Evolving utility of exosomes in pancreatic cancer management

Despite the development of newer oncological treatment,the survival of patients with pancreatic cancer(PC)remains poor.Recent studies have identified exosomes as essential mediators of intercellular communications and play a vital role in tumor initiation,metastasis and chemoresistance.Thus,the utility of liquid biopsies using exosomes in PC management can be used for early detection,diagnosis,monitoring as well as drug delivery vehicles for cancer therapy.This review summarizes the function,and clinical applications of exosomes in cancers as minimally invasive liquid biomarker in diagnostic,prognostic and therapeutic roles.

Decline of Japanese encephalitis in Eastern Uttar Pradesh,India,2009-2019

Japanese encephalitis(JE),one of the major viral encephalitides,is caused by Flavivirus circulating in rural areas of Asia and Western Pacific regions[1]and is a neglected tropical viral disease due to its endemicity[2].The culicine mosquitoes,mainly of Culex tritaeniorhynchus and Culex vishnui group,are the vectors of JE virus(JEV)[1].Being a neurologic infection,JE manifests with a set of serious symptoms leading to death in many cases and/or change in behaviour of the patients leading to permanent disability[3].

Protective role of concomitant administration of flax lignan concentrate and omega-3-fatty acid on myocardial damage in doxorubicin-induced cardiotoxicity

The severe cardiotoxicity incurred due to doxorubicin limits the use of their therapeutic potential.The current study aims to investigate the cardioprotective effect of concomitant administration of flax lignan concentrate(FLC)and omega-3-fatty acid(ω-3-FA)on myocardial damage in doxorubicin-induced cardiotoxicity in Wistar rats.Cardiotoxicity was induced by intraperitoneal injection of doxorubicin(4 mg/kg)on day 7th,14th,21st and 28th day in normal saline.Concomitant administration of FLC(500 mg/kg)andω-3-FA(1 mL/kg)lowered TNF-αlevel,normalized ST,QT and mean arterial blood pressure,elevation in endogenous enzymes levels such as glutathione and lowering in malondialdehyde,super oxide dismutase followed by normalized lipid profile and reduced the mortality rate.The treatment had antiapoptotic potential at cellular level also histopathology of heart tissue(light and electron microscopical).Thus concomitant action of FLC andω-3-FA may be antioxidant,antihyperlipidemic,anti-inflammatory and anti-apoptotic actions seem to the probable mechanisms in doxorubicin induced cardiotoxicity.It can be concluded that FLC andω-3-FA both have distinct mechanism for cardioprotection and hence the additive effect was observed in the present study due to concomitant administration of FLC andω-3-FA.©2013 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Activation of angiotensin Ⅱ type 1 receptors in the median preoptic nucleus induces a diuretic and natriuretic response in rats

Objective： To investigate the effect of activation of angiotensin Ⅱ（AngⅡ） type 1 （AT1） receptors in the median preoptic nucleus （MnPO） of rats on renal sodium excretion. Methods： After anesthesia, the rats were injected into the MnPO via an implanted cannula. Urine samples were collected via a bladder cannula, and the urine sodium concentration was assayed with flame spectrophotometry. The serum level of endogenous digitalis-like factor （EDLF） and Na^＋,K^＋-ATPase activity in the renal cortex tissue were assayed respectively with a radioimmunoassay and with an ammonium molybdophosphate-based kit. Results： Both the urinary volume and the sodium excretion peaked 60 min after AngⅡ was administered into the MnPO. The responses were accompanied by an increase in serum EDLF and a decrease in Na^＋,K^＋-ATPase activity in the renal cortex. The responses of diuresis and natriuresis, as well as an increase in serum EDLF and a decrease in Na^＋,K^＋-ATPase activity in the renal cortex induced by MnPO adminstration with AngⅡ were inhibited by pior treatment with the AngⅡ receptor blocking agent losartan into the MnPO. Conclusion： These results suggest that activation of AT1 receptors in the MnPO of rat induces diuretic and natriuretic responses. The responses are associated with an increase release of EDLF and with the inhibition of Na^＋,K^＋-ATPase activity in renal cortex tissue.

Does a biological link exist between periodontitis and rheumatoid arthritis?

Periodontitis or Periodontal disease(PD) and Rheumatoid arthritis(RA) are two the most common chronic inflammatory diseases. Periodontitis is a biofilm associated destructive inflammatory disease of the periodontium caused by specific microorganisms. Rheumatoid arthritis is an autoimmune condition and is identified by elevated serum autoantibody titre directed against citrullinated peptides or rheumatoid factor. Periodontitis may involve some elements of autoimmunity. Recent studies have established that PD and RA show a common pathway and could be closely associated through a common dysregulation and dysfunction in inflammatory mechanism. The enzyme peptidyl arginine deiminase(PAD), expressed by Porphyromonas gingivalis(P. gingivalis) is responsible for the enzymatic deimination of arginine residuals to citrulline resulting in protein citrullination and its increased accumulation in RA.Citrullination by PAD may act as a putative biologic link between PD and RA. Association of Human leukocytic antigen-DR4 antigen has been established both with RA and PD. Several interleukins and inflammatory mediators(ILs) and Nuclear factor kappa beta ligand are linked to these common chronic inflammatory diseases. Antibodies directed against heat shock protein(hsp 70 ab) of P. gingivalis, P. melanogenicus and P. intermedia are raised in PD as well as RA. Both the conditions share many pathological and immunological similarities. Bacterial infection, genetic susceptibility, altered immune reaction and inflammatory mediators considered responsible for RA are also associated with PD. So it is plausible that a biological link may exist between PD and RA. Therapies aimed at modifying the expression and effect of inflammatory mediators and effector molecules such as matrix metalloproteinases, proinflammatory cytokines and autoantibodies of structural proteins may probably reduce the severity of both RA and PD.

Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders

Inherited genetic disorders of the liver pose a significant public health burden.Liver transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive therapy.To overcome these limitations,nucleic acid therapy provides a hopeful alternative that enables gene repair,gene supplementation,and gene silencing with suitable vectors.Though viral vectors are the most efficient and preferred for gene therapy,pre-existing immunity debilitating immune responses limit their use.As a potential alternative,lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms,including pDNA,mRNA,siRNA,and proteins.Herein,we discuss the broader applications of lipid nanoparticles,from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing,as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.