Recent advances on the role of long non-coding RNAs in Alzheimer’s disease

Dementia is a progressive cognitive impairment that affects the activities of daily living. Alzheimer’s disease (AD) is the most common form of the dementia worldwide accounting for 60–80% of all dementia cases. With an estimated cost exceeding $290 billion in the USA, understanding and development of future therapeutic strategies is vital. In this perspective, we will be examining the current thinking of AD research and therapeutic strategies, while proposing a possible new direction for diagnosis, understanding, and treatment targets. Non-coding RNA accounts for the largest population of the human transcriptome. Long noncoding RNA (lncRNA) is a recent molecule of interest in the biomedical research which is non protein coding and is of length greater than 200 nucleotides. LncRNAs have been shown to play diverse roles within the cells such as posttranscriptional and posttranslational regulation, chromatin modulation, and protein complex organization. Given the flexible and diverse role in disease pathophysiology, lncRNAs may serve as novel therapeutic targets for diagnosis and treatment. Evidently, recent studies showed that dysregulation of lncRNA influences the clinical course of tumorigenesis, neurological disorders, cardiovascular disease, diabetes, and acquired immunodeficiency syndrome (Kazimierczyk et al., 2020). This indicates that lncRNA can provide a unique avenue of research and possible therapeutic targets in AD

Estimation of Epiphytic Macrolichen Biomass in Binsar Wildlife Sanctuary (BWS), Almora, Uttarakhand, India

The lichen litter fallen on the forest floor from canopy and main branches between elevations of 900-2500 m was estimated for the Binsar Wildlife Sanctuary (BWS) of Almora district in Uttarakhand, India. The forest of the sanctuary was divided in 5 major forest stands, viz., Quercus, Alnus, Pinus, Rhododendron and Mixed. At each stand ten, 1-m2 quadrats were randomly placed and the lichen litter was collected in April 2013. Lichen biomass was highest in Quercus stand (2.55 g m-2) followed by Alnus (2.33 g m-2), Mixed stand (2.00 g m-2), Rhododendron (0.82 g m-2), and Pinus with the lowest lichen litter biomass (0.21 g m-2). The highest biomass was recorded for Matrix lichens (0.8944 g m-2), followed by Forage lichens (0.6976 g m-2) and Cyanolichens (0.0064 g m-2)

Seasonal Variation on Physico-Chemical Characteristics of Leachate in Active and Closed Municipal Solid Waste Landfill Site in Lucknow, India

Inappropriate disposal of municipal solid waste (MSW) results in the leaching of inorganic and organic chemicals, which can contaminate the groundwater, posing great contamination risk to humans. Due to unscientific landfilling, many fast growing cities of India are falling under high risk category of groundwater pollution. This paper attempts to assess the physico-chemical characteristics of leachate due to seasonal variation in the active and closed non-engineered MSW landfill sites of Lucknow city of Uttar Pradesh, India. Leachates from different landfill sites, which are either presently active or closed, were characterized and their relationships with season were examined. Concentrations of various physicochemical parameters such as colour, turbidity, total hardness, electrical conductivity, total dissolved solids, NO3−2, NH3-N and SO4 2- were determined in leachate samples

Role of autogenic relaxation in management of diabetic cardiovascular autonomic neuropathy in type II diabetes mellitus patients

Background: Cardiac autonomic neuropathy (CAN) is a very common complication of Type II diabetes mellitus patients. Early detection and treatment of CAN is necessary for reduction of mortality and morbidity in type II diabetes patients.Methods: The study included 120 diagnosed cases of type 2 diabetes mellitus with autonomic neuropathy both male & female, with more than 5 years duration of disease. Age group of the study subjects was between 30 – 70 years. All the 120 diabetic subjects were assessed for their heart rate variability. These 120 diabetic subjects were further divided in two groups by sealed envelope technique, with 60 subjects in each group. Subjects in Group I (Study group) were given relaxation therapy in the form of Rajyoga meditation, as guided by Rajyoga teachers. This group was asked to continue drug therapy for type 2 diabetes mellitus as prescribed by physician. On other hand, Group II (Control group) was given drug therapy as directed by physician but without relaxation therapy. At the end of 12 weeks HRV parameters, were re-evaluated and compared between the two groups.Results: Post intervention, Heart Rate Variability results showed that mean RR interval was significantly increased, whereas mean HR was significantly decreased in group I than in group II. All Time Domain parameters (i.e SDNN, RMSSD, NN50, pNN50 & Variance) were significantly increased in group I than in group II. The Frequency Domain parameter i.e LF/HF ratio was significantly decreased in group I than in group II. Thus the results showed that Raj Yoga meditation had a beneficial effect by improving the HRV parameters in diabetic patients with autonomic neuropathy.Conclusions: The study showed there is better improvement in all parameters of HRV in group I as compared to group II with the help of simple yet effective technique of Rajyoga meditation in type II diabetes mellitus patients with cardiac autonomic neuropathy

Analysis of spontaneously reported adverse drug reactions to pharmacovigilance cell of a tertiary care hospital

Background: The objective of the study was to study the clinical patterns, causality and severity of adverse drug reactions in a tertiary care hospital.Methods: Total 131 ADR forms were collected from January 2012 to December 2012 and evaluated. Patient’s characteristics, ADR and drug characteristics, causality, severity and preventability of collected ADR were analyzed.Results: Total 131 ADR forms were evaluated. Male patient experiencing ADR were more (73, 55.7%) than female (58, 44.2%). Adult patients (12-60 years) experienced 110 (84%) ADR followed by pediatric patients (60 years) 10 (7.63%). Antimicrobial were the most common group of drugs responsible for ADR followed by NSAIDs and antipsychotic group.Conclusions: Present study shows lack of awareness among health care professionals for reporting of an ADR. Training and collaboration of health care professionals are needed for improvement in ADR reporting. Appropriate feedback from ADR reporting will help in selection of drug and promotes safer use of drugs

Drug utilization pattern of antimicrobial agents in an outpatient department of otorhinolaryngology in a tertiary care hospital: a prospective, cross-sectional study

Background: Study based on antimicrobial drug utilization pattern and focus on factors related to prescribing, administering and its associated events. The aim of this study is to assess the prescribing patterns of antimicrobials, to assess the appropriateness of prescribed antimicrobials in an ear, nose and throat (ENT) infections.Methods: A prospective observational drug utilization study was carried out in otorhinolaryngology department for a period of 4 months. Patients who attended the ENT outpatient department (OPD) with ENT infections were included in the study and patients who were not willing to participate in the study were excluded and the data were analyzed.Results: Out of 155 patients, the average number of drugs per patient was 1.2. The percentage of drugs prescribed with the generic name was 26.32%. During this study, it was found that the most commonly prescribed groups of antimicrobials were penicillins (34.87%) followed by fluroqinolones (26.32%) and nitroimidazole (25%). During the study, it was observed that 46.71% patients visited for treating ear infections, 12.5% for nasal infections and 40.79% for throat infections. The routes of administration were oral (74.23%) and topical (20.10%).Conclusions: Our study shows some rational prescription patterns like less utilization of antimicrobials in ENT infections and were according to standard treatment guideline. The results of this study will be useful in future for making standard treatment guidelines. It also promotes the rational prescription and rational use of drugs

Cell cycle-dependent regulation of the bi-directional overlapping promoter of human BRCA2/ZAR2 genes in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>BRCA2 gene expression is tightly regulated during the cell cycle in human breast cells. The expression of BRCA2 gene is silenced at the G0/G1 phase of cell growth and is de-silenced at the S/G2 phase. While studying the activity of BRCA2 gene promoter in breast cancer cells, we discovered that this promoter has bi-directional activity and the product of the reverse activity (a ZAR1-like protein, we named ZAR2) silences the forward promoter at the G0/G1 phase of the cell. Standard techniques like cell synchronization by serum starvation, flow cytometry, N-terminal or C-terminal FLAG epitope-tagged protein expression, immunofluorescence confocal microscopy, dual luciferase assay for promoter evaluation, and chromatin immunoprecipitation assay were employed during this study.</p> <p>Results</p> <p>Human <it>BRCA2 </it>gene promoter is active in both the forward and the reverse orientations. This promoter is 8-20 fold more active in the reverse orientation than in the forward orientation when the cells are in the non-dividing stage (G0/G1). When the cells are in the dividing state (S/G₂), the forward activity of the promoter is 5-8 folds higher than the reverse activity. The reverse activity transcribes the ZAR2 mRNA with 966 nt coding sequence which codes for a 321 amino acid protein. ZAR2 has two C4 type zinc fingers at the carboxyl terminus. In the G0/G1 growth phase ZAR2 is predominantly located inside the nucleus of the breast cells, binds to the BRCA2 promoter and inhibits the expression of BRCA2. In the dividing cells, ZAR2 is trapped in the cytoplasm.</p> <p>Conclusions</p> <p><it>BRCA2 </it>gene promoter has bi-directional activity, expressing BRCA2 and a novel C4-type zinc finger containing transcription factor ZAR2. Subcellular location of ZAR2 and its expression from the reverse promoter of the BRCA2 gene are stringently regulated in a cell cycle dependent manner. ZAR2 binds to BRCA2/ZAR2 bi-directional promoter <it>in vivo </it>and is responsible, at least in part, for the silencing of BRCA2 gene expression in the G0/G1 phase in human breast cells.</p

EVALUATION OF ANTI-INFLAMMATORY, ANALGESIC, AND ANTIPYRETIC EFFECT OF ETHANOLIC EXTRACT OF PEDALIUM MUREX LINN. FRUITS

This study investigated the possible anti-inflammatory, analgesic, and antipyretic effects of ethanolic extract of Pedalium murex Linn. fruits, in selected experimental animal models. Anti-inflammatory activity of Pedalium murex Linn. with doses of 200 mg/kg and 400 mg/kg, p.o., was evaluated by λ-carrageenan induced paw oedema in wistar albino rats; analgesic activity with doses of 280 mg/kg and 560 mg/kg, p.o., was evaluated by hot plate method and acetic acid induced writhing method in swiss albino mice; and antipyretic activity with doses of 110 mg/kg and 220 mg/kg, p.o., was evaluated in Newzealand white rabbits by injecting gram –ve lipopolysaccharide obtained from E. coli. Results were analyzed by one way ANOVA followed by Dunnet’s multiple comparison test. Pedalium murex Linn. showed significant anti-inflammatory activity from 15 min to 180 min as compared to vehicle treated animals. It was comparable to diclofenac sodium at 180 min. It did not prolong the reaction time on hot plate method but significantly reduced the number of writhing after acetic acid administration. It didn’t show any antipyretic activity on lipopolysaccharide induced pyrexia. Ethanolic extract of Pedalium murex Linn. fruits have an anti-inflammatory and peripheral analgesic effects

A New Era of RNA Personalized Vaccines for Cancer and Cancer-Causing Infectious Diseases

RNA vaccines for cancer and cancer-causing infectious agents are recognized as new therapeutics and are perceived as potential alternatives to conventional vaccines. Cancer is a leading cause of death worldwide, and infections (certain viruses, bacteria, and parasites) are linked to about 15–20% of cancers. Since the last decade, developments in genomics methodologies have provided a valuable tool to analyze the specific mutations, fusions, and translocations of the driver genes in specific cancer tissues. The landscape of the mutations identified by genome sequencing and data analysis can be a vital route to personalized medicine. This chapter will discuss the present state of mRNA vaccine development and ongoing clinical trials in oncology

Design, development and evaluation of furrow opener for differential depth fertilizer application

A differential depth furrow opener for tractor-drawn seed-cum-fertilizer drill under raised beds sowing was designed, developed and evaluated at ICAR-Central Institute of Agricultural Engineering, Bhopal, MP, India. The basic aim of this development was to apply fertilizer at different depth in crop root zone to enhance the fertilizer use efficiency. The furrow opener was evaluated based on draught and power requirements under soil bin at four depths (5, 10, 15, and 20 cm), four forward speeds (1.8, 3.2, 4.3 and 5.4 km/h) and three compaction level (200, 400 and 600 kPa). The field performance evaluation of furrow opener was done in two wheat crop varieties; HI-1544 (Triticum aestivum L.) and HI-8663 (T. durum) under raised beds. The experiment consisted of different fertilizer placement depths, i.e. application of NPK mixed fertilizer on surface (T1) and 5 cm (T2), 10 cm (T3), 15 cm (T4) and 20 cm (T5) below the surface in split-plot design. The root weight/plant shows significant results under all treatments, maximum and minimum root weight/plant were observed 16.01 and 9.63 g in T3 and T5, respectively. Highest grain yield was observed in treatment T4 (6 048 kg/ha) followed by T3 (5 611), T2 (5 223), T1 (4 739) and T5 (4 493 kg/ha). Higher NDVI values were observed in T3 (0.95) and T4 (0.96) at heading stage of wheat crop. From crop attributes point of view, parallel results were observed for T3 (10 cm) and T4 (15cm). But considering the draught and power requirement, 15 cm deep fertilization required 47% and 42% higher draught and power, respectively as compared to 10 cm deep fertilization