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OBJECTIVE: The objective of the current study was to investigate the cytotoxic potentials of Galactosylated Chitosan Nanoparticles. Specifically, the study aimed to develop Tubermycin B coated on Galactosylated Chitosan Nanoparticles using a new green method that replaces sodium borohydride in the reduction process. MATERIALS AND METHODS: The study synthesized Tubermycin B coated on Galactosylated Chitosan Nanoparticles through a new green method. The cytotoxicity of these nanoparticles was evaluated in a mice intestinal tract model that had been induced with chlorpyrifos, which causes oxidative stress-related enterotoxicity. Multiple activities, including the apoptosis of intestinal macrophages and the activation of Ikappa a/ß kinase (IKKa/ß), were examined as indicators of the nanoparticles' efficacy. The stability of the synthesized Chitosan Nanoparticles was also assessed. Additionally, the encapsulation efficiency of Boscia angustifalia and Boscia senegalensis extracts within the nanoparticles was determined. RESULTS: The results of the study showed that Tubermycin B coated on Galactosylated Chitosan Nanoparticles effectively alleviated the oxidative stress-related enterotoxicity in the mice intestinal tract induced by chlorpyrifos. The nanoparticles prevented the apoptosis of intestinal macrophages and inhibited the activation of IKKa/ß. The synthesized chitosan nanoparticles exhibited high stability. The encapsulation efficiency of Boscia angustifalia extract was recorded as 46.58%, whereas for Boscia senegalensis extract, it was 9.77%. The nanoparticles showed no cytotoxicity at all tested concentrations and demonstrated a medium-level anticancer effect. CONCLUSIONS: Based on the findings, it can be concluded that Tubermycin B coated on Galactosylated Chitosan Nanoparticles has the potential to alleviate oxidative stress-related enterotoxicity in the mice intestinal tract. The nanoparticles showed high stability and exhibited a medium-level anticancer effect. Furthermore, the study demonstrated that Boscia angustifalia extract exhibited higher anti-hepatitis C virus antibodies (anti-HCV) activity compared to Boscia senegalensis extract in an in-vitro system. Therefore, Boscia angustifalia could be considered a promising candidate for the development of an anti-HCV drug for future in-vivo studies. [ABSTRACT FROM AUTHOR]

Waleed Hakami,1 Gasim Dobie,1 Khadija A Alneami,1 Misk Shaabi,1 Khaled Essawi,1 Muhammad Saboor,2 Aymen M Madkhali,1 Mohammed H Nahari,3 Hassan H Almasoudi,3 Mohammad S Akhter,1 Fasial H Hakami,4 Fatimah A Zarbatan,5 Ali Hakamy,6 Rama M Chandika,7 Ali A Fageehi,1 Abdullah A Mobarki,1 Hassan A Hamali1 1Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 2Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; 3Department of Medical Laboratory Technology, Najran University, Najran, Saudi Arabia; 4Department of Epidemiology, College of Public Health and Tropical Medicine, Jazan University, Jazan, Saudi Arabia; 5Respiratory Care Department, King Fahad Central Hospital, Jazan, Ministry of Health, Jazan, Saudi Arabia; 6Department of Respiratory Therapy, Faculty of Applied Medical Sciences, Jazan University, Gizan, Saudi Arabia; 7Department of Clinical Nutrition, College of Applied Medical Sciences, Jazan University, Jazan, Saudi ArabiaCorrespondence: Hassan A Hamali, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, P.O. Box 1906, Gizan, 45142, Saudi Arabia, Email hhamali@jazanu.edu.saBackground: Nutritional anemia is a significant public health concern worldwide, particularly affecting young adults and children in Saudi Arabia, where inadequate nutrition is considered a primary contributing factor. This study aims to (i) examine the levels of serum iron, folate, and vitamin B12 in young adult students, with a focus on identifying any deficiencies and their association with anemia; (ii) explore the prevalence of mixed-deficiency anemia resulting from deficiencies in serum iron, folate, and vitamin B12 (iii) explore how sociodemographic characteristics and dietary habits influence serum iron, folate, and vitamin B12 levels.Materials and Methods: This cross-sectional study encompassed 158 young adult students at Jazan University, Saudi Arabia. Blood samples were collected following a comprehensive questionnaire addressing sociodemographic and health characteristics. These samples were analyzed for complete blood count, serum iron, folate, and vitamin B12 levels.Results: The findings of this study revealed a significant decrease in serum iron levels, with 70.6% of males and 88% in females exhibiting reduced level. Additionally, low levels of folate were observed in 4% of the study population, while deficiency in vitamin B12 was found in 2.2% of the study population. However, the simultaneous presence of low serum iron levels along with deficiencies in folate or vitamin B12 was not observed in the study participants.Conclusion: The study indicates that there is a high incidence of low serum iron and ferritin levels among university students in Saudi Arabia, which poses a considerable public health concern. Conversely, the prevalence of folate and vitamin B12 deficiencies among the students was comparatively low, and notably, there were no cases where these deficiencies were observed alongside iron deficiency.Keywords: anemia, folate, vitamin B12, serum iron, iron deficiency

Novel series of nitric oxide-releasing thiazolidine-2,4-diones ( NO-TZD-3a-d,5,6 ) and 3,4,5-trimethoxychalcone-based multifunctional 1,4-dihydropyrimidines ( CDHPM-10a-g ) have been designed and synthesised as potent broad-spectrum anticancer agents with potential VEGFR-2 inhibition. The designed analogs were evaluated for their anticancer activities towards a full panel of NCI-60 tumour cell lines and CDHPM-10a-g emerged mean %inhibitions ranging from 76.40 to 147.69%. Among them, CDHPM-10e and CDHPM-10f demonstrated the highest MGI% of 147.69 and 140.24%, respectively. Compounds CDHPM-10a,b,d-f showed higher mean %inhibitory activity than the reference drug sorafenib (MGI% = 105.46%). Superiorly, the hybrid CDHPM-10e displayed the highest potencies towards all the herein tested subpanels of nine types of cancer with MGI 50 of 1.83 µM. Also, it revealed potent cytostatic single-digit micromolar activity towards the herein examined cancer cell lines. The designed compounds CDHPM-10a-g were exposed as potent non-selective broad-spectrum anticancer agents over all NCI subpanels with an SI range of 0.66-1.97. In addition, the target analog CDHPM-10e revealed potency towards VEGFR-2 kinase comparable to that of sorafenib with a sub-micromolar IC 50 value of 0.11 µM. Also, CDHPM-10e could effectively induce Sub-G1-phase arrest and prompt apoptosis via caspase and p53-dependent mechanisms. Furthermore, CDHPM-10e revealed significant anti-metastatic activity as detected by wound healing assay. The modelling study implies that CDHPM-10e overlaid well with sorafenib and formed a strong H-bond in the DFG binding domain. The ADMET studies hinted out that CDHPM-10e met Pfizer's drug-likeness criteria. The presented novel potent anticancer agent merits further devotion as a new lead product in developing more chalcone-based VEGFR-2 inhibitors.

Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis and play roles in both anti-cancer immunity and tumour progression. Here we use a chimeric mouse model of chronic myeloid leukaemia (CML) and human bone marrow (BM) derived macrophages to study the impact of the dysregulated BM microenvironment on bystander macrophages. Utilising single-cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages we reveal unique subpopulations of immature macrophages residing in the CML BM microenvironment. CML exposed macrophages separate from their normal counterparts by reduced expression of the surface marker CD36, which significantly reduces clearance of apoptotic cells. We uncover aberrant production of CML-secreted factors, including the immune modulatory protein lactotransferrin (LTF), that suppresses efferocytosis, phagocytosis, and CD36 surface expression in BM macrophages, indicating that the elevated secretion of LTF is, at least partially responsible for the supressed clearance function of Ph- macrophages., (© 2024. The Author(s).)

Whilst it is recognised that targeting self-renewal is an effective way to functionally impair the quiescent leukaemic stem cells (LSC) that persist as residual disease in chronic myeloid leukaemia (CML), developing therapeutic strategies to achieve this have proved challenging. We demonstrate that the regulatory programmes of quiescent LSC in chronic phase CML are similar to that of embryonic stem cells, pointing to a role for wild type p53 in LSC self-renewal. In support of this, increasing p53 activity in primitive CML cells using an MDM2 inhibitor in combination with a tyrosine kinase inhibitor resulted in reduced CFC outputs and engraftment potential, followed by loss of multilineage priming potential and LSC exhaustion when combination treatment was discontinued. Our work provides evidence that targeting LSC self-renewal is exploitable in the clinic to irreversibly impair quiescent LSC function in CML residual disease - with the potential to enable more CML patients to discontinue therapy and remain in therapy-free remission., (© 2024. The Author(s).)

Objective: The objective of the current study was to investigate the cytotoxic potentials of Galactosylated Chitosan Nanoparticles. Specifically, the study aimed to develop Tubermycin B coated on Galactosylated Chitosan Nanoparticles using a new green method that replaces sodium borohydride in the reduction process., Materials and Methods: The study synthesized Tubermycin B coated on Galactosylated Chitosan Nanoparticles through a new green method. The cytotoxicity of these nanoparticles was evaluated in a mice intestinal tract model that had been induced with chlorpyrifos, which causes oxidative stress-related enterotoxicity. Multiple activities, including the apoptosis of intestinal macrophages and the activation of Ikappa α/β kinase (IKKα/β), were examined as indicators of the nanoparticles' efficacy. The stability of the synthesized Chitosan Nanoparticles was also assessed. Additionally, the encapsulation efficiency of Boscia angustifalia and Boscia senegalensis extracts within the nanoparticles was determined., Results: The results of the study showed that Tubermycin B coated on Galactosylated Chitosan Nanoparticles effectively alleviated the oxidative stress-related enterotoxicity in the mice intestinal tract induced by chlorpyrifos. The nanoparticles prevented the apoptosis of intestinal macrophages and inhibited the activation of IKKα/β. The synthesized chitosan nanoparticles exhibited high stability. The encapsulation efficiency of Boscia angustifalia extract was recorded as 46.58%, whereas for Boscia senegalensis extract, it was 9.77%. The nanoparticles showed no cytotoxicity at all tested concentrations and demonstrated a medium-level anticancer effect., Conclusions: Based on the findings, it can be concluded that Tubermycin B coated on Galactosylated Chitosan Nanoparticles has the potential to alleviate oxidative stress-related enterotoxicity in the mice intestinal tract. The nanoparticles showed high stability and exhibited a medium-level anticancer effect. Furthermore, the study demonstrated that Boscia angustifalia extract exhibited higher anti-hepatitis C virus antibodies (anti-HCV) activity compared to Boscia senegalensis extract in an in-vitro system. Therefore, Boscia angustifalia could be considered a promising candidate for the development of an anti-HCV drug for future in-vivo studies.