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The world poultry industry is under great stress due to parasitic diseases; coccidiosis being one which is responsible for substantial economic losses worldwide. In 1948 the first research paper was published about the treatment of coccidiosis with sulphaquinoxaline. After six decades, researcher's attention has focused on DNA vaccination, especially as certain anticoccidials have failed due to drug resistance and residues. Thus far vaccination is partially successful but is accompanied by disadvantages: e.g. instability, inferiority control, cost-effectiveness, and inefficiency in opposition to a large number of coccidian strains which are prevalent in different geographical areas. Due to developments whereby genetically engineered DNA can be administered in vaccine form to provoke cellular and humoral immune responses; there has been huge development in the practical application of this field. In the last decade a number of DNA vaccines employing different strategies have been tested to produce appropriate immune responses against coccidiosis. The DNA fragments taken from all the four important species, E. tenella, E. necatrix, E. maxima and E. acervulina were able to provoke appropriate immune responses against challenging infections with homologous species; however, most of them were not able to provoke a response with heterologous infection. The shared DNA antigen in two different species of Eimeria; E. tenella and E. acervulina was able to produce sufficient immune responses, not only against these species but also against E. necatrix, but not against E. maxima. E. maximum is the biggest and most complex of all the seven species and it has come ahead as a challenge for DNA vaccine researchers. [ABSTRACT FROM PUBLISHER]

Rosai Dorfman disease is an uncommon benign condition presenting with massive enlargement of cervical lymph nodes. We describe one such young female patient with similar presentation who had an aggressive course with fatal outcome. [ABSTRACT FROM AUTHOR]

Abstract Background Transgender males are at high risk for sexually transmitted diseases including AIDS caused by the notorious Human Immunodeficiency Virus (HIV), yet little consideration is given by the policy makers, researchers and non-governmental organizations (NGOs) towards this sensitive issue in Pakistan. Methods In this study, we have investigated the prevalence of HIV infection among 306 transgender males with a median age of 29 years (range 15–64 years) residing in Rawalpindi, Pakistan. Rapid HIV antibody-screening methods including the strip test and Enzyme Linked Immuno-absorbent tests were employed to detect HIV antibodies among the subjects. For further confirmation, Polymerase Chain Reaction (PCR) was carried out. Statistical analytical techniques utilized included logistic regression and chi-square. Results HIV-1 was found to be the predominant viral subtype. PCR confirmed 21.6% (Confidence Interval 0.17-0.26) of the respondents were reported being HIV positive. 15.7% of the transgender men who shave at home and 13.7% of the transgender men who were educated below 5th grade were found to have HIV. Conclusion This study shows a very high prevalence of HIV among transgender males. Unawareness among these individuals about the ramifications of this infection owes largely to lack of education. The spread rate is alarming and HIV epidemic is imminent if awareness is not widespread.

Abstract Recently it has been recognized that bacteriophages, the natural predators of bacteria can be used efficiently in modern biotechnology. They have been proposed as alternatives to antibiotics for many antibiotic resistant bacterial strains. Phages can be used as biocontrol agents in agriculture and petroleum industry. Moreover phages are used as vehicles for vaccines both DNA and protein, for the detection of pathogenic bacterial strain, as display system for many proteins and antibodies. Bacteriophages are diverse group of viruses which are easily manipulated and therefore they have potential uses in biotechnology, research, and therapeutics. The aim of this review article is to enable the wide range of researchers, scientists, and biotechnologist who are putting phages into practice, to accelerate the progress and development in the field of biotechnology.

Abstract Chronic Hepatitis C virus has the potential of inducing insulin resistance and type 2 Diabetes Mellitus in vitro as well as in vivo . Structural and non-structural proteins of HCV modulate cellular gene expression in such a way that insulin signaling is hampered, concomitantly leads toward diabetes mellitus. A number of mechanisms have been proposed in regard to the HCV induced insulin resistance involving the upregulation of Inflammatory cytokine TNF-α, hypophosphorylation of IRS-1 and IRS-2, phosphorylation of Akt, up-regulation of gluconeogenic genes, accumulation of lipids and targeting lipid storage organelles. This review provides an insight of molecular mechanisms by which HCV structural and non-structural proteins can induce insulin resistance.

Abstract Hepatitis C virus (HCV) is a major health problem in developing countries including Pakistan. Chronic HCV infection results in progressive liver disease including fibrosis, cirrhosis, insulin resistance and eventually hepatocellular carcinoma (HCC). Ionotrophic purinergic (P2X) receptors are identified to involve in a spectrum of physiological and pathophysiological processes. However, the role of P2X receptors in HCV liver associated diseases still remains to be investigated. The current study was designed to identify the presence of P2X receptors in human liver cells. Furthermore, it investigates the response of P2X receptors towards HCV structural proteins (E1E2). To determine that how many isoforms of P2X receptors are expressed in human liver cells, human hepatoma cell line (Huh-7) was used. Transcripts (mRNA) of five different isoforms of P2X receptors were identified in Huh-7 cells. To examine the gene expression of identified isoforms of P2X receptors in presence of HCV structural proteins E1E2, Huh-7/E1E2 cell line (stably expressing HCV structural proteins E1E2) was used. The results showed significant increase (6.2 fold) in gene expression of P2X4 receptors in Huh-7/E1E2 cells as compared to control Huh-7 cells. The findings of present study confirmed the presence of transcripts of five different isoforms of P2X receptors in human liver cells and suggest that P2X4 receptors could be represented an important component of the purinergic signaling complex in HCV induced liver pathogenesis.

Abstract Background Epstein Barr Virus (EBV) plays a significant role as a cofactor in the process of tumorigenesis and has consistently been associated with a variety of malignancies. EBV encoded RNAs (EBER1 and EBER2) are the most abundant viral transcripts in latently EBV-infected cells and their role in viral infection is still unclear. Formalin Fixed Paraffin Embedded (FFPE) tissues of surgically removed carcinoma biopsies are widely available form but have never been exploited for expressional studies previously in Pakistan. Immunohistochemistry (IHC) and in situ hybridization (ISH) in FFPE biopsy tissues remains the gold standard for proving EBV relationship in a histopathological lesion but their reagents associated limitations confines their reliability in some applications. Recently introduced targeted drug delivery systems induce viral lytic gene expression and therefore require more sensitive method to quantify viral as well as cellular gene expression. Methods Eight (8) lymphoma samples were screened to detect the EBV genome. Qualitative and quantitative expression of EBV Encoded RNAs (EBER1, EBER2) and anti-inflammatory cytokine (interleukin-10) in FFPE EBV positive lymphoma tissue samples were then analysed by using Reverse transcriptase Polymerase Chain Reaction (RT-PCR) and Real Time Polymerase Chain Reaction (qRT-PCR), respectively. Results In this study we have successfully quantified elevated expressional levels of both cellular and viral transcripts, namely EBER1, EBER2 and anti-inflammatory cytokine (IL-10) in the FFPE Burkitt's lymphoma (BL) specimens of Pakistani origin. Conclusions These results indicate that FFPE samples may retain viral as well as cellular RNA expression information at detectable level. To our knowledge, this is first study which represents elevated expressional levels of EBER1, EBER2 and IL-10 in FFPE tissue samples of Burkitt's lymphoma in Pakistan. These observations will potentially improve current lacunas in clinical as well as diagnostic practices in Pakistan and can be further exploited to develop new strategies for studying cellular and/or viral gene expression.

Abstract Hepatitis C virus (HCV) is the main cause of severe liver disease, including hepatocellular carcinoma, cirrhosis and end stage liver disease. In Pakistan most of HCV positive patients have history of facial/armpit shaving from barbers. 79% of barbers are rubbing Potash Alum stone on facial shaving cuts. Dark blood spots are analyzed on Potash Alum stones being used at different barber shops. The aim of the study was to check the viability of hepatitis C virus on potash alum stone being used at barber shops. Blood samples from HCV positive patients were taken and treated with 0.1, 0.2, 0.3, 0.4 and 0.5 molar concentrations of Potash Alum for different periods of time. Blood was centrifuged to isolate the serum; HCV RNA was extracted from serum and subjected to first strand synthesis and PCR. PCR fragments were confirmed by sequencing. PCR amplification was observed in all the samples, treated with different concentrations of Potash Alum, indicated that the virus remains alive on Potash Alum stone for a long period of time. Potash Alum being used by barbers on facial shaving cuts has definite role in HCV transmission in Pakistani population. Therefore use of Potash Alum stone should be banned on facial shaving cuts at barber shops.

Abstract Background Hepatitis B virus (HBV) infections play an important role in the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. HBx is known to interact with DNA helicase components of TFIIH, a basal transcriptional factor and an integral component of DNA excision repair. Results In this study, the functional relevance of this association was further investigated in the context to DNA repair. By site-directed mutagenesis HBx's critical residues for interaction with TFIIH were identified. Similarly, TFIIH mutants lacking ATPase domain and the conserved carboxyl-terminal domain failed to interact with HBx. Yeast and mammalian cells expressing HBxwt conferred hypersensitivity to UV irradiation, which is interpreted as a basic deficiency in nucleotide excision repair. HBxmut120 (Glu to Val) was defective in binding to TFIIH and failed to respond to UV. Conclusions We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, thereby contributing to HCC development.

Lymphoma is the sixth most prevalent cancer globally. Non-Hodgkin's lymphomas are the majority group of lymphomas, with B cells accounting for approximately 95% of these lymphomas. A key feature of B-cell lymphoma is the functional perturbations of essential biological pathways caused by genetic aberrations. These lead to atypical gene expression, providing cells with a selective growth advantage. Molecular analysis reveals that each lymphoma subtype has unique molecular mutations, which pose challenges in disease management and treatment. Substantial efforts over the last decade have led to the integration of this information into clinical applications, resulting in crucial insights into clinical diagnosis and targeted therapies. However, with the growing need for more effective medication development, we anticipate a deeper understanding of signaling pathways and their interactions to emerge. This review aims to demonstrate how the BCR, specific signaling pathways like PI3K/AKT/mTOR, NF-kB, and JAK/STAT are diverse in common types of B-cell lymphoma. Furthermore, it offers a detailed examination of each pathway and a synopsis of the approved or in-development targeted therapies. In conclusion, finding the activated signaling pathways is crucial for developing effective treatment plans to improve the prognosis of patients with relapsed or refractory lymphoma. Trial Registration: ClinicalTrials.gov identifier: NCT02180724, NCT02029443, NCT02477696, NCT03836261, NCT02343120, NCT04440059, NCT01882803, NCT01258998, NCT01742988, NCT02055820, NCT02285062, NCT01855750, NCT03422679, NCT01897571., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Abdullah Alfaifi et al.)

Background: Lymphoma ranks fifth in prevalence among common cancer types worldwide. This lymphatic system cancer arises from T or B cells. Diffuse large B cell lymphomas (DLBCLs) are associated with most non-Hodgkin lymphomas. Non-coding microRNAs (miRNAs) greatly affect gene expression. A single miRNA can target numerous genes, thus largely influencing gene expression networks. MiRNAs can act as oncogenes or tumor suppressors in controlling DLBCL progression. This study investigated the roles of miRNAs in patients with DLBCL through next-generation sequencing, which was found to be sensitive, accurate, and robust., Methods: The study involved seven patients with DLBCLs and three controls at a hematology-oncology clinic. MiRNA was extracted from existing formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Illumina next-generation sequencing was used to sequence samples for miRNA profiling., Results: Samples from patients showed expression of various hsa-mir miRNAs (1248, 3607, 21, 142, 1244, 182, 6516, 766, 1291, 4449, and 181a), whereas those from healthy individuals showed expression of hsa-mir 1248, 3607, 21, 142, and 877. Hsa-mir-877-3p is known to target multiple genes, and miRNAs such as hsa-mir-877-3p, hsa-mir-1291, and hsa-mir-181a-5p interact primarily with target genes., Conclusions: MiRNA profiling in FFPE tissues from patients with DLBCL suggested that miRNA levels can distinguish patients with DLBCL from controls, and therefore may provide prognostic or diagnostic biomarkers for DLBCL. Altered genes and miRNAs may also be potential therapeutic targets., (© 2024 The Authors.)

Phage therapy has recently attracted a great deal of attention to counteract the rapid emergence of antibiotic-resistant bacteria. In comparison to monophage therapy, phage cocktails are typically used to treat individual and/or multi-bacterial infections since the bacterial agents are unlikely to become resistant as a result of exposure to multiple phages simultaneously. The bacteriolytic effect of phage cocktails may produce efficient killing effect in comparison to individual phage. However, multiple use of phages (complex cocktails) may lead to undesirable side effects such as dysbiosis, horizontal gene transfer, phage resistance, cross resistance, and/or higher cost of production. Cocktail formulation, therefore, representa compromise between limiting the complexity of the cocktail and achieving substantial bacterial load reduction towards the targeted host organisms. Despite some constraints, the applications of monophage therapy have been well documented in the literature. However, phage cocktails-based approaches and their role for the control of pathogens have not been well investigated. In this review, we discuss the principle of phage cocktail formulations, their optimization strategies, major phage cocktail preparations, and their efficacy in inactivating various food borne bacterial pathogens.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a serious public health threat in multiple clinical settings. In this study, we detail the isolation of a lytic bacteriophage, vB_PseuP-SA22, from wastewater using a clinical strain of CRPA. Transmission electron microscopy (TEM) analysis identified that the phage had a podovirus morphology, which agreed with the results of whole genome sequencing. BLASTn search allowed us to classify vB_PseuP-SA22 into the genus Bruynoghevirus . The genome of vB_PseuP-SA22 consisted of 45,458 bp of double-stranded DNA, with a GC content of 52.5%. Of all the open reading frames (ORFs), only 26 (44.8%) were predicted to encode certain functional proteins, whereas the remaining 32 (55.2%) ORFs were annotated as sequences coding functionally uncharacterized hypothetical proteins. The genome lacked genes coding for toxins or markers of lysogenic phages, including integrases, repressors, recombinases, or excisionases. The phage produced round, halo plaques with a diameter of 1.5 ± 2.5 mm on the bacterial lawn. The TEM revealed that vB_PseuP-SA22 has an icosahedral head of 57.5 ± 4.5 nm in length and a short, non-contractile tail (19.5 ± 1.4 nm). The phage showed a latent period of 30 min, a burst size of 300 PFU/infected cells, and a broad host range. vB_PseuP-SA22 was found to be stable between 4-60 °C for 1 h, while the viability of the virus was reduced at temperatures above 60 °C. The phage showed stability at pH levels between 5 and 11. vB_PauP-SA22 reduced the number of live bacteria in P . aeruginosa biofilm by almost five logs. The overall results indicated that the isolated phage could be a candidate to control CRPA infections. However, experimental in vivo studies are essential to ensure the safety and efficacy of vB_PauP-SA22 before its use in humans.

A wide range of histological as well as clinical properties are exhibited by B-cell non-Hodgkin's lymphomas. These properties could make the diagnostics process complicated. The diagnosis of lymphomas at an initial stage is essential because early remedial actions taken against destructive subtypes are commonly deliberated as successful and restorative. Therefore, better protective action is needed to improve the condition of those patients who are extensively affected by cancer when diagnosed for the first time. The development of new and efficient methods for early detection of cancer has become crucial nowadays. Biomarkers are urgently needed for diagnosing B-cell non-Hodgkin's lymphoma and assessing the severity of the disease and its prognosis. New possibilities are now open for diagnosing cancer with the help of metabolomics. The study of all the metabolites synthesised in the human body is called "metabolomics." A patient's phenotype is directly linked with metabolomics, which can help in providing some clinically beneficial biomarkers and is applied in the diagnostics of B-cell non-Hodgkin's lymphoma. In cancer research, it can analyse the cancerous metabolome to identify the metabolic biomarkers. This review provides an understanding of B-cell non-Hodgkin's lymphoma metabolism and its applications in medical diagnostics. A description of the workflow based on metabolomics is also provided, along with the benefits and drawbacks of various techniques. The use of predictive metabolic biomarkers for the diagnosis and prognosis of B-cell non-Hodgkin's lymphoma is also explored. Thus, we can say that abnormalities related to metabolic processes can occur in a vast range of B-cell non-Hodgkin's lymphomas. The metabolic biomarkers could only be discovered and identified as innovative therapeutic objects if we explored and researched them. In the near future, the innovations involving metabolomics could prove fruitful for predicting outcomes and bringing out novel remedial approaches.

Bacteria and their predators, bacteriophages, or phages are continuously engaged in an arms race for their survival using various defense strategies. Several studies indicated that the bacterial immune arsenal towards phage is quite diverse and uses different components of the host machinery. Most studied antiphage systems are associated with phages, whose genomic matter is double-stranded-DNA. These defense mechanisms are mainly related to either the host or phage-derived proteins and other associated structures and biomolecules. Some of these strategies include DNA restriction-modification (R-M), spontaneous mutations, blocking of phage receptors, production of competitive inhibitors and extracellular matrix which prevent the entry of phage DNA into the host cytoplasm, assembly interference, abortive infection, toxin-antitoxin systems, bacterial retrons, and secondary metabolite-based replication interference. On the contrary, phages develop anti-phage resistance defense mechanisms in consortium with each of these bacterial phage resistance strategies with small fitness cost. These mechanisms allow phages to undergo their replication safely inside their bacterial host's cytoplasm and be able to produce viable, competent, and immunologically endured progeny virions for the next generation. In this review, we highlight the major bacterial defense systems developed against their predators and some of the phage counterstrategies and suggest potential research directions.

Ticks and tick-borne diseases are considered a major challenge for human and animal health in tropical, sub-tropical, and temperate regions of the world. However, only scarce information is available on the characterization of tick species infesting dogs in Pakistan. In this study, we present a comprehensive report on the epidemiological and phylogenetic aspects of ticks infesting dogs in Pakistan using the mitochondrial markers i.e. Cytochrome c oxidase subunit 1 (cox1) and 16S ribosomal RNA (16S rRNA) nucleotide sequences. A total of 300 dogs were examined and 1150 ixodid ticks were collected across central Khyber Pakhtunkhwa, Pakistan. The morpho-molecular characterization of hard ticks revealed the presence of two ixodid tick genera on dogs, i.e., Hyalomma and Rhipicephalus, including six tick species viz. Hyalomma dromedarii (15.9%), Hyalomma excavatum (3%), Rhipicephalus sanguineus s.l. (41.3%), Rhipicephalus turanicus s.s. (28.7%), Rhipicephalus haemaphysaloides (10.2%), and Rhipicephalus microplus (2%). The total prevalence of tick infestation in dogs was 61%. The district with the highest tick prevalence rate in dogs was Mardan (14.7%), followed by Peshawar (13%), Swabi (12%), Charsadda (11%), and Malakand (10.3%), respectively. Risk factors analysis indicated that some demographic and host management-associated factors such as host age, breed, exposure to acaricides treatment, and previous tick infestation history were associated with a higher risk of tick infestation on dogs. This is the first molecular report confirming the infestation of Hyalomma and Rhipicephalus tick species in the dog population from the study area. The present study also reported a new tick−host association between Hy. excavatum, Hy. dromedarii, and dogs. Phylogenetic analysis revealed that cox1 partial nucleotide sequences of Hy. excavatum in our dataset were 100% identical to similar tick specimens identified in Turkey, and those of Hy. dromedarii were identical to tick specimens from Iran. Whereas, Rh. haemaphysaloides and Rh. microplus’ cox1 partial nucleotide sequences were identical to sequences previously published from Pakistan. Rhipicephalus turanicus s.s. ‘s cox1 isolates from the present study were 99.8−100% identical to Pakistani-reported isolates, and those of Rh. sanguineus s.l. were 100% identical to Chinese specimens. Results on the genetic characterization of ticks were further confirmed by 16S rRNA partial nucleotide sequences analysis, which revealed 100% identity between the tick isolates of this study and those of Hy. excavatum reported from Turkey; Hy. dromedarii specimens reported from Senegal; Rh. haemaphysaloides, Rh. microplus, and Rh. turanicus s.s., previously published from Pakistan, and Rh. sanguineus s.l., published from China. Furthermore, phylogenetic analysis showed that the Rh. sanguineus s.l. isolates of this study clustered with specimens of the tropical lineage with 7.7−10% nucleotide divergence from the specimens of the temperate lineage. Further molecular works need to be performed throughout Pakistan to present a more detailed map of tick distribution with information about dog host associations, biological characteristics, and pathogen competence.

Foodborne microorganisms are an important cause of human illness worldwide. Two-thirds of human foodborne diseases are caused by bacterial pathogens throughout the globe, especially in developing nations. Despite enormous developments in conventional foodborne pathogen detection methods, progress is limited by the assay complexity and a prolonged time-to-result. The specificity and sensitivity of assays for live pathogen detection may also depend on the nature of the samples being analyzed and the immunological or molecular reagents used. Bacteriophage-based biosensors offer several benefits, including specificity to their host organism, the detection of only live pathogens, and resistance to extreme environmental factors such as organic solvents, high temperatures, and a wide pH range. Phage-based biosensors are receiving increasing attention owing to their high degree of accuracy, specificity, and reduced assay times. These characteristics, coupled with their abundant supply, make phages a novel bio-recognition molecule in assay development, including biosensors for the detection of foodborne bacterial pathogens to ensure food safety. This review provides comprehensive information about the different types of phage-based biosensor platforms, such as magnetoelastic sensors, quartz crystal microbalance, and electrochemical and surface plasmon resonance for the detection of several foodborne bacterial pathogens from various representative food matrices and environmental samples.

Colorectal cancer (CRC) is the second most common cause of death worldwide, affecting approximately 1.9 million individuals in 2020. Therapeutics of the disease are not yet available and discovering a novel anticancer drug candidate against the disease is an urgent need. Thymidylate synthase (TS) is an important enzyme and prime precursor for DNA biosynthesis that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) that has emerged as a novel drug target against the disease. Elevated expression of TS in proliferating cells promotes oncogenesis as well as CRC. Therefore, this study aimed to identify potential natural anticancer agents that can inhibit the activity of the TS protein, subsequently blocking the progression of colorectal cancer. Initially, molecular docking was implied on 63 natural compounds identified from Catharanthus roseus and Avicennia marina to evaluate their binding affinity to the desired protein. Subsequently, molecular dynamics (MD) simulation, ADME (Absorption, Distribution, Metabolism, and Excretion), toxicity, and quantum chemical-based DFT (density-functional theory) approaches were applied to evaluate the efficacy of the selected compounds. Molecular docking analysis initially identified four compounds (PubChem CID: 5281349, CID: 102004710, CID: 11969465, CID: 198912) that have better binding affinity to the target protein. The ADME and toxicity properties indicated good pharmacokinetics (PK) and toxicity ability of the selected compounds. Additionally, the quantum chemical calculation of the selected molecules found low chemical reactivity indicating the bioactivity of the drug candidate. The global descriptor and HOMO-LUMO energy gap values indicated a satisfactory and remarkable profile of the selected molecules. Furthermore, MD simulations of the compounds identified better binding stability of the compounds to the desired protein. To sum up, the phytoconstituents from two plants showed better anticancer activity against TS protein that can be further developed as an anti-CRC drug.

In August 2020 powdery mildew was observed on pear cv. Fertility at the University research field in Shalimar, Srinagar (J&K), India (34° 08' 30.5'' N and 74° 51' 42.0'' E) with a disease incidence up to 30% (100 leaves observed from ten trees). White irregularly shaped fungal colonies were observed on the abaxial leaf surface which latter covered the whole leaf surface and developed black chasmothecia. The affected leaves appeared brittle, slightly curved upwards and dropped prematurely. Mycelium was hypophyllous, septate and measured 2.0 to 5.0 μm in width. Appressoria were nipple shaped, solitary or present in opposite pairs. Conidiophores were erect, up to 440.0 µm long (n=50), mostly centrally on upper surface of mother cells. Conidiophore foot-cells were filiform, followed by 1 to 3 shorter cells, producing single conidia at the tip. Conidia were hyaline, lanceolate, with a non-papillate rounded apex, measuring55.5 to 81.4 × 14.8 to 22.5 µm (n=50) and devoid of any conspicuous fibrosin bodies. Germ tube was, filiform, twisted, arose basally and measured 2.0 to 5.0 µm in width. Chasmothecia were hypophyllous, black, scattered, globose and measured 195.0 to 255.0 µm in diameter (n=50) having 8 to 12 equatorial, acicular, up to 270.0 µm length appendages with 25.9 to 44.4 µm diameter bulbous base (n=50) and obtuse or subacute apex. Asci in a chasmothecium were clavate to saccate, 62.9 to 81.4 × 18.5 to 22.2 µm (n=50), stalked, and two- spored. Ascospores were 33.3 to 40.7 × 12.9 to 18.5 µm (n=50), pale yellowish or golden brown in color. All morphological features were consistent with Phyllactinia pyri-serotinae (Braun and Cook 2012). To confirm the fungus identity at molecular level, DNA of two isolates was extracted from chasmothecia. The internal transcribed spacer (ITS) sequence of ribosomal DNA was amplified with the primers ITS1 and ITS4 (White et al. 1990) and sequenced. The ITS sequences submitted to NCBI GenBank under Accession No. MZ505441 and MZ505442 have 97 (416/427) & 96 (424/440) per cent and 99 (424/430) & 98 (428/438) per cent base pair matching, with that of P. pyri-serotinae isolates from Japan (AB080521 and AB985507), respectively. Thus, the pathogen was identified as Phyllactinia pyri-serotinae Sawada based on morphological and molecular sequence analyses. The pathogenicity tests of both the isolates were carried out on one year old pear saplings (cv. Fertility) and repeated twice. The inoculum was prepared by collecting P. pyri-serotinae conidia in sterile distilled water from infected pear leaves. Three saplings were inoculated by spraying (15ml per sapling) the inoculum (3 x 105 spores ml-1) on leaf surfaces, while same number of saplings sprayed with sterile distilled water served as non-inoculated controls. After 15 days of incubation at 25oC in a green house, similar symptoms as observed on naturally infected plants were observed on inoculated plants and uninoculated plants remained symptomless. The pathogen of interest observed on inoculated plants was morphologically characterized and found to be similar to P. pyri-serotinae. The voucher specimen was deposited in the Herbarium Crytogamae Indiae Orientalis (HCIO), IARI, New Delhi under accession number 52213. Pear is the third most important temperate fruit grown in India (Chattopadhyay 2009) and our study reveal P. pyri-serotinae as the new causal agent of powdery mildew in addition to P. guttata (Dhar and Shah 1982) under Indian conditions.

B-cell lymphomas exhibit a vast variety of clinical and histological characteristics that might complicate the diagnosis. Timely diagnosis is crucial, as treatments for aggressive subtypes are considered successful and frequently curative, whereas indolent B-cell lymphomas are incurable and often need several therapies. The purpose of this review is to explore the current advancements achieved in B-cell lymphomas metabolism and how these indicators help to early detect metabolic changes in B-cell lymphomas and the use of predictive biological markers in refractory or relapsed disease. Since the year 1920, the Warburg effect has been known as an integral part of metabolic reprogramming. Compared to normal cells, cancerous cells require more glucose. These cancer cells undergo aerobic glycolysis instead of oxidative phosphorylation to metabolize glucose and form lactate as an end product. With the help of these metabolic alterations, a novel biomass is generated by the formation of various precursors. An aggressive metabolic phenotype is an aerobic glycolysis that has the advantage of producing high-rate ATP and preparing the biomass for the amino acid, as well as fatty acid, synthesis needed for a rapid proliferation of cells, while aerobic glycolysis is commonly thought to be the dominant metabolism in cancer cells. Later on, many metabolic biomarkers, such as increased levels of lactate dehydrogenase (LDH), plasma lactate, and deficiency of thiamine in B-cell lymphoma patients, were discovered. Various kinds of molecules can be used as biomarkers, such as genes, proteins, or hormones, because they all refer to body health. Here, we focus only on significant metabolic biomarkers in B-cell lymphomas. In conclusion, many metabolic biomarkers have been shown to have clinical validity, but many others have not been subjected to extensive testing to demonstrate their clinical usefulness in B-cell lymphoma. Furthermore, they play an essential role in the discovery of new therapeutic targets.

Background: Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses, including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection. However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy ineffective., Objectives: Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin (PEG-IFN/RIB) therapy., Methods: Twenty patients with HCV infection and ten healthy controls were enrolled in this study and patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder (HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology, using a MAGPIX instrument (Luminex Corporation, USA)., Results: A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/ RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN, MIG, RANTES, and MIP-1β, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy., Conclusion: Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma., Limitations: Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be the reason for the lack of association between some of the inflammatory markers evaluated and the SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. Most of the ACE2 inhibitors discovered till now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals' inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a 3D structure-based-pharmacophore model (SBPM) has been developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based on their binding affinity (-7.5, -7.1, -7.1, and -7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell., (Copyright © 2021 Elsevier B.V. All rights reserved.)

MicroRNA is a small non-coding RNA (sncRNA) involved in gene silencing and regulating post-transcriptional gene expression. miRNAs play an essential role in the pathogenesis of numerous diseases, including diabetes, cardiovascular diseases, viral diseases and cancer. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma (NHL), arising from different stages of B-cell differentiation whose pathogenesis involves miRNAs. Various viral and non-viral vectors are used as a delivery vehicle for introducing specific miRNA inside the cell. Adenoviruses are linear, double-stranded DNA viruses with 35 kb genome size and are extensively used in gene therapy. Meanwhile, Adeno-associated viruses accommodate up to 4.8 kb foreign genetic material and are favorable for transferring miRNA due to small size of miRNA. The genetic material is integrated into the DNA of the host cell by retroviruses so that only dividing cells are infected and stable expression of miRNA is achieved. Over the years, remarkable progress was made to understand DLBCL biology using advanced genomics and epigenomics technologies enabling oncologists to uncover multiple genetic mutations in DLBCL patients. These genetic mutations are involved in epigenetic modification, ability to escape immunosurveillance, impaired BCL6 and NF-κβ signaling pathways and blocking terminal differentiation. These pathways have since been identified and used as therapeutic targets for the treatment of DLBCL. Recently miRNAs were also identified to act either as oncogenes or tumor suppressors in DLBCL pathology by altering the expression levels of some of the known DLBCL related oncogenes. i.e., miR-155, miR-17-92 and miR-21 act as oncogenes by altering the expression levels of MYC , SHIP and FOXO1, respectively, conversely; miR-34a, mir-144 and miR-181a act as tumor suppressors by altering the expression levels of SIRT1, BCL6 and CARD11, respectively. Hundreds of miRNAs have already been identified as biomarkers in the prognosis and diagnosis of DLBCL because of their significant roles in DLBCL pathogenesis. In conclusion, miRNAs in addition to their role as biomarkers of prognosis and diagnosis could also serve as potential therapeutic targets for treating DLBCL.

Minichromosome maintenance complex component 7 (MCM7) belongs to the minichromosome maintenance family that is important for the initiation of eukaryotic DNA replication. Overexpression of the MCM7 protein is relative to cellular proliferation and responsible for aggressive malignancy in various cancers. Mechanistically, inhibition of MCM7 significantly reduces the cellular proliferation associated with cancer. To date, no effective small molecular candidate has been identified that can block the progression of cancer induced by the MCM7 protein. Therefore, the study has been designed to identify small molecular-like natural drug candidates against aggressive malignancy associated with various cancers by targeting MCM7 protein. To identify potential compounds against the targeted protein a comprehensive in silico drug design including molecular docking, ADME (Absorption, Distribution, Metabolism and Excretion), toxicity, and molecular dynamics (MD) simulation approaches has been applied. Seventy phytochemicals isolated from the neem tree (Azadiractha indica) were retrieved and screened against MCM7 protein by using the molecular docking simulation method, where the top four compounds have been chosen for further evaluation based on their binding affinities. Analysis of ADME and toxicity properties reveals the efficacy and safety of the selected four compounds. To validate the stability of the protein-ligand complex structure MD simulations approach has also been performed to the protein-ligand complex structure, which confirmed the stability of the selected three compounds including CAS ID:105377-74-0, CID:12308716 and CID:10505484 to the binding site of the protein. In the study, a comprehensive data screening process has performed based on the docking, ADMET properties, and MD simulation approaches, which found a good value of the selected four compounds against the targeted MCM7 protein and indicates as a promising and effective human anticancer agent., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy >-9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD.

Cardiovascular diseases (CVD), primarily inflammatory cardiomyopathy, are characterized by the infiltration of inflammatory cells into the myocardium. It has a relatively high risk of deteriorating heart function and has heterogeneous etiologies. Inflammatory cardiomyopathy is mainly mediated by viral infections but can also be mediated by protozoa, fungal or bacterial infections. Besides that, there are a wide variety of drugs, toxic substances, and systemic immune-mediated diseases that result in the development of cardiovascular diseases (CVDs). Despite broad research, inflammatory cardiomyopathy has a poor prognosis. The roles of the pathogens, host genomic counterparts and environmental triggers in the progression of disease are still under consideration, including the role of some viruses as active inducers and others as bystanders. In this review article, we review the available evidence on the types, pathogenesis and treatment of myocarditis, inflammatory cardiomyopathy, and atherosclerosis with a particular focus on virus-associated cardiac diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cholangiocarcinoma (CCA) comprises of extra-hepatic cholangiocarcinoma and intrahepatic cholangiocarcinoma cancers as a result of inflammation of epithelium cell lining of the bile duct. The incidence rate is increasing dramatically worldwide with highest rates in Eastern and South Asian regions. Major risk factors involve chronic damage and inflammation of bile duct epithelium from primary sclerosing cholangitis, chronic hepatitis virus infection, gallstones and liver fluke infection. Various genetic variants have also been identified and as CCA develops on the background of biliary inflammation, diverse range of molecular mechanisms are involved in its progression. Among these, the Notch signalling pathway acts as a major driver of cholangiocarcinogenesis and its components (receptors, ligands and downstream signalling molecules) represent a promising therapeutic targets. Gamma-Secretase Inhibitors have been recognized in inhibiting the Notch pathway efficiently. A comprehensive knowledge of the molecular pathways activated by the Notch signalling cascade as well as its functional crosstalk with other signalling pathways provide better approach in developing innovative therapies against CCA., Competing Interests: Conflict-of-interest statement: The authors declare no potential financial interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatitis E Virus (HEV) imposes a major health concern in areas with very poor sanitation in Africa and Asia. The pathogen is transmitted mainly through ingesting contaminated water or food, coming into contact with affected people, and blood transfusions. Very few reports including old reports are available on the prevalence of HEV in Saudi Arabia in humans and no reports exist on HEV prevalence in camels. Dromedary camel trade and farming are increasing in Saudi Arabia with importation occurring unidirectionally from Africa to Saudi Arabia. DcHEV transmission to humans has been reported in one case from the United Arab Emeritus (UAE). This instigated us to perform this investigation of the seroprevalence of HEV in imported and domestic camels in Saudi Arabia. Serum samples were collected from imported and domestic camels. DcHEV-Abs were detected in collected sera using ELISA. The prevalence of DcHEV in the collected samples was 23.1% with slightly lower prevalence in imported camels than domestic camels (22.4% vs. 25.4%, p value = 0.3). Gender was significantly associated with the prevalence of HEV in the collected camels ( p value = 0.015) where males (31.6%) were more infected than females (13.4%). This study is the first study to investigate the prevalence of HEV in dromedary camels from Saudi Arabia. The high seroprevalence of DcHEV in dromedaries might indicate their role as a zoonotic reservoir for viral infection to humans. Future HEV seroprevalence studies in humans are needed to investigate the role of DcHEV in the Saudi human population.

Aim: The aim of this study was to investigate the effectiveness of blended learning with a flipped classroom design on student academic achievement in a Bachelor of Science in Nursing course., Design: A quasi-experimental study., Method: Students were split into an experimental blended learning with a flipped classroom design group and a control group using the traditional, teacher-centred learning method. Data were collected during spring 2018 (13.3 weeks) and student's grades for the registered course and their grade point average (GPA) were recorded., Results: Findings showed statistically significant increases in student grades in the experimental group. Predictability calculations also showed better achievement of learning outcomes if a blended learning with a flipped classroom design is continued to be used in the future., Competing Interests: The authors declare no conflict of interest to report., (© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

The present study was carried out to evaluate the in vitro cytoprotective effects of Psidium guajava and their isolated quercetin fraction to reduce the CCl 4 (carbon tetrachloride) induced toxicity in HepG2 cell lines (Hepatocellular carcinoma G2). Silymarin was used as a standard drug to compare the protective effects of plant extracts in infected cell lines. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay, cell viability assay, leakage parameters [Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Lactate dehydrogenase (LDH)], lipid peroxidation and reduced glutathione (GSH) levels were used to find out the protection of human derived HepG2 cells against CCl 4 -induced damage. The levels of cytotoxicity, viability and GSH were reduced. While the activities of AST, ALT, LDH and lipid peroxidation was increased in CCl 4 -treated groups. The treatment of P. guajava and their isolated quercetin fractions (100, 200, 300 µg/mL) decreased the elevated levels of all these parameters. The results of the present study suggest that the ethanolic extract of P. guajava leaf and their isolated quercetin fractions can able to reduce the CCl 4 -induced cytotoxicity in HepG2 cell lines., Competing Interests: Conflict of interestThe authors declare no conflict of interest.

Introduction: Admission to a pediatric intensive care unit (PICU) with a Staphylococcus aureus (SA) infection is associated with considerable mortality and morbidity. There is paucity of data about epidemiology of SA infection in a PICU. This study was aimed at elucidating the clinicoepidemiological profile and outcome of children admitted to ICU with S. aureus infection., Methods: This study was carried out in a PICU at a tertiary care hospital in northern India. Children admitted with culture positive S. aureus infection were enrolled in this study. Children suspected of having S. aureus infection on clinical grounds only without a positive culture were excluded from the study. Baseline characteristics of the subjects were recorded on admission and daily follow up maintained till death or discharge from PICU. The course during PICU stay, ensuing complication, and outcome was recorded., Results: There were 2,480 total admissions to the PICU during study period of one year, out of which 120 (4.83%) admissions had a culture proven S. aureus infection. Fifty-six (46.6%) were male and 64 (53.3%) were female. Most of the subjects fell in the age groups of 1-5 years and 10-15 years having 56 (46.6%) and 40 (33.3%) subjects, respectively. Pneumonia (43.3%), septicaemia (20.8), and bone/joint space infections (15%) were the three main clinical manifestations. Forty-two (35%) of specimens were reported as methicillin resistant. Incidence of methicillin resistant SA (MRSA) infection was 1.6 and that of methicillin sensitive SA (MSSA) 3.1 per 100 admissions to PICU. On sensitivity testing, none of the specimens was found to be vancomycin resistant. There were 240 total deaths in PICU during study period out of which 25 (10.4%) were observed from the study group. Mortality rate was 20.8%. Mortality was high in the MRSA group., Conclusion: The incidence of S. aureus infection and associated mortality is high in PICU. MRSA infection was more common in children admitted with chronic disease and is associated with higher mortality. Our study found a bimodal age distribution for serious staph infection, a finding that needs further evaluation., How to Cite This Article: Qadri I, Malik I, Ahmed K. Staphylococcus aureus Infection in A Pediatric ICU: A Hospital Based Prospective Observational Study. Indian J Crit Care Med 2019;23(5):210-212., Competing Interests: Source of support: Nil Conflict of interest: None

Dengue, West Nile and Zika virus belongs to the family flaviviridae and genus flavivirus. It is of interest to design and develop inhibitors with improved activity against these diseases. We used the helicases target to screen for potential inhibitors against these viruses using molecular docking analysis. NS3 helicases of flavivirus family of viruses such as Dengue, West Nile and Zika are prime targets for drug development. The computer aided molecular docking analysis of netropsin and novobiocin with the viral protein targets HABD, MTD and RCD is reported for further consideration.

MicroRNA (miRNAs), a class of small, endogenous non-coding RNA molecules of about 21-24 nucleotides in length, have unraveled a new modulatory network of RNAs that form an additional level of posttranscriptional gene regulation by targeting messenger RNAs (mRNAs). These miRNAs possess the ability to regulate gene expression by modulating the stability of mRNAs, controlling their translation rates, and consequently regulating protein synthesis. Substantial experimental evidence established the involvement of miRNAs in most biological processes like growth, differentiation, development, and metabolism in mammals including humans. An aberrant expression of miRNAs has been implicated in several pathologies, including cancer. The association of miRNAs with tumor growth, development, and metastasis depicts their potential as effective diagnostic and prognostic biomarkers. Furthermore, exploitation of the role of different miRNAs as oncogenes or tumor suppressors has aided in designing several miRNA-based therapeutic approaches for treating cancer patients whose clinical trials are underway. In this review, we aim to summarize the biogenesis of miRNAs and the dysregulations in these pathways that result in various pathologies and in some cases, resistance to drug treatment. We provide a detailed review of the miRNA expression signatures in different cancers along with their diagnostic and prognostic utility. Furthermore, we elaborate on the potential employment of miRNAs to enhance cancer cell apoptosis, regress tumor progression and even overcome miRNA-induced drug resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Epstein-Barr virus (EBV) is a herpesvirus infecting more than 90% of the human population. The tropism of EBV for B lymphocytes is evidenced in its association with many lymphoproliferative disorders. Different types of EBV (EBV-1 and EBV-2), classified on the basis of EBV nuclear antigen-2 (EBNA-2) genotyping, have been reported in benign and malignant pathologies, but there is almost no information about their frequency in the Pakistani population. The aim of this study was to determine the frequency and distribution of EBNA-2-based EBV genotypes in lymphoma patients. Genomic DNA was extracted from formalin-fixed paraffin embedded (FFPE) tissue samples obtained from 73 EBV-DNA-positive lymphoma patients. The β-globin gene was amplified to assess the presence and quality of cellular DNA from all samples. EBER-1 DNA was detected by PCR to confirm EBV presence in tissue samples. EBNA-1 mRNA relative quantification done by quantitative PCR substantiated EBNA-1 mRNA overexpression in 43.8% of EBV-positive cases in comparison to EBV-positive control cell line. EBNA-2 genotyping was done by nested PCR. Among typable samples, EBV-1 was found in 90.7% of samples while EBV-2 was present in 9.3% cases. These results show that EBV-1 was the most prevalent type in the lymphoma population of Pakistan. This epidemiology of EBV in Pakistani lymphoma patients represents an important first step in using EBV for prognosis and monitoring treatment response., (Creative Commons Attribution License)

Hepatitis C virus plays a significant role in the development of hepatocellular carcinoma (HCC) globally. The pathogenic mechanisms of hepatocellular carcinoma with HCV infection are generally linked with inflammation, cytokines, fibrosis, cellular signaling pathways, and liver cell proliferation modulating pathways. HCV encoded proteins (Core, NS3, NS4, NS5A) interact with a broad range of hepatocytes derived factors to modulate an array of activities such as cell signaling, DNA repair, transcription and translational regulation, cell propagation, apoptosis, membrane topology. These four viral proteins are also implicated to show a strong conversion potential in tissue culture. Furthermore, Core and NS5A also trigger the accretion of the β-catenin pathway as a common target to contribute viral induced transformation. There is a strong association between HCV variants within Core, NS4, and NS5A and host single nucleotide polymorphisms (SNPs) with the HCC pathogenesis. Identification of such viral mutants and host SNPs is very critical to determine the risk of HCC and response to antiviral therapy. In this review, we highlight the association of key variants, mutated proteins, and host SNPs in development of HCV induced HCC. How such viral mutants may modulate the interaction with cellular host machinery is also discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hepatitis C virus (HCV) is a common opportunistic pathogen especially among Human immunodeficiency virus (HIV) infected patients. Due to incongruous studies, the pathological effect of HCV on HIV induced disease are still not fully understood. While some studies have showed no effect of HCV on HIV infection, others reported a defined role of HCV in aggravating the rates of AIDS-related illnesses and mortality. The explanation of such variances may be due to the host immune response, viral genotypes, sub-type and quasi-species distribution. The factors that complicate the management of HIV/HCV patients are: (1) reduced HCV antibody production, (2) drug interactions, (3) liver disease and (4) different epidemiologic characteristics. However, it is abundantly clear that the morbidity and mortality caused by HCV have increased since the introduction of highly active antiretroviral therapy (HAART) against HIV. In this review, the consequence of HIV/HCV co-infection on host immune response, viral replication, disease progression, mortality and morbidity, viral load, persistence and current treatment options have been discussed. Based on the clinical studies, it is necessary to evaluate the effect of HCV therapy on HIV progression and to provide a fully active HCV treatment for patients receiving HIV treatment. In conclusion, it is recommended to provide fully active HAART therapy in combination with a known HCV therapy.

The FOXO (Forkhead box O) transcription factors are implicated in several signaling pathways and play a vital role in various cellular and physiological processes include for instance, ROS (reactive oxygen species) response, cell proliferation, regulation of programmed cell death, longevity, metabolism and cancer and regulation of cell cycle. In humans, the four FOXO family members are responsible for resemblance in their structure, regulation and functions. FOXO1 gene is highly expressed in adipose tissues and it affects the regulation of glycogenolysis and gluconeogenesis through insulin signaling. The gene of FOXO3 is highly expressed in the kidney, heart, spleen and brain and is characterized as diverse forkhead DNA-binding domain of transcription factors. The FOXO3 is a tumor suppressor gene and found to interact with p53, the trigger for apoptosis through BCl2 family genes and a regulator of Notch signaling pathway for the self-renewal of stem cells. Therefore, FOXOs remains to be a fascinating and potential target to acquire novel therapeutic approaches to cure cancer. This review will provide a comprehensive overview about the biology of FOXO proteins, which can be utilized for developing current therapeutic approaches to treat cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Besides liver cirrhosis and hepatocellular carcinoma, chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations (EHMs). HCV exhibits lymphotropism that is responsible for various EHM. An important characteristic of HCV is escape from the immune system, which enables it to produce chronic infections and autoimmune disorders along with accumulation of circulating immune complexes. These EHMs have large spectrum, because they affect many organs such as heart, lungs, kidney, brain, thyroid, and skin. HCV-related cardiac and pulmonary manifestations include myocarditis, cardiomyopathies, cardiovascular diseases (i.e., Stroke, ischemic heart disease), chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and interstitial lung diseases. This review discusses etiology and pathogenesis of HCV-associated cardiac and pulmonary manifestations and how different genes, immune system, indirectly linked factors (mixed cryoglobulinemia), liver cirrhosis, and antiviral treatment are involved in HCV-related heart and lung diseases, however, their exact mechanism is not clear.

This study presents an efficient acoustic and hybrid three-dimensional (3D)-printed electrochemical biosensors for the detection of liver cancer cells. The biosensors function by recognizing the highly expressed tumor marker CD133, which is located on the surface of liver cancer cells. Detection was achieved by recrystallizing a recombinant S-layer fusion protein (rSbpA/ZZ) on the surface of the sensors. The fused ZZ-domain enables immobilization of the anti-CD133 antibody in a defined manner. These highly accessible anti-CD133 antibodies were employed as a sensing layer, thereby enabling the efficient detection of liver cancer cells (HepG2). The recognition of HepG2 cells was investigated in situ using a quartz crystal microbalance with dissipation monitoring (QCM-D), which enabled the label-free, real-time detection of living cells on the modified sensor surface under controlled conditions. Furthermore, the hybrid 3D additive printing strategy for biosensors facilitates both rapid development and small-scale manufacturing. The hybrid strategy of combining 3D-printed parts and more traditionally fabricated parts enables the use of optimal materials: a ceramic substrate with noble metals for the sensing element and 3D-printed capillary channels to guide and constrain the clinical sample. Cyclic voltammetry (CV) measurements confirmed the efficiency of the fabricated sensors. Most importantly, these sensors offer low-cost and disposable detection platforms for real-world applications. Thus, as demonstrated in this study, both fabricated acoustic and electrochemical sensing platforms can detect cancer cells and therefore may have further potential in other clinical applications and drug-screening studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic to certain regions of the world and infects around 10-20 million people. HTLV-1 is the etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated neurological disorders including mainly HTLV-1 associated myelopathy/Tropical spastic paraparesis. The involvement of the central nervous diseases occurs among: HTLV-1 infected patients from endemic areas, HIV positive individuals and drug users. The ability of HTLV-1 to cause associated neuropathies starts with the virus crossing the blood brain barrier (BBB), then entering and infecting the cells of the central nervous system. As a consequence, to the viral attack, HTLV-1 infected lymphocytes produce pro-inflammatory cytokines like tumor necrosis factor alpha, Interleukin 1 beta and interleukin 6 which further disrupts the BBB. Different serological tests have been used in the diagnosis of HTLV-1. These include: ELISA, Western Blotting (WB), Immunofluorescence, Particle Agglutination and Polymerase Chain Reaction which is used as a confirmatory test. Danazol, pentoxifylline, azathioprine and vitamin C have been used in the treatment of the HTLV-1 associated neurological disorders. Other antiviral drugs (lamivudine, zidovudine), monoclonal antibodies (Daclizumab) and therapeutic agents (valporic acid, interferons) have also been evaluated. No known drug, so far, has been shown to be efficacious. The aim of this review is to present the complexities of HTLV-1 associated neurological disorders and their current ongoing treatment. In addition to discussing future possible therapeutic strategies, by targeting HTVL-1 viral components and gene/s products, for the treatment of those neurological conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Hepatitis B and C infections can be either acute or chronic. The chronic infection can culminate in liver cirrhosis and hepatocellular carcinoma. Influence of the host genetic makeup on conversion of acute to chronic infection, development of cirrhosis, and hepatocellular carcinoma is an interesting area of research. Variability in different immune system genes may account for such differences in the outcome of infection. This article discusses single nucleotide polymorphisms in different host immunomodulator genes that have been frequently reported to influence the outcome of infection and severity of disease. The genetic variability could be utilized for the prediction of disease outcome and treatment responses.

Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders.

Hepatocellular carcinoma (HCC) is etiologically linked with hepatitis B virus (HBV) and is the leading cause of death amongst 80% of HBV patients. Among HBV affected patients, genetic factors are also involved in modifying the risk factors of HCC. However, the genetic factors that regulate progression to HCC still remain to be determined. In this review, we discuss several single nucleotide polymorphisms (SNPs) which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection such as cyclooxygenase (COX)-2 expression specifically at COX-2 -1195G/A in Chinese, Turkish and Egyptian populations, tumor necrosis factor α and the three most commonly studied SNPs: PAT-/+, Lys939Gln (A33512C, rs2228001) and Ala499Val (C21151T, rs2228000). In genome-wide association studies, strong associations have also been found at loci 1p36.22, 11q22.3, 6p21 (rs1419881, rs3997872, rs7453920 and rs7768538), 8p12 (rs2275959 and rs37821974) and 22q11.21. The genes implicated in these studies include HLA-DQB2, HLA-DQA1, TCF19, HLA-C, UBE2L3, LTL, FDX1, MICA, UBE4B and PG. The SNPs found to be associated with the above-mentioned genes still require validation in association studies in order to be considered good prognostic candidates for HCC. Screening of these polymorphisms is very beneficial in clinical experiments to stratify the higher or lower risk for HCC and may help in designing effective and efficient HCC surveillance programs for chronic HBV-infected patients if further genetic vulnerabilities are detected.