Cerebral malaria pathogenesis: Dissecting the role of CD4+ and CD8+ T-cells as major effectors in disease pathology.

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum (P. falciparum) infection, with complex pathogenesis involving multiple factors, including the host's immunological response. T lymphocytes, specifically CD4+ T helper cells and CD8+ cytotoxic T cells, are crucial in controlling parasite growth and activating cells for parasite clearance via cytokine secretion. Contrary to this, reports also suggest the pathogenic nature of T lymphocytes as they are often involved in disease progression and severity. CD8+ cytotoxic T cells migrate to the host's brain vasculature, disrupting the blood-brain barrier and causing neurological manifestations. CD4+ T helper cells on the other hand play a variety of functions as they differentiate into different subtypes which may function as pro-inflammatory or anti-inflammatory. The excessive pro-inflammatory response in CM can lead to multi-organ failure, necessitating a check mechanism to maintain immune homeostasis. This is achieved by regulatory T cells and their characteristic cytokines, which counterbalance the pro-inflammatory immune response. Maintaining a critical balance between pro and anti-inflammatory responses is crucial for determining disease outcomes in CM. A slight change in this balance may contribute to a disease severity owing to an extreme inflammatory response or unrestricted parasite growth, a potential target for designing immunotherapeutic treatment approaches. The review briefly discusses the pathogenesis of CM and various mechanisms responsible for the disruption of the blood-brain barrier. It also highlights the role of different T cell subsets during infection and emphasizes the importance of balance between pro and anti-inflammatory T cells that ultimately decides the outcome of the disease.

CM is potentially fatal complication of P. falciparum infection that presents with high mortality and morbidity. Vaccines are extensively being developed against the Plasmodium parasite but very few of them are effective. Artemisinin Combination Therapy (ACT) is a major treatment for malaria, but its effectiveness is declining due to Plasmodium sp. developing resistance to it, necessitating the need for development of new drugs and treatments. During infection, the parasite is responsible for causing infected red blood cell (RBC) sequestration and cytoadherence in brain vasculature and extreme pro-inflammatory response that ultimately causes endothelial dysfunction and bloodbrain barrier (BBB) disruption. The host initiates a pro-inflammatory response against the parasite which includes activation of cells of both innate and adaptive immune response. These cells control the parasite growth and aid in parasite clearance from host's body. The inflammatory response generally targets foreign pathogens and provides protection against possible infection but can also cause harm to the self when left unchecked. It has been reported that activated immune cells, mainly T-lymphocytes often migrate to brain vasculature and ultimately results in neuronal damage characteristic CM. To counteract the overwhelming pro-inflammatory response, the host immune system deploys an anti-inflammatory response, which often involves regulatory cells and cytokines that help the body maintain immunological homeostasis. The review briefly highlights the necessity of balancing the pro- and anti-inflammatory responses for successful parasite clearance without the deleterious effects to the host that might increase disease severity in CM.

Research Progress of Indole Alkaloids: Targeting MAP Kinase Signaling Pathways in Cancer Treatment.

Cancer is the leading cause of morbidity and mortality in people throughout the world. There are many signaling pathways associated with cancerous diseases, from which the Mitogen-activated protein kinase (MAPK) pathway performs a significant role in this regard. Apoptosis and proliferation are correlated with MAPK signaling pathways. Plenty of experimental investigations were carried out to assess the role of indole alkaloids in MAPK-mediated cancerous diseases. Previous reports established that indole alkaloids, such as vincristine and evodiamine are useful small molecules in cancer treatment via the MAPK signaling system. Indole alkaloids have the anticancer potential through different pathways. Vincristine and evodiamine are naturally occurring indole alkaloids that have strong anticancer properties. Additionally, much research is ongoing or completed with molecules belonging to this group. The current review aims to evaluate how indole alkaloids affect the MAPK signaling pathway in cancer treatment. Additionally, we focused on the advancement in the role of indole alkaloids, with the intention of modifying the MAPK signaling pathways to investigate potential new anticancer small molecules. Furthermore, clinical trials with indole alkaloids in cancer treatment are also highlighted.

Liver Extracellular Matrix-Based Nanofiber Scaffolds for the Culture of Primary Hepatocytes and Drug Screening.

Immortalized liver cell lines and primary hepatocytes are currently used as in vitro models for hepatotoxic drug screening. However, a decline in the viability and functionality of hepatocytes with time is an important limitation of these culture models. Advancements in tissue engineering techniques have allowed us to overcome this challenge by designing suitable scaffolds for maintaining viable and functional primary hepatocytes for a longer period of time in culture. In the current study, we fabricated liver-specific nanofiber scaffolds with polylactic acid (PLA) along with a decellularized liver extracellular matrix (LEM) by the electrospinning technique. The fabricated hybrid PLA-LEM scaffolds were more hydrophilic and had better swelling properties than the PLA scaffolds. The hybrid scaffolds had a pore size of 38 ± 8 µm and supported primary rat hepatocyte cultures for 10 days. Increased viability (2-fold increase in the number of live cells) and functionality (5-fold increase in albumin secretion) were observed in primary hepatocytes cultured on the PLA-LEM scaffolds as compared to those on conventional collagen-coated plates on day 10 of culture. A significant increase in CYP1A2 enzyme activity was observed in hepatocytes cultured on PLA-LEM hybrid scaffolds in comparison to those on collagen upon induction with phenobarbital. Drugs like acetaminophen and rifampicin showed the highest toxicity in hepatocytes cultured on hybrid scaffolds. Also, the lethal dose of these drugs in rodents was accurately predicted as 1.6 g/kg and 594 mg/kg, respectively, from the corresponding IC50 values obtained from drug-treated hepatocytes on hybrid scaffolds. Thus, the fabricated liver-specific electrospun scaffolds maintained primary hepatocyte viability and functionality for an extended period in culture and served as an effective ex vivo drug screening platform to predict an accurate in vivo drug-induced hepatotoxicity.

Antifungal action and targeted mechanism of Bio fabricated zinc oxide (ZnO) nanoparticles against Ascochytafabae.

The current work focuses on analysing the structural, optical, and anti-fungal efficacy of ZnO nanoparticles using well diffusion agar methods and minimum inhibitory concentration (MIC). ZnO nanoparticles were created using the sol gel method. To check the synthesized material's spatial and optical characteristics, XRD, UV, and RAMAN studies were performed. The median diameter of produced nanostructures is in the region of nanometre, according to XRD measurements. Results from Raman Spectroscopy for the nanostructure are provided, together with comparisons to current development theory and reliable experimental data. The band gap of the zinc oxide sample is found by graphing (h) 2versus input photon energy and gradually decreasing the linear component of the (h) 2 to zero. The band gap energy is expressed by the line's intersection with the energy axis. Calculations show that the energy band gap is 3.22eV.The fungus Ascochytafabae is in control of the Phaseolus vulgaris L. (beans) blight disease. It mostly affects the plant's stem, leaves, and fruits. Phaseolus vulgaris plant leaf with Ascochytafabae infection was isolated, and ZnO nanoparticle effects were observed. It emerged that the synthesized ZnO nanoparticles were highly efficient against Ascochytafabae. By using the well diffusion method and an absolute concentration of ZnO nanoparticles, the maximum inhibitory concentration was 15.0 ± 0.2 mm.

Natural polymers as potential P-glycoprotein inhibitors: Pre-ADMET profile and computational analysis as a proof of concept to fight multidrug resistance in cancer.

P-glycoprotein (P-gp) is known as the "multidrug resistance protein" because it contributes to tumor resistance to several different classes of anticancer drugs. The effectiveness of such polymers in treating cancer and delivering drugs has been shown in a wide range of in vitro and in vivo experiments. The primary objective of the present study was to investigate the inhibitory effects of several naturally occurring polymers on P-gp efflux, as it is known that P-gp inhibition can impede the elimination of medications. The objective of our study is to identify polymers that possess the potential to inhibit P-gp, a protein involved in drug resistance, with the aim of enhancing the effectiveness of anticancer drug formulations. The ADMET profile of all the selected polymers (Agarose, Alginate, Carrageenan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid) has been studied, and binding affinities were investigated through a computational approach using the recently released crystal structure of P-gp with PDB ID: 7O9W. The advanced computational study was also done with the help of molecular dynamics simulation. The aim of the present study is to overcome MDR resulting from the activity of P-gp by using such polymers that can inhibit P-gp when used in formulations. The docking scores of native ligand, Agarose, Alginate, Carrageenan, Chitosan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid were found to be -10.7, -8.5, -6.6, -8.7, -8.6, -24.5, -6.7, -8.3, and -7.9, respectively. It was observed that, Cyclodextrin possess multiple properties in drug delivery science and here also demonstrated excellent binding affinity. We propose that drug efflux-related MDR may be prevented by the use of Agarose, Carregeenan, Chitosan, Cyclodextrin, Hyaluronic acid, and/or Polysialic acid in the administration of anticancer drugs.

Nanoscale designing of metal organic framework moieties as efficient tools for environmental decontamination.

Environmental pollutants, being a major and detrimental component of the ecological imbalance, need to be controlled. Serious health issues can get intensified due to contaminants present in the air, water, and soil. Accurate and rapid monitoring of environmental pollutants is imperative for the detoxification of the environment and hence living beings. Metal-organic frameworks (MOFs) are a class of porous and highly diverse adsorbent materials with tunable surface area and diverse functionality. Similarly, the conversion of MOFs into nanoscale regime leads to the formation of nanometal-organic frameworks (NMOFs) with increased selectivity, sensitivity, detection ability, and portability. The present review majorly focuses on a variety of synthetic methods including the ex situ and in situ synthesis of MOF nanocomposites and direct synthesis of NMOFs. Furthermore, a variety of applications such as nanoabsorbent, nanocatalysts, and nanosensors for different dyes, antibiotics, toxic ions, gases, pesticides, etc., are described along with illustrations. An initiative is depicted hereby using nanostructures of MOFs to decontaminate hazardous environmental toxicants.

Identification of a long noncoding RNA required for temperature induced expression of stage-specific rRNA in malaria parasites.

Protozoan parasites of the genus Plasmodium cause malaria, a mosquito borne disease responsible for substantial health and economic costs throughout the developing world. During transition from human host to insect vector, the parasites undergo profound changes in morphology, host cell tropism and gene expression. Unique among eukaryotes, Plasmodium differentiation through each stage of development includes differential expression of singular, stage-specific ribosomal RNAs, permitting real-time adaptability to major environmental changes. In the mosquito vector, these Plasmodium parasites respond to changes in temperature by modulating transcriptional activities, allowing real-time responses to environmental cues. Here, we identify a novel form of long noncoding RNA: a temperature-regulated untranslated lncRNA (tru-lncRNA) that influences the Plasmodium parasite's ability to respond to changes in its local environment. Expression of this tru-lncRNA is specifically induced by shifts in temperature from 37 °C to ambient temperature that parallels the transition from mammalian host to insect vector. Interestingly, deletion of tru-lncRNA from the genome may prevent processing of S-type rRNA thereby affecting the protein synthesis machinery. Malaria prevention and mitigation strategies aimed at disrupting the Plasmodium life cycle will benefit from the characterization of ancillary biomolecules (including tru-lncRNAs) that are constitutively sensitive to micro- environmental parameters.

In vitro chemo-preventive efficacy of synthetic progestin Norethindrone in human epithelial ovarian cancer.

Progestin-only based oral contraceptives are majorly used as 'minipill' to prevent unintended pregnancy and treat conditions like polycystic ovary syndrome, hirsutism, and acne. However, the dearth of literature has constrained our comprehension of the exogenous progestin in relation to ovarian cancer progression. Therefore, the aim of the present study was to evaluate the chemo-preventive potential of synthetic progestin Norethindrone (NET) in epithelial ovarian cancer in vitro. Briefly, SKOV3 cells were treated with 1, 10 and 100 µM concentrations of NET for seven days period. The assays for cell viability, wound-healing, cell cycle progression, detection of reactive oxygen species (ROS) and apoptosis were executed to illustrate the protective role of NET. To further clarify the underlying process, quantitative analysis of mRNA levels of oncogenes linked to angiogenesis, inflammation, proliferation, and metastasis (VEGF, HIF-1α, COX-2, and PGRMC1) and tumour suppressor (TP53) genes was conducted. Our study revealed that NET treatment significantly reduced SKOV3 cell growth by inducing cell cycle arrest at G2/M phase, elevating ROS levels, triggering cell death via apoptosis and necrosis, and inhibiting cell migration in a dose-dependent manner. Notably, NET also upregulated TP53 expression while concurrently downregulating VEGF, HIF-1α, COX-2, and PGRMC1 expression. Our results demonstrated that the chemo-preventive effect of Norethindrone may originate from the interaction of genes which exert a protective effect against ovarian carcinogenesis. The current findings also support further investigation, which may lead to changes in prescription practices or health-related advice for women.

Carotenoids: Role in Neurodegenerative Diseases Remediation.

Numerous factors can contribute to the development of neurodegenerative disorders (NDs), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Oxidative stress (OS), a fairly common ND symptom, can be caused by more reactive oxygen species being made. In addition, the pathological state of NDs, which includes a high number of protein aggregates, could make chronic inflammation worse by activating microglia. Carotenoids, often known as "CTs", are pigments that exist naturally and play a vital role in the prevention of several brain illnesses. CTs are organic pigments with major significance in ND prevention. More than 600 CTs have been discovered in nature, and they may be found in a wide variety of creatures. Different forms of CTs are responsible for the red, yellow, and orange pigments seen in many animals and plants. Because of their unique structure, CTs exhibit a wide range of bioactive effects, such as anti-inflammatory and antioxidant effects. The preventive effects of CTs have led researchers to find a strong correlation between CT levels in the body and the avoidance and treatment of several ailments, including NDs. To further understand the connection between OS, neuroinflammation, and NDs, a literature review has been compiled. In addition, we have focused on the anti-inflammatory and antioxidant properties of CTs for the treatment and management of NDs.

Studies on antimicrobial stress with reference to biofilm formation of faecal microbial communities from Apatani tribe of Arunachal Pradesh.

PURPOSE: Antibiotic resistant bacteria have created serious health conditions worldwide, disseminating various infections to people and community along with direct clinical implications in therapeutic options. METHODS: The present study analysed 20 samples from human faeces of Apatani tribe, Arunachal Pradesh, India. Biofilm assay, antimicrobial susceptibility tests and antimicrobial profiling were performed along with phylogenetic analysis. RESULTS: Phenotypic screening indicated the presence of 21 aerobic isolates comprising Escherichia sp 42.8% (n â€‹= â€‹9), Citrobacter sp 9.52% (n â€‹= â€‹2), Klebsiella sp 23.8% (n â€‹= â€‹5) and Enterococcus sp 23.8% (n â€‹= â€‹5). Tetracycline, ciprofloxacin, ceftadizime, gentamicine, vancomycin and erythromycin were observed to highly dominate the biofilm producing bacteria. Antimicrobial activity of Escherichia sp, Citrobacter sp, Klebsiella sp, and Enterococcus sp inhibited the growth of at least one of the tested pathogens. Phylogenetic analysis revealed that antibiotic resistant Klebsiella sp belonged to Klebsiella pneumonia; Escherichia sp belonged to Escherichia fergusonii and Escherichia coli; Enterococcus sp belonged to Enterococcus faecium while Citrobacter sp belonged to Citrobacter freundii. CONCLUSION: The present work shows that antibiotic resistant bacteria-Klebsiella sp, Enterococcus sp, Escherichia sp and Citrobacter sp were highly prevalent in the faecal microbial communities of Apatani tribe from Arunachal Pradesh. Presence of such antibiotic resistance and biofilm formation in faecal microbiota poses serious concerns regarding health and therapeutic options as this tribe mostly resides in remote vicinities of Arunachal Pradesh. Thus, exploring the mechanisms for dissemination of antibiotic resistance in this tribe helped us to identify key factors pertaining to the health of this tribe as well as their environment.

Promoter methylation status of key genes and its implications in the pathogenesis of endometriosis, endometrioid carcinoma of ovary and endometrioid endometrial cancer.

Background: Epigenetic processes play an important role in various physiological processes as well as in the pathogenesis of many diseases. The role of altered DNA methylation in the pathogenesis of endometriosis and associated ovarian and endometrial cancers has not been explored in detail. Therefore, this study aimed to determine the promoter methylation status of genes involved in key biological processes in the pathogenesis of these three gynecological diseases. Methods: Tissue samples of endometriosis, endometrioid carcinoma of the ovary, endometrioid endometrial cancer, and control endometrium (n = 10 each) were obtained. DNA was extracted and subjected to bisulfite conversion using commercially available kits. The methylation status of COX2, VEGF, HIF1A, TNF, MYC, and TP53 genes was checked by methylation-specific PCR. The mRNA levels of MYC and TP53 were determined using qRT-PCR in all tissue samples. Results: The promoter methylation status of COX2, VEGF, HIF1A, and TNF genes was significantly reduced in all three diseased study subjects (P < 0.05), whereas no significant difference was observed in the promoter methylation frequency of MYC and TP53 genes. Transcriptional expression of the MYC gene was significantly increased in all diseased groups (P < 0.001) whereas, transcriptional expression of the TP53 gene was significantly reduced in endometriosis and endometrioid carcinoma of the ovary and significantly increased in endometrioid endometrial cancer subjects compared to control subjects (P < 0.001). Conclusion: The findings suggest that the promoter regions of pro-inflammatory and pro-angiogenic genes involved in the common molecular pathophysiology of these three disorders were significantly hypomethylated and could be the reason for their over-expression associated with them. This indicates the role of epigenetics in the pathogenesis of these three diseases.

Left-Sided Colonic Tuberculosis Presenting as Colonic Stricture: A Rare Presentation of a Common Disease.

Gastrointestinal tuberculosis (TB) mainly presents as an ileocecal disease, and colonic TB is more often seen with terminal ileal involvement. Isolated involvement of the descending colon by TB is uncommon and usually presents with chronic colitis. An acute presentation as intestinal obstruction because of tubercular stricture of the descending colon has not been reported. We encountered a young woman who presented with features of acute bowel obstruction. On evaluation, she was diagnosed with a case of descending colon stricture with a provisional diagnosis of malignant colonic stricture. Left hemicolectomy was performed, and histopathology revealed it to be tubercular stricture. Antitubercular therapy was given for 9 months, and she is doing well at follow-up. A differential diagnosis of TB at an unusual location should always be considered even when presented with atypical symptoms, especially for patients from the endemic zone of TB.

Elucidating the gut microbiome alterations of tribal community of Arunachal Pradesh: perspectives on their lifestyle or food habits.

Gut microbiota studies of ethnic populations reveal gut microbial biomarkers for therapeutic options and detection of the disease state. The present study aimed to analyze the gut microbiome signatures in thirty individuals from the Adi, Apatani and Nyshi tribes of Arunachal Pradesh (ten in each cohort) by sequencing the V3 and V4 regions of 16S rRNA on the Illumina MiSeq Platform. The gut microbiome was highly predominated by Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidates in the three studied tribal groups. At the genus level, significant abundance of Bifidobacterium, Collinsella, Bacteroides, Prevotella, Lactobacillus, Streptococcus, Clostridium, Coprococcus, Dorea, Lachnospira, Roseburia, Ruminococcus, Faecalibacterium, Catenibacterium, Eubacterium, Citrobacter and Enterobacter were observed amongst the three tribes. The tribal communities residing in remote areas and following traditional lifestyle had higher gut microbiome diversity with a high prevalence of Prevotella and Collinsella in the Adi and Nyshi tribes, and Bifidobacterium and Catenibacterium in the Apatani tribe. Elucidating the gut microbiome of the tribal community of Arunachal Pradesh will add to the knowledge on relationships between microbial communities, dietary food factors, and the overall state of health of humans worldwide.

Empirical assessment of allele frequencies of genome wide association study variants associated with obstructive sleep apnea.

OBJECTIVE: Obstructive Sleep Apnea (OSA) is a heterogeneous disorder with a complex interplay of genetic and environmental factors. Over the years, with advancement in genotyping and sequencing techniques, various loci have shown an association with OSA. It is pertinent to understand the status of these associated variants in different ethnic groups. The aim of the study was to assess the genetic affinity among different population groups by evaluating the risk allele frequencies of variants associated with OSA. METHOD: The variants associated with OSA were obtained from the GWAS catalog with a significant p value of <5 × 10-7; 95 variants were obtained (www.ebi.ac.uk/gwas). Further, the variants were narrowed down on the basis of risk allele frequencies (>5%). The fst was calculated to assess the genetic affinity between super population groups and among the sub-population groups present in the 1000 genome project. RESULT: The fst values observed indicated all super populations were genetically related (SAS, AMR, EAS and EUR) except in the African (AFR) population group. Further, the closely related super population i.e., SAS, AMR, EAS and EUR when bifurcated on the basis of sub-population groups shows population stratification and SAS population groups form separate clusters on the MDS plot. CONCLUSION: The study highlights genetic heterogeneity among different population groups that gets diluted and results are biased when the samples are pooled irrespective of their endogamous groups. Our results provide insight to researchers to target specific endogamous groups for future studies on OSA.

The first study of epidemiology of adolescent idiopathic scoliosis shows lower prevalence in females of Jammu and Kashmir, India.

AIS is a heterogeneous 3D spinal deformity with Cobb angle ≥10°. It affects children in the age group of 10-16 years globally with 2-3% prevalence and significant female predominance. The exact etiology of AIS is not known however, it is supposed to be associated with factors such as anthropometric, metabolic, neuromuscular abnormalities and genetics. OBJECTIVES: To determine the prevalence of AIS and association of anthropometric factors with AIS in the studied population group. METHODOLOGY: Scoliosis screening of 9,500 individuals was carried out at different educational institutions of Jammu region in Jammu and Kashmir, India using a scoliosis-meter. The subjects were later examined radiologically. RESULTS: In population of the region, AIS was most prevalent among all types of scoliosis with overall prevalence of 0.61%. The prevalence was observed to be lower in females (0.31%) than males (0.88%). Based on angle of trunk rotation (ATR), lumbar curves were more prevalent than thoracic curves. Average Cobb angle in males and females were 24.9° and 22.6°, respectively. BMI showed significant association with AIS in the age group of 12-16 years (P value =0.028). Furthermore, height was significantly associated with AIS in the overall screened population (P-value =0.029). CONCLUSIONS: The AIS patients in the Jammu region of India have unique clinical features. In contrast to the global prevalence data, the prevalence of AIS in females in the region was less in comparison to males. Based on epidemiological literature and our findings, we hypothesized that genetic factors might be a major contributor in the AIS pathogenesis along with other confounding factors such as height, BMI, ethnicity, etc.

Microwave-Assisted Green Synthesis of Carbon Quantum Dots Derived from Calotropis Gigantea as a Fluorescent Probe for Bioimaging.

An eco-friendly, cost-effective, and convenient approach for synthesizing biocompatible fluorescent carbon quantum dots (CQDs) from the leaf extract of the medicinal plant Calotropis gigantea, commonly known as crown flower, has been demonstrated in this work. Fluorescence quantum yields of up to 4.24 percent were observed in as-synthesized CQDs. The size distribution of the as-synthesized CQDs varied from 2.7 to 10.4 nm, with a significant proportion of sp2 and sp3 carbon groups verified by nuclear magnetic resonance analysis. The zeta potential of as-synthesized CQDs was measured to be -13.8 mV, indicating the existence of a negatively charged surface with incipient instability in aqueous suspension. Furthermore, as an alternative to organic or synthetic dyes, the development of simple, inexpensive, and non-destructive fluorescence-based staining agents are highly desired. In this regard, as-synthesized CQDs have shown remarkable fluorescent staining capabilities in this work and might be utilised as a suitable probe for optical and bio-imaging of bacteria, fungi, and plant cells.

Draft Genome Sequence of Streptomyces albidoflavus 09MW18-IS, Cultivated from the Atlantic Ocean off the Coast of Virginia.

We report a draft genome sequence for Streptomyces albidoflavus strain 09MW18-IS, isolated from the Atlantic slope off the coast of Virginia. The whole-genome sequence will provide novel insights into biosynthetic gene clusters and ecological adaptation in an oligotrophic environment.

Role of serum microRNAs as biomarkers for endometriosis, endometrioid carcinoma of ovary & endometrioid endometrial cancer.

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.

A retrospective study reveals the Porcine circovirus-2f genotype predominant in the indigenous pig population of North-eastern India.

Porcine circovirus-2 (PCV2) is a widespread virus and presents sub-clinically in most of the swineherd. Globally, eight genotypes of PCV2 have been identified that is PCV2a to 2h. To determine the region-wide genotype distribution of PCV2 infection, with additional reference to indigenous breeds, a total of 1314 pig's clinical samples from the eight states of North-eastern India between 2011 and 2014; were analyzed. The overall prevalence rate of PCV2 in this region was 28.2% (370/1314) by PCR. The state-wise PCR based PCV2 prevalence rate was: Tripura (20.8%), Nagaland (25.0%), Meghalaya (25.8%), Assam (32.1%), Sikkim (32.6%), Manipur (33.3%), Mizoram (36.7%) and Arunachal Pradesh (42.3%). Subsequently, a total of 29 complete genomes of PCV2 were amplified and sequenced from these PCV2 positive samples. The phylogenetic tree represents that the 29 PCV2 isolates of this study were divided into four distinct genetic groups; PCV2a, PCV2b, PCV2d, and PCV2f. Among these, 14 PCV2 strains were classified as PCV2f, 13 classified as PCV2d, and one isolate of each classified as PCV2a and PCV2b. All the 14 PCV2f strains appeared from indigenous pigs of this region. Based on the date of collection, the present study further describes that the PCV2f genotypes circulate in the indigenous pigs' population back in 2011. The amino acid residues and the atomic coordinate structure (3D model) of PCV2f capsid protein represents similarity to PCV2d capsid protein support the efficacy of the existing PCV2 vaccine against the PCV2f. The observation of this study helps to understand the genotype distribution of PCV2 and stands as a reference for future molecular epidemiological studies in North-eastern India.