Cell Surface Binding and Lipid Interactions behind Chemotherapy-Drug-Induced Ion Pore Formation in Membranes

Chemotherapy drugs (CDs) disrupt the lipid membrane's insulation properties by inducing stable ion pores across bilayer membranes. The underlying molecular mechanisms behind pore formation have been revealed in this study using several methods that confirm molecular interactions and detect associated energetics of drugs on the cell surface in general and in lipid bilayers in particular. Liposome adsorption and cell surface binding of CD colchicine has been demonstrated experimentally. Buffer dissolved CDs were considerably adsorbed in the incubated phospholipid liposomes, measured using the patented 'direct detection method'. The drug adsorption process is regulated by the membrane environment, demonstrated in cholesterol-containing liposomes. We then detailed the phenomenology and energetics of the low nanoscale dimension cell surface (membrane) drug distribution, using atomic force microscopy (AFM) imaging what addresses the surface morphology and measures adhesion force (reducible to adhesive energy). Liposome adsorption and cell surface binding data helped model the cell surface drug distribution. The underlying molecular interactions behind surface binding energetics of drugs have been addressed in silico numerical computations (NCs) utilizing the screened Coulomb interactions among charges in a drug-drug/lipid cluster. Molecular dynamics (MD) simulations of the CD-lipid complexes detected primarily important CD-lipid electrostatic and van der Waals (vdW) interaction energies. From the energetics point of view, both liposome and cell surface membrane adsorption of drugs are therefore obvious findings. Colchicine treated cell surface AFM images provide a few important phenomenological conclusions, such as drugs bind generally with the cell surface, bind independently as well as in clusters of various sizes in random cell surface locations. The related adhesion energy decreases with increasing drug cluster size before saturating for larger clusters. MD simulation detected electrostatic and vdW and NC-derived charge-based interactions explain molecularly of the cause of cell surface binding of drugs. The membrane binding/association of drugs may help create drug-lipid complexes with specific energetics and statistically lead to the creation of ion channels. We reveal here crucial molecular understanding and features of the pore formation inside lipid membranes that may be applied universally for most of the pore-forming existing agents and novel candidate drugs

Knowledge, attitudes, practices, and its associated factors toward COVID-19 pandemic among Bangladeshi older adults.

BackgroundThe newly emerged COVID-19 has an unprecedented impact on all classes of people, particularly the elderly. The knowledge, attitudes, and practices (KAP) of older adults toward COVID-19 are currently unknown. This study aimed to investigate the KAP and its associated factors toward COVID-19 among older adults in Bangladesh.MethodsA cross-sectional survey was conducted from April to May 2021 among Bangladeshi older adults. Face-to-face interviews were used to collect data from five selected divisions in Bangladesh using simple random sampling. The questionnaire consisted of socio-demographic characteristics, disease conditions, and KAP toward COVID-19. Descriptive statistics, t-tests, one-way analysis of variance (ANOVA), and logistic regression analyses were performed.ResultsOut of 900 respondents, the majority of older adults (82.9%) indicated that COVID-19 is a viral disease and the major clinical symptom of COVID-19 (86.5%). Only 22.1% of participants always washed their hands with soap or hand sanitizer, and 27.6% wore a mask to protect against the virus when going outside the home. Overall, 55.2% had adequate knowledge, 50.2% had positive attitudes toward COVID-19 and only 22.7% had good practices. Out of 30 scores, mean score values were 20.8±6.7 in the knowledge section, 21.2±4.3 in the attitude section, and 11.3±6.7 in the practice section out of 30. In binary logistic regression analysis, factors associated with poor knowledge, and practices were being male, aged >70 years, having a primary education, less income ConclusionThe findings highlight the need for immediate implementation of health education programs and adequate intervention programs for COVID-19 which integrates consideration of associated factors to improve the level of older adults' knowledge, attitudes, and practices

Lipid Specific Membrane Interaction of Aptamers and Cytotoxicity

We aim to discover diagnostic tools to detect phosphatidylserine (PS) externalization on apoptotic cell surface using PS binding aptamers, AAAGAC and TAAAGA, and hence to understand chemotherapy drug efficacy when inducing apoptosis into cancer cells. The entropic fragment-based approach designed aptamers have been investigated to inspect three aspects: lipid specificity in aptamers’ membrane binding and bilayer physical properties-induced regulation of binding mechanisms, the apoptosis-induced cancer cell surface binding of aptamers, and the aptamer-induced cytotoxicity. The liposome binding assays show preferred membrane binding of aptamers due to presence of PS in predominantly phosphatidylcholine-contained liposomes. Two membrane stiffness reducing amphiphiles triton X-100 and capsaicin were found to enhance membrane’s aptamer adsorption suggesting that bilayer physical properties influence membrane’s adsorption of drugs. Microscopic images of fluorescence-tagged aptamer treated LoVo cells show strong fluorescence intensity only if apoptosis is induced. Aptamers find enhanced PS molecules to bind with on the surface of apoptotic over nonapoptotic cells. In cytotoxicity experiments, TAAAGA (over poor PS binding aptamer CAGAAAAAAAC) was found cytotoxic towards RBL cells due to perhaps binding with nonapoptotic externalized PS randomly and thus slowly breaching plasma membrane integrity. In these three experimental investigations, we found aptamers to act on membranes at comparable concentrations and specifically with PS binding manner. Earlier, we reported the origins of actions through molecular mechanism studies—aptamers interact with lipids using mainly charge-based interactions. Lipids and aptamers hold distinguishable charge properties, and hence, lipid–aptamer association follows distinguishable energetics due to electrostatic and van der Waals interactions. We discover that our PS binding aptamers, due to lipid-specific interactions, appear as diagnostic tools capable of detecting drug-induced apoptosis in cancer cells

Socio-demographic and clinical characteristics of the older people (n = 900).

Socio-demographic and clinical characteristics of the older people (n = 900).</p

Respondents practice toward COVID-19 pandemic (n = 900).

Respondents practice toward COVID-19 pandemic (n = 900).</p

Association between sociodemographic characteristics and mean KAP score among Bangladeshi older people (n = 900).

Association between sociodemographic characteristics and mean KAP score among Bangladeshi older people (n = 900).</p

Respondents’ knowledge towards COVID-19 pandemic (n = 900).

Respondents’ knowledge towards COVID-19 pandemic (n = 900).</p

Respondents attitude towards COVID-19 pandemic (n = 900).

Respondents attitude towards COVID-19 pandemic (n = 900).</p

Factors associated with poor knowledge, negative attitudes, and poor practices toward COVID-19 in using a multivariate logistic regression model (n = 900).

Factors associated with poor knowledge, negative attitudes, and poor practices toward COVID-19 in using a multivariate logistic regression model (n = 900).</p