Bruton\u27s Tyrosine Kinase Targeting in Multiple Myeloma.

Multiple myeloma (MM), a clonal plasma cell disorder, disrupts the bones\u27 hematopoiesis and microenvironment homeostasis and ability to mediate an immune response against malignant clones. Despite prominent survival improvement with newer treatment modalities since the 2000s, MM is still considered a non-curable disease. Patients experience disease recurrence episodes with clonal evolution, and with each relapse disease comes back with a more aggressive phenotype. Bruton\u27s Tyrosine Kinase (BTK) has been a major target for B cell clonal disorders and its role in clonal plasma cell disorders is under active investigation. BTK is a cytosolic kinase which plays a major role in the immune system and its related malignancies. The BTK pathway has been shown to provide survival for malignant clone and multiple myeloma stem cells (MMSCs). BTK also regulates the malignant clones\u27 interaction with the bone marrow microenvironment. Hence, BTK inhibition is a promising therapeutic strategy for MM patients. In this review, the role of BTK and its signal transduction pathways are outlined in the context of MM

Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy

Drug resistance, a major challenge in cancer therapy, is typically attributed to mutations and genetic heterogeneity. Emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance. However, the underlying mechanisms remain poorly understood. Here, we present a new mathematical approach with game theoretical underpinnings that we developed to model real-time growth data of non-small cell lung cancer (NSCLC) cells and discern patterns in response to treatment with cisplatin. We show that the cisplatin-sensitive and cisplatin-tolerant NSCLC cells, when co-cultured in the absence or presence of the drug, display dynamic group behavior strategies. Tolerant cells exhibit a \u27persister-like\u27 behavior and are attenuated by sensitive cells; they also appear to \u27educate\u27 sensitive cells to evade chemotherapy. Further, tolerant cells can switch phenotypes to become sensitive, especially at low cisplatin concentrations. Finally, switching treatment from continuous to an intermittent regimen can attenuate the emergence of tolerant cells, suggesting that intermittent chemotherapy may improve outcomes in lung cancer

Risk of secondhand smoke exposure and severity of COVID-19 infection: multicenter case–control study

IntroductionExposure to secondhand smoke (SHS) is an established causal risk factor for cardiovascular disease (CVD) and chronic lung disease. Numerous studies have evaluated the role of tobacco in COVID-19 infection, severity, and mortality but missed the opportunity to assess the role of SHS. Therefore, this study was conducted to determine whether SHS is an independent risk factor for COVID-19 infection, severity, mortality, and other co-morbidities.MethodologyMulticentric case–control study was conducted across six states in India. Severe COVID-19 patients were chosen as our study cases, and mild and moderate COVID-19 as control were evaluated for exposure to SHS. The sample size was calculated using Epi-info version 7. A neighborhood-matching technique was utilized to address ecological variability and enhance comparability between cases and controls, considering age and sex as additional matching criteria. The binary logistic regression model was used to measure the association, and the results were presented using an adjusted odds ratio. The data were analyzed using SPSS version 24 (SPSS Inc., Chicago, IL, USA).ResultsA total of 672 cases of severe COVID-19 and 681 controls of mild and moderate COVID-19 were recruited in this study. The adjusted odds ratio (AOR) for SHS exposure at home was 3.03 (CI 95%: 2.29–4.02) compared to mild/moderate COVID-19, while SHS exposure at the workplace had odds of 2.19 (CI 95%: 1.43–3.35). Other factors significantly related to the severity of COVID-19 were a history of COVID-19 vaccination before illness, body mass index (BMI), and attached kitchen at home.DiscussionThe results of this study suggest that cumulative exposure to secondhand cigarette smoke is an independent risk factor for severe COVID-19 illness. More studies with the use of biomarkers and quantification of SHS exposure in the future are needed

Curcumin-Loaded Apotransferrin Nanoparticles Provide Efficient Cellular Uptake and Effectively Inhibit HIV-1 Replication In Vitro

Curcumin (diferuloylmethane) shows significant activity across a wide spectrum of conditions, but its usefulness is rather limited because of its low bioavailability. Use of nanoparticle formulations to enhance curcumin bioavailability is an emerging area of research.In the present study, curcumin-loaded apotransferrin nanoparticles (nano-curcumin) prepared by sol-oil chemistry and were characterized by electron and atomic force microscopy. Confocal studies and fluorimetric analysis revealed that these particles enter T cells through transferrin-mediated endocytosis. Nano-curcumin releases significant quantities of drug gradually over a fairly long period, ∼50% of curcumin still remaining at 6 h of time. In contrast, intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 µM) is twice more toxic than nano-curcumin (GI(50) = 32.5 µM), nano-curcumin (IC(50)<1.75 µM) shows a higher anti-HIV activity compared to sol-curcumin (IC(50) = 5.1 µM). Studies in vitro showed that nano-curcumin prominently inhibited the HIV-1 induced expression of Topo II α, IL-1β and COX-2, an effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of Topoisomerase II β and TNF α. This point out that nano-curcumin affects the HIV-1 induced inflammatory responses through pathways downstream or independent of TNF α. Furthermore, nano-curcumin completely blocks the synthesis of viral cDNA in the gag region suggesting that the nano-curcumin mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis.Curcumin-loaded apotransferrin nanoparticles are highly efficacious inhibitors of HIV-1 replication in vitro and promise a high potential for clinical usefulness

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

A study on Beijing genotype in the clinical isolates of pulmonary drug-resistant tuberculosis

Background: Mycobacterium tuberculosis (MTB) Beijing strains are spread worldwide and are responsible for major outbreaks of tuberculosis (TB), sometimes spreading multidrug resistance (MDR). Aim: The aim of this study was to explore clinical features associated with the infection with Beijing strains among MDR patients of pulmonary TB in Lucknow and surrounding areas. Materials and Methods: It was a hospital-based epidemiological study. Our study population was selected from all the newly diagnosed patients attending outpatient department and admitted patients of Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India. Those isolates which were characterized to be MTB by morphological and molecular techniques were tested for their resistance against the first-line drugs; after which each patient's isolate was genotyped. Results: The results suggested that the presence of Beijing genotype in 31.78% of strains. Conclusion: Our results predicted that genotypic patterns reveal a large diversity among the MTB Beijing strain population. Increasing frequency of Beijing strains demands further research to unravel the factors behind its propensity to prevail

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Not AvailableThe evidences point out that farmers are keen to adopt drip irrigation, primarily to cope with the scarcity in at least one of three factors of production, namely water, power, and labour. The results indicate that micro irrigation has a positive impact on improving crop productivity and addressed the scarcity of water, power, and labour. The study clearly establishes micro irrigation is a worthy technology for improving water use efficiency and realizing other associated benefitsNot Availabl

Synthesis, insecticidal and antimicrobial activities of some heterocyclic derivatives of quinazolinone

2558-2565Some new 4-phenyl-2,3-dihydro-6-(substitutedaminoethyl)-10-iodo[1,2,4]-triazino[2,3-c]-quina-zolin-5-ones 6-14 have been synthesized from 4-(phenyl-2,3-dihydro-6-methyl-10-iodo [1,2,4]-triazino[2,3-c]quinazolin-5-one 5 by introducing different heterocyclic nuclei. Compounds 5 and 6-14 have been screened for insecticidal, anti-fungal and antibacterial activities. Compound 4-phenyl-2, 3-dihydro-6-(b-naphthylaminoethyl)-10-iodo[1, 2, 4]-triazino[2,3-c]-quinazolin-5-one 14 has been found to be the most potent compound of the present study which shows mortality of insects at 190.6 min while standard compounds exhibit at 280 min at a concentration of 5 g/L. Moreover, this compound also possesses anti-bacterial activity. The structures of these compounds have been elucidated by IR, 1H NMR, mass spectroscopy and elemental analysis