Neuroprotective Potential of Novel Multi-Targeted Isoalloxazine Derivatives in Rodent Models of Alzheimer’s Disease Through Activation of Canonical Wnt/β-Catenin Signalling Pathway

Previous reports suggest that Alzheimer’s disease is protected by cholinesterase inhibitors. We synthesized some isoalloxazine derivatives and evaluated them using in vitro cholinesterase inhibition assay. Two of the compounds (7m and 7q) were figured out as potent cholinesterase inhibitors. They further showed anti-Aβ aggregatory activity in the in vitro assay. The current study deals with the evaluation of neuroprotective potentials of the potent compounds (7m and 7q) using different in vitro and in vivo experiments. The compounds were first assessed for their tendency to cross blood–brain barrier using in vitro permeation assay. They were evaluated using scopolamine-induced amnesic mice model. Additionally, ROS scavenging and anti-apoptotic properties of 7m and 7q were established against Aβ_1–42-induced toxicity in rat hippocampal neuronal cells. 7m and 7q were also evaluated using Aβ_1–42-induced Alzheimer’s rat model. Lastly, their involvement in Wnt/β-catenin pathway was also demonstrated. The results indicated good CNS penetration for 7m and 7q. The neuroprotective effects of 7m and 7q were evidenced by improved cognitive ability in both scopolamine and Aβ_1–42-induced Alzheimer’s-like condition in rodents. The in vivo results also confirmed their anti-cholinesterase and anti-oxidant potential. Immunoblot results showed that treatment with 7m and 7q decreased Aβ_1–42, p-tau, cleaved caspase-3, and cleaved PARP levels in Aβ_1–42-induced Alzheimer’s rat brain. Additionally, immunoblot results demonstrated that 7m and 7q activated the Wnt/β-catenin pathway as evidenced by increased p-GSK-3, β-catenin, and neuroD1 levels in Aβ_1–42-induced Alzheimer’s rat brain. These findings have shown that isoalloxazine derivatives (7m and 7q) could be the potential leads for developing effective drugs for the treatment of AD.     

Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study

Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1β and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1β -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11–0.62; p = 0.002; OR = 0.462; 95% CI = 0.253–0.845, p = 0.01). In conclusion, subjects with IL-1β -511TT genotype or IL-1β*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.     

Gene expression profiles of T cells from hepatitis E virus infected patients in acute and resolving phase

Background and Aims  

Approximately 50% of acute viral hepatitis in young adults and in pregnant women is due to hepatitis E virus (HEV) infection in developing countries. T cell-mediated immune injury probably plays a key role in the pathogenesis of acute hepatitis illness. However, there is a paucity of data on the global gene expression programs activated on T cells, which are subsequently responsible for T cell recruitment to the liver and triggering of immune injury.     

The practice of cytopathology during the era of COVID-19: challenges and changes

This paper reviews the challenges faced by cytology laboratories during the COVID-19 pandemic. Various safety guidelines regarding collection, handling, transport and sampling in cytology laboratory are presented. A brief literature overview of adapted changes regarding new safety techniques, processing, sampling techniques implemented by the cytology laboratories in this part of the world is presented. The use of cytology in COVID-19 patients is discussed. The authors have also tried to present the challenges and changes faced for training and education during this time. Migration from multi-headed scope in-person sign-out to digital based platforms were adapted to continue medical education. The potential long-term implications of these adaptations on cytology services are also touched upon.     

Preparation of a Noncytotoxic Hemocompatible Ion Gel by Self‐Polymerization of HEMA in a Green Deep Eutectic Solvent

Self‐polymerization of optimized amount of 2‐hydroxyethylmethacrylate (HEMA) in a natural deep eutectic solvent (NADES) is obtained by the complexation between choline chloride and fructose (ChCl:Fruc. 2:1) in the presence of indomethacin, an anti‐inflammatory drug resulted formation of a drug‐immobilized ion gel. The ion gel thus obtained is found to be stable in gastrointestinal fluid pH (GIF) and sustained release in simulated lower intestinal fluid for 20 h (88% release) at pH 6.8 and 96% release at pH 7.4 for 15 h (colon & blood pH) at physiological human body temperature (37 °C) of the drug is recorded. The drug can be stored in the gel matrices at room temperature for long durations such as 6 months without any degradation. The ion gel of poly‐HEMA obtained in the NADES does not appear to inhibit the growth of mammalian cells in vitro and is found to be compatible to human blood thus implying toward their potential for therapeutic applications as pH‐sensitive hydrophobic drug carrier for oral application as well as in tissue engineering.

     

Two cases of asystolic cardiac arrests managed with therapeutic hypothermia

Poor neurological outcome is a common sequel of prolonged cardiac arrest. Although Therapeutic Hypothermia (TH) for neuroprotection has been a subject for research for over Half a century, its use has been limited because of many controversies and lack of clear guidelines. However for over two decades there has been a revival of interest in mild therapeutic hypothermia (32-34°C) for neuroprotection. However its use after primary asystolic cardiac arrest has been questioned.Herein presenting two cases of prolonged asystolic arrest (39 minutes and 25 minutes); where therapeutic hypothermia was successfully used in following prolonged cardio pulmonary resuscitation. On patients who were in deep coma after resuscitation, TH was applied for 24 hours as per institutional protocol with full neurological recovery in both the cases. Therapeutic hypothermia might have a potential role in even in non-shockable arrests and should be considered in every successful cardiopulmonary resuscitation with poor neurological status.     

A 40‐Year‐Old Male with An Intraventricular Tumor

Combined tumors showing histologic features of both ependymoma and subependymoma have been described. In this report we present a case of combined tanycytic ependymoma with foci of subependymoma (WHO grade II), occurring in a 40 year‐old male, which arose in the wall of the lateral ventricle. The tanycytic ependymoma component showed elongated fibrillary cells with a fascicular pattern of growth, while the subependymoma component showed clustered cell bodies surrounded by a fibrillary stroma with a microcystic appearance. We consider the present case to be an unusual example of tanycytic ependymoma; which to the best of our knowledge has not been associated with a subependymoma.     

Detection of biofilm formation among the clinical isolates of Staphylococci: an evaluation of three different screening methods

Purpose: The purpose of this study was to evaluate three methods for detection of biofilm formation in staphylococci. Methods: For detection of biofilm formation, 152 clinical isolates of Staphylococcus spp. were screened by tissue culture plate (TCP), Tube method (TM) and Congo red agar (CRA) method. Results: Of the 152 Staphylococcus spp. 88(57.8%) displayed a biofilm-positive phenotype under the optimized conditions in the TCP method and strains were further classified as high 22 (14.47 %) and moderate 60 (39.4 %) while in 70 (46.0 %) isolates weak or no biofilm was detected. Though TM correlated well with the TCP test for 18 (11.8 %) strongly biofilm producing strains, weak producers were difficult to discriminate from biofilm negative isolates. Screening on CRA does not correlate well with either of the two methods for detecting biofilm formation in staphylococci. Conclusion: The TCP method was found to be most sensitive, accurate and reproducible screening method for detection of biofilm formation by staphylococci and has the advantage of being a quantitative model to study the adherence of staphylococci on biomedical devices.