Cytotoxicity of Gemcitabine-Loaded-Microemulsions in Breast and Colon Cancer Cells

Purpose: To evaluate the antitumor activity of gemcitabine (GEM), incorporated in microemulsions with varying surfactant-to-oil (S/O) ratio, against MCF-7 breast cancer cells and HCT 116 colon cancer cells.Methods: The microemulsion formulations consisted of Tween 80, Span 20, isopropyl myristate (IPM) and aqueous ethanol (40 %). Anticancer assessment involved determination of hemolysis activity, screening for cytotoxicity using sulphorhodamine B assay and determination of the mechanism of cell death using light microscope and ApopNexin FITC apoptosis detection kit.Results: Hemolysis activity of all the microemulsion formulations, either blank or drug-loaded, was significantly less than that of GEM solution. On average, MCF-7 cell viability significantly (p < 0.05) decreased from 38.53 ± 6.04 to 30.1 ± 4.66 % when the administered microemulsion concentration in modified eagle medium (MEM), increased from 0.03 to 0.3 % v/v but significantly (p < 0.05) increased by 1.4-fold when exposed to GEM solution at equivalent concentrations. In contrast, the cytotoxicity of the microemulsion formulation against HCT116 cells was similar to that of 0.03 % v/v GEM solution but greater than that of GEM solution by 1.5-fold when their concentration in MEM increased to 0.3 %v/v. Microscopic studies show that the microemulsions stimulated apoptosis in MCF-7 and HCT116 cell within 48 h and at low concentration (0.03 %v/v).Conclusion: Microemulsion formulations improved the efficacy of GEM and induced apoptosis in MCF- 7 and HCT116 cells.Keywords: Apoptosis, MCF-7 breast cancer cells, HCT116 colon cancer cells, Hemolysis, Sulphorhodamine B assay, Microemulsio

Impact of Nanoparticles on Cancer Therapy

The tremendous contribution of nanotechnology to the treatment and diagnosis of medical diseases has recently attracted the attention of anticancer researchers. Most of the new nanoparticle carriers haveimproved drug bioavailability and reduced the cytotoxic effects of the drugs. This article presents an overview of the recent advances of nanotechnology in cancer therapy. It covers the mechanisms of cellular uptake for anticancer drugs delivered in nanoscale systems by either active or passive targeting.The various nanoscale systems employed in drug delivery and their immense potential in diagnosis and imaging of cancerous tumors are also addressed.Keywords: Nanocarriers, Drug delivery, Liposomes, Micelles, Dendrimers, Emulsification system

Effect of three calmodulin antagonists on subpopulations of CD44/CD24 immunophenotypes in breast cancer cell lines

Purpose: To determine the effect of three calmodulin antagonists (A-7, W-7 and W-13) on the subpopulations of CD44/CD24  immunophenotypes in MDA-MB-231 and MDA-MB-468 breast cancer cell lines.Methods: Flow cytometry analysis was used to determine the proportion of the various subpopulations of the immunophenotypes, viz, CD44+CD24-, CD44-CD24+ and CD44+CD24+, when MDA-MB-231 and MDA-MB-468 cells were subjected to calmodulin antagonists. The effect of W-13 on the invasion properties of  MDA-MB-231 and MDA-MB-468 was investigated using Matrigel invasion assay.Results: A-7, W-7 and W-13 caused alterations in the subpopulation of CD44+CD24- in MDA-MB-231 cells. The most potent antagonist was W-13 as it reduced the proportion of tumorigenic CD44+CD24- to 0.64 ± 0.05 at a concentration of 80 μM. In contrast, the subpopulation of MDA-MB-468 cells, which had a low fraction of  CD44+CD24-, was not altered when administered with W-7 but showed variations when incubated with W-13. Specifically, when the concentration of W-13 increased from 20 – 100 μM, the proportion of CD44+CD24+ was reduced from 92.93 ± 3.2 to 60.96 ± 2.4. The effect of W-13 on the subpopulations of CD44+CD24- and CD44+CD24+ in MDA-MB-231 and MDA-MB-468, respectively, reduced the invasion properties of the cells.Conclusion: The calmodulin antagonist, W-13, has a significant antitumor effect on MDA-MB-231 and MDA-MB-468 breast cancer cells

AI-Driven Decision Support Framework for Preventing Medical Equipment Failure and Enhancing Patient Safety: A New Perspective

Sara Awni Alkhatib,1,2 Rateb Katmah,1 Doua Kosaji,1 Syed Usama Bin Afzal,3 Muhammad Hamza Tariq,1 Mecit Can Emre Simsekler,4 Samer Ellahham5 1Department of Biomedical Engineering and Biotechnology, Khalifa University of Science & Technology, Abu Dhabi, United Arab Emirates; 2Center for Catalysis and Separation (CeCaS), Khalifa University of Science & Technology, Abu Dhabi, United Arab Emirates; 3Department of Electrical and Computer Engineering, Khalifa University of Science & Technology, Abu Dhabi, United Arab Emirates; 4Department of Management Science & Engineering, Khalifa University of Science & Technology, Abu Dhabi, United Arab Emirates; 5Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab EmiratesCorrespondence: Mecit Can Emre Simsekler, Email [email protected]: Medical equipment failures pose serious risks to patient safety and healthcare system efficiency. Although AI-based predictive maintenance (PdM) has shown promise in other industries, its application in healthcare remains fragmented and insufficiently aligned with human-centered principles. This perspective paper proposes a novel AI-driven decision support framework that integrates systems thinking and prioritizes human-centered design. By leveraging real-time sensor data and historical maintenance records, the framework proactively predicts equipment failures and reduces downtime. It incorporates insights from key stakeholders, including biomedical engineers, technicians, patients, and administrators, to ensure human-centered and ethically responsible implementation. The paper also addresses major challenges such as data integration, human factors, and organizational readiness, offering practical strategies for sustainable adoption. This work contributes to the evolving role of AI in healthcare by emphasizing empathy, stakeholder collaboration, and safety, ultimately promoting more reliable medical devices and improved patient outcomes.Keywords: artificial intelligence, equipment failure analysis, maintenance, predictive, patient safety, human factors, clinical decision support system

The HIV Envelope but Not VSV Glycoprotein Is Capable of Mediating HIV Latent Infection of Resting CD4 T Cells

HIV fusion and entry into CD4 T cells are mediated by two receptors, CD4 and CXCR4. This receptor requirement can be abrogated by pseudotyping the virion with the vesicular stomatitis virus glycoprotein (VSV-G) that mediates viral entry through endocytosis. The VSV-G-pseudotyped HIV is highly infectious for transformed cells, although the virus circumvents the viral receptors and the actin cortex. In HIV infection, gp120 binding to the receptors also transduces signals. Recently, we demonstrated a unique requirement for CXCR4 signaling in HIV latent infection of blood resting CD4 T cells. Thus, we performed parallel studies in which the VSV-G-pseudotyped HIV was used to infect both transformed and resting T cells in the absence of coreceptor signaling. Our results indicate that in transformed T cells, the VSV-G-pseudotyping results in lower viral DNA synthesis but a higher rate of nuclear migration. However, in resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration. The viral particles entering through the endocytotic pathway were destroyed within 1–2 days. These results indicate that the VSV-G-mediated endocytotic pathway, although active in transformed cells, is defective and is not a pathway that can establish HIV latent infection of primary resting T cells. Our results highlight the importance of the genuine HIV envelope and its signaling capacity in the latent infection of blood resting T cells. These results also call for caution on the endocytotic entry model of HIV-1, and on data interpretation where the VSV-G-pseudotyped HIV was used for identifying HIV restriction factors in resting T cells

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

The macrophage in HIV-1 infection: From activation to deactivation?

Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-γ display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care