Innovations in dengue virus detection: An overview of conventional and electrochemical biosensor approaches.

Globally, people are in great threat due to the highly spreading of viral infectious diseases. Every year like 100-300 million cases of infections are found, and among them, above 80% are not recognized and irrelevant. Dengue virus (DENV) is an arbovirus infection that currently infects people most frequently. DENV encompasses four viral serotypes, and they each express comparable sign. From a mild febrile sickness to a potentially fatal dengue hemorrhagic fever, dengue can induce a variety of symptoms. Presently, the globe is being challenged by the untimely identification of dengue infection. Therefore, this review summarizes advances in the detection of dengue from conventional methods (nucleic acid-based, polymerase chain reaction-based, and serological approaches) to novel biosensors. This work illustrates an extensive study of the current designs and fabrication approaches involved in the formation of electrochemical biosensors for untimely identifications of dengue. Additionally, in electrochemical sensing of DENV, we skimmed through significances of biorecognition molecules like lectins, nucleic acid, and antibodies. The introduction of emerging techniques such as the CRISPR/Cas' system and their integration with biosensing platforms has also been summarized. Furthermore, the review revealed the importance of electrochemical approach compared with traditional diagnostic methods.

Current paradigms in epigenetic anticancer therapeutics and future challenges.

Any alteration at the genetic or epigenetic level, may result in multiplex of diseases including tumorigenesis which ultimately results in the cancer development. Restoration of the normal epigenome by reversing the epigenetic alterations have been reported in tumors paving the way for development of an effective epigenetic treatment in cancer. However, delineating various epigenetic events has been a challenging task so far despite substantial progress in understanding DNA methylation and histone modifications during transcription of genes. Many inhibitors in the form of epigenetic drugs mostly targeting chromatin and histone modifying enzymes including DNA methyltransferase (DNMT) enzyme inhibitors and a histone deacetylases (HDACs) inhibitor, have been in use subsequent to the approval by FDA for cancer treatment. Similarly, other inhibitory drugs, such as FK228, suberoylanilide hydroxamic acid (SAHA) and MS-275, have been successfully tested in clinical studies. Despite all these advancements, still we see a hazy view as far as a promising epigenetic anticancer therapy is concerned. The challenges are to have more specific and effective inhibitors with negligible side effects. Moreover, the alterations seen in tumors are not well understood for which one has to gain deeper insight into the tumor pathology as well. Current review focusses on such epigenetic alterations occurring in cancer and the effective strategies to utilize such alterations for potential therapeutic use and treatment in cancer.

Reconnoitring the antioxidant and antibacterial potential of different fruits after tannin acyl hydrolase mediated biotransformation.

Condensed and hydrolyzable tannins are secondary metabolites present in almost every plant part. Tannase enzyme acts on hydrolyzable tannins to produce gallic acid and tannase-mediated end-products with immense therapeutic potential. Seven different fruits with significant presence of hydrolyzable tannin content were selected to check for phenol, tannin, and hydrolyzable tannin contents. Prunus domestica had the maximum phenol content, that is, 85.4 ± 0.207, followed by Syzygium cumini, Fragaria ananassa, Rubus fruticosus, and Psidium guajava. Plum showed the maximum number of hydrolyzable tannins. Fruit extracts were subjected to tannase hydrolysis and their antimicrobial and antioxidant activities were determined. There was a significant increase in the antioxidant abilities of the fruits with Punica granatum extract, displaying the highest decline of 132 units of IC50 followed by F. ananassa hydrolyzable extract, showing a decrease from 224.75 to 119.98 µg/mL. The extracts also depicted a significant increase in antibacterial activity after hydrolysis against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Staphylococcus aureus with Rubus idaeus aqueous extract observed to be most effective against E. coli. The increase in antioxidant and antibacterial activity can be attributed to the production of tannase-mediated products formed after the biotransformation of hydrolyzable tannins present in the aqueous extracts.

An insight into microbial sources, classification, and industrial applications of xylanases: A rapid review.

Endo 1,4-ß-d-xylanases (EC3.2.1.8) are one of the key lignocellulose hydrolyzing enzymes. Xylan, which is present in copious amounts on earth, forms the primary substrate of endo-xylanases, which can unchain the constituent monosaccharides linked via ß-1,4-glycosidic bonds from the xylan backbone. Researchers have shown keen interest in the xylanases belonging to glycoside hydrolase families 10 and 11, whereas those placed in other glycoside hydrolase families are yet to be investigated. Various microbes such as bacteria and fungi harbor these enzymes for the metabolism of their lignocellulose fibers. These microbes can be used as miniature biofactories of xylanase enzymes for a plethora of environmentally benign applications in pulp and paper industry, biofuel production, and for improving the quality of food in bread baking and fruit juice industry. This review highlights the potential of microbes in production of xylanase for industrial biotechnology.

Pectinases as promising green biocatalysts having broad-spectrum applications: Recent trends, scope, and relevance.

Pectinases are a collection of multiple enzymes that have a common substrate, that is, pectin. They can act on different parts of pectin due to the structural heterogeneity of pectin. Therefore, they have been placed in different groups, such as protopectinases, polygalacturonases, polymethylesterases, pectin lyases, and pectate lyases. They are naturally present both in multicellular organisms such as higher plants and in unicellular organisms such as microbes. In past decade, it has been witnessed that chemical and mechanical methods employed in industrial processes have led to environmental hazards and serious health disorders, thus increasing the search for eco-friendly approaches with minimal health risks. Hence, microbial enzymes have been extensively used as safer alternative for these environmentally unsafe methods. Among these microbial enzymes, pectinases hold great significance and is one of the principal enzymes that have been used commercially. It is predominantly used as a green biocatalyst for fruit, fiber, oil, textile, beverage, pulp, and paper industry. Thus, this review focuses on the structure of pectin, microbial sources of pectin, and principle industrial applications of pectinases.

Microbiome dysbiosis in cancer: Exploring therapeutic strategies to counter the disease.

Cancer being a multiplex disease which involves many genomic and physiological alterations that occur consistently in the cancerous tissue, making the treatment and management of the disease even more complicated. The human gut microbiota (GM) harbors collective genomes of microbes comprising of trillions of bacteria along with fungi, archaea, and viruses that have the tendency to affect the development and progression of cancer. Moreover, inter-microbial interactions, diversity and distinct differences among the GM populations could influence the course of disease, making the microbiome an ideal target or to be modulated in such a way so as to improve cancer therapeutics with better efficacy and reduced toxicity. Current review focuses upon exploring the association of gut microbiota with the progression of cancer for which a structured search of bibliographic databases for peer-reviewed research literature has been carried out using focused review questions and inclusion/exclusion criteria. Through this review one could envisage a wide-spectrum role of microbiota in maintaining host metabolism, immune homeostasis paving the way for an anticancer diagnostic and therapeutic solution that has the potential to counter the menace of anti-cancer drug resistance as well.

Probiotics in microbiome ecological balance providing a therapeutic window against cancer.

The gut microbiota composition and dietary factors in our food along with the use of prebiotics and probiotics play an important role in the maintenance of human health. A well-balanced gut microbial population is necessary for the host and the microbiota to coexist in a mutually beneficial relationship maintaining homeostasis. Considering the potential of modern technological tools, it is possible nowadays to engineer prebiotic bacteria having a positive influence on the microbiome on one hand while on the other one may have the ease to get rid of the pathogenic proinflammatory microbes or elements causing dysbiosis. Past studies have seen that in cancer there is a loss of inter-microbial relationship cum interactions within microbiota members, the metabolic products produced by them and the host immune system in a microbial ecosystem, leading to dysbiosis. Current review highlights the importance of probiotics in the management of cancer by bringing together majority of the studies together at a single platform and moreover, stresses upon the need to maintain eubiosis in order to evade and inhibit the progression of cancer. Continuous expansion in knowledge about probiotics, their effect on various cancers and the underlying mechanism of action has raised the global scientific interest towards their possible use against different cancers. Furthermore, the article emphasizes upon the need to explore newer therapeutic targets comprising of the microbiome which could further pave the way to the concept of personalized medicines for various kinds of malignancies so as to derive maximum benefits of a treatment modality and to preserve the microbial homeostasis.

Multifaceted antiviral therapeutic potential of dietary flavonoids: Emerging trends and future perspectives.

Phytochemicals are the natural biomolecules produced by plants via primary or secondary metabolism, which have been known to have many potential health benefits to human beings. Flavonoids or phytoestrogens constitute a major group of such phytochemicals widely available in variety of vegetables, fruits, herbs, tea, and so forth, implicated in a variety of bio-pharmacological and biochemical activities against diseases including bacterial, viral, cancer, inflammatory, and autoimmune disorders. More recently, these natural biomolecules have been shown to have effective antiviral properties via therapeutically active ingredients within them, acting at different stages of infection. Current review emphasizes upon the role of these flavonoids in physiological functions, prevention and treatment of viral diseases. More so the review focuses specifically upon the antiviral effects exhibited by these natural biomolecules against RNA viruses including coronaviruses. Furthermore, the article would certainly provide a lead to the scientific community for the effective therapeutic antiviral use of flavonoids using potential cost-effective tools for improvement of the pharmacokinetics, bioavailability, and biodistribution of such compounds for the concrete action along with the promotion of human health.

A comparative molecular dynamic simulation study on potent ligands targeting mTOR/FRB domain for breast cancer therapy.

Our study aimed to develop and find out the best drug candidate against the mechanistic target of rapamycin (mTOR/FRB) domain having a critical role in the aetiology of breast cancer. The FKBP12-rapamycin-binding (FRB) domain in the essential phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been a vital player in the disease progression in breast cancer. By using structure-based drug designing , the best possible targets have been identified and developed. The three-dimensional structure of the target protein was generated using I-TASSER. The ligands were generated against the most suitable target active site using standard tools for active site identification. Furthermore, the seed molecule was drawn using Chemsketch, which was then grown into the pocket using Ligbuilder. The obtained ligands were further validated using online programs for bioavailability and toxicity, followed by molecular dynamic simulations. The study concludes that the equilibrated NVT-NPT complexes indicate LIG2 stability over LIG3. RMSD and RMSF have shown that the complex of LIG2 is more stable than LIG3. LIG2 has the potential antagonistic properties to target the mTOR/FRB domain and has therapeutic implications for breast cancer.

Virus distribution and early pathogenesis of highly pathogenic peste-des-petits-ruminants virus in experimentally infected goats.

INTRODUCTION: Despite causing one of the most dreaded diseases of small ruminants, relatively little is known about the pathogenic events, antigen distribution and the cells responsible for the uptake and transmission of peste-des-petits-ruminants virus (PPRV) during primitive stages of infection. OBJECTIVES: We aimed at deciphering the sequential tissue tropism, pathological events and putative role of M2c macrophages during incubatory, prodromal and invasive stages of PPRV infection. METHODOLOGY: A total of 10 goats were sequentially sacrificed at 1, 2, 3, 4, and 5 days post-infection (dpi, n = 2 per time-point) following intranasal inoculation with a highly virulent strain of PPRV (lineage IV PPRV/Izatnagar/94). Histological evaluation to assess PPRV mediated pathologies, RT-qPCR and immunohistochemistry (IHC) to decipher sequential virus distribution, and dual immunolabelling to determine the role of M2c macrophage in early PPRV uptake and transmission was performed. RESULTS: PPRV/Izatnagar/94 caused major pathologies in the lung tissues. Unprecedentedly, PPRV nucleic acid and antigens were detected in various tissues as early as one dpi. RT-qPCR revealed PPRV in the nasal cavity, trachea, bronchi, tongue and lymph nodes draining these tissues from 1 dpi. IHC affirms cells residing in the lamina propria and submucosa of the respiratory tract and tongue and peribronchiolar areas of lungs as the primary target of PPRV. Following initial replication in the respiratory tract, PPRV is transmitted to the regional lymph nodes where primary viral amplification occurs. After viraemia and secondary replication in generalized lymphoid tissues, PPRV infects and replicates in the epithelial cells. Further, we localized CD163+ M2c macrophages in the goat tissues, but dual IHC elucidated that M2c macrophages do not facilitate uptake and transmission of PPRV during the early stages of infection. CONCLUSION: Our study substantiates the disease establishment process and pathogenesis of PPRV/Izatnagar/94 during the incubatory and prodromal stages of infection. Further, we have also observed M2c macrophage distribution in the goat tissues and demonstrated that they do not pick and transmit PPRV.

Melamine contamination and associated health risks: Gut microbiota does make a difference.

Melamine is a nitrogenous organic compound containing high amounts of nitrogen, which is interpreted as high protein in various standard protein measuring tests, therefore added to foods to boost the protein content. Illegal addition of melamine has been in practice by food manufacturers, which leads to toxicity and stone formation in kidneys of individuals consuming melamine-contaminated milk products. A focused and thorough structured search of bibliographic databases for peer-reviewed researches reported in the literature was carried out with a focused attention on melamine contamination, associated health risks, and the role of gut microbiota. The overall outcomes of the research and review articles pertaining to searched keywords along with analysis of the interventions have been described employing a deductive qualitative content analysis approach. Current review focuses on the various health risks associated with consumption of melamine-contaminated foods and the need to develop better and effective methods for its testing. Moreover, the importance of gut microbiota in mediating toxicity due to melamine has also been discussed as there is a link between toxicity and activities of gut microbiota.

Recent nanotechnological interventions targeting PI3K/Akt/mTOR pathway: A focus on breast cancer.

Breast cancer is the major cause of deaths in women worldwide. Detection and treatment of breast cancer at earlier stages of the disease has shown encouraging results. Modern genomic technologies facilitated several therapeutic options however the diagnosis of the disease at an advanced stage claim more deaths. Therefore more research directed towards genomics and proteomics into this area may lead to novel biomarkers thereby enhancing the survival rates in breast cancer patients. Phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was shown to be hyperactivated in most of the breast carcinomas resulting in excessive growth, proliferation, and tumor development. Development of nanotechnology has provided many interesting avenues to target the PI3K/Akt/mTOR pathway both at the pre-clinical and clinical stages. Therefore, the current review summarizes the underlying mechanism and the importance of targeting PI3K/Akt/mTOR pathway, novel biomarkers and use of nanotechnological interventions in breast cancer.

Understanding the microbiome: Emerging biomarkers for exploiting the microbiota for personalized medicine against cancer.

The human body is a home to more than 1 trillion microbes with a diverse variety of commensal microbes that play a crucial role towards the health of the individual. These microbes occupy different habitats such as gut, skin, vagina, oral etc. Not only the types and abundance of microbes are different in different organs, but also these may differ in different individuals. The genome of these microbiota and their ecosystem constitute to form a microbiome. Factors such as diet, environment, host genetics etc. may be the reason behind the wide microbial diversity. A number of studies performed on human microbiome have revealed that microbiota present in healthy and diseased individuals are distinct. Altered microbiome is many a times the reason behind the overexpression of genes which may cause complex diseases including cancer. Manipulation of the human microbiome can be done by microbial supplements such as probiotics or synbiotics, diet or prebiotics and microbial suppression strategies using antibiotics. Recent advances in genome sequencing technologies and metagenomic analysis provide us the broader understanding of these commensal microbes and highlighting the distinctive features of microbiome during healthy and disease states. Molecular pathological epidemiology (MPE) studies have been very helpful in providing insights into the pathological process behind disease evolution and progression by determining the specific etiological factors. New emerging field of research targets the microbiome for therapeutic purposes by which personalized medicines can be made for treating various types of tumors. Screening programmes might be helpful in identifying patients who are at the verge of developing cancer and in delivering appropriate approaches according to individual risk modes so that disease could be prevented.

Partial replacement of dietary buffalo meat on the bone with chicken carcass improves serum antioxidant profile of zoo-housed Indian leopards (Panthera pardus fusca).

This experiment was conducted to study the effect of gradual replacement of dietary buffalo meat on the bone (BMB) with chicken carcass (CC) on nutrient utilization, serum cortisol, and total serum antioxidant profile of zoo-housed Indian leopard. Twelve adult leopards were randomly distributed into a replicated Latin square design comprising three treatments, three periods, four animals, and three sequences. Leopards in group T1 were fed normal zoo diet of BMB. On the basis of dry matter, 10% and 20% of BMB was replaced with CC in groups T2 and T3 , respectively. Each experimental period comprised 21 days. During each period, a digestion trial of 4-day collection period was conducted after an adaptation period of 17 days. On Day 21 of each experimental period, blood was collected from all the animals by puncturing the ventral coccygial vein. Intake and apparent digestibility of major nutrients were similar among the groups. Replacement of 20% BMB with addition of CC increased (p < 0.001) the calculated supply of I, niacin, and vitamin A. Carotenoid intake increased (p < 0.01) with increased level of CC in the diet. Serum concentration of cortisol decreased (p < 0.01) whereas serum concentration of total carotenoids increased (p < 0.001) with increased level of CC in the diet. Serum concentration of antioxidant enzymes increased (p < 0.001) with increased level of CC in the diet. It was concluded that replacement of 20% of BMB with CC increased antioxidant profile. This may reduce oxidative stress in zoo-housed Indian leopards without any adverse effect on nutrient utilization.

The Effectiveness and Risks of Fluoroscopically Guided Lumbar Interlaminar Epidural Steroid Injections: A Systematic Review with Comprehensive Analysis of the Published Data.

Objective: To determine the effectiveness and risks of fluoroscopically guided lumbar interlaminar epidural steroid injections. Design: Systematic review of the literature with comprehensive analysis of the published data. Interventions: Three reviewers with formal training in evidence-based medicine searched the literature on fluoroscopically guided lumbar interlaminar epidural steroid injections. A larger team consisting of five reviewers independently assessed the methodology of studies found and appraised the quality of the evidence presented. Outcome Measures: The primary outcome assessed was pain relief. Other outcomes such as functional improvement, reduction in surgery rate, decreased use of opioids/medications, and complications were noted, if reported. The evidence on each outcome was appraised in accordance with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system of evaluating evidence. Results: The search yielded 71 primary publications addressing fluoroscopically guided lumbar interlaminar epidural steroid injections. There were no explanatory studies and all pragmatic studies identified were of low quality, yielding evidence comparable to observational studies. Conclusions: The body of evidence regarding effectiveness of fluoroscopically guided interlaminar epidural steroid injection is of low quality according to GRADE. Studies suggest a lack of effectiveness of fluoroscopically guided lumbar interlaminar epidural steroid injections in treating primarily axial pain regardless of etiology. Most studies on radicular pain due to lumbar disc herniation and stenosis do, however, report statistically significant short-term improvement in pain.

Design and evaluation of acrylate polymeric carriers for fabrication of pH-sensitive microparticles.

Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid-butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of -27.4 and -29.0 mV. Entrapment of drug in the microparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. However, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed amorphous nature of microparticles due to the dilution effect of amorphous polymer. The microparticles released less than 5% drug at pH 1.2, while more than 90% of the drug load was released at pH 7.4. This suggested the colon targeting nature of the formulations. In experimentally developed colitis in Wistar rats, the microparticle formulation showed significant reduction (p < .05) in the disease activity score (disease symptoms), the colon-to-body weight ratio (tissue edema) and the myeloperoxidase, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß activities.

Molecular targets of gambogic acid in cancer: recent trends and advancements.

Natural compounds have been known as biosafety agents for their significant clinical and biological activity against dreadful diseases, including cancer, cardiovascular, and neurodegenerative disorders. Gambogic acid (GA), a naturally occurring xanthone-based moiety, reported from Garcinia hanburyi tree, is known to perform numerous intracellular and extracellular actions, including programmed cell death, autophagy, cell cycle arrest, antiangiogenesis, antimetastatic, and anti-inflammatory activities. In addition, GA-based synergistic approaches have been proven to enhance the healing strength of existing chemotherapeutic agents along with lesser side effects. The present review uncovers the bio-therapeutic potential of gambogic acid along with the possible mechanistic interactions of GA with its recognized cellular targets.

Cardiomyopathy and Worsened Ischemic Heart Failure in SM22-α Cre-Mediated Neuropilin-1 Null Mice: Dysregulation of PGC1α and Mitochondrial Homeostasis.

OBJECTIVE: Neuropilin-1 (NRP-1) is a multidomain membrane receptor involved in angiogenesis and development of neuronal circuits, however, the role of NRP-1 in cardiovascular pathophysiology remains elusive. APPROACH AND RESULTS: In this study, we first observed that deletion of NRP-1 induced peroxisome proliferator-activated receptor γ coactivator 1α in cardiomyocytes and vascular smooth muscle cells, which was accompanied by dysregulated cardiac mitochondrial accumulation and induction of cardiac hypertrophy- and stress-related markers. To investigate the role of NRP-1 in vivo, we generated mice lacking Nrp-1 in cardiomyocytes and vascular smooth muscle cells (SM22-α-Nrp-1 KO), which exhibited decreased survival rates, developed cardiomyopathy, and aggravated ischemia-induced heart failure. Mechanistically, we found that NRP-1 specifically controls peroxisome proliferator-activated receptor γ coactivator 1 α and peroxisome proliferator-activated receptor γ in cardiomyocytes through crosstalk with Notch1 and Smad2 signaling pathways, respectively. Moreover, SM22-α-Nrp-1 KO mice exhibited impaired physical activities and altered metabolite levels in serum, liver, and adipose tissues, as demonstrated by global metabolic profiling analysis. CONCLUSIONS: Our findings provide new insights into the cardioprotective role of NRP-1 and its influence on global metabolism.

Validation of putative reference genes for gene expression studies in heat stressed and α-MSH treated melanocyte cells of Bos indicus using real-time quantitative PCR.

Normalization of cellular mRNA data using internal reference gene (IRG) is an essential step in expression analysis studies. MIQE guidelines ensure that the choice and appropriateness of IRG should be validated for particular tissues or cell types and specific experimental designs. The objective of the present study was to assess 15 IRGs from different functional classes that could serve as best IRGs for Bos indicus (Tharparkar cattle) melanocyte cells under heat stress and hormonal treatment. We implemented the use of geNorm, NormFinder and BestKeeper algorithm to measure the stability of the gene transcript. A total of 15 IRGs (ACTB, BZM, EEF1, GAPDH, GTP, HMBS, HPRT, RPL22, RPL4, RPS15, RPS18, RPS23, RPS9, UBC and UXT) from different functional classes were evaluated. Pair wise comparisons using geNorm revealed that HPRT and RPS23 were the most stable combination of IRGs with M-value of 0.29 followed by UXT (0.30) and RPL4 (0.31). The NormFinder analysis also identified the same set of stably expressed genes (UXT, RPL4, RPS23 and HPRT); however, the rank order was little different. The UXT gene showed lowest crossing point SD and CV values of 0.30 and 1.17, respectively indicating its maximum expression stability through BestKeeper analysis. The present study indicated that, ACTB and HMB were not reliable IRGs for melanocytes cells on account of their lower expression stability. Current study further revealed that UXT, HPRT and RPS23 are the best IRGs for normalization of qPCR data in Bos indicus melanocyte cells under heat stress and hormonal treatment.