A clinical study and laboratory evaluation of the cardiac and hepatic toxic effects of paraphenylenediamine.

INTRODUCTION: Paraphenylenediamine is the main component in many commercial hair dyes, and can produce severe local and systemic toxicity reactions after acute ingestion or dermal absorption. The aim of this study was to assess the factors contributing to morbidity and mortality in cases of acute paraphenylenediamine poisoning, with a focus on evaluating the resultant hepatic and cardiac toxicity. METHODS: This observational study was conducted on patients with acute paraphenylenediamine poisoning presenting to Sohag University Hospitals, and included a retrospective part from February 2021 to January 2022 and a prospective part from February 2022 to July 2022. Clinical data were extracted and receiver operating characteristic curves created to identify prognostic markers. RESULTS: Among 50 eligible patients 39 (78 percent) recovered, and 11 (22 percent) died or had permanent complications. Angioedema and anuria were the most frequent features in complicated cases. By receiver operating characteristic analysis, either an increase in aspartate aminotransferase activity greater than 644 IU/L or alanine aminotransferase activity greater than 798 IU/L, a time delay to presentation of greater than 4.5 hours, and a pH of less than 7.32 were associated with a significant increase in morbidity and mortality. While cardiac enzyme activities, and concentrations of blood urea nitrogen and creatinine increased in most cases, they were not associated with mortality. DISCUSSION: Management of patients with paraphenylenediamine poisoning is mainly supportive, as there is no specific antidote. Respiratory failure and kidney failure are the most life threatening complications. Hepatoxicity and cardiotoxicity also occur. The ability to predict the events can help guide patient disposition and care. CONCLUSION: Elevated liver enzyme activities, increased time delay to admission, decreased pH, and the presence of angioedema and anuria can be used as predictors of morbidity and mortality in patients with acute paraphenylenediamine poisoning.

Suppression by central adenosine A3 receptors of the cholinergic defense against cardiovascular aberrations of sepsis: role of PI3K/MAPKs/NFκB signaling.

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.

In Vitro Evaluation of Remineralization Potential of Five Toothpastes on Soft Drink-Eroded Human Enamel and Dentine.

OBJECTIVE: The purpose of this in vitro study was to evaluate the potential remineralization of enamel and dentine erosion lesions after the application of five different toothpastes. METHODOLOGY: A total of 104 enamel and dentine samples were prepared from maxillary third molars. Each group was divided according to the toothpaste application mode (topical = 56; brushing = 48) and the toothpaste used seven topical groups and six brushing groups (n = 8). The groups included negative control (NC), positive control (PC), Sensodyne Pronamel (SP), Regenerate (R), Regenerate with boosting serum (R+), Colgate Duraphat 5000 (CD), and tooth mousse (TM). RESULTS: The statistical analysis showed significant surface microhardness (SMH) change. All enamel groups showed a significant decrease in SMH compared to NC for both application modes. However, no significance was recorded between test groups. Similar results were observed between dentine groups and their relevant controls for both application modes, except brushed R and R+ groups, which were insignificant to their NC. For topical groups, TM showed a significant increase in SMH. While R and R+ showed lower loss than SP and CD. CONCLUSIONS: All tested agents offered a degree of remineralization in both enamel and dentine with no significant difference between agents in enamel groups while R, R+, and TM offered better results in dentine groups. CLINICAL SIGNIFICANCE:  For dentine groups, similar findings were observed with superior tooth surface protection with the application of TM over other agents. Tooth surface remineralization was achieved when agents were either applied topically or brushed over the surface.

Antimicrobial resistance patterns among critical priority pathogens in an intensive care unit at a tertiary hospital in Egypt: a descriptive analysis comparing pre- and COVID-19 eras.

Background. The intensified global challenge of antimicrobial resistance, set against the backdrop of the COVID-19 pandemic, is a cause for major concern. Within healthcare settings, intensive care units are recognized as focal points for Gram-negative infections. The study pursued to assess the prevalence and antimicrobial resistance patterns of critical priority pathogens (Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacteriaceae, comprising Klebsiella pneumoniae and Escherichia coli) during both pre- and COVID-19 periods.Gap Statement. The decision to explore this topic stemmed from the urgent need to understand how the exceptional healthcare crisis of COVID-19 affected AMR patterns.Methods. This was an observational retrospective analysis of 1056 clinical specimens obtained from 950 patients who were admitted to the Medical Intensive Care Unit at Kasr Al-Aini Hospital, Cairo University, Egypt.Results. In the period before COVID-19, 342 pathogenic isolates (135 K. pneumoniae, 83 P. aeruginosa, 76 A. baumannii and 48 E. coli) were obtained from samples collected from 450 patients. Conversely, during the COVID-19 period, 714 isolates (237 K. pneumoniae, 205 A. baumannii, 199 P. aeruginosa and 73 E. coli) were collected from the same number of patients. In the course of the pandemic, there is a slight increase in A. baumannii and P. aeruginosa infections, whereas E. coli and K. pneumoniae exhibit a distinct trend with a noticeable reduction in infection rates during COVID-19. During the COVID-19 period, a noticeable rise in resistance rates was observed for all antibiotics utilized. The results from Fisher's exact test indicated a substantial increase in resistance towards certain antibiotics. Specifically, a significant rise in resistance was observed for E. coli to ciprofloxacin (P = 0.00), gentamicin and P. aeruginosa (P = 0.02), levofloxacin and A. baumannii (P = 0.01), piperacillin-tazobactam and A. baumannii (P = 0.04), and piperacillin-tazobactam and P. aeruginosa (P = 0.01).Conclusion. Our results display how the pandemic impacted bacterial infections and antibiotic resistance, indicating a general increase in resistance rates. These findings are crucial for guiding healthcare practices, emphasizing the need for continued surveillance and potentially checking antibiotic usage schemes.

Synthesis, and Biological Evaluation of Benzamide compounds as Insecticides Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae).

Due to its severe damage, Spodoptera frugiperda is receiving attention as one of the biggest dangers to world food security. Although there are numerous insecticides that are widely and successfully used to control S. frugiperda, they do not have an immediate effect. In our work focusing for synthesized twelve novel benzamide derivatives and examined their insecticidal effectiveness against S. frugiperda larvae in their second & fourth larvae instars, with the aim of further improving the insecticidal activity based on combination principles. Several spectroscopic methods, including elemental analysis, NMR & infrared spectroscopy, were employed for confirming the structure of the newly designed products. It has been discovered that most compounds show good of promising efficacy. With an LC50 of 24.8 mg/L for larvae in the second instar & 56.2 mg/L for larvae in the fourth instar, compound 23 was the most active. Among all compounds 11, 22 and 20 exhibited excellent results. Furthermore, a number of biological and histopathological properties of the demonstration compounds of the produced goods under laboratory conditions were also examined. This work further demonstrates the anti-proliferation of S. frugiperda and offers fresh ideas for the manufacture of benzamide derivatives.

Exploring the Significance of Microglial Phenotypes and Morphological Diversity in Neuroinflammation and Neurodegenerative Diseases: From Mechanisms to Potential Therapeutic Targets.

Studying various microglial phenotypes and their functions in neurodegenerative diseases is crucial due to the intricate nature of their phenomics and their vital immunological role. Microglia undergo substantial phenomic changes, encompassing morphological, transcriptional, and functional aspects, resulting in distinct cell types with diverse structures, functions, properties, and implications. The traditional classification of microglia as ramified, M1 (proinflammatory), or M2 (anti-inflammatory) phenotypes is overly simplistic, failing to capture the wide range of recently identified microglial phenotypes in various brain regions affected by neurodegenerative diseases. Altered and activated microglial phenotypes deviating from the typical ramified structure are significant features of many neurodegenerative conditions. Understanding the precise role of each microglial phenotype is intricate and sometimes contradictory. This review specifically focuses on elucidating recent modifications in microglial phenotypes within neurodegenerative diseases. Recognizing the heterogeneity of microglial phenotypes in diseased states can unveil novel therapeutic strategies for targeting microglia in neurodegenerative diseases. Moreover, the exploration of the use of healthy isolated microglia to mitigate disease progression has provided an innovative perspective. In conclusion, this review discusses the dynamic landscape of mysterious microglial phenotypes, emphasizing the need for a nuanced understanding to pave the way for innovative therapeutic strategies for neurodegenerative diseases.

Novel HER2-based multi-epitope vaccine (HER2-MEV) against HER2-positive breast cancer: In silico design and validation.

Breast cancer (BC) continues to be the malignancy with the highest diagnosis rate worldwide. Between 15 % and 30 % of BC patients show overexpressed human epidermal growth factor receptor 2 (HER2), which is linked to poor clinical results in terms of invasiveness and recurrence risk. Passive immunity-based therapeutic approaches for treating HER2-enriched BC, are not effective and significant problems need to be tackled. Constructing multi-epitope vaccines is favored over single-epitope vaccines due to its ability to induce immunity against a variety of antigenic targets which will improve the efficacy of the vaccine. The current study describes a multi-epitope vaccine from HER2 protein against HER2-positive BC using several immunoinformatic techniques to achieve a potent and durable immune response. Nine Cytotoxic T lymphocytes (CTL) and five Helper T lymphocytes (HTL) epitopes were predicted and validated from HER2 protein using in silico tools. The expressed protein of the designed vaccine is predicted to be highly thermostable with better solubility. The predicted vaccine 3D structure was validated by ProSA servers and by the ERRAT server. Molecular docking analysis revealed a high binding affinity and stability of the designed vaccine with MHCI and TLR-2, 4, 7, and 9 receptors. The analysis of the C-ImmSim server revealed that the novel vaccine construct had the ability to elicit robust anti-cancerous innate, humoral, and cell-mediated immune responses. The vaccine can be a suitable option for HER2-positive BC patients and other patients with HER2-positive cancers to evoke immune responses. However, in vitro and in vivo experiments are needed to assess its effectiveness and safety.

Novel amino-ethyl carboxymethyl cellulose crosslinked ampholyte hydrogel development for Methyl orange removal from waste water.

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.

In Vivo and in Vitro activity of colistin-conjugated bimetallic silver-copper oxide nanoparticles against Pandrug-resistant Pseudomonas aeruginosa.

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.

Immunological and molecular assessment of HIV-1 mutations for antiretroviral drug resistance in Saudi Arabia.

Human Immunodeficiency Virus (HIV) is a significant threat to public health. HIV genotyping and antiretroviral resistance testing may have contributed to improved non-treated management. Immune markers might assist HIV-1 diagnosis and drug-resistant variant identification. HIV-1 immunogenicity and molecular characteristics of antiretroviral drug resistance are evaluated in 56 treatment-naive HIV patients. DNA sequencing and retroviral resistance testing identified HIV-1 genotypes. 55.4% of patients were susceptible to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) antiretroviral drugs, whereas 44.6% had drug-resistance mutations against at least one antiretroviral drug. 3.6% of cases had PI-resistant mutations, while 30.4% had NRTI-resistant mutations, and 30.4% had NNRTI-resistant mutations. In patients who are susceptible to PI, the mean value of human plasma sCD80 is 2.11 ± 0.65 ng/mL; in patients with mutations, it is 3.93 ± 2.91 ng/mL. Individuals who are susceptible to PI have plasma sCD27 levels of 78.7 ± 63.2 U/mL, whereas individuals who are mutant have levels of 56.5 ± 32.1 U/mL. IP-10's mean value was 363 ± 109.2 pg/mL for the susceptible patients and 429 ± 20.7 pg/mL for the mutated patients. In susceptible patients, the plasma sCD4 level is 0.163 ± 0.229 ng/mL; in mutant patients, it is 0.084 ± 0.012 ng/mL. The data showed a relative relation between immunological parameters such as sCD80, sCD27, sCD4, and IP-10 and mutation for drug resistance.

Changing patterns of bacterial profile and antimicrobial resistance in high-risk patients during the COVID-19 pandemic at a tertiary oncology hospital.

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.

Graphene nanosheet reinforcement of polyurethane nanocomposite for green and sustainable photoluminescence, superhydrophobic, and anticorrosive paint.

A simple and environmentally friendly method was developed for smart and efficient waterborne polyurethane (PUR) paint. Sugarcane bagasse was recycled into reduced graphene oxide nanosheets (rGONSs). Both lanthanide-doped aluminate nanoparticles (LAN; photoluminescent agent, 7-9 nm) and rGONSs (reinforcement agent) were integrated into a waterborne polyurethane to produce a novel photoluminescent, hydrophobic, and anticorrosive nanocomposite coating. Using ferrocene-based oxidation under masked circumstances, graphene oxide nanosheets were produced from sugarcane bagasse. The oxidized semicarbazide (SCB) nanostructures were integrated into polyurethane coatings as a drying, anticorrosion, and crosslinking agent. Polyurethane coatings with varying amounts of phosphor pigment were prepared and subsequently applied to mild steel. The produced paints (LAN/rGONSs@PUR) were tested for their hydrophobicity, hardness, and scratch resistance. Commission Internationale de l'éclairage (CIE) Laboratory parameters and photoluminescence analysis established the opacity and colourimetric properties of the nanocomposite coatings. When excited at 365 nm, the luminescent transparent paints emitted a strong greenish light at 517 nm. The anticorrosion characteristics of the coated steel were investigated. The phosphor-containing (11% w/w) polyurethane coatings displayed the most pronounced anticorrosion capability and long-persistent luminosity. The prepared waterborne polyurethane paints were very photostable and durable.

Bioinspired poly-dopamine/nano-hydroxyapatite: an upgrading biocompatible coat for 3D-printed polylactic acid scaffold for bone regeneration.

Poly-lactic acid (PLA) has been proposed in dentistry for several regenerative procedures owing to its biocompatibility and biodegradability. However, the presence of methyl groups renders PLA hydrophobic, making the surface less ideal for cell attachment, and it does not promote tissue regeneration. Upgrading PLA with inductive biomaterial is a crucial step to increase the bioactivity of the PLA and allow cellular adhesion. Our purpose is to evaluate biocompatibility, bioactivity, cellular adhesion, and mechanical properties of 3D-printed PLA scaffold coated with poly-dopamine (PDA) and nano-hydroxyapatite (n-HA) versus PLA and PLA/n-HA scaffolds. The fused deposition modelling technique was used to print PLA, PLA with embedded n-HA particles, and PLA scaffold coated with PDA/n-HA by immersion. After matrices characterization for their chemical composition and surface properties, testing the compressive strength was pursued using a universal testing machine. The bioactivity of scaffolds was evaluated by monitoring the formation of calcium phosphate compounds after simulated body fluid immersion. The PLA/PDA/n-HA scaffold showed the highest compressive strength which was 29.11 ± 7.58 MPa with enhancing calcium phosphate crystals deposition with a specific calcium polyphosphate phase formed exclusively on PLA/PDA/n-HA. With cell viability assay, the PDA/n-HA-coated matrix was biocompatible with increase in the IC50, reaching ⁓ 176.8 at 72 without cytotoxic effect on the mesenchymal stem cells, promoting their adhesion and proliferation evaluated by confocal microscopy. The study explored the biocompatibility, bioactivity, and the cell adhesion ability of PDA/n-HA coat on a 3D-printed PLA scaffold that qualifies its use as a promising regenerative material.

Genetic Association of Interleukin 16 Gene Polymorphisms (rs11556218 & rs4778889) with Type 1 Diabetes in Egyptian Children: A Case-Control Study.

BACKGROUND: Type 1 diabetes (T1D) is a serious chronic autoimmune condition. Even though the underlying reason for the onset of T1D is unknown, due to their effector and regulatory roles in immune responses, cytokines are essential in developing autoimmune disorders. Interleukin (IL)16 is an immunomodulatory cytokine implicated in several inflammatory and autoimmune diseases. OBJECTIVE: This study was designed to examine the association of IL16 gene polymorphisms, rs11556218 T > G and rs4778889 T > C, with the risk of T1D in Egyptian children. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, we analyzed rs11556218 T > G and rs4778889 T > C polymorphisms of the IL16 gene in 100 T1D subjects and 93 controls. RESULTS: Rs11556218 T > G polymorphism of the IL16 gene was not associated with the risk of developing T1D. Analysis of IL16 gene rs4778889 T > C showed that the TT genotype had a considerably higher risk of T1D than the TC genotype [OR = 2.195 (1.205-3.999)]. In comparison to patients with the C allele [OR = 0.6914 (0.38-1.2569)], patients with the T allele [OR = 1.45 (0.7956-2.6296)] were notably more likely to have T1D. A significant decrease was found in the frequency of GT (OR = 0.43, p = .03) and TC (OR = 0.32, p = .011) haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms in T1D patients compared with controls. CONCLUSION: IL16 gene rs4778889 T > C polymorphism might be associated with susceptibility to T1D. Egyptians with TT genotypes are more likely to develop T1D. However, GT and TC haplotypes of IL16 gene rs11556218 T > G and rs4778889 T > C polymorphisms highlight their protective role againstT1D disease.

Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia.

Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4+ T cell responses in vitro and whether HVEM gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). HVEM gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4+ T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. HVEM expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, p = 0.086) compared with normal embryonic kidney cells (Hek293). CD4+ T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells (p = 0.0033). Significant HVEM differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL (p = 0.0011) and relapsed/refractory (p = 0.0051) B cell ALL (p = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 (p = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.

Bacterial sealing ability of calcium silicate-based sealer for endodontic surgery: an in-vitro study.

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.

Validated chromatographic methods for determination of teriflunomide and investigation of its intrinsic stability.

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.

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.

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.

The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats.

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-/ß-glucosaminidase (ß-NAG), ß-Galactosidase (ß-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.