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Nanoscale materials can improve cancer treatment by safely and efficiently delivering chemotherapeutic drugs. This study was designated to load the anticancer drug doxorubicin (DOX) into chitosan-coated Pb2Mn2Fe12O22 magnetic nanoparticles (CT-MNPs) and compare their physicochemical and biological effects with free drug, in addition to the therapeutic role of DOX-CT-MNPs to acting efficaciously in restraint of cancer cells growth and evolution using Ehrlich solid tumor model (EST). Forty female mice were randomly and equally split into four groups (EST; EST + Free DOX; EST + CT-MNPs; and EST + DOX-CT-MNPs). Our findings show that treating EST with DOX, either free or loaded on CT-MNPs, inhibits tumour growth by producing oxidative stress, disrupting the antioxidant system, activating apoptosis, and arresting the cell cycle. Furthermore, DOX loaded on CT-MNPs had greater anticancer activity than DOX in its free form. This highlights the potential advantages of CT-MNPs in tumour therapy and drug delivery.

Background Working environment should not present a risk of injury or disease but many thousands of workers worldwide remain exposed to hazardous substances particularly in developing countries. Flour dust is one of those hazardous substances to which the flour mills workers are exposed to, inhalation of flour dust may cause diverse lung diseases with different severity of symptoms ranging from simple irritation to allergic reaction and chronic respiratory disorders, including asthma. Therefore, the present study was done to detect the prevalence of respiratory problems among flour mills workers. Methods The study was carried out in the flour mills of Assiut, it was a cross-sectional study among 203 workers. The study instruments were a semi-structured questionnaire about respiratory symptoms, chest examination and pulmonary function tests (PFT). Results The age of the study workers ranged from 19 to 60 years old, 94.1% were males, 50.7% were from urban regions. Pulmonary function abnormalities were found in 36.4% of them and 20.7% were diagnosed with bronchial asthma. Significant relationships were detected between abnormal pulmonary function tests and workers ≥ 40 years old, low educational level and those who worked in the flour mills for ≥ 10 years. Conclusions Flour dust cause respiratory symptoms and impair the pulmonary function of the flour mills workers and they may develop bronchial asthma which affect their work efficiency. Recommendations Medical care must be provided regularly to the flour mills workers and safety measures are mandatory. Trial registration ClinicalTrials.gov. NCT03678519. Registered August 10, 2022.

Background The pathogenesis of chronic obstructive pulmonary disease (COPD) is multifactorial; oxidative stress is suggested to be one of the pathogenetic factors. Objective The aim of this study was to assess the role of antioxidant status in pathogenesis of COPD and in predicting the severity of airway obstruction. Patients and methods This case-controlled study was carried on 60 patients with COPD, and on 15 apparently healthy age-matched smokers and 15 apparently healthy age-matched nonsmokers, which served as control groups. Bronchoscopy with bronchoalveolar lavage was carried out for 10 COPD patients. Chest radiography, pulmonary function testing, and arterial blood gases were carried out for all groups. Serum level of total antioxidant (TAO) was also measured in all groups by using the enzyme-linked immunosorbent assay kit. Results Serum TAO level was significantly reduced in COPD patients and healthy smokers compared with healthy nonsmokers ( P <0.001, respectively); moreover, serum TAO level was significantly reduced in COPD compared with healthy smokers ( P <0.001), and serum TAO was significantly reduced in severe and very severe COPD compared with mild and moderate COPD ( P =0.01 and 0.006, respectively). TAO level significantly negatively correlated with each of PaCO2 and HCO 3 in COPD patients, and it was significantly positively correlated with each of forced expiratory volume in 1 s/forced vital capacity and forced expiratory volume in 1 s %. TAO had a sensitivity and specificity of 86.67 and 93.33, respectively, as a biomarker for identification and predicting the severity of COPD with an area under the curve of 0.921. Conclusion Serum TAO is a valuable biomarker in identifying and predicting the severity of COPD.

Background Lung cancer (LC) is one of the leading causes of death worldwide. Programmed cell death receptor 1 (PD-1) interacts with its ligand (PDL-1) on T cells inhibiting its functioning which may affect the patient's immunological response. Aim Investigate if there is a link between smoking and tissue expression of PDL-1 and vitamin D receptor (VDR) in lung cancer patients. In addition, the relation of vitamin D with smoking and these biochemical markers. Methods PDL-1 and VDR expressions were evaluated by real-time PCR in 54 lung cancer biopsy samples and 36 controls to prove this hypothesis. Vitamin D levels in the blood were measured using an ELISA. Results Expressions of PDL-1 were significantly upregulated in LC patients than in controls. The highest expression was in stage II and in squamous cell carcinoma followed by small cell carcinoma then adenocarcinoma. However, VDR expressions and vitamin D levels in serum were significantly downregulating in LC patients than in controls. There was a positive correlation between PDL-1expression and duration of smoking but not smoking index. Also, there is an inverse correlation between duration of smoking, smoking index, and VDR. Conclusion Expression of PDL-1 in LC was significantly upregulated and correlated with staging. Interestingly, our current study for the first time explained the role of duration of smoking on PDL-1 and VDR in the pathogenesis of LC. As PDL-1 expression increased with duration of smoking whereas VDR decreased, this novel findings may provide a possible link between the cumulative effect of smoking and the level of expressions of these biomarkers.

Nanoscale materials can improve cancer treatment by safely and efficiently delivering chemotherapeutic drugs. This study was designated to load the anticancer drug doxorubicin (DOX) into chitosan-coated Pb2Mn2Fe12O22 magnetic nanoparticles (CT-MNPs) and compare their physicochemical and biological effects with free drug, in addition to the therapeutic role of DOX-CT-MNPs to acting efficaciously in restraint of cancer cells growth and evolution using Ehrlich solid tumor model (EST). Forty female mice were randomly and equally split into four groups (EST; EST + Free DOX; EST + CT-MNPs; and EST + DOX-CT-MNPs). Our findings show that treating EST with DOX, either free or loaded on CT-MNPs, inhibits tumour growth by producing oxidative stress, disrupting the antioxidant system, activating apoptosis, and arresting the cell cycle. Furthermore, DOX loaded on CT-MNPs had greater anticancer activity than DOX in its free form. This highlights the potential advantages of CT-MNPs in tumour therapy and drug delivery.

Background Allergic reactions have been implicated as contributions in a number of atopic disorders, including atopic dermatitis (AD), allergic rhinitis (AR) and bronchial asthma (BA). However, the potential for filaggrin protein, eosinophil major basic protein (MBP) and immunoglobulin E (IgE) to elicit allergic response or to contribute to atopic disorders remains largely unexplored in pediatric patients. This study was undertaken to investigate the status and contribution of filaggrin protein, eosinophil MBP and total IgE in pediatric patients with AD, AR and BA. Methods Sera from 395 pediatric patients of AD, AR or BA with varying levels of disease activity according to the disease activity index and 410 age-matched non-atopic healthy controls were evaluated for serum levels of atopic markers, including filaggrin, eosinophil MBP and IgE. Results Serum analysis showed that filaggrin levels were remarkably high in pediatric patients with AD, followed by BA and AR, whereas its levels were low in non-atopic pediatric controls. Eosinophil MBP levels in sera of atopic patients were significantly high as compared with their respective controls, but its levels were highest in AR patients, followed by AD and BA. Total IgE in sera of AD patients was markedly high, followed by AR and BA patients, whereas its levels were low in non-atopic pediatric controls. Interestingly, not only was an increased number of subjects positive for filaggrin protein, eosinophil MBP or total IgE, but also their levels were statistically significantly higher among those atopic patients whose disease activity scores were higher as compared with atopic patients with lower disease activity scores. Conclusions These findings strongly support a role of filaggrin protein, eosinophil MBP and IgE in the onset of allergic reactions in pediatric patients with AD, AR and BA. The data suggest that filaggrin, eosinophil MBP or IgE might be useful in evaluating the progression of AD, AR or BA and in elucidating the mechanisms involved in the pathogenesis of these pediatric disorders.

Background Zoonotic human tuberculosis (TB) caused by Mycobacterium bovis ( M. bovis ) is as vital as Mycobacterium tuberculosis , however with scarce available information. We aimed to use whole-genome sequencing (WGS) technology to take a deep insight into the circulating genotypes of human M. bovis and the genomic characteristics underlying virulence and drug resistance. Methods The study included smear positive Ziehl-Neelsen samples from patients with suspected tuberculosis. Samples were cultured on Lowenstein-Jensen media and suspected colonies of M. bovis were selected to undergo DNA extraction and WGS. Data was analysed using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC), and online bioinformatics tools. A phylogenetic tree was constructed for our sequenced strains, in addition to a set of 59 previously sequenced M. bovis genomes from different hosts and countries. Results Out of total 112 mycobacterial positive cultures, five M. bovis were isolated and underwent WGS. All sequenced strains belonged to Mycobacterium tuberculosis var bovis , spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide ( pncA and rpsA) , isoniazid ( KatG and ahpC ), ethambutol ( embB , embC , embR and ubiA ), streptomycin ( rpsl ) and fluoroquinolones ( gyrA and gyrB ). Rifampin ( rpoB and rpoC ) and delamanid ( fbiC ) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system. The phylogenetic analysis revealed close genetic relatedness of three sequenced M. bovis strains to previous reported cow strains from Egypt and human strains from France, as well as relatedness of one M. bovis strain to four human Algerian strains. One sequenced strain was related to one cow strain from Egypt and a human strain from South Africa. Conclusions All sequenced M. bovis isolates showed the same spoligotype, but diverse phylogeny. Resistance gene mutations were detected for anti-TB drugs including pyrazinamide, isoniazid, streptomycin, ethambutol, fluoroquinolones, cycloserine, rifampin and delamanid. The virulence profile comprised genes assigned mainly to secretion system, cell surface components and regulation system. Phylogenetic analysis revealed genetic relatedness between our isolates and previously sequenced bovine strains from Egypt as well as human strains from other nearby countries in the region.

Background Non-ischemic reactive myocardial fibrosis (MF) is a significant global cause of chronic heart failure (CHF) related to fatalities and morbidity. Punicalagin (PUN), a primary phenolic component in pomegranate, has been acknowledged as cardioprotective agent in isoproterenol (ISO)-induced ischemic MF. However, the therapeutic roles of PUN individually and in combination with captopril in ameliorating the progression of reactive myocardial fibrosis were not previously explored. Aim of the study Our study was designed to explore the potential therapeutic benefits of PUN alone and in combination with captopril (CAP) in ISO-induced reactive MF. Material and methods Thirty-five male rats of the Sprague–Dawley species, 220–240 g, were randomly allocated across the 5 groups. Group1: Normal control; ISO Group2: received single daily subcutaneous injections of isoprenaline (5 mg/kg/day) for 10 days Captopril (CAP) group3: orally administered in a dose of 15 mg/kg/day for 60 days; PUN group4: orally administered in a dose of 200 mg/kg/day60 days, and CAP/PUN group5: rats were administered both CAP and PUN in the aforementioned doses and duration. Results Bioinformatically, CD68 protein showed co-expressional associations with TGF-β1, PPAR-γ, and Akt proteins, for which PUN displayed significant affinities via molecular docking. In ISO-injected rats, PUN and/or CAP lowered abnormally elevated parameters, but the combination therapy demonstrated superior effects in near normalizing most parameters including cardiac hemodynamics (in contrast to ISO group, HR, SBP, DBP, and DBP were by 53%, 21%, and 39%, respectively, with concomitant increase in EF by 70% and decrease in IVSD and LVDD by 43% and 66%, respectively, alongside with amelioration of the ISO-driven higher cardiac TGF-β1, Smad2/3, PTEN, and Wnt/β-catenin levels by 57%, 74%, 69%, 70% and 67%, respectively, in addition to considerable 1.6-, 1.2-, onefold, 1.45-fold increases in cardiac PPAR-γ, PI3K, p AKT, and Smad7 expression levels, respectively). Histopathological MF generated by ISO was reversed after PUN and/or CAP administration. The immunohistochemical study of fibrotic heart tissues revealed a noticeable increase in CD68 + macrophages and TGF-β1, which were reduced after PUN and/or CAP. Conclusion Phenotypical CD68 + macrophages have a pathophysiological role in ISO-induced reactive MF. Besides, punicalagin alone or in combination with captopril plays complementary therapeutic functions in experimentally reactive MF, suggesting their combination as a potential novel therapeutic approach for MF. Graphical abstract