Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced drug efflux, cell death inhibition, and various other molecular and cellular mechanisms, are responsible for the development of resistance against anticancer agents. Drug resistance can also depend on cellular autophagic and hypoxic status. The expression of drug-resistant genes and the regulatory mechanisms that determine drug resistance are also discussed. Methods to circumvent MDR, including immunoprevention, the use of microparticles and nanomedicine might result in better strategies for fighting cancer.

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: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes problems with memory, thinking, and behavior. Currently, there is no drug that can reduce the pathological events of this degenerative disease but symptomatic relief is possible that can abate the disease condition. N-methyl-D-aspartate (NMDA) receptors exert a critical role for synaptic plasticity as well as transmission. Overstimulation of glutamate receptors, predominantly NMDA type, may cause excitotoxic effects on neurons and is recommended as a mechanism for neurodegeneration. Atypical activation of the NMDA receptor has been suggested for AD by synaptic dysfunction. NMDA receptor antagonists especially memantine block the NMDA receptor and can reduce the influx of calcium (Ca2+) ions into neuron, thus, toxic intracellular events are not activated. This review represents the role of NMDA receptors antagonists as potential therapeutic agents to reduce AD. Moreover, this review highlights the repositioning of memantine as a potential novel therapeutic multitargeting agent for AD.

ObjectiveTo estimate the proportion of SARS-CoV-2 and influenza virus coinfection among severe acute respiratory infection (SARI) cases-patients during the first wave of COVID-19 pandemic in Bangladesh.DesignDescriptive study.SettingNine tertiary level hospitals across Bangladesh.ParticipantsPatients admitted as SARI (defined as cases with subjective or measured fever of ≥38 C° and cough with onset within the last 10 days and requiring hospital admission) case-patients.Primary and secondary outcomesProportion of SARS-CoV-2 and influenza virus coinfection and proportion of mortality among SARI case-patients.ResultsWe enrolled 1986 SARI case-patients with a median age: 28 years (IQR: 1.2–53 years), and 67.6% were male. Among them, 285 (14.3%) were infected with SARS-CoV-2; 175 (8.8%) were infected with the influenza virus, and five (0.3%) were coinfected with both viruses. There was a non-appearance of influenza during the usual peak season (May to July) in Bangladesh. SARS-CoV-2 infection was significantly more associated with diabetes (14.0% vs 5.9%, p<0.001) and hypertension (26.7% vs 11.5%, p<0.001). But influenza among SARI case-patients was significantly less associated with diabetes (4.0% vs 7.4%, p=0.047) and hypertension (5.7% vs 14.4%, p=0.001). The proportion of in-hospital deaths among SARS-CoV-2 infected SARI case-patients were higher (10.9% (n=31) vs 4.4% (n=75), p<0.001) than those without SARS-CoV-2 infection; the proportion of postdischarge deaths within 30 days was also higher (9.1% (n=25) vs 4.6% (n=74), p=0.001) among SARS-CoV-2 infected SARI case-patients than those without infection. No in-hospital mortality or postdischarge mortality was registered among the five coinfected SARI case-patients.ConclusionsOur findings suggest that coinfection with SARS-CoV-2 and influenza virus was not very common and had less disease severity considering mortality in Bangladesh. There was no circulating influenza virus during the influenza peak season during the COVID-19 pandemic in 2020. Future studies are warranted for further exploration.

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Mass spectrometry imaging (MSI) is well-known for the non-labeling visualization of analytes, including drugs and their metabolites in biological samples. In this study, we applied three different tools of MSI, desorption electrospray ionization (DESI)-MSI, matrix-assisted laser desorption ionization (MALDI)-MSI, and a newly developed atmospheric pressure (AP)-MALDI-MSI known as iMScopeTM QT for rapid mapping of imipramine, chloroquine, and their metabolites in C57BL/6 male wild-type mice. Among three MSI tools, better detection capability for targeted drugs at higher speed (up to 32 pixels/s) was observed in iMScope QT. It revealed that imipramine and its metabolites were significantly accumulated in the renal cortex of mice, but chloroquine and its metabolites were highly accumulated in the renal pelvis and renal medulla of mice. Additionally, a higher accumulation of imipramine was noted in the thalamus, hypothalamus, septum, and hindbrain of mice brains. However, chloroquine and its metabolites showed notable accumulation in the lateral ventricle, fourth ventricle, and fornix of the mice brains. These findings of our study can be helpful in understanding clinically relevant properties, efficacy, and potential side effects of these drugs. Our study also showed the potentiality of iMScope QT for rapid mapping of small drugs and their metabolites in biological samples.

Introduction The COVID-19 pandemic is thought to have led to increased “inappropriate” or “unjustified” seeking and consumption of antibiotics by individuals in the community. However, little reference has been made to antibiotic seeking and using behaviors from the perspectives of users in Bangladesh during this health crisis. Purpose This study seeks to document how antibiotic medicines are sought and used during a complex health crisis, and, within different contexts, what are the nuanced reasons why patients may utilize these medicines sub-optimally. Methods We used an exploratory, qualitative design. Forty semi-structured telephone interviews were conducted with people diagnosed with COVID-19 (n=20), who had symptoms suggestive of COVID-19 (n=20), and who had received care at home in two cities between May and June 2021 in Bangladesh. In this study, an inductive thematic analysis was performed. Results The analysis highlighted the interlinked relationships of antibiotic seeking and consumption behaviors with the diversity of information disseminated during a health crisis. Antibiotic-seeking behaviors are related to previous experience of use, perceived severity of illness, perceived vulnerability, risk of infection, management of an “unknown” illness and anxiety, distrust of expert advice, and intrinsic agency on antimicrobial resistance (AMR). Suboptimal adherence, such as modifying treatment regimes and using medication prescribed for others, were found to be part of care strategies used when proven therapeutics were unavailable to treat COVID-19. Early cessation of therapy was found to be a rational practice to avoid side effects and unknown risks. Conclusion Based on the results, we highly recommend the take up of a pandemic specific antimicrobial stewardship (AMS) program in the community. To deliver better outcomes of AMS, incorporating users’ perspectives could be a critical strategy. Therefore, a co-produced AMS intervention that is appropriate for a specific cultural context is an essential requirement to reduce the overuse of antibiotics during the COVID-19 pandemic and beyond.

Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, has significant health benefits. Previous studies reported decreased levels of DHA and DHA-containing phosphatidylcholines in the brain of animals suffering from Alzheimer’s disease, the most common type of dementia; furthermore, DHA supplementation has been found to improve brain DHA levels and memory efficiency in dementia. Oil extracted from the seeds of Plukenetia volubilis (green nut oil; GNO) is also expected to have DHA like effects as it contains approximately 50% α-linolenic acid, a precursor of DHA. Despite this, changes in the spatial distribution of DHA in the brain of animals with dementia following GNO or DHA supplementation remain unexplored. In this study, desorption electrospray ionization imaging mass spectrometry (DESI-IMS) was applied to observe the effects of GNO or DHA supplementation upon the distribution of DHA in the brain of male senescence-accelerated mouse-prone 8 (SAMP8) mice, a mouse model of dementia. DESI-IMS revealed that brain DHA distribution increased 1.85-fold and 3.67-fold in GNO-fed and DHA-fed SAMP8 mice, respectively, compared to corn oil-fed SAMP8 mice. Memory efficiency in SAMP8 mice was also improved by GNO or DHA supplementation. In summary, this study suggests the possibility of GNO or DHA supplementation for the prevention of dementia.