Melanoma, a type of skin cancer, fifth leading cause of cancer-related mortality due to its propensity to metastasize from the skin to other organs, largely driven by the constitutive activation of the PI3K/AKT signaling axis. This study aimed to investigate the inhibitory mechanisms and biological pathways of Arbutin (ArB) in melanoma. ArB, a bioactive compound, and its targets were identified from CTD, PharmMapper, Swiss Target Prediction, and ETCM. Similarly, disease-related targets were obtained using GeneCards, GEO, and the CTD database. A Venn diagram showed overlapping targets between the two groups. GO, KEGG enrichment analysis, and PPI networks were adopted to identify potential core targets associated with ArB and melanoma. Stability and affinity were evaluated using molecular docking, 100 ns molecular dynamics (MD) simulation, principal component analysis (PCA), free energy landscape (FEL), and density functional theory (DFT) analyses. AKT1 emerged as a key gene with strong binding to ArB, exhibiting an affinity of -7.9 kcal/mol as determined by molecular docking. MMGBSA and MMPBSA ΔTotal energies of -37.17 and − 22.15 kcal/mol, respectively, further supported the effective binding affinity. Furthermore, DFT calculations determined a HOMO-LUMO energy gap of 5.72 eV, confirming the molecule’s kinetic stability and favorable electronic reactivity. ADMET analysis confirmed a safety profile but can induce nephrotoxicity, which should be evaluated in vivo. We explored ArB as a potential AKT1 inhibitor and propose that it could serve as a lead compound for the development of targeted melanoma treatments.

The oral microbiome is central to the maintenance of oral health, and disruptions in its composition contribute to persistent infections, including endodontic pathologies. Among bacteria and other members of the microbial community, Olsenella uli is a concerning pathogen responsible for several endodontic infections. Despite its clinical significance, organism-specific therapeutic targets for O. uli remain largely unexplored. In this study, a systematic comparative subtractive proteomics pipeline was employed to identify novel drug targets unique to O. uli DSM 7084. Comparative KEGG pathway mapping revealed 21 pathogen-specific metabolic pathways, from which 14 non-homologous essential proteins were identified. Physicochemical characterization further priortized these to eight stable proteins prioritized for druggability screening. Druggability analysis using DrugBank identified corresponding FDA-approved compounds, and three-dimensional structures generated through I-TASSER enabled downstream molecular docking. Docking simulations highlighted three high-affinity protein–drug complexes—UDP-N-acetylmuramoylalanine–D-glutamate ligase, alanine racemase, and UDP-N-acetylglucosamine-1-carboxyvinyltransferase—with strong inhibitory potential. These findings provide a comprehensive in silico foundation for the rapid development of targeted antimicrobial strategies against O. uli, supporting future experimental validation for improved management of persistent oral and endodontic infections.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a global One Health challenge with a potential pandemic threat, with no approved vaccines or antiviral drugs available to date. Thus, there is an urgent need for a safe and effective vaccine. Herein, we developed a recombinant subunit self-adjuvanted fusion protein vaccine targeting the MERS-CoV S1 subunit to CD40-expessing APCs (S1-F/CD40L). We found that intramuscular injection of S1-F/CD40L in conjunction with Alum and CpG was superior to Alum or CpG alone in terms of systemic Ag-specific humoral and cellular responses and Th1-dominant phenotype. Furthermore, the immunogenicity of co-adjuvanted S1-F/CD40L was compared to that of S1 alone via both intramuscular and intranasal immunization. Two intramuscular and intranasal doses of S1-F/CD40L and S1 were immunogenic in eliciting systemic and mucosal humoral and cellular immunity, including IgG, IgA, neutralizing antibodies (nAbs), and T cell responses in mice, with a greater response in the CD40-targeted S1 group. Intranasal vaccination with S1-F/CD40L induced systemic humoral and cellular immune responses comparable to those induced by intramuscular vaccination, including binding and nAbs and T cell responses. Importantly, intranasal vaccine was able to elicit significantly higher local mucosal humoral and cellular immune responses in mouse lungs and markedly elevated circulating IgA levels compared to intramuscular vaccination. Collectively, our results suggest that the S1-F/CD40L vaccine co-adjuvanted with Alum and CpG can be used as an effective and safe mucosal candidate vaccine against MERS-CoV. Furthermore, these data demonstrate that the incorporation of CD40L as APCs targeting ligand and molecular adjuvant enhances immunogenicity, thus offering a promising platform that could be explored further to respond to future emerging pathogens and possible outbreaks.

Background:Antibiotic-resistant bacteria are becoming a significant global concern. To combat the spread of resistance or reverse multidrug resistance, developing novel antimicrobials and/or resistance modulators is essential. This study aimed to evaluate the synergistic effects of the methanolic extract of Pandanus fascicularis fruits (MEPFF) in combination with azithromycin against multidrug-resistant bacteria. Methods:Phytochemical analysis along with the determination of total phenolic content (TPC), total flavonoid content (TFC), and total antioxidant capacity (TAC) of MEPFF, was performed using standard procedure. The extract's DPPH free radical scavenging activity was assessed to evaluate its potential antioxidant activity. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of MEPFF against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa were determined, followed by an analysis of the synergistic effect with azithromycin, as well as the activity of azithromycin alone. Subsequently, the drug-likeness, antibacterial activity, and toxicological properties were analyzed using in silico tools. Results:The quantitative investigation found terpenoids, flavonoids, tannins, phenolics, saponins, cardiac glycosides, and alkaloids in MEPFF. The TFC, TPC, and TAC of MEPFF were found at 183 ± 9.54 mg QE, 248.33 ± 11.06 mg GAE, and 95.33 ± 8.33 mg AAE/gm extract. The extract showed significant antioxidant activity in the DPPH experiment, with an IC50 value of 12.13±0.53 µg/ml. Azithromycin and the extract together have far greater antibacterial action against all four bacterial strains. The minimal inhibitory concentration (MIC) is 3.67 ± 1.15 to 5.83 ± 0.76 mg/mL, while the minimum bactericidal concentration (MBC) is 4.33 ± 1.26 to 7.33 ± 1.04 mg/mL. In silico studies revealed that pandamarilactone-1, nonpandamarilactone-B, and thiamine had the best docking energy (-9.9, -8.9, and -8.5 kcal/mol), suggesting most active compounds against MPh-II protein. Conclusion:The extract enhances antibiotic therapy and suggests that the aforesaid synergistic drug-herb combinations may treat MDR bacterial infections.

The pandemic potential of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) highlights the critical need for effective vaccines due to its high fatality rate of around 36%. In this review, we identified a variety of immunotherapeutic molecules and diagnostic biomarkers that could be used in MERS vaccine development as human-derived adjuvants. We identified immune molecules that have been incorporated into standard clinical diagnostics such as CXCL10/IP10, CXCL8/IL-8, CCL5/RANTES, IL-6, and the complement proteins Ca3 and Ca5. Utilization of different human monoclonal antibodies in the treatment of MERS-CoV patients demonstrates promising outcomes in combatting MERS-CoV infections in vivo, such as hMS-1, 4C2H, 3B11-N, NBMS10-FC, HR2P-M2, SAB-301, M336, LCA60, REGN3051, REGN3048, MCA1, MERs-4, MERs-27, MERs-gd27, and MERs-gd33. Host-derived adjuvants such as CCL28, CCL27, RANTES, TCA3, and GM-CSF have shown significant improvements in immune responses, underscoring their potential to bolster both systemic and mucosal immunity. In conclusion, we believe that host-derived adjuvants like HBD-2, CD40L, and LL-37 offer significant advantages over synthetic options in vaccine development, underscoring the need for clinical trials to validate their efficacy.

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 formalinfixed, 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-8773p, 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.

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.

The journal retracts the article, “Isolation and Characterization of a Novel Lytic Phage, vB_PseuP-SA22, and Its Efficacy against Carbapenem-Resistant Pseudomonas aeruginosa”, cited above [...]

This study explores the potential of antimicrobial peptides (AMPs) derived from camel milk lactoferrin as novel agents against antibiotic-resistant pathogens. Through in silico screening and molecular dynamics simulations, seven lactoferrin-derived peptides were identified as potential AMPs, with peptides P1 and P33 showing promising inhibitory effects against methicillin-resistant Staphylococcus aureus (MRSA). In vitro assays confirmed the efficacy of P33 against pathogenic strains, notably exhibiting activity against multi-drug-resistant strains. Moreover, the lactoferrin-derived peptide P33 demonstrated relatively low cytotoxicity on human fibroblast cells. These findings suggest that P33 holds significant potential as an antimicrobial agent, particularly against antibiotic-resistant bacteria, warranting further in vivo investigations for efficacy and safety. This study highlights the importance of exploring alternative sources of antimicrobial peptides, such as camel milk lactoferrin, in combating the growing threat of antibiotic resistance.

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.

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.

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.

The appearance of several variants of concern (VOCs) of SARS-CoV-2 affects the efficacy of currently available vaccines and causes continuous spread and reinfection between humans. These variants possess different spike (S) protein mutations, which could affect viral pathogenicity, transmission, and immune escape. Herein, we develop a synthetic codon-optimized DNA vaccine (VIU-1007) expressing full-length S protein. The developed vaccine is stabilized by two K986P and V987P proline substitutions and resistant to cleavage by proteases such as furin by deletion of arginine residues (R682, R683, and R685) in multibasic furin cleavage site (RRAR). Additionally, it carries K417N, E484K, N501Y, and D614G substitutions in the receptor binding domain (RBD) derived from the beta VOC. Following the validation and characterization of the in vitro S protein expression, the humoral and cellular immunogenicity of VIU-1007 was assessed in immunized Balb/c mice. While both regimens elicited a Th-1-biased immune response based on S1-specific binding IgG isotypes, three vaccine doses significantly enhanced IgG levels. Furthermore, CD4+ and CD8+ memory T cell responses in spleens and draining inguinal lymph nodes were significantly higher in mice received three doses of VIU-1007 when compared to those received two doses only. Importantly, sera from mice immunized with three doses showed broad neutralization breadth against several SARS-CoV-2 variants, including alpha, beta, gamma, delta, and omicron VOCs. Moreover, the sera showed limited neutralization capacity against SARS-CoV-1, Bat SARS-like coronavirus WIV1, and MERS-CoV. Together, while these data suggest the presence of common neutralizing-rich epitopes between SARS-CoV-2 variants and some other betacoronaviruses, the ongoing evolution of SARS-CoV-2 could result in escape from vaccine-induced immunity, which requires a continuous update of vaccines.

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.

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.

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.

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.