Prevalence of IBS and its association with academic stress and dormitory lifestyle among medical students of Bangladesh: A cross-sectional study.

Introduction: Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder affecting a substantial portion of the global population. While the prevalence of IBS is well-documented worldwide, limited research has explored its occurrence and associated factors among medical students in Bangladesh, a population exposed to high academic stress. This cross-sectional study aimed to assess the prevalence of IBS among medical students and investigate its potential association with stress levels and the dormitory lifestyle. Methods: Data were collected from 402 medical students using a self-administered questionnaire covering sociodemographic information, academic stress, lifestyle factors, and the Rome III Criteria for diagnosing IBS. Statistical analysis included bivariate and logistic regression analyses to identify significant associations and predictors of IBS prevalence. Results: This study among 402 university students found an overall irritable bowel syndrome (IBS) prevalence of 22.88 %, with 35.87 % diarrhea-predominant, 26.08 % constipation-predominant, and 38.04 % mixed subtype. Hostel residents had 2.11 times higher adjusted odds of IBS (95 % CI: 1.05-4.25, p < 0.001) than non-residents. IBS prevalence increased from 20.25 % for <1 year to 24.24 % for 1-3 years and 29.13 % for >3 years of hostel stay. Age 23-28 years (OR = 1.86, p = 0.030), lack of senior support (OR = 2.36, p = 0.05), second study phase (OR = 2.43, p = 0.002), inadequate exercise (OR = 2.11, p = 0.036), and frequent fatty food intake (OR = 2.98, p = 0.03) increased IBS risk. Higher academic stress (OR = 2.03, p = 0.002) predicted IBS, with 54.44 % vs. 43.78 % (p = 0.035) high stress among hostel residents who exercised less (48.23 % vs. 51.77 %) and consumed more fatty foods (53.33 % vs. 46.67 %). Mediation analysis revealed dormitory living impacts stress, physical activity, and diet - established IBS risk factors. Conclusion: The high prevalence of IBS among medical students in Bangladesh highlights the need for interventions to address changeable factors like academic stress, dormitory living conditions, lack of physical activity, and unhealthy eating habits to improve their health and wellness.

COVID-19 Vaccine Effectiveness Studies against Symptomatic and Severe Outcomes during the Omicron Period in Four Countries in the Eastern Mediterranean Region.

Vaccine effectiveness (VE) studies provide real-world evidence to monitor vaccine performance and inform policy. The WHO Regional Office for the Eastern Mediterranean supported a regional study to assess the VE of COVID-19 vaccines against different clinical outcomes in four countries between June 2021 and August 2023. Health worker cohort studies were conducted in 2707 health workers in Egypt and Pakistan, of whom 171 experienced symptomatic laboratory-confirmed SARS-CoV-2 infection. Test-negative design case-control studies were conducted in Iran and Jordan in 4017 severe acute respiratory infection (SARI) patients (2347 controls and 1670 cases) during the Omicron variant dominant period. VE estimates were calculated for each study and pooled by study design for several vaccine types (BBIBP-CorV, AZD1222, BNT162b2, and mRNA-1273, among others). Among health workers, VE against symptomatic infection of a complete primary series could only be computed compared to partial vaccination, suggesting a benefit of providing an additional dose of mRNA vaccines (VE: 88.9%, 95%CI: 15.3-98.6%), while results were inconclusive for other vaccine products. Among SARI patients, VE against hospitalization of a complete primary series with any vaccine compared to non-vaccinated was 20.9% (95%CI: 4.5-34.5%). Effectiveness estimates for individual vaccines, booster doses, and secondary outcomes (intensive care unit admission and death) were inconclusive. Future VE studies will need to address challenges in both design and analysis when conducted late during a pandemic and will be able to utilize the strengthened capacities in countries.

Investigating the causal relationship between wealth index and ICT skills: a mediation analysis approach.

This study examines the relationship between the wealth index (WI) and Information and Communication Technology (ICT) skills among women aged 15-49 in Bangladesh. The research aims to establish a cause-and-effect relationship between WI and ICT skills, while also examining how education mediates this relationship. Using the data from the Bangladesh Multiple Indicator Cluster Survey (MICS) Program 2019, a two-stage stratified clustered sampling method yielded a sample of 64,378 women. The analysis employed inverse probability weighting (IPW) to assess the causal effect of WI on ICT skills while investigating the mediating role of education in this cause-and-effect relationship through causal mediation analysis. The findings demonstrate a significant relationship between higher economic status and increased ICT proficiency among women aged 15-49 in Bangladesh. Mediation analysis reveals education status as a significant mediator, indicating that educational attainment plays a vital role in linking wealth and ICT skills among women. Sensitivity analysis indicates the observed effect estimates are robust to unmeasured confounding. This research underscores the importance of economic empowerment and educational interventions in narrowing the digital divide and fostering ICT skills development among women, particularly in rural and economically disadvantaged communities.

Metformin in Combination with Standard Therapy in Patients with Diffuse Large B-Cell Lymphoma: A Randomized Phase II Clinical Trial.

BACKGROUND: Metformin has been shown to have antitumor activity in different tumor types. In DLBCL (Diffuse large B cell lymphoma), using metformin with front-line chemotherapy & immunotherapy resulted in improved clinical outcomes. OBJECTIVES: To assess the effectiveness of incorporating metformin into the standard initial treatment regimen of R-CHOP for patients with DLBCL. The evaluation metrics included response rate, toxicity, progression-free survival (PFS), and overall survival (OS). PATIENTS AND METHODS: This prospective phase 2 trial included 100 adult patients with histopathological evidence of DLBCL, eligible for first-line treatment with R-CHOP, life expectancy of at least 6 months, and performance status (PS) ≤ 2. Patients were randomized to receive either metformin plus R-CHOP or R-CHOP alone. RESULTS: Each group included 50 patients. The metformin arm had more females than the standard arm (p=0.016). Nausea was significantly higher in the test arm than the standard arm (p=0.008). Metformin group had higher rates of complete remission (CR) at the end of treatment (92% vs 74%; p=0.017), lower rates of relapse/progression (10% vs 36%; p=0.002), and lower rates of overall mortality (4% vs 20%; p=0.014). The mean disease-free survival (DFS) was 24.5 months in the metformin group versus 20.2 months in the control arm (p=0.023). Likewise, the mean progression-free survival (PFS) was 25.91 versus 19.81 months and the mean overall survival (OS) was 27.39 versus 23.8 months (p-values= 0.002, and 0.013 respectively). By multivariate analysis of response and relapse, the use of metformin was an independent prognostic factor of CR and relapse. CONCLUSIONS: The addition of metformin to standard R-CHOP could improve clinical outcomes in patients with DLBCL with a tolerable safety profile.

A Comparative Study of "Grafting to" and "Grafting from" Conjugation Methods for the Preparation of Antibody-Temperature-Responsive Polymer Conjugates.

Early diagnosis of infectious diseases is still challenging particularly in a nonlaboratory environment or limited resources areas. Thus, sensitive, inexpensive, and easily handled diagnostic approaches are required. The lateral flow immunoassay (LFIA) is commonly used in the screening of infectious diseases despite its poor sensitivity, especially with low pathogenic loads (early stages of infection). This article introduces a novel polymeric material that might help in the enrichment and concentration of pathogens to overcome the LFIA misdiagnosis. To achieve this, we evaluated the efficiency of introducing poly(N-isopropylacrylamide) (PNIPAAm) into immunoglobulin G (IgG) as a model antibody using two different conjugation methods: grafting to (GT) and grafting from (GF). The IgG-PNIPAAm conjugates were characterized using SDS-PAGE, DLS, and temperature-responsive phase transition behavior. SDS-PAGE analysis revealed that the GF method was more efficient in introducing the polymer than the GT method, with calculated polymer introduction ratios of 61% and 34%, respectively. The GF method proved to be less susceptible to steric hindrance and more efficient in introducing high-molecular-weight polymers into proteins. These results are consistent with previous studies comparing the GT and GF methods in similar systems. This study represents an important step toward understanding how the choice of polymer incorporation method affects the properties of IgG-PNIPAAm conjugates. The synthesized polymer allowed binding and enrichment of mouse IgG that was used as a model antigen with a clear LFIA band. On the basis of our findings, this system might help in improving the sensitivity of simple diagnostics.

Evaluation of urea breath test as a diagnostic tool for Helicobacter pylori infection in adult dyspeptic patients.

In this editorial, we discuss the article in the World Journal of Gastroenterology. The article conducts a meta-analysis of the diagnostic accuracy of the urea breath test (UBT), a non-invasive method for detecting Helicobacter pylori (H. pylori) infection in humans. It is based on radionuclide-labeled urea. Various methods, both invasive and non-invasive, are available for diagnosing H. pylori infection, including endoscopy with biopsy, serology for immunoglobulin titers, stool antigen analysis, and UBT. Several guidelines recommend UBTs as the primary choice for diagnosing H. pylori infection and for reexamining after eradication therapy. It is used to be the first choice non-invasive test due to their high accuracy, specificity, rapid results, and simplicity. Moreover, its performance remains unaffected by the distribution of H. pylori in the stomach, allowing a high flow of patients to be tested. Despite its widespread use, the performance characteristics of UBT have been inconsistently described and remain incompletely defined. There are two UBTs available with Food and Drug Administration approval: The 13C and 14C tests. Both tests are affordable and can provide real-time results. Physicians may prefer the 13C test because it is non-radioactive, compared to 14C which uses a radioactive isotope, especially in young children and pregnant women. Although there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs, 13C-UBT consistently outperforms the 14C-UBT. This makes the 13C-UBT the preferred diagnostic approach. Furthermore, the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage, assessment timing, and measurement techniques for both the 13C-UBT and 14C-UBT, to enhance diagnostic precision.

The renoprotective activity of amikacin-gamma-amino butyric acid-chitosan nanoparticles: a comparative study.

The development of nanoparticles (NPs) with active components with upgraded stability, and prolonged release helps in enhanced tissue regeneration. In addition, NPs are feasible strategy to boost antibiotic effectiveness and reduce drug side effects. Our study focuses on the use of amikacin (AMK) and gamma amino butyric acid (GABA) unloaded combinations or loaded on chitosan nanoparticles (CSNPs) for kidney protection. The AMK-GABA-CSNPs were prepared with the ionic gelation method, the morphology was studied using transmission electron microscopy (TEM), zetasizer and the Fourier transform-infrared spectroscopy (FT-IR) spectrum of the synthesized NPs was observed. The average size of AMK-GABA-CSNPs was 77.5 ± 16.5 nm. Zeta potential was + 38.94 ± 2.65 mV. AMK-GABA-CSNPs revealed significant in vitro antioxidant, anti-coagulation, non-hemolytic properties and good cell compatibility. To compare the effects of the unloaded AMK-GABA combination and AMK-GABA-CSNPs on the renal tissue, 42 healthy Sprague-Dawley rats were divided into seven groups. G1: normal control (NC), normal saline; G2: low-dose nephrotoxic group (LDN), AMK (20 mg/kg/day; i.p.); G3: unloaded AMK (20 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.); G4: AMK-GABA-CSNPs (20 mg/kg/day; i.p.); G5: high-dose nephrotoxic group (HDN), AMK (30 mg/kg/day; i.p.); G6: unloaded AMK (30 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.) and G7: AMK-GABA-CSNPs (30 mg/kg/day; i.p.). The results showed that AMK-GABA-CSNPs formulation is superior to unloaded AMK-GABA combination as it ameliorated kidney functions, oxidative stress and displayed a significant homeostatic role via suppression of inflammatory cytokines of Th1, Th2 and Th17 types. Hence, AMK-GABA-CSNPs could afford a potential nano-based therapeutic formula for the management of AMK-nephrotoxicity.

Does lateral extra-articular tenodesis affect knee stability in cases with isolated anterior cruciate ligament reconstruction?

Objective: The purpose of this randomised controlled trial was to assess the effect on knee function and stabilising effectiveness of lateral extra-articular tenodesis (LET) in anterior cruciate ligament (ACL) restoration. Methods: A prospective randomised clinical study that compared the functional outcomes of two groups-one undergoing anatomic single bundle ACL reconstruction (ASB-ACLR) with ilio-tibial band tenodesis (LET) for 20 patients, and the other undergoing ASB-ACLR-was carried out between February 2020 and August 2022. Results: By combining Lateral Extra-articular Tenodesis (LET) with intra-articular Anterior Cruciate Ligament Reconstruction (ACLR), our study observed a significant reduction in the occurrence of high-grade pivot-shift phenomena. Prior to surgery, both Groups A and B exhibited graded (D) pivot-shift test results. However, post-surgery, the pivot-shift test yielded negative results in 60% of patients in Group A and 90% of patients in Group B. The statistical analysis revealed a notable difference between the two groups, as indicated by a P-value of 0.003. Upon conducting a brief follow-up, we evaluated the Lysholm score, and anterior knee stability of ACLR with LET, finding no statistically significant difference compared to those of single ACLR. The Lachman tests also revealed no significant disparity between the two groups (p = 0.106). Analyzing the Lysholm scores in Group A and Group B, we observed an increase to 90.70% and 91.10%, respectively. Conclusion: Rotational stability is much improved when lateral extra-articular tenodesis (LET) utilizing the ilio-tibial band as an augmentation is used in ACL restoration. Especially useful for high-grade pivot-shift phenomena is this technique.

Histopathological effects of the fruit extract of Citrullus colocynthis on the ovary of the tick Hyalomma dromedarii.

Hyalomma dromedarii is the predominant tick species parasitizing camels in Egypt which leads to mortalities in young animals that result in economic losses. It can transmit a lot of pathogens to animals and humans, such as the Crimean-Congo hemorrhagic fever virus, the Dhori virus, Kadam virus, Theileria annulata and spotted fever rickettsia. The continuous use of chemical acaricides has negative impact on the environment and almost led to acaricidal resistance, and hence the plant extracts represent alternative methods for controlling ticks. The present study was carried out to assess the histopathological effects on the ovary of fed female Hyalomma dromedarii following immersion in the ethanolic extract of fruits of Citrullus colocynthis (100 mg/mL). Light, scanning and transmission electron microscopy observations provided evidence that Citrullus colocynthis caused extensive damage to oocytes. Destruction of the internal organelles of oocytes, along with delay and/or inhibition of vitellogenesis were demonstrated. This is the first histological study that points to damage in H. dromedarii ovaries following treatment with the ethanolic extract of fruits of C. colocynthis. The data presented suggest that the plant extract affects the ovary either directly by entering the oocytes and/or indirectly by damaging the gut cells and digestion of blood that interfere with the development of oocytes, so it can be used as a promising agent for tick control.

Development of Apoptotic-Cell-Inspired Antibody-Drug Conjugate for Effective Immune Modulation.

BACKGROUND: Apoptotic cells' phosphoserine (PS) groups have a significant immunosuppressive effect. They inhibit proinflammatory signals by interacting with various immune cells, including macrophages, dendritic cells, and CD4+ cells. Previously, we synthesized PS-group-immobilized polymers and verified their immunomodulatory effects. Despite its confirmed immunomodulatory potential, the PS group has not been considered as a payload for antibody-drug conjugates (ADCs) in a targeted anti-inflammatory approach. AIM: We conducted this research to introduce an apoptotic-cell-inspired antibody-drug conjugate for effective immunomodulation. METHOD: Poly(2-hydroxyethyl methacrylate-co-2-methacryloyloxyethyl phosphorylserine) (p(HEMA-co-MPS)) was synthesized as a payload using RAFT polymerization, and goat anti-mouse IgG was selected as a model antibody, which was conjugated with the synthesized p(HEMA-co-MPS) via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-Hydroxysuccinimide (EDC/NHS) reaction. The antibody-binding affinity, anti-inflammatory potential, and cytotoxicity measurements were evaluated. RESULTS: We successfully synthesized ADCs with a significant anti-inflammatory effect and optimized the antibody-polymer ratio to achieve the highest antibody-binding affinity. CONCLUSION: We successfully introduced p(HEMA-co-MPS) to IgG without decreasing the anti-inflammatory potential of the polymer while maintaining its targeting ability. We suggest that the antibody-polymer ratio be appropriately adjusted for effective therapy. In the future, this technology can be applied to therapeutic antibodies, such as Tocilizumab or Abatacept.

A facile, flexible, and multifunctional thermo-chemotherapy system for customized treatment of drug-resistant breast cancer.

Anticancer drug resistance invariably emerges and poses a significant barrier to curative therapy for various breast cancers. This results in a lack of satisfactory therapeutic medicine for cancer treatment. Herein, a universal vector system for drug-resistance breast cancer was designed to meet the needs of reversed multidrug resistance, thermo-chemotherapy, and long-term drug release behavior. The vector system comprises polycaprolactone (PCL) nanofiber mesh and magnetic nanoparticles (MNPs). PCL has excellent biocompatibility and electrospinning performance. In this study, MNPs were tailored to be thermogenic in response to an alternating magnetic field (AMF). PCL nanofiber can deliver various chemotherapy drugs, and suitable MNPs encapsulated in the nanofiber can generate hyperthermia and synergistic effect with those chemotherapy drugs. Therefore, a more personalized treatment system can be developed for different breast malignancies. In addition, the PCL nanofiber mesh (NFM) enables sustained release of the drugs for up two months, avoiding the burden on patients caused by repeated administration. Through model drugs doxorubicin (DOX) and chemosensitizers curcumin (CUR), we systematically verified the therapeutic effect of DOX-resistance breast cancer and inhibition of tumor generation in vivo. These findings represent a multifaceted platform of importance for validating strategic reversed MDR in pursuit of promoted thermo-chemotherapeutic outcomes. More importantly, the low cost and excellent safety and efficacy of this nanofiber mesh demonstrate that this can be customized multi-function vector system may be a promising candidate for refractory cancer therapy in clinical.

Design of an apoptotic cell-mimetic wound dressing using phosphoserine-chitosan hydrogels.

Inflammatory M1 macrophages create a hostile environment that impedes wound healing. Phosphoserine (PS) is a naturally occurring immunosuppressive molecule capable of polarizing macrophages from an inflammatory phenotype (M1) to an anti-inflammatory phenotype (M2). In this study, we designed, fabricated, and characterized PS-immobilized chitosan hydrogels as potential wound dressing materials. A PS group precursor was synthesized via a phosphoramidite reaction and subsequently immobilized onto the chitosan chain through an EDC/N-hydroxysuccinimide reaction using a crosslink moiety HPA. The PS/HPA-conjugated chitosan (CS-PS) was successfully synthesized by deprotecting the PS group in HCl. In addition, the hydrogels were prepared by the HRP/H2O2 enzyme-catalyzed reaction with different PS group contents (0, 7.27, 44.28 and 56.88 µmol g-1). The immobilization of the PS group improved the hydrophilicity of the hydrogels. Interestingly, CS-PS hydrogel treatment upregulated both pro-inflammatory and anti-inflammatory cytokines. This treatment also resulted in alterations in the macrophage cell morphology from the M1 to M2 phenotype. The CS-PS hydrogel significantly accelerated diabetic wound healing. Overall, this study provides insights into the potential of PS-immobilized hydrogel materials for improved inflammatory disease therapy.

Eobania vermiculata whole-body muscle extract-loaded chitosan nanoparticles enhanced skin regeneration and decreased pro-inflammatory cytokines in vivo.

BACKGROUND: Usually, wounds recover in four to six weeks. Wounds that take longer time than this to heal are referred to as chronic wounds. Impaired healing can be caused by several circumstances like hypoxia, microbial colonization, deficiency of blood flow, reperfusion damage, abnormal cellular reaction and deficiencies in collagen production. Treatment of wounds can be enhanced through systemic injection of the antibacterial drugs and/or other topical applications of medications. However, there are a number of disadvantages to these techniques, including the limited or insufficient medication penetration into the underlying skin tissue and the development of bacterial resistance with repeated antibiotic treatment. One of the more recent treatment options may involve using nanotherapeutics in combination with naturally occurring biological components, such as snail extracts (SE). In this investigation, chitosan nanoparticles (CS NPs) were loaded with an Eobania vermiculata whole-body muscle extract. The safety of the synthesized NPs was investigated in vitro to determine if these NPs might be utilized to treat full-skin induced wounds in vivo. RESULTS: SEM and TEM images showed uniformly distributed, spherical, smooth prepared CS NPs and snail extract-loaded chitosan nanoparticles (SE-CS NPs) with size ranges of 76-81 and 91-95 nm, respectively. The zeta potential of the synthesized SE-CS NPs was - 24.5 mV, while that of the CS NPs was 25 mV. SE-CS NPs showed a remarkable, in vitro, antioxidant, anti-inflammatory and antimicrobial activities. Successfully, SE-CS NPs (50 mg/kg) reduced the oxidative stress marker (malondialdehyde), reduced inflammation, increased the levels of the antioxidant enzymes (superoxide dismutase and glutathione), and assisted the healing of induced wounds. SE-CS NPs (50 mg/kg) can be recommended to treat induced wounds safely. SE was composed of a collection of several wound healing bioactive components [fatty acids, amino acids, minerals and vitamins) that were loaded on CS NPs. CONCLUSIONS: The nanostructure enabled bioactive SE components to pass through cell membranes and exhibit their antioxidant and anti-inflammatory actions, accelerating the healing process of wounds. Finally, it is advised to treat rats' wounds with SE-CS NPs.

COVID-19-induced transaminitis and hyperbilirubinemia: Presentation and outcomes.

The risk of liver injury in patients with coronavirus disease 2019 (COVID-19) infection is quite evident. Furthermore, liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines. This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury, such as chronic liver disease, to elucidate COVID-19-induced liver function abnormalities and their severity, pathophysiology, clinical manifestations, and clinical and laboratory outcomes. We also discuss the effect of vaccination against COVID-19 to better understand host factors, such as age, gender, and race, on the incidence and severity of liver dysfunction at initial presentation and during the illness. Finally, we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.

Comparative evaluation of gold nanoparticles and Alum as immune enhancers against rabies vaccine and related immune reactivity, physiological, and histopathological alterations: in vivo study.

Purpose: The present study aimed to compare the immune-enhancing potential of gold nanoparticles (AuNPs) to Alum against rabies vaccine and the related immunological, physiological, and histopathological effects. Materials and Methods: Alum and AuNPs sole and in combination with rabies vaccine were used at 0.35 mg/mL and 40 nM/mL, respectively. Rats used were categorized into six groups (20/each): control rats, rabies vaccine, aluminum phosphate gel, rabies vaccine adsorbed to Alum, AuNPs, and rabies vaccine adjuvant AuNPs. Results: Liver and kidney functions were in the normal range after AuNPs and Alum adjuvanted vaccine compared to control. Interleukin-6 and interferon-γ levels were significantly increased in groups immunized with Alum and AuNPs adjuvanted vaccine, the peak level was in the case of AuNP adjuvanted vaccine on the 14th day. Ninety days post-vaccination, total immunoglobulin G (IgG) against adjuvanted rabies vaccine showed a significantly elevated anti-rabies IgG with AuNPs and Alum adsorbed vaccine compared with unadjuvanted one. The total antioxidant capacity, malondialdehyde (MDA) levels, superoxide dismutase, and glutathione peroxidase activities were significantly increased post-adjuvanted AuNPs adjuvanted vaccine vaccination than in Alum adsorbed vaccine, while MDA was significantly decreased. The histopathological examination revealed detectable alterations post-AuNPs and Alum adjuvanted vaccine immunization compared with liver and kidney profiles post-administration of unadjuvanted and non-immunized groups, meanwhile, splenic tissue revealed hyperplasia of lymphoid follicles indicating increased immune reactivity. Conclusion: The AuNPs are promising enhancers of the immune response as Alum, and the undesirable effects of AuNPs could be managed by using suitable sizes, shapes, and concentrations.

Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFRWT and EGFRT790M inhibitors.

Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle and apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx cancer (HEP2), lung cancer (H460), colon cancers (HCT116 and Caco2), and hypopharyngeal cancer (FADU), and normal Vero cell lines were used. Compounds 8 and 14 displayed outstanding effects on the investigated cell lines and were further tested for their antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, and Vero cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), and nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection and cell cycle DNA index using the HEPG-2 cell line were established on both compounds as well. Furthermore, compounds 8 and 14 were assessed for their EGFR kinase (Wild and T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, and SAR studies were carried out for the investigated candidates.

Silver nanoparticles induced testicular damage targeting NQO1 and APE1 dysregulation, apoptosis via Bax/Bcl-2 pathway, fibrosis via TGF-ß/α-SMA upregulation in rats.

In medicine, silver nanoparticles (AgNPs) are employed often. They do, however, have negative impacts, particularly on the reproductive organs. This research aimed to assess AgNP impact on the testis and the possible intracellular mechanisms to induce testicular deteriorations in rats at various concentrations and different time intervals. Sprague Dawley rats (n = 40) were allocated into four equal groups: the control one, and three other groups injected intra-peritoneally with AgNP solution 0.25, 0.5, and 1 mg/kg b.w. respectively for 15 and 30 days. Our findings revealed that AgNPs reduced body and testicular weights, estradiol (E2) and testosterone (T) hormone levels, and sperm parameters while elevating the nitric oxide and malondialdehyde levels with inhibition of reduced glutathione contents in testicular tissue. Interestingly, AgNPs significantly upregulated the testicular inducible nitric oxide synthase, B cell lymphoma 2 (Bcl-2)-associated X, transforming growth factor, and alpha-smooth muscle actin (α-SMA) expression levels. However, apurinic/apyrimidinic endo deoxyribonuclease 1 (APE1), NAD (P) H quinone dehydrogenase 1 (NQO1), and Bcl-2 expression levels were all downregulated indicating exhaustion of body antioxidant and repairing defense mechanisms in testicles in comparison with the control rats. Various histological alterations were also detected which dramatically increased in rats sacrificed after 30 days such as loss of the lining cells of seminiferous tubules with no spermatozoa and tubular irregularities associated with thickening of their basement membranes. Immunolabeling implicated in the apoptotic pathway revealed a negative expression of Bcl-2 and marked immunoreactivity for caspase-3 after 30 days of AgNP treatment in comparison to the control rats. To our knowledge, there have been no previous publications on the role of the α-SMA, APE1, and NQO1 genes in the molecular pathogenesis of AgNP testicular cytotoxicity following AgNP acute and chronic exposure.

Comparative evaluation of gold nanoparticles and Alum as immune enhancers against rabies vaccine and related immune reactivity, physiological, and histopathological alterations: in vivo study

Purpose@#The present study aimed to compare the immune-enhancing potential of gold nanoparticles (AuNPs) to Alum against rabies vaccine and the related immunological, physiological, and histopathological effects. @*Materials and Methods@#Alum and AuNPs sole and in combination with rabies vaccine were used at 0.35 mg/mL and 40 nM/mL, respectively. Rats used were categorized into six groups (20/each): control rats, rabies vaccine, aluminum phosphate gel, rabies vaccine adsorbed to Alum, AuNPs, and rabies vaccine adjuvant AuNPs. @*Results@#Liver and kidney functions were in the normal range after AuNPs and Alum adjuvanted vaccine compared to control. Interleukin-6 and interferon-γ levels were significantly increased in groups immunized with Alum and AuNPs adjuvanted vaccine, the peak level was in the case of AuNP adjuvanted vaccine on the 14th day. Ninety days post-vaccination, total immunoglobulin G (IgG) against adjuvanted rabies vaccine showed a significantly elevated anti-rabies IgG with AuNPs and Alum adsorbed vaccine compared with unadjuvanted one. The total antioxidant capacity, malondialdehyde (MDA) levels, superoxide dismutase, and glutathione peroxidase activities were significantly increased post-adjuvanted AuNPs adjuvanted vaccine vaccination than in Alum adsorbed vaccine, while MDA was significantly decreased. The histopathological examination revealed detectable alterations post-AuNPs and Alum adjuvanted vaccine immunization compared with liver and kidney profiles post-administration of unadjuvanted and non-immunized groups, meanwhile, splenic tissue revealed hyperplasia of lymphoid follicles indicating increased immune reactivity. @*Conclusion@#The AuNPs are promising enhancers of the immune response as Alum, and the undesirable effects of AuNPs could be managed by using suitable sizes, shapes, and concentrations.

Preparation of Temperature-Responsive Antibody-Nanoparticles by RAFT-Mediated Grafting from Polymerization.

Herein, we report the preparation of temperature-responsive antibody-nanoparticles by the direct polymerization of N-isopropylacrylamide (NIPAAm) from immunoglobulin G (IgG). To this end, a chain transfer agent (CTA) was introduced into IgG, followed by the precipitation polymerization of NIPAAm in an aqueous medium via reversible addition-fragmentation chain transfer polymerization above the lower critical solution temperature (LCST). Consequently, antibody-polymer particles with diameters of approximately 100-200 nm were formed. Owing to the entanglement of the grafted polymers via partial chemical crosslinking, the antibody-nanoparticles maintained their stability even at temperatures below the LCST. Further, the dispersed nanoparticles could be collected by thermal precipitation above the LCST. Additionally, the antibody-nanoparticles formulation could maintain its binding constant and exhibited a good resistance against enzymatic treatment. Thus, the proposed antibody-nanoparticles can be useful for maximizing the therapeutic potential of antibody-drug conjugates or efficacies of immunoassays and antibody recovery and recycling.