Interaction Between Nucleoside Diphosphate Kinase And Graphene Oxide And Its Impact On Cardiovascular Diseases

Here we report possibly for the first time the computational understanding of the interactions between the nanomaterial Graphene Oxide (GO) and the enzyme Nuclear Diphosphate Kinase (NDPK) and its implications. Nanoscale Molecular Dynamics (NAMD) and Visual Molecular Dynamics (VMD) were used to run simulations and analyze the interactions between NDPK and GO. The simulations have run for 100 ns, and it is observed that GO is able to block the active site of the enzyme. Graphene oxide is being used because of its excellent biocompatibility, high water dispersibility, and large surface area. NDPK has numerous roles in the body, such as activating G-proteins and transferring a phosphate from ATP to GDP (resulting in ADP and GTP). It also plays a role in cell proliferation, development, signal transduction, endocytosis, etc[2]. Normally, increased activity of NDPK yields the synthesis of the second messenger cyclic adenosine monophosphate (cAMP) . However, during heart failure, NDPK suppresses cAMP formation due to altered signal transduction pathways via G-proteins. In a healthy heart, nitric oxide (NO) is produced by the body in the endothelium that lines the walls of blood vessels so that the veins and arteries can dilate and blood can flow through the body. However, during heart failure, the endothelium lining is damaged, which inhibits the production of NO. cAMP signal transduction pathways have the potential to produce NO after the endothelium lining is in the process of being damaged . Therefore, when NDPK suppresses cAMP during heart failure, it in turn inhibits the production of nitric oxide— which is crucial for a healthy heart. Using NAMD simulations and analysis using VMD, it is observed that graphene oxide is attracted to the active site of NDPK. Strong interactive forces (van der Waals forces) exist between the primary residue of the active site of NDPK (histidine 118) and graphene oxide. Also, throughout the simulation, the structure of the enzyme is preserved. From the 100 ns worth of simulation, it is observed that the graphene oxide blocks the primary residue of the active site of NDPK and can therefore cease the enzyme’s function, lower the rate of reaction, and potentially affect heart failure

Inhibition of Allergic Inflammation in a Murine Model of Asthma by Expression of a Dominant-Negative Mutant of GATA-3

AbstractThe cytokines IL-4, IL-5, and IL-13, secreted by Th2 cells, have distinct functions in the pathogenesis of asthma. We have previously shown that the transcription factor GATA-3 is expressed in Th2 but not Th1 cells. However, it was unclear whether GATA-3 controls the expression of all Th2 cytokines. Expression of a dominant-negative mutant of GATA-3 in mice in a T cell–specific fashion led to a reduction in the levels of all the Th2 cytokines IL-4, IL-5, and IL-13. Airway eosinophilia, mucus production, and IgE synthesis, all key features of asthma, were severely attenuated in the transgenic mice. Thus, targeting GATA-3 activity alone is sufficient to blunt Th2 responses in vivo, thereby establishing GATA-3 as a potential therapeutic target in the treatment of asthma and allergic diseases

An Assessment Of The AFL Mask® And LUNA Wallmount, The New Developments In The AirPurifier Industry For Preventing The Airborne Pathogens

The current unprecedented situation with the COVID-19 (Coronavirus Disease 2019) poses a great challenge to the scientific world, demanding immediate development of technologies to fight with and prevent transmission of pathogens, especially in regards to airborne pathogens and surface contaminants. It also urges us to reevaluate designs of advanced Personal Protective Equipment (PPE). We have been working on the development and assessment of the AFL-Photo Catalytic Oxidation (AFLPCO®) Nanotechnology to combat with airborne pathogens and different forms of impurities and pollutants present in the indoor air. Various types of facemasks are available in the world market and have become the most important personal protective equipment for healthcare workers and the public. Depending upon their filters, they can provide protection against dreaded contagious diseases and several types of pollution. With the current 2 spread of the COVID-19 Pandemic, facemasks and powerful air purification equipment are considered as lifesaving apparatus necessary for survival and living a healthy life. The facemasks filter fine airborne particles from reaching the respiratory system and prevent infection. We have designed a new type of facemask, AFL Mask® and LUNA Wall Mount Sanifier® air purification unit to combat with the airborne pathogen and increased air pollution. The AFL Mask® has proven to prevent the entry of the PM2.5 and airborne pathogen up to 99% and provide internal air, reducing the chances of building up moisture on the face. This newly designed AFL Mask® and LUNA Wall Mount Sanifier® can be used to prevent the pathogens and particulate matters significantly. We also tested the LUNA Wall Mount Sanifier® (LNT2-6000 Model), AFL Car Sanifier® and AFL Mask® for Ozone emission. All the equipment tested were proven safe to international standards in terms of Ozone emission. &nbsp

A Computational Approach for Understanding the Interactions between Graphene Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure

During a heart failure, an increased content and activity of nucleoside diphosphate kinase (NDPK) in the sarcolemmal membrane is responsible for suppressing the formation of the second messenger cyclic adenosine monophosphate (cAMP)—a key component required for calcium ion homeostasis for the proper systolic and diastolic functions. Typically, this increased NDPK content lets the surplus NDPK react with a mutated G protein in the beta-adrenergic signal transduction pathway, thereby inhibiting cAMP synthesis. Thus, it is thus that inhibition of NDPK may cause a substantial increase in adenylate cyclase activity, which in turn may be a potential therapy for end-stage heart failure patients. However, there is little information available about the molecular events at the interface of NDPK and any prospective molecule that may potentially influence its reactive site (His118). Here we report a novel computational approach for understanding the interactions between graphene oxide (GO) and NDPK. Using molecular dynamics, it is found that GO interacts favorably with the His118 residue of NDPK to potentially prevent its binding with adenosine triphosphate (ATP), which otherwise would trigger the phosphorylation of the mutated G protein. Therefore, this will result in an increase in cAMP levels during heart failure.https://doi.org/10.3390/nano802005

Atomic scale chemical fluctuation in LaSrVMoO6: A proposed halfmetallic antiferromagnet

Half metallic antiferromagnets (HMAFM) have been proposed theoretically long ago but have not been realized experimentally yet. Recently, a double perovskite compound, LaSrVMoO6, has been claimed to be an almost real HMAFM system. Here, we report detailed experimental and theoretical studies on this compound. Our results reveal that the compound is neither a half metal nor an ordered antiferromagnet. Most importantly, an unusual chemical fluctuation is observed locally, which finally accounts for all the electronic and magnetic properties of this compound.Comment: 10 pages, 3 figures, 3 table

Specially treated woven jute geotextiles for river bank protection

In this paper, studies on treatment of jute geotextile with isothiazolinone and fluorocarbon derivatives to impart antimicrobial and water repellent property have been reported for its improved end use specific performance. It is observed that the treated jute geotextile possesses higher durability in water as well as soil-water ambience

Intensity modulated radiotherapy in carcinoma cervix with metastatic para-aortic nodes: an institutional experience from a Regional Cancer Centre of Eastern India

BACKGROUND: Cervical cancer is a major health problem, especially in developing countries like India. Extended field radiotherapy (EFRT) for cancer cervix treatment remains a challenging task for radiation oncologists. In the last decade studies have shown that EFRT using intensity modulated radiotherapy (IMRT) is feasible in treating gynaecological malignancies but there is a dearth of literature on this specific topic from this part of the world where patient profile differs greatly in several aspects from that of the western world. The aim of the study was evaluation of treatment response and toxicity profile in cases of carcinoma cervix with metastatic para-aortic nodes treated with intensity modulated radiotherapy technique. MATERIALS AND METHODS: In this retrospective study the treatment records of 45 para-aortic node positive cervical cancer patients treated with EFRT (IMRT) and concurrent cisplatin were analysed for evaluation of loco-regional control and toxicities. RESULTS: Forty-four patients received full course of treatment. Among those 44 patients, 93.2% achieved complete response. Overall, the treatment was tolerated well and toxicities were within acceptable limits. Acute grade 3-4 toxicities were observed mostly in the form of anaemia and leucopenia. Most common late toxicities were those of small and large intestine. CONCLUSION: EFRT with concurrent chemotherapy was successfully delivered for para-aortic nodes positive cervical cancer patients in Indian scenario where under-nutrition, infection, anaemia and several other factors adversely influence treatment outcome. Pelvic and para-aortic control rates were satisfactory. The technique was associated with an acceptable acute and late toxicity profile

Interleukin-22 inhibits respiratory syncytial virus production by blocking virus-mediated subversion of cellular autophagy

Respiratory syncytial virus (RSV) infection can cause severe bronchiolitis in infants requiring hospitalization, whereas the elderly and immunocompromised are prone to RSV-induced pneumonia. RSV primarily infects lung epithelial cells. Given that no vaccine against RSV is currently available, we tested the ability of the epithelial-barrier protective cytokine interleukin-22 (IL-22) to control RSV production. When used in a therapeutic modality, IL-22 efficiently blunted RSV production from infected human airway and alveolar epithelial cells and IL-22 administration drastically reduced virus titer in the lungs of infected newborn mice. RSV infection resulted in increased expression of LC3B, a key component of the cellular autophagic machinery, and knockdown of LC3B ablated virus production. RSV subverted LC3B with evidence of co-localization and caused a significant reduction in autophagic flux, both reversed by IL-22 treatment. Our findings inform a previously unrecognized anti-viral effect of IL-22 that can be harnessed to prevent RSV-induced severe respiratory disease