Viral Response Research Articles

Immunotherapy Using HBV Vaccine Pulsed DCs and Induced T-Cells Combined Antiviral Drugs in Treatment Naive CHB Patients-A Multi-Centre Phase II Study.

Dendritic cells are the most potent antigen-presenting cells in immune therapeutic approaches for chronic hepatitis B (CHB) infection. Here, we developed a clinical trial to evaluate the efficacy and safety of autologous HBV vaccine-pulsed DCs and their induced T cells (HPDCT) in CHB patients. This was a randomised, prospective, open-label, multicentre, superiority study and 309 treatment-naive CHB patients were divided into HPDCT plus nucleos(t)ide analogues (NAs) group (n = 84), NAs mono-therapy group (n = 82), HPDCT plus Peg-interferon (Peg-IFN) group (n = 69), Peg-IFN mono-therapy group (n = 74). Twelve times of HPDCT vaccinations were given intravenously, and all the patients were followed up for 72 weeks. In total, 1836 HPDCT infusions were administered with no obvious toxicity and side effect although few patients had self-limited low fever. More patients got HBsAg loss in those receiving HPDCT therapy. Patients of HPDCT plus Peg-IFN group with HBV DNA < 1 × 107 IU/mL at baseline exhibited earlier, stronger and longer lasting of viral response, especially HBV DNA < 20 IU/mL, than those patients of Peg-IFN mono-therapy group, from week 24 till week 72 (p < 0.05). Comparable efficacy was observed between the patients of HPDCT plus NAs group and NAs mono-therapy groups. In addition, CD25 on CD8+ T cells and HBV-specific CD8+ T cell increased significantly in patients of HPDCT combined antiviral drugs therapy. HPDCT combined with antiviral drugs was safe and able to enhance T cell immunity. Furthermore, HPDCT combined with Peg-IFN could provide an incremental benefit to patients with baseline levels of lower HBV DNA. Trial Registration: ClinicalTrials.gov identifier: NCT01935635.

Decreased SynMuv B gene activity in response to viral infection leads to activation of the antiviral RNAi pathway in C. elegans.

RNA interference (RNAi) mediates antiviral defense in many eukaryotes. Caenorhabditis elegans mutants that disable RNAi are more sensitive to viral infection. Many mutants that enhance RNAi have also been identified; these mutations may reveal genes that are normally down-regulated in antiviral defense. About one-third of the score of mutants that enhance RNAi are in synMuv B genes, identified 30 years ago in unrelated screens for increased growth factor signaling. Many synMuv B genes encode dREAM complex chromatin-regulatory proteins found in nearly all animals and plants. We show that mRNAs which are highly induced in synMuv B mutants are congruent with those induced by Orsay RNA virus infection, suggesting that the enhanced RNAi of synMuv B mutants may also be triggered by down-regulation of synMuvB gene activity in an Orsay virus infection of wild type. The multivulval (Muv) phenotype of synMuv B mutants requires the presence of a second nematode-specific synMuv A gene mutation, but the enhanced RNAi of synMuv B mutants does not require a second synMuv A mutation. To test if Orsay viral infection down-regulates synMuv B gene activity, we infected a single synMuv A mutant with Orsay virus and found that a Muv phenotype could be induced. Thus, decreased synMuv B gene activity is part of the normal C. elegans viral defense response. In support of the model that decreased syn- Muv B gene activity enhances antiviral response, we found that synMuv B mutants have 50 to 100× lower viral RNA levels during an Orsay virus infection than wild type. Thus down-regulation of synMuv B activity to enhance RNAi is a key component in the defense response to viral infection. Small RNA deep sequencing analysis of dREAM complex mutants revealed siRNA profiles indicative of such a response. Thus, the pan-eukaryotic synMuv B genes constitute an element in C. elegans antiviral defense which is conserved across many eukaryotes where it also may act in viral defense. The enhanced RNAi and conservation of the dREAM complex mutants suggests new therapeutic avenues to boost antiviral defenses.

Post-pandemic insights on COVID-19 and premature ovarian insufficiency.

The COVID-19 pandemic has raised concerns regarding its potential impact on premature ovarian insufficiency (POI). This overview examines the possible interactions between COVID-19 and POI, while also suggesting preventive measures. The viral infection's inflammatory response and immune dysregulation may adversely affect ovarian tissues, leading to inflammation and damage. Additionally, alterations in vascular function could impair ovarian blood flow and hormonal imbalances may disrupt normal ovarian function. Long-term health effects, such as "long COVID," may exacerbate these issues through chronic inflammation and immune dysfunction. Public health measures, such as vaccination and home isolation, may indirectly protect ovarian health by reducing systemic inflammation. Vaccines could mitigate the severity of COVID-19's impact on ovarian function, while isolation may reduce stress and inflammation. However, further research is needed to validate these mechanisms.

Do people prefer to share political information that boosts their ingroup or derogates the outgroup?

Recent analyses of social media activity indicate that outgroup animosity drives user engagement more than ingroup favoritism, with content that derogates the outgroup tending to generate more viral responses online. However, it is unclear whether those findings are due to most people's underlying preferences or structural features of the social media landscape. To address this uncertainty, we conducted three experimental studies (Noverall = 609) to examine how intended impact (ingroup favoritism/outgroup derogation) influences intentions to share both true and false news posts among U.S. partisans who regularly use social media. Participants consistently preferred to share posts that favor their own party over those that denigrate the opposition-a preference that was largely maintained despite a manipulation of ingroup threat or a manipulated desire to share viral content in Studies 2 and 3. We discuss the influence of polarized politicians and their followers, malign actors, and social media algorithms as potential drivers of earlier results that highlight the virality of derogatory content. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Mapping cell-cell fusion at single-cell resolution.

Cell-cell fusion is a tightly controlled process in the human body known to be involved in fertilization, placental development, muscle growth, bone remodeling, and viral response. Fusion between cancer cells results first in a whole-genome doubled state, which may be followed by the generation of aneuploidies; these genomic alterations are known drivers of tumor evolution. The role of cell-cell fusion in cancer progression and treatment response has been understudied due to limited experimental systems for tracking and analyzing individual fusion events. To meet this need, we developed a molecular toolkit to map the origins and outcomes of individual cell fusion events within a tumor cell population. This platform, ClonMapper Duo ('CMDuo'), identifies cells that have undergone cell-cell fusion through a combination of reporter expression and engineered fluorescence-associated index sequences paired to randomly generated nucleotide barcodes. scRNA-seq of the indexed barcodes enables the mapping of each set of parental cells and fusion progeny throughout the cell population. In triple-negative breast cancer cells CMDuo uncovered subclonal transcriptomic hybridization and unveiled distinct cell-states which arise in direct consequence of homotypic cell-cell fusion. CMDuo is a platform that enables mapping of cell-cell fusion events in high-throughput single cell data and enables the study of cell fusion in disease progression and therapeutic response.

Visualizing Tomato Spotted Wilt Virus Protein Localization: Cross-Kingdom Comparisons of Protein-Protein Interactions.

Tomato spotted wilt virus (TSWV) is an orthotospovirus that infects both plants and insect vectors, and understanding its protein localization and interactions is crucial for unraveling the infection cycle and host-virus interactions. We investigated and compared the localization of TSWV proteins. The localization between plant and insect cells was overall consistent, indicating a similar mechanism is utilized by the virus in both types of cells. However, a change in localization over time was associated with the viral proteins that did not contain signal peptides and transmembrane domains such as N, NSs, and NSm, which only occurred in the plant cells and not in the insect cells. We also tested the localization of the proteins during an active plant infection using free red fluorescent protein (RFP) as a marker to highlight the nucleus and cytoplasm. Voids in the cytoplasm were shown only during infection, and N, NSs, NSm, and to a lesser extent GN and GC were surrounding these areas, suggesting it may be a site of replication or morphogenesis. Furthermore, we tested the interactions of viral proteins using both bimolecular fluorescence complementation (BiFC) and membrane-based yeast two-hybrid (MbY2H) assays. These revealed self-interactions of NSm, N, GN, GC, and NSs. We also identified interactions between different TSWV proteins, indicating their possible roles, such as between NSs and GC and N and GC, which may be necessary during the replication and assembly processes, respectively. This research expands our knowledge of TSWV infection and elaborates on the intricate relationships between viral proteins, cellular dynamics, and host responses. [Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Targeting MXD1 sensitises pancreatic cancer to trametinib

BackgroundThe resistance of pancreatic ductal adenocarcinoma (PDAC) to trametinib therapy limits its clinical use. However, the molecular mechanisms underlying trametinib resistance in PDAC remain unclear.ObjectiveWe aimed to illustrate the mechanisms...

Beyond the Herald Patch: Exploring the Complex Landscape of Pityriasis Rosea.

Pityriasis rosea (PR) is a prevalent dermatological condition characterized by a distinctive herald patch, followed by secondary eruptions, often forming a "Christmas tree" pattern on the trunk. Despite its recognizable clinical presentation, the etiology of PR remains uncertain, with hypotheses pointing to both infectious and noninfectious origins. Human herpesviruses (HHV) 6 and 7 have been implicated, with evidence suggesting viral reactivation as a potential trigger. Epidemiologically, PR affects children, adolescents, and young adults, with a higher incidence in females. The condition is observed globally, with varying incidence rates and seasonal variations, suggesting an infectious component. While PR is generally benign and self-limiting, it can cause significant discomfort owing to pruritus, and atypical presentations and recurrences complicate diagnosis and management. This review evaluates the current understanding of PR's pathogenesis, highlighting both infectious and noninfectious hypotheses, including viral reactivation and immune response mechanisms. It also examines treatment options, such as antivirals and phototherapy, which have shown varying degrees of effectiveness. Further research is needed to clarify etiological factors and to explore the efficacy and safety of various treatment modalities. Understanding these aspects is crucial for improving patient outcomes and developing targeted therapies, especially for atypical or recurrent cases.

OAS1: A Protective Mechanism for Alzheimer's Disease? An Exploration of Data and Possible Mechanisms.

The immune system and neuroinflammation are now well established in the aetiology of neurodegeneration. Previous studies of transcriptomic and gene association studies have highlighted the potential of the 2'-5' oligoadenylate synthetase 1 (OAS1) to play a role in Alzheimer's disease. OAS1 is a viral response gene, interferon-induced, dsRNA activated enzyme, which binds RNase L to degrade dsRNA, and has been associated with COVID-19 response. This study explores whether a viral defence gene could play a vital role in neurodegeneration pathology. The genotyping of five SNPs across the OAS1 locus was conducted in the Brains for Dementia Research (BDR) Cohort for association with AD. RNA-sequencing data were explored for differences in OAS1 gene expression between phenotypes and genotypes. Finally, levels of dsRNA were measured in control cell lines, prior to and after exposure to amyloid oligomers and in cells harbouring a dementia-relevant mutation. No association of any of the OAS1 SNPs investigated were associated with the AD phenotype in the BDR cohort. However, gene expression data supported the previous observation that the minor allele haplotype was associated with higher levels of the OAS1 gene expression and the presence of an alternative transcript. Further to this, the presence of endogenous dsRNA was found to increase with exposure to amyloid oligomers and in the cell line with a dementia-relevant mutation. The data presented here suggest further exploration of the OAS1 gene in relation to dementia is warranted. Investigations of whether carriers of the protective OAS1 haplotype lower dsRNA presence and in turn lower inflammation and cell death are required to support the role of the gene as a moderator of neurodegeneration.

Enterovirus and Parechovirus Neurologic Infections in Children: Clinical Presentations and Neuropathogenesis.

Enteroviruses (EVs) and parechoviruses (PeVs) are common pathogens of childhood. Enteroviral infections cause a range of clinical syndromes from mild illness to neurologic manifestations of meningitis, encephalitis, and acute flaccid myelitis. Disease manifestations are driven by a combination of viral replication and host immune response. Despite ubiquitousness and clinical importance, there are no approved targeted therapies for these viruses and most are without an available vaccine. Studies of EV neuropathogenesis began with poliovirus and are ongoing for other nonpolio EVs and PeVs. Many unanswered questions remain with regard to cellular tropism, mechanisms of dissemination, receptor usage, immunologic control, and cellular death. This review describes what is known about epidemiology, clinical presentations, and neuropathogenesis of these important pathogens.

Chronic viral mimicry induction following p53 loss promotes immune evasion.

Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through 'viral mimicry' responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize premalignant lesions of the fallopian tube along with syngeneic epithelial ovarian cancer models to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss permits transcription of immunogenic repetitive elements and chronic viral mimicry activation that increases cellular tolerance of cytosolic nucleic acids and diminishes cellular immunogenicity. This selection process can be partially attenuated pharmacologically. Altogether, these results reveal that viral mimicry conditioning following p53 loss promotes immune evasion and may represent a pharmacological target for early cancer interception.

Identification and Validation of Potential Biomarkers and Therapeutic Targets of COVID-19-related Depression.

The prevalence of depression in COVID-19 patients is notably high, disrupting daily life routines and compounding the burden of other chronic health conditions. In addition, to elucidate the connection between COVID-19 and depression, we conducted an analysis of commonly differentially expressed genes [co-DEGs], uncovering potential biomarkers and therapeutic avenues specific to COVID-19-related depression. We obtained gene expression profiles from the Gene Expression Omnibus [GEO] database with strategic keyword searches ["COVID-19", "depression," and "SARS"]. We used functional enrichment analysis of the co-DEGs to decipher their likely biological roles. Then, we utilized protein-protein interaction [PPI] network analysis to identify hub genes among the co- DEGs. These findings were validated via an independent third-party dataset. Our analysis of blood samples from COVID-19 patients revealed 10,716 upregulated genes and 10,319 downregulated genes. In addition, by applying the same approach to depression samples, we identified 571 upregulated and 847 downregulated genes. Furthermore, by intersecting these datasets, we extracted 121 upregulated and 175 downregulated co-DEGs. Through PPI network construction and hub gene selection, we identified MPO, ARG1, CD163, FCGR1A, ELANE, LCN2, and CR1 as co-upregulated hub genes and MRPL13, RPS23, and MRPL1 as co-downregulated hub genes. The incorporation of third-party datasets revealed that these hub genes are specific targets of SARS-CoV-2, not generic viral response mechanisms. The identification of potential biomarkers represents a groundbreaking strategy for assessing and treating depression in the context of COVID-19, with the potential to reduce its prevalence among these patients. However, to fully harness this potential, additional clinical research is paramount.

E3 ubiquitin ligase TRIM7 alleviates LPS-induced acute lung injury via inhibiting NLRP3 inflammasome activation.

Acute lung injury (ALI) is a clinically common disease with high mortality, characterized by tissue damage caused by excessive activation of inflammation. TRIM7 is an E3 ligase that plays an important role in regulating viral infection, tumor progression and innate immune response. But its function in ALI is unclear. In this study, LPS was used to stimulate C57BL/6j mice and HULEC-5a cells to establish ALI models in vivo and in vitro. The results showed that TRIM7 expression was down-regulated during ALI. Further, overexpressing of TRIM7 in HULEC-5a cells relieved cell damage and inflammatory activation induced by LPS stimulation. TRIM7 knockdown has the opposite effect. Trim7-overexpressing mice were established by endotracheal injection of AAV6-Trim7 virus in vivo, and then the ALI model was induced by LPS stimulation. It was proved that overexpression of TRIM7 could alleviate lung tissue injury, pulmonary interstitial hemorrhage, increased alveolar and vascular permeability, inflammatory cell infiltration and secretion of inflammatory factors induced by LPS stimulation. Mechanistically, TRIM7 has been shown to inhibit the expression of NLRP3 and the activation of NLRP3 inflammasome. The regulatory effect of TRIM7 on ALI depends on NLRP3 inflammasome. This investigation for the first time found the inhibitory effect of TRIM7 on ALI and the activation of NLRP3 inflammasome, which providing new targets and ideas for the mechanism research and treatment of ALI.

Transcriptional analysis reveals the suppression of RAD51 and disruption of the homologous recombination pathway during PEDV infection in IPEC-J2 cells

PEDV is a highly contagious enteric pathogen that can cause severe diarrhea and death in neonatal pigs. Despite extensive research, the molecular mechanisms of host’s response to PEDV infection remain unclear. In this study, differentially expressed genes (DEGs), time-specific coexpression modules, and key regulatory genes associated with PEDV infection were identified. The analysis revealed 2,275, 1,492, and 3,409 DEGs in infected vs. mock-treated pigs at 12 h, 24 h, and 48 h, respectively. Time series analysis revealed that the upregulated genes were involved mainly in antiviral pathways such as the viral defense response and the regulation of immune system processes. Protein–protein interaction network analysis identified the top 20 core genes in the interaction network, which included six upregulated genes (TFRC, SUOX, RMI1, CD74, IFIH1, and CD86) and 14 downregulated genes (FOS, CDC6, CDCA3, PIK3R2, TUFM, VARS, ASF1B, POLD1, MCM8, POLA1, CDC45, BCS1L, RAD51, and RPA2). In addition, GSEA enrichment analysis revealed that pathways such as DNA replication and homologous recombination involving RAD51, CDC6, and RPA2 were significantly inhibited during viral infection. Our findings not only reveal dynamic changes in the transcriptome profile of PEDV-infected IPEC-J2 cells but also provide novel insights into the mechanism of PEDV infection of the host.

The Molecular Basis of Asthma Exacerbations Triggered by Viral Infections: The Role of Specific miRNAs.

Viral respiratory infections are a significant clinical problem among the pediatric population and are one of the leading causes of hospitalization. Most often, upper respiratory tract infections are self-limiting. Still, those that involve the lower respiratory tract are usually associated with asthma exacerbations, leading to worsening or even the initiation of the disease. A key role in regulating the immune response and inflammation during viral infections and their impact on the progression of asthma has been demonstrated for miRNA molecules (microRNA). Their interaction with mRNA (messenger RNA) regulates gene expression in innate and acquired immune responses, making them valuable biomarkers for diagnostics, monitoring, and predicting asthma exacerbations. The following paper presents changes in the expression of miRNAs during the five most common viral infections causing asthma worsening, with particular emphasis on the pediatric population. In addition, we describe the molecular mechanisms by which miRNAs influence the pathogenesis of viral infection, immune responses, and asthma exacerbations. These molecules represent promising targets for future innovative therapeutic strategies, paving the way for developing personalized medicine for patients with viral-induced asthma exacerbations.

Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic HepatitisC After Treatment.

Despite achieving sustained viral response (SVR) after treatment with direct-acting antivirals (DAAs), the risk of liver disease progression and extrahepatic complications in chronic hepatitisC (CHC) remains. We aimed to determine the role of residual HCV-RNA in peripheral blood mononuclear cells (PBMCs), a condition known as occult hepatitis C (OCI), and systemic inflammatory markers as predictors of long-term outcomes in patients treated with DAAs. We followed 42 patients treated with DAAs with OCI status determined after therapy, for a median of 6.3years. Plasma levels of 16 cytokines and chemokines were measured in samples collected 12-15months after end of treatment. Samples from 10 patients with CHC and 8healthy controls were used for comparison. The presence of HCV-RNA in PBMCs correlated with adverse outcomes [odds ratio (OR) 17.6, confidence interval (CI) 1.8-175); p = 0.011], and an elevated platelet-to-lymphocyte ratio (PLR) was associated with mortality. Patients with residual HCV-RNA had higher levels of macrophage-derived chemokine (MDC/CCL22) (p = 0.026) and interleukin-18 (IL-18) (p = 0.009), but lower levels of fractalkine/CX3CL1 (p = 0.007), interferon gamma (IFNγ) (p = 0.016), IL-13 (p = 0.009), and lymphotoxin alpha (LTα) (p = 0.007) compared to those without OCI. The profile of immune mediators in patients with OCI differed more from healthy controls than from patients without OCI. These findings suggest that residual HCV-RNA and elevated PLR are potential predictors of poor long-term outcomes in patients treated with DAAs, possibly linked to an altered cytokine/chemokine response.

Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2.

T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19. Functionality and magnitude of acute SARS2-specific CD4+ and CD8+ T cell responses were evaluated, in addition to antibody responses. Most individuals with acute COVID-19 developed SARS2-specific T cell responses within 6 days of COVID-19 symptom onset. Early CD4+ T cell and CD8+ T cell responses were polyfunctional, and both strongly associated with reduced upper respiratory tract SARS2 viral RNA, independent of neutralizing antibody titers. Overall, these findings provide evidence for protective roles for circulating SARS2-specific CD4+ and CD8+ T cells during acute COVID-19.

Reinfection and resistance associated substitutions following a minimal monitoring approach for HCV treatment in MINMON trial.

Simplified approaches to HCV treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on response in the ACTG A5360 (MINMON) trial. HCV RNA evaluations were scheduled at weeks 0, 24 (sustained viral response [SVR] visit), 48 and 72. Participants with post-entry HCV RNA ≥ lower limit of quantification (LLoQ) had deep sequencing of NS5A and NS5B genes performed. Phylogenetic analysis distinguished between reinfection and treatment failure. Reinfection rates per 100 person-years (PYS) were calculated with 95%CI constructed using Poisson distribution. Of 397 participants with post-entry HCV RNA, 29 had ≥LLoQ and available sequencing data. Of those 29, 5 participants initially designated as non-SVR, and 12 participants initially attaining SVR (evaluated at week-24) were determined to have reinfections (total 17 reinfections) (reinfection rate 3.9/100 PYS [95%CI 2.4-6.2]). All 17 participants with HCV reinfection were male (13 MSM and 15 with HIV). Of 29 had ≥LLoQ, 12 were identified as treatment failure. SVR (excluding reinfections) in presence and absence of baseline RAS was 93.5% (43/46) and 97% (337/346), respectively, with an overall SVR rate of 97.0% [95%CI 94.8-98.3] (385/397). Accounting for reinfections, SVR in MINMON was 97.0% further supporting simplified HCV treatment. No significant difference in SVR was found by baseline velpatasvir RAS. The high reinfection rate, especially among MSM with HIV, underscores the need to scale-up evidence-based interventions to reduce reinfection.

Gut virome dysbiosis impairs antitumor immunity and reduces 5-fluorouracil treatment efficacy for colorectal cancer.

Despite the established influence of gut bacteria, the role of the gut virome in modulating colorectal cancer (CRC) patient chemotherapy response remains poorly understood. In this study, we investigated the impact of antiviral (AV) drug-induced gut virome dysbiosis on the efficacy of 5-FU in CRC treatment. Using a subcutaneous CRC mouse model, we assessed tumor growth and immune responses following AV treatment, fecal microbiota transplantation (FMT), and 5-FU administration. AV therapy reduced the abundance of gut DNA and RNA viruses, leading to accelerated tumor growth, shortened survival, and diminished chemotherapy efficacy. FMT restored the gut virome, improving tumor suppression and extending the survival of 5-FU-treated mice. Metagenomic sequencing revealed significant changes in virome composition, AV treatment expanded Kahnovirus, Petivirales, and Enterogokushovirus, whereas FMT enriched Peduovirus STYP1, Mahlunavirus rarus, and Jouyvirus ev207. AV treatment reduced the number of dendritic cells and CD8+ T cells in peripheral blood and tumor tissues, impairing antitumor immunity, FMT reversed these deficiencies. To further investigate the underlying mechanisms, we examined the TLR3-IRF3-IFN-β pathway, essential for recognizing viral RNA and triggering immune responses. AV treatment downregulated this pathway, impairing immune cell recruitment and reducing chemotherapy efficacy, while activation of TLR3 with Poly(I:C) restored pathway function and enhanced the effectiveness of 5-FU. These findings suggest the importance of maintaining gut virome integrity or activating TLR3 as adjunct strategies to enhance chemotherapy outcomes in CRC patients.

A Snapshot of Cytokine Dynamics: A Fine Balance Between Health and Disease.

Health and disease are intricately intertwined and often determined by the delicate balance of biological processes. Cytokines, a family of small signalling molecules, are pivotal in maintaining this balance, ensuring the body's immune system functions optimally. In a healthy condition, cytokines act as potent mediators of immune responses. They orchestrate the activities of immune cells, coordinating their proliferation, differentiation, and migration. This intricate role of cytokine signalling enables the body to effectively combat infections, repair damaged tissues, and regulate inflammation. However, the delicate equilibrium of cytokine production is susceptible to disruption. Excessive or abnormal cytokine levels can lead to a cascade of pathological conditions, including autoimmune diseases, chronic inflammation, infections, allergies, and even cancer. Interestingly, from the bunch of cytokines, few cytokines play an essential role in maintaining the balance between normal physiological status and diseases. In this review, we have appraised key cytokines' potential role and feedback loops in augmenting the imbalances in the body's biological functions, presenting a critical link between inflammation and disease pathology. Moreover, we have also highlighted the significance of cytokines and their molecular interplay, particularly in the recent viral pandemic COVID-19 disease. Hence, understandings regarding the interplay between viral infection and cytokine responses are essential and fascinating for developing effective therapeutic strategies.