Functionalized Carbon Nano-Onions as a Smart Drug Delivery System for the Poorly Soluble Drug Carmustine for the Management of Glioblastoma.

The drug delivery system for transporting anticancer agents to targeted tissues in the body is a challenging issue. In search of a suitable biocompatible carrier having controlled and sustained drug release properties of poorly soluble drugs, carbon nano-onions (CNOs) were loaded with an anticancer drug, bis-chloroethyl nitrosourea (BCNU/carmustine). CNOs being autofluorescent, drug-loaded functionalized CNOs (f-CNO-BCNU) can be detected in vivo. Transmission electron microscopy (TEM) and differential light scattering (DLS) techniques were used to analyze the sizes of these f-CNOs. The molecular study revealed that the f-CNO-BCNU readily and noncovalently binds with the folate receptors present on the cancer cell surface in excess. Computer modeling and molecular dynamics simulation followed by binding free energy calculation shows f-CNOs have -29.9 kcal/mol binding free energy, and it noncovalently binds the receptor FRα using loop dynamics of three essential loops present in the protein along with polar stabilization interactions provided by Asp55 and Glu86 residues present in the active site. The f-CNO effectively decreased cancer cell viability with a low IC50 value (the concentration that led to 50% killing of the cells). The cell-based Franz diffusion assay was performed to study the drug release profile. The f-CNO-BCNUs also decreased the mitochondrial membrane potential of U87 cells, increased reactive oxygen species release, and caused a loss of mitochondrial membrane integrity. The f-CNOs also increased the percentage of apoptotic cells observed by the Annexin V assay. Based on observed results, it can be concluded that the f-CNO-BCNU efficiently targets the cancer cells, enhances the bioavailability of carmustine, and can be used as a smart chemotherapeutic agent. This strategy offers better patient compliance and greater bioavailability of the drug.

Recent updates on the role of phytochemicals in the treatment of glioblastoma multiforme.

ABSTRACTS: Glioblastoma multiforme (GBM) is a malignant type of glioma. This malignant brain tumor is a devastating disease and is often fatal. The spectrum of illness and poor prognosis associated with brain tumors extract a terrible toll on patients and their families. The inoperability of these tumors and resistance to radiation and chemotherapy contribute to the fatal outcome of this disease. Thus, scientists are hunting for the new drug candidate and safer chemoprevention, especially the phytochemicals that possess potent anti-tumor properties. We have summarized the cellular and biochemical impacts of different phytochemicals that can successfully encounter GBM via induction of apoptosis and active interference in different cell and molecular pathways associated with GBM in brain tumors. The in silico predictive model determining the blood-brain barrier permeability of the compound and their potential druggability are discussed in the review.

Change in Normal Health Condition Due to COVID-19 Infection: Analysis by ANFIS Technique.

The COVID-19 pandemic has crippled the world population. Our present work aims to formulate a model to analyze the change in normal health conditions due to COVID-19 infection. For this purpose, we have collected data of seven parameters, namely, age, systolic pressure (SP), diastolic paper (DP), respiratory distress (RD), fasting blood sugar (FBS), cholesterol (CHL), and insomnia (INS) of 156 persons of Birnagar municipality, Nadia, India; before and after COVID-19 infection. Ultimately, using an adaptive neuro-fuzzy inference system (ANFIS), we have formulated our desired model, a Takagi-Sugeno fuzzy inference system. Further, with the help of this model, we have established one's change in health condition with age due to COVID-19 infection. Finally, we have derived that older people are more affected by COVID-19 infection than younger people.

An ANFIS model-based approach to investigate the effect of lockdown due to COVID-19 on public health.

During the first and second quarters of the year 2020, most of the countries had implemented complete or partial lockdown policies to slow down the transmission of the COVID-19. To cultivate the effect of lockdown due to COVID-19 on public health, we have collected the data of six primary parameters, namely systolic blood pressure, diastolic blood pressure, fasting blood sugar, insomnia, cholesterol, and respiratory distress of 200 randomly chosen people from a municipality region of West Bengal, India before and after lockdown. With the help of these data and Adaptive Neuro-Fuzzy Inference System (ANFIS), we have formulated a model that has established that lockdown due to COVID-19 has negligible impacts on the individuals with better health condition but has significant effects on the health conditions to those populations who have poor health.

Quercetin: a silent retarder of fatty acid oxidation in breast cancer metastasis through steering of mitochondrial CPT1.

BACKGROUND: Recent evidence confirmed that the maximum energy in metastatic breast cancer progression is supplied by fatty acid oxidation (FAO) governed by a rate-limiting enzyme, carnitine palmitoyltransferase 1 (CPT1). Therefore, the active limitation of FAO could be an emerging aspect to inhibit breast cancer progression. Herein, for the first time, we have introduced quercetin (QT) from a non-dietary source (Mikania micrantha Kunth) to limit the FAO in triple-negative breast cancer cells (TNBC) through an active targeting of CPT1. METHODS: Molecular quantification of QT was confirmed through high-performance thin-layer chromatography (HPTLC). Computational docking analyses predicted the binding affinity of QT to CPT1. Cell-based seahorse energy efflux investigated the mitochondrial respiration rate, glycolytic function and ATP production rate. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) investigated the FAO-associated gene expression. Matrigel cell invasion and fluorescence-activated cell sorting analyses investigated anti-metastatic and apoptotic cell death induction activities, respectively. In vivo antitumor activities were checked using the female breast cancer mice (BALB/c) model. RESULTS: QT resulted in a significant reduction in the intracellular mitochondrial respiration and glycolytic function, limiting extensive ATP production. In turn, QT elevated the reactive oxygen species (ROS) and depleted antioxidant levels to induce anti-metastatic and cell apoptosis activities. qRT-PCR resulted in active healing of altered FAO-associated gene expression which was well predicted through the successful in silico molecular binding potentiality of QT to CPT1. Subsequently, QT has shown excellent in vivo antitumor activities through the altered lipid profile and oxidative stress-healing capabilities. CONCLUSIONS: All the obtained data significantly grounded the fact that QT could be a promising metabolism-targeted breast cancer therapeutic.

COVID-19 and central nervous system interplay: A big picture beyond clinical manifestation.

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) has been declared a pandemic. Global research updates confirm that the infected patients manifest a range of clinical symptoms and sometimes remain entirely asymptomatic, posing a greater threat to the people coming in contact. Despite several case reports coming up every day, our knowledge about the neurotropic mechanism of the SARS-CoV-2, immunological responses, and the mode of disease progression and mechanism of crosstalk between the central nervous system (CNS), heart, lungs, and other major organs is not complete. Report of anosmia, ataxia, dysgeusia, and altered psychological status of the infected COVID-19 patients offers some clue to the possible route of viral entry and multiplication. In this review, we have critically assessed the involvement of CNS dysregulation in COVID-19 patients. The probable mechanism of immunological responses, the impairment of the coagulation pathway, the onset of cytokine storm, its interplay with the HPA axis, and hypoxia are discussed in detail here. Based on the latest research findings and some case reports of hospitalized COVID-19 patients, it is evident that the CNS involvement in disease progression is alarming. Accurate and timely detection of viral load in CNS is necessary to allow prompt and effective treatment modalities.