickness was decreased (331.79 ± 0.73), the fibrocartilaginous layer was broadened (0.96 ± 0.04), and the amount of the trabecular bone was distinctive (19.35 ± 1.07). The mean values for the collagen amount were increased (12.29 ± 1.38) whereas the mean values for the NF-κB expression were decreased (0.62 ± 0.15). Combination therapy of HA hydrogel and BMSCs-CM is better than using HA hydrogel or BMSCs-CM, separately to repair degenerative changes in rats’ TMJs associated with CFA-induced arthritis.

Abstract Background Hepatic encephalopathy (HE) is a pathological state characterized by the abrupt or chronic failure of the liver. This study intends to conduct a comparative analysis of potential benefits of icariin (ICA), a primary component of flavonoids found in the Chinese medicinal plant Epimedium, with silymarin (SLY) as a hepatic and brain support agent in a model of HE rats, focusing on assessment of the behavioral and biochemical effects. Thioacetamide (TAA) was given intraperitoneally to rats at a dosage of 200 mg/kg on three separate days to induce HE. Oral gavage of silymarin or ICA (100 mg/kg) was given daily for 14 days following HE induction. All rats underwent behavioral assessments (open field and Y maze). Estimates were made for hepatic functions and brain cortex oxidative stress indicators as well as cytochrome c and caspase-3. Results The findings demonstrated that the administration of ICA to rodents with HE induced by TAA led to a recovery of hepatic enzymes activities and behavioral adjustments as shown by an improvement in locomotor and memory functions. Furthermore, Icariin demonstrated a reduction in cortex biochemical indicators through the amelioration of hyperammonemia and enhancement of antioxidant status. This was achieved by reducing malondialdehyde, calcium, nitric oxide contents and downregulating lactate dehydrogenase activities. In addition, ICA maintains alteration of glutamate and glutamine contents. Conclusion ICA suggested to possess the capacity to serve as a beneficial hepatotherapeutic and neurotherapeutic adjunct in brain disorders associated with hyperammonemia–glutamate-mediated excitotoxicity.

Background and Study Aim. Premenstrual syndrome (PMS) affects a significant proportion of women, impacting their daily lives and well-being. The association between physical activity levels, the prevalence of premenstrual syndrome (PMS), and the severity of PMS remains debatable. Therefore, this study aimed to identify physical activity levels among a cohort of Egyptian females with PMS. Material and Methods. This study included one hundred females with PMS. Physical activity levels, anaerobic power, aerobic capacity, BMI, and dysmenorrhea were investigated. PMS severity was assessed using the Premenstrual Syndrome Scale (PMSS), and the females' physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ). The 1-mile submaximal test and the Running-Based Anaerobic Sprint Test (RAST) were used to assess aerobic capacity and anaerobic power, respectively. Results. The findings revealed a significant association between PMS severity and physical activity (p < 0.05). There was no significant difference in aerobic capacity among those with mild, moderate, and severe PMS (p > 0.05). There was no significant association between PMS severity and marital status (p > 0.05), whereas there was a significant association with dysmenorrhea (p < 0.05), especially among moderate and severe PMS sufferers. Females with severe PMS had a significantly higher BMI than those with mild PMS (p < 0.05) and those with moderate PMS (p < 0.05). Mild and moderate PMS females showed no significant difference in BMI (p > 0.05). Conclusions. It can be concluded that physical activity levels and BMI may affect PMS. Therefore, being physically active and maintaining a normal-range BMI might reduce PMS severity.

Abstract Background Glass ionomer cements with extended setting time and inferior mechanical properties present significant challenges for dentists in clinical practice. Thus, various alterations aimed to enhance their properties. Aim of the study To study the effect of adding TiO2 and SiO2 nanoparticles on properties of conventional glass ionomer cement. Methods 2.5 wt% TiO2 and 2.5 wt% SiO2 were added to the glass ionomer cement (GC Gold Label Luting & Lining Cement, Japan). Microhardness, compressive strength, setting time and color changes were evaluated using Vickers hardness tester, Universal testing machine, Gillmore needle apparatus and spectrophotometer, respectively. Results Data were analyzed using SPSS 18. Mean, SD, and confidence intervals were reported. Normality was checked using Kolmogorov–Smirnov test. The experimental group revealed a higher hardness value than the control group. Meanwhile, Compressive strength results revealed a higher value of the control group than experimental group. Setting time was longer for the experimental group, in the meantime no perceptible color change for the experimental group was recorded. Conclusions Adding 2.5 wt% TiO2 and 2.5 wt% SiO2 to conventional glass ionomer had a positive effect on microhardness without affecting the perceptible color.

Abstract Background and objectives Platelet indices are widely available and relatively cheap platelet parameters. The critical objective of this study is to assess the reliability of platelet indices as biomarkers for diagnosis and prognosis in adult thrombocytopenic patients. Methods A retrospective case–control study, including 81 immune thrombocytopenia (ITP) cases, 50 aplastic anemia (AA) cases, and 150 participants as a control group. This study included patients admitted from 2016 to 2021 to the Clinical Hematology Unit, Department of Internal Medicine, University Hospital. The collected data included sociodemographic information, clinical data, laboratory data, and an assessment of the therapeutic response in the studied groups. Results For the diagnosis of adult thrombocytopenic patients, platelet distribution width (PDW) showed the best diagnostic accuracy (85% for ITP and 91.9% for AA) at cutoff points of 14.9% and 17.2%, respectively. This was followed by mean platelet volume (MPV) with diagnostic accuracies of 77% for ITP and 89.3% for AA at a cutoff point of 9.4 fl. Platelet large cell ratio (PLCR) demonstrated insignificant accuracy in diagnosing either ITP or AA. Conclusion Platelet indices can play a crucial influence in the diagnosis, not the prognosis, of adult thrombocytopenia. Trial registration NCT05116033. https://classic.clinicaltrials.gov/ct2/show/NCT05116033

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.

Background: Hepatocellular carcinoma is the most prevalent type of primary liver cancer and remains the foremost cause of cancer-related deaths globally. Dill (Anethum graveolens) seeds, rich in phytoconstituents, is renowned for their pharmacological properties. Objectives: This study performed an in vitro evaluation to assess the cytotoxic effects of dill seed extract (DS-EE) on the Huh-7 hepatocellular carcinoma cell line. Moreover, the study investigated its effects on cell viability, cellular morphology, oxidative damage, levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and the expression of apoptosis-related genes in Huh-7 cells. Methods: Huh-7 cells were treated with DS-EE at concentrations ranging from 5 to 100 μg/mL for a duration of 24 h. Results: The cytotoxicity findings showed that DS-EE decreased cell viability and suppressed the growth of Huh-7 cells in a dose-dependent way, with an IC50 value of 60 μg/mL. Exposure to DS-EE extract for 24 h resulted in a significant elevation in lipid peroxidation (LPO) and a notable decrease in glutathione (GSH) content compared to the control. Furthermore, DS-EE significantly increased ROS production while notably decreasing the MMP level in Huh-7 cells. Moreover, DS-EE induces cell apoptosis by upregulating the expression of proapoptotic genes (p53, caspase-3, caspase-9, and Bax) and downregulating the expression of the antiapoptotic gene, Bcl-2. Conclusion: DS-EE exhibited a notable cytotoxic effect on Huh-7 cells by increasing oxidative damage and subsequently modulating the expression of apoptosis-related genes. The results of this study highlight the anticancer effectiveness of DS-EE, indicating its potential as a promising agent for hepatocellular carcinoma management.

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.

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.

Abstract Inflammation is a part of the body’s intricate biological reaction to noxious stimuli and defensive reactions. So, the aim of this investigation was to study the anti-inflammatory activity of exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats. A halophilic bacterial strain was isolated from marine sediments in the Red Sea in Egypt. The isolate has been visually and physiologically recognized, as well as by analyzing its 16S rRNA gene, which confirms Kocuria sp. clone Asker4. This particular isolate can be referenced using the accession number OL798051.1. EPSSM was subjected to purification and fractionation by a DEAE-cellulose column. Preliminary chemical analysis of EPSSM indicated that the monosaccharides were fructose, glucuronic acid, and xylose, with 2.0, 0.5, and 1.0, respectively. The antioxidant potential of EPSSM was investigated, and it was discovered that the level of activity increased independently of the concentrations, reaching a maximum threshold of 94.13% at 100 µg/mL of EPSSM for 120 min. Also, EPSSM at 50 mg/kg orally produced a significant anti-inflammatory effect on the carrageenan model at 2, 3, and 4 intervals. The EPSSM intervention resulted in reductions in the levels of catalase and superoxide dismutase enzymes, as well as a decrease in glutathione. Furthermore, the levels of nitric oxide, lipid peroxidation, and reactive oxygen species resulting from carrageenan-induced edema showed a significant reduction subsequent to the administration of EPSSM. Moreover, the findings indicated that the protein expression levels of cyclooxygenase-2 and interleukin-6 were reduced following treatment with EPSSM, resulting in a reduction of paw edema.

Abstract Metabolic syndrome (MetS) is defined as a cluster of glucose intolerance, hypertension, dyslipidemia, and central obesity with insulin resistance. The role of gut microbiota in metabolic disorders is increasingly considered. To investigate the effects of probiotic supplements and hypocaloric high fiber regimen on MetS in obese Egyptian women. A longitudinal follow-up intervention study included 58 obese Egyptian women, with a mean age of 41.62 ± 10.70 years. They were grouped according to the criteria of MetS into 2 groups; 23 obese women with MetS and 35 ones without MetS. They followed a hypocaloric high fiber regimen weight loss program, light physical exercise, and received a probiotic supplement daily for 3 months. For each participating woman, blood pressure, anthropometric measurements, basal metabolic rate (BMR), dietary recalls, laboratory investigations, and microbiota analysis were acquired before and after 3 months of follow-up. After intervention by the probiotic and hypocaloric high fiber regimen and light exercise, reduction ranged from numerical to significant difference in the anthropometric parameters, blood pressure, and BMR was reported. All the biochemical parameters characterized by MetS decreased significantly at p ≤ 0.05–0.01. Before the intervention, results revealed abundant of Bacteroidetes bacteria over Firmicutes with a low Firmicutes/Bacteroidetes ratio. After the intervention, Log Lactobacillus, Log Bifidobacteria, and Log Bacteroidetes increased significantly in both groups, while Log Firmicutes and the Firmicutes/Bacteroidetes Ratio revealed a significant decrease. In conclusion, this study’s results highlight a positive trend of probiotics supplementation with hypocaloric high-fiber diets in amelioration of the criteria of the Mets in obese Egyptian women.

Introduction: Despite the established role of peripheral adenosine receptors in sepsis-induced organ dysfunction, little or no data is available on the interaction of central adenosine receptors with sepsis. The current study tested the hypothesis that central adenosine A3 receptors (A3ARs) modulate the cardiovascular aberrations and neuroinflammation triggered by sepsis and their counteraction by the cholinergic antiinflammatory pathway.Methods: Sepsis was induced by cecal ligation and puncture (CLP) in rats pre-instrumented with femoral and intracisternal (i.c.) catheters for hemodynamic monitoring and central drug administration, respectively.Results: The CLP-induced hypotension, reduction in overall heart rate variability (HRV) and sympathovagal imbalance towards parasympathetic predominance were abolished by i.v. nicotine (100 μg/kg) or i.c. VUF5574 (A3AR antagonist, 2 µg/rat). In addition, the selective A3AR agonist, 3-iodobenzyl-5′-N-methylcarboxamidoadenosine IB-MECA, 4 µg/rat, i.c.) exaggerated the hypotension and cardiac autonomic dysfunction induced by sepsis and opposed the favorable nicotine actions against these septic manifestations. Immunohistochemically, IB-MECA abolished the nicotine-mediated downregulation of NFκB and NOX2 expression in rostral ventrolateral medullary areas (RVLM) of brainstem of septic rats. The inhibitory actions of IB-MECA on nicotine responses disappeared after i.c. administration of PD98059 (MAPK-ERK inhibitor), SP600125 (MAPK-JNK inhibitor) or wortmannin (PI3K inhibitor). Moreover, infliximab (TNFα inhibitor) eliminated the IB-MECA-induced rises in RVLM-NFκB expression and falls in HRV, but not blood pressure.Conclusion: Central PI3K/MAPKs pathway mediates the A3AR counteraction of cholinergic defenses against cardiovascular and neuroinflammatory aberrations in sepsis.

Abstract Background Caspase recruitment domain family, member 11 (CARD11) is an important protein which plays a fundamental role in the activation of NF-κβ pathway in lymphocytes. CARD11 deficiency can be inherited in either autosomal dominant or autosomal recessive forms and present with different phenotypes including combined immunodeficiency, atopic dermatitis, and other variable manifestations. The present report describes clinical phenotypes and immunological defects of two unrelated patients with missense homozygous variants in CARD11 presenting with combined immunodeficiency (CID) and atopic skin disease resembling that reported in dominant negative CARD11 deficiency. The patients underwent next generation sequencing, immunophenotyping of T and B subsets by flow cytometry, T cell stimulation, and evaluation of CARD11 expression. Results Both patients had features suggesting CID including repeated pneumoniae with ICU admissions, chronic diarrhea, and itchy atopic skin disease. Patient-1 has homozygous missense variant in the C terminal domain (c.2839G > A, p.Glu947Lys), and patient-2 has homozygous variant in the inhibitory domain (c.1073C > G, p.Pro568Arg). Both have profound defects in Tregs with normal recent thymic emigrants, memory, and naïve CD4+ T cells. However, in response to stimulation, T cells failed to upregulate the expression of CD25. CARD11 expression by flow cytometry was decreased rather than abolished as previously described in patients with autosomal recessive CARD11 deficiency. B cells showed marked deficiency of switched memory and increase in transitional B cells. Conclusion Missense variants causing CARD11 deficiency may affect the protein function rather than the expression and can result in a phenotype combining the atopic skin disease and the features of CID.

Abstract Background Chronic inflammation plays a crucial role in developing various cardiovascular and metabolic disorders. Obstructive sleep apnea (OSA) is a unique condition characterized by the coexistence of cardiovascular and metabolic disturbances, where chronic inflammation may exacerbate disease progression and severity. This study investigated how different hematological inflammatory cells and mediators can serve as predictive indicators of severe OSA. Methods In a retrospective cohort study, 150 patients suspected of having obstructive sleep apnea (OSA) underwent polysomnography (PSG) to confirm the diagnosis. Based on their apnea-hypopnea index (AHI), the patients were categorized into three groups: mild, moderate, and severe OSA. Blood samples were collected for the assessment of inflammatory blood cells and mediators at the time of diagnosis. Results Among the 150 patients studied, 90 were diagnosed with OSA, and 43 had severe OSA, representing a prevalence rate of 47.7%. Patients with severe OSA were notably older and more likely to have diabetes mellitus and hypertension. After adjusting for age and sex, each one-unit increase in Systemic Inflammatory Response Index (SIRI), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels was associated with a doubling in the likelihood of having moderate and severe OSA (p < 0.05 for all). However, hypertension was linked to a 16-fold increase in the likelihood of moderate and severe OSA (p = 0.01). Conclusion Our research indicates that comorbidity and inflammatory cells and markers (SIRI, CRP, and ESR) are significantly related to the severity of OSA.

In wireless networks, there are two prominent challenges. The first challenge is ensuring that users have opportunities to access channels and request new services. The second challenge is maintaining connections for data flows. These challenges are compounded by the occurrence of channel failures, which often occur due to characteristics of radio transmission such as signal attenuation, signal blockage or device and power outages. Channel failures can significantly impact the effectiveness of both the primary and secondary networks. Therefore, it becomes crucial to prioritize retainability which denotes the need to maintain uninterrupted user connections even during network disruptions. This paper proposes an analytical model that evaluates performance of cognitive radio networks in the context of random channel failure rates. Additionally, the dynamic channel reservation (DCR) scheme is introduced. It can be integrated into dynamic spectrum access (DSA) strategies. This integration aims to give priority to existing services over requests from users to provide cognitive networks with more opportunities to allocate idle channels or maintain their current services. Moreover, the cost functions for both the primary user (PU) and the secondary user (SU) are calculated. This calculation considers the failure rate specifically in either reserved channels (RCN) or non-reserved channels (N-RCN) to meet different performance requirements. The results show a decrease in the SUs cost function, which guarantees that the quality of service (QoS) requirements for the PU are fulfilled. Importantly, this reduction in SU cost leads to an enhancement in SU channel availability or throughput when compared to previous models.

Abstract The present study introduces a new and straightforward method for the amination of Chitosan. This method involves coupling Chitosan (CS) with 2-chloroethylamine (ENH2) in a single step to produce an amino-ethyl Chitosan derivatives with increased amine group content (CS-ENH2) using click chemistry. The resulting derivatives were then crosslinked using Glutaraldehyde to form amino-ethyl Chitosan Schiff bases. The novel amino-ethyl Chitosan Schiff bases were subsequently utilized as adsorbents for the removal of Methyl Orange (MO) dye from aqueous solutions using a batch technique, and the performance of the produced Schiff bases was compared with that of the native Chitosan Schiff base. The CS-ENH2 adsorbents show improved adsorption capacity up to 300% of the native Chitosan Schiff base with almost double removal rate. The adsorption temperature has a positive impact in general while almost 100% of MO removed at 60 °C using CS-ENH2 adsorbents compared with 66% of the native Chitosan Schiff base adsorbent. The adsorption pH shows a negative impact on the MO removal percent. That effect reduced sharply using the CS-ENH2 adsorbents with higher amination degree while the MO removal percent almost being constant over a wide range of pH; 2.0–7.0. The agitation speed has the same positive effect over all the adsorbents. However, the rate of MO removal percent decreased with increase the agitation speed up to 250 rpm. The experimental findings demonstrated that the highest percentage of MO dye removal was achieved under the conditions of pH 2.0, a temperature of 60 °C, agitation speed of 250 rpm, and adsorption duration of 90 min. These Schiff bases were subsequently characterized using advanced analytical techniques including Fourier Transform Infrared spectroscopy, Thermal analysis (TGA and DSC), and Scanning Electron Microscopy.

In the current study, the effects of enhancing semen quality, brain neurotransmitters, and antioxidant status in rabbits under heat stress with acacia gum, vitamin C, and lycopene as dietary supplements were estimated in vitro and in silico. A total of 40 males from New Zealand White rabbits aged 3 months were equally divided into four groups (n = 10). The first group was a control. The other three groups were the heat stress group (oral acacia gum, 100 mg/kg body weight), the ascorbic acid group (30 mg/kg body weight), and the lycopene group (50 mg/kg body weight). All semen showed physical characteristics in terms of increasing sperm motility, motility index, sperm normality, and live sperm as compared to the control group. On the other hand, sperm abnormalities, and dead sperm significantly (p

Chronic inflammatory bowel disorders (IBDs) are characterized by altered intestinal permeability, prompting inflammatory, oxidative stress, and immunological factors. Gut microbiota disorders impact brain function via the bidirectional gut–brain axis, influencing behavior through inflammatory cascades, oxidative stress, and neurotransmitter levels. This study highlights the potential effect of integrating lyophilized milk kefir alone and lyophilized milk kefir as solid carriers loaded with a self-nanoemulsifying self-nanosuspension (SNESNS) of licorice extract on an induced chronic IBD-like model in rats. Licorice-SNESNS was prepared by the homogenization of 30 mg of licorice extract in 1 g of the selected SNEDDS (30% Caraway oil, 60% Tween 20, and 10% propylene glycol (w/w)). Licorice-SNESNS was mixed with milk kefir and then freeze-dried. Dynamic TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Daily oral administration of lyophilized milk kefir (100 mg/kg) loaded with SNESNS (10 mg/kg Caraway oil and 1 mg/kg licorice) restored normal body weight and intestinal mucosa while significantly reducing submucosal inflammatory cell infiltration in induced rats. Importantly, this treatment demonstrated superior efficacy compared to lyophilized milk kefir alone by leading to a more significant alleviation of neurotransmitter levels and improved memory functions, thereby addressing gut–brain axis disorders. Additionally, it normalized fecal microbiome constituents, inflammatory cytokine levels, and oxidative stress in examined tissues and serum. Moreover, daily administration of kefir-loaded SNESNS normalized the disease activity index, alleviated histopathological changes induced by IBD induction, and partially restored the normal gut microbiota. These alterations are associated with improved cognitive functions, attributed to the maintenance of normal neurotransmitter levels and the alleviation of triggered inflammatory factors and oxidative stress levels.

Effects of the road, such as speed bumps, can significantly affect a car’s stability. This study focuses on how a quarter-car model is affected by a basic harmonic speed hump and how Cubic Negative Velocity Control (CNVC) is used to control the amplitude of disturbances. This study differs from earlier research in considering various control and force kinds that impact the system. The external forces in this context are a component of a non-linear dynamic system. Two-degree-of-freedom (2DOF) differential coupled equations describe the system’s equation. Numerous numerical experiments have been conducted, including proportional derivative (PD), negative derivative feedback (NDF), positive position feedback (PPF), linear negative velocity control (LNVC), and CNVC; the results show that when the hump is represented as a simple harmonic hump, CNVC has the best effect and can regulate vibrations more precisely than the other approaches on this system. Subsequently, the vibration value of the system was numerically analyzed both before and after the control was implemented. Using the frequency response equation and phase plane approaches in conjunction with the Runge–Kutta fourth order method (RK-4) in the context of resonance situation analysis, the stability of the numerical solution has been evaluated.

Asthma is a chronic disease affecting people of all ages. Asthma medications are associated with adverse effects restricting their long-term usage, demanding newer alternative therapies. This study aimed to investigate the anti-asthmatic properties of Ruta graveolens extract and its prepared nano-cubosomal dispersion (Ruta-ND). Firstly, the R. graveolens methanolic extract exhibited higher anti-inflammatory activity on Lipopolysaccharide (LPS)-activated BEAS-2B cells. To ensure best bioavailability and hence best cellular uptake, R. graveolens extract was loaded in nano-cubosomal dispersion (ND). Then, the anti-asthmatic effects of Ruta extract and ND were simultaneously evaluated in rats’ model with ovalbumin-induced allergic asthma. R. graveolens extract and Ruta-ND subsided asthma score and improved lung function by restoring FEV1/FVC ratio to the expected values in control rats. Also, it showed strong antioxidant and anti-inflammatory activities manifested by lowering levels of malondialdehyde (MDA), IL-4, IL-7, TGF-β, and Ig-E, and increasing levels of superoxide dismutase (SOD) and INF-γ in bronchoalveolar lavage fluid. Our research findings also indicate autophagy induction and apoptosis inhibition by Ruta extract and Ruta-ND. Finally, the HPLC MS/MS phytochemical profiling of R. graveolens extract evident production of various alkaloids, flavonoids, coumarins, and other phenolics with reported pharmacological properties corresponding to/emphasize our study findings. In conclusion, R. graveolens exhibited promise in managing Ova-induced allergic asthma and could be developed as an alternative anti-allergic asthma drug.

Abstract This study aims to prepare Ag-CuO nanoparticles and assess their efficiency in protecting the copper substrate. The prepared Ag-CuO nanoparticle was characterized using, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope/energy-dispersive X-ray (SEM/EDX), and transmission electron microscope (TEM). The anticorrosion performance of the epoxy coatings containing various weight percentages of Ag-CuO nanoparticles was evaluated in 3.5 wt% NaCl solution using potentiodynamic polarization (PDP), and electrochemical impedance spectroscopy (EIS) techniques. The results showed that corrosion potential shifted from − 0.211 V for uncoated copper to − 0.120 V for 5.0 wt% Ag-CuO/epoxy hybrid nanocomposite. Electrochemical measurements indicated that the coating 5.0 wt% coating exhibited excellent inhibiting properties with an efficiency of 99.9%. Wettability and mechanical properties were measured for both uncoated and coated copper substrates. The contact angle for 5.0 wt% coating is equal to 104° enhancing the hydrophobic character of the surface. The study clearly establishes that the hybrid composite has a significant potential for protecting the copper substrate.

Abstract Synucleinopathies are a group of neurodegenerative disorders characterized by pathologic aggregates of neural and glial α-synuclein (α-syn) in the form of Lewy bodies (LBs), Lewy neurites, and cytoplasmic inclusions in both neurons and glia. Two major classes of synucleinopathies are LB disease and multiple system atrophy. LB diseases include Parkinson’s disease (PD), PD with dementia, and dementia with LBs. All are increasing in prevalence. Effective diagnostics, disease-modifying therapies, and therapeutic monitoring are urgently needed. Diagnostics capable of differentiating LB diseases are based on signs and symptoms which might overlap. To date, no specific diagnostic test exists despite disease-specific pathologies. Diagnostics are aided by brain imaging and cerebrospinal fluid evaluations, but more accessible biomarkers remain in need. Mechanisms of α-syn evolution to pathologic oligomers and insoluble fibrils can provide one of a spectrum of biomarkers to link complex neural pathways to effective therapies. With these in mind, we review promising biomarkers linked to effective disease-modifying interventions.

Abstract Background The DNA in each cell in our body is constantly in danger of becoming damaged. Most DNA damage gets repaired straight away via many different proteins encoded by DNA—repair genes. MSH3 and MSH6 are pivotal DNA repair genes maintaining human genome integrity. Dysregulated expression of such genes has its implications resulting in developing of adverse reactions in cancer breast patients receiving taxanes. Cancer chemotherapy with some of taxane class of agents are associated with significant neurotoxicity, arthralgias and myalgias that may offset the therapeutic benefits of taxane use. Our aim is to identify gene expression pattern of MSH3 and MSH6 DNA mismatch repair genes in female breast cancer patients who develop adverse reactions to taxane-based therapy. One hundred and five patients with histologically proven breast cancer who received paclitaxel (PTX) as a single agent or combination therapy have been enrolled along with a group of 50 females with benign breast lesions serving as controls.Gene expression studies of mismatch repair genes (MMR) genes; MSH3 and MSH6; have been performed by real-time PCR. Patients were divided into groups according to the determined type/grade of PTX-based toxicity and fold changes of both genes were estimated. Results In the present work both MMR genes showed significantly lower expression in all the studied patients compared to benign cases as a control group. Toxicity findings were encountered in 75.2% of the studied patient cohort. The most common observed type of toxicity was peripheral neuropathy (PN), 58.1% of the studied patients. Both MSH3 and MSH6 genes were significantly down-regulated in the presence of high grade PN toxicity ≥ 2 (p = 0.034 and 0.01); diarrhea toxicity (p = 0.02 and 0.008); dyspnea (p = 0.01 and 0.016) respectively and bone pain (p = 0.024 for MSH6 only). Conclusion Dysregulated expression of MMR GENES [MSH3and MSH6] can be implicated in paclitaxel—induced toxicity experienced by some cancer breast patients.

Abstract The cholinergic pathway plays a crucial role in improving inflammatory end-organ damage. Given the interplay between cholinergic and adenosinergic neurotransmission, we tested the hypothesis that central adenosine A1 receptors (A1ARs) modulate the nicotine counteraction of cardiovascular and inflammatory insults induced by sepsis in rats. Sepsis was induced by cecal ligation and puncture (CLP) 24-h before cardiovascular measurements. Nicotine (25–100 µg/kg i.v.) dose-dependently reversed septic manifestations of hypotension and impaired heart rate variability (HRV) and cardiac sympathovagal balance. Like nicotine, intracisternal (i.c.) administration of N(6)-cyclopentyladenosine (CPA, A1AR agonist) to CLP rats increased indices of HRV and sympathovagal balance. Moreover, greater surges in these parameters were noted upon simultaneous nicotine/CPA administration. The favorable influences of nicotine on blood pressure and HRV in sepsis were diminished after central blockade of A1ARs by i.c. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). Molecular studies revealed that (i) septic rises in myocardial and brainstem nucleus of solitary tract (NTS) NFκB expression were abrogated by nicotine and largely reinstated after blockade of A1ARs, and (ii) A1AR expression in the same areas was reduced by DPCPX. It is concluded that myocardial and medullary A1ARs facilitate the cholinergic counteraction of cardiac and neuroinflammation induced by sepsis and interrelated cardiomyopathic and neuropathic hitches.

Abstract Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening result obtained against DdRp, top two compounds, namely Tigecycline and Eravacycline with docking scores of − 8.88 and − 7.87 kcal/mol, respectively, were selected for further analysis. Omadacycline and minocycline, with docking scores of − 10.60 and − 7.51 kcal/mol, are the top two compounds obtained after screening proteinase with the drug library. These compounds, along with reference compounds GTP for DdRp and tecovirimat for proteinase, were used to form protein–ligand complexes, followed by their evaluation through a 300 ns molecular dynamic simulation. The MM/GBSA binding free energy calculation and principal components analysis of these selected complexes were also conducted for understanding the dynamic stability and binding affinity of these compounds with respective target proteins. Overall, this study demonstrates the repurposing of tetracycline-derived drugs as a therapeutic solution for monkeypox viral infection.

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

The non-invasive brain sensing modulation technology field is experiencing rapid development, with new techniques constantly emerging. This study delves into the field of non-invasive brain neuromodulation, a safer and potentially effective approach for treating a spectrum of neurological and psychiatric disorders. Unlike traditional deep brain stimulation (DBS) surgery, non-invasive techniques employ ultrasound, electrical currents, and electromagnetic field stimulation to stimulate the brain from outside the skull, thereby eliminating surgery risks and enhancing patient comfort. This study explores the mechanisms of various modalities, including transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), highlighting their potential to address chronic pain, anxiety, Parkinson’s disease, and depression. We also probe into the concept of closed-loop neuromodulation, which personalizes stimulation based on real-time brain activity. While we acknowledge the limitations of current technologies, our study concludes by proposing future research avenues to advance this rapidly evolving field with its immense potential to revolutionize neurological and psychiatric care and lay the foundation for the continuing advancement of innovative non-invasive brain sensing technologies.

Abstract Purpose Autoimmune rheumatic diseases (ARD) are groups of diseases that are commonly associated with cardiac and pulmonary manifestations and may affect the morbidity and mortality of the patients. The study aimed to the assessment of cardiopulmonary manifestations and their correlation with the semi-quantitative scoring of high-resolution computed tomography (HRCT) in ARD patients. Methods and patients 30 patients with ARD were included in the study (mean age 42.2 ± 9.76 years) [10 patients were scleroderma (SSc), 10 patients were rheumatoid arthritis (RA), and 10 patients were systemic lupus erythematosus (SLE)]. They all met the diagnostic criteria of the American College of Rheumatology and underwent spirometry, echocardiography, and chest HRCT. The HRCT was assessed by a semi-quantitative score for parenchymal abnormalities. Correlation between HRCT lung scores and: inflammatory markers, lung volumes in spirometry, and echocardiographic indices has been performed. Results The total lung score (TLS) by HRCT was 14.8 ± 8.78 (mean ± SD), ground glass opacity score (GGO) was 7.20 ± 5.79 (mean ± SD) and fibrosis lung score (F) was 7.63 ± 6.05 (mean ± SD). TLS correlated significantly with ESR (r 0.528, p 0.003), CRP (r 0.439, p 0.015), PaO2 (r -0.395, P 0.031) FVC% (r -0.687, p 0.001), and echocardiographic Tricuspid E (r -0.370, p 0.044), Tricuspid E/è (r -0.397,p 0.03), ESPAP (r 0.459,p 0.011), TAPSE (r -0.405, p 0.027), MPI-TDI (r -0.428, p 0.018) and RV Global strain(r -0.567, p 0.001). GGO score correlated significantly with ESR (r 0.597, p 0.001), CRP (r 0.473, p 0.008), FVC% (r -0.558, p 0.001), and RV Global strain(r -0.496, p 0.005). F score correlated significantly with FVC% (r -0.397, p 0.030), Tricuspid E/è (r -0.445, p 0.014), ESPAP (r 0.402, p 0.028), and MPI-TDI (r -0.448, p 0.013). Conclusion The total lung score and GGO score in ARD were found to be consistently significantly correlated with FVC% predicted, PaO2, inflammatory markers, and RV functions. Fibrotic score correlated with ESPAP. Therefore, in a clinical setting, most clinicians who monitor patients suffering from ARD should concern with the applicability of semiquantitative HRCT scoring in clinical practice.

Background: Depressive and anxiety disorders are among the leading causes of burden of disease worldwide with prevalence estimates and disability weights comparatively higher than many other diseases among university students age group. University students are at a developmentally crucial period and are prone to experience variable levels of stresses which can lead to mental health disorders such as anxiety and depression. Identifying the prevalence of these disorders and the associated factors is crucial for prevention and control of these disorders. Objective(s): The current study was conducted to estimate the prevalence of anxiety and depression and their associated and predicting factors among university students. Methods: An observational cross-sectional study was conducted in Alexandria and Alamein universities from March till April 2023, where all students at both universities were invited to participate. Data collection was done using a self-administered structured online questionnaire using Google Forms that was divided into 3 parts. The first part was prepared to collect data regarding the sociodemographic characteristics, personal habits, history of chronic diseases and mental illness, family history of mental illness, academic environment and students’ perspective towards studying. The second part included the validated Arabic version of The Generalized Anxiety Disorder Assessment (GAD-7) questionnaire, and the third part included the validated Arabic version of the Patient Health Questionnaire-9 (PHQ-9) the depression module. Respondents were asked to rate how often each symptom occurred over the preceding 2 weeks. Results: Among 2589 valid questionnaires, the overall prevalence of moderate to severe anxiety symptoms were found among nearly half the students (48.4%). Moderate to severe depression symptoms constituted 70%. Predictors that were statistically significantly associated with anxiety symptoms after binary logistic regression were age, sex, faculty type, smoking, history of mental illness, sleeping hours, and time available to study, while predictors of depression symptoms were faculty type and academic year. Conclusion: Our study suggests that a lot of university students experience depression and anxiety symptoms, and highlighted factors that are related to these mental disorders. Anonymous screening can have an important role in identifying students with mental disorders overcoming stigma that prevents them from seeking help.

The syntheses of two benzylidenehydrazine derivatives, namely, (E)-N′-(4-chloro-3-nitrobenzylidene)acetohydrazide, C9H8ClN3O3, and (E)-2-(4-chlorobenzylidene)-1-(quinolin-8-yl)hydrazine, C16H12ClN3, are reported. The molecules have been characterized using IR, 1H NMR, 13C NMR and mass spectroscopic and elemental analysis techniques, and their structures have been determined by single-crystal X-ray diffraction.

Abstract Nitazoxanide (NTX) is an antimicrobial drug that was used for the treatment of various protozoa. However, during the coronavirus pandemic, NTX has been redirected for the treatment of such virus that primarily infect the respiratory tract system. NTX is now used as a broad-spectrum antiviral agent. In this study, a highly sensitive and green spectrofluorometric method was developed to detect NTX in various dosage forms and its metabolite, tizoxanide (TX), in human plasma samples using nitrogen and sulfur co-doped carbon quantum dots nanosensors (C-dots). A simple and eco-friendly hydrothermal method was used to synthetize water soluble C-dots from citric acid and l-cysteine. After excitation at 345 nm, the luminescence intensity was measured at 416 nm. Quenching of C-dots luminescence occurred upon the addition of NTX and was proportional to NTX concentration. Assessment of the quenching mechanism was performed to prove that inner filter effect is the underlying molecular mechanism of NTX quenching accomplished. After optimizing all experimental parameters, the analytical procedure was evaluated and validated using the ICH guidelines. The method linearity, detection and quantification limits of NTX were 15 × 10–3–15.00 µg/mL, 56.00 × 10–4 and 15 × 10–3 µg/mL, respectively. The proposed method was applied for the determination of NTX in its commercial pharmaceutical products; Nanazoxid® oral suspension and tablets. The obtained % recovery, relative standard deviation and % relative error were satisfactory. Comparison with other reported spectrofluorimetric methods revealed the superior sensitivity of the proposed method. Such high sensitivity permitted the selective determination of TX, the main metabolite of NTX, in human plasma samples making this study the first spectrofluorimetric method in literature that determine TX in human plasma samples. Moreover, the method greenness was assessed using both Eco-Scale and AGREE approaches to prove the superiority of the proposed method greenness over other previously published spectrofluorimetric methods for the analysis of NTX and its metabolite, TX, in various dosage forms and in human plasma samples.

Abstract Three smart carbon paste electrodes were fabricated to quantify dorzolamide hydrochloride DRZ, including conventional carbon paste I, modified carbon paste embedding Silica II, and modified carbon paste embedding β-cyclodextrin III. This study is based on the insertion of DRZ with phosphomolybdic acid to create an electroactive moiety dorzolamide-phosphomolybdate ion exchanger using a solvent mediator dibutyl phthalate. The three constructed carbon paste electrodes displayed Nernstian responses and linear concentration ranges with lower detection limits. The vital performance of the created electrodes was verified in relation to various parameters. The electrodes enhance the selective determination of DRZ in the presence of inorganic ions, a co-formulated drug in the dosage form timolol maleate, and the excipient benzalkonium chloride. The modified carbon paste electrode including Silica was utilized to detect DRZ in ophthalmic eye drop form utilizing the direct calibration curve and potentiometric titration methods. Satisfactory findings were achieved by comparing them to other reported methods.

Abstract Background Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) represent a major health problem among hospitalized patients leading to consequent morbidity and mortality specially after Covid-19 era and spread of multidrug-resistance organisms)MDRO) in hospitals. Aim This study aimed to analyze the commonest microorganisms responsible for HAP and VAP at Tanta University Chest Hospital. Methods This prospective observational study was done at Chest Department, Faculty of Medicine, started from June 2022 to February 2023. Fifty HAP patients’ sputum samples and 50 VAP patients (25 endotracheal aspirates and 25 bronchoalveolar lavages) were included. All collected samples were submitted to standard microbiological tests at Microbiology Department, Tanta Faculty of Medicine. Results A total number of 50 HAP and 50 VAP cases were included. Microbial isolates were relatively the same in both groups, where Klebsiella pneumoniae was the predominant isolates (56) followed by Staphylococcus aureus (25), Escherichia coli (14), Pseudomonas aeruginosa (13), Acinetobacter baumannii (5), Streptococcus pneumoniae (4), Enterococci (3), Stenotrophomonas maltophilia (2), Citrobacter freundii (2), Streptococcus pyogenes (2), Providencia stuartii (1), and 7 isolates of Candida. Antimicrobial susceptibility showed predominance of drug-resistance organisms in VAP (78%) versus HAP (28%), P-value:

Abstract Background Severe COVID-19 disease is typically associated with an urgent need for supplemental oxygen therapy that may be successfully delivered through conventional methods or require invasive mechanical ventilation. Early prediction of the need for invasive mechanical ventilation could significantly improve outcomes of COVID-19 patients. Plasma levels of D-dimer and a number of inflammatory markers as well as values of complete blood counts, all measured in the first two days of hospital admission of COVID-19 patients, were evaluated for their significance as predictors of the eventual need for invasive mechanical ventilation support as well as their values as predictors of post-ventilation morbidly and mortality. Methods This retrospective cohort study was conducted at a single center and included data pertaining to 200 patients with previously confirmed moderate to severe COVID-19 disease in the period between May 2021 and the end of December 2022. Data were retrieved from medical records for further analysis. Results The mean (SD) age of patients stood at 59 (14) years of age, and with a majority of patients being male (77%). About 18% of cases, all of significantly older age, had been connected to invasive mechanical ventilation (IMV). Total leucocytic count (TLC), as well as levels of urea, creatinine, D-dimer, ferritin, and CRP in IMV patients were significantly higher than non-ventilated patients (p

Abstract Introduction Chemoprevention refers to using specific substances during oncogenesis. Curcumin and catechins are both polyphenol types of phytochemicals present in curcuma longa and green tea. The effect of curcumin is synergistic with epigallocatechin gallate, the most abundant polyphenol in tea. Aim To evaluate and compares the chemopreventive effect of both green tea and curcumin (each individually and in combination) through induction of hamster buccal pouch carcinoma. Materials and methods Squamous cell carcinoma was chemically induced in fifty Syrian golden hamsters divided into 5 groups (10 each). The first group was used as a normal control group. The second group received the carcinogenic agent only. The other three groups received green tea, curcumin, and a combination of both, respectively. Flow cytometry, immunofluorescence, and immunohistochemical assays were used to evaluate apoptosis, proliferation, and angiogenesis. ANOVA test was used to analyze the results between the study groups. Results The cells of the positive control group (B) resulted in 11.57% apoptosis. In the study groups, treatment of the cells with green tea (C), and curcumin (D) and both of them (E) showed increased apoptosis. The fluorescent image in group B showed an increase of the red fluorescence in the nucleus and cytoplasm of the squamous cell carcinoma cells while groups C, D, and E showed a decrease of the red fluorescence in the nuclei of the squamous cell carcinoma cells. The microvessel density was higher in the positive control group as compared to the treated groups. Conclusions The combination of green tea and curcumin has a significant chemopreventive effect against oral carcinogenesis.