Virus Infection Research Articles

Probiotics and Prebiotics Intervention in Respiratory and Digestive Infections Linked to Covid-19.

Probiotics and prebiotics have been suggested as natural agents against viral infections and dysbiosis and may encourage clinical applications. This review aims to analyze the main and recent advances related to viral infections such as Covid-19 and its gastrointestinal complications, antiviral immunity generated and possible preventive role that probiotics and/or prebiotics can play in controlling and promoting antiviral immunity. The literature search was performed through a critical analysis of relevant publications reported in PubMed and Scopus databases on clinical trials and assays conducted in vitro on colon cells and in vivo on mice. Some studies using probiotics and prebiotics for the prevention of viral infection in different age groups are discussed. Covid-19 patients have been shown to suffer from gastrointestinal complications in addition to respiratory symptoms due to interactions between the respiratory system and the gastrointestinal tract infected with SARS-CoV-2. Unfortunately, therapies used to prevent (or treat) symptoms of Covid-19 have proven to be of limited effectiveness. In addition, the lack of access to coronavirus vaccines around the world and vaccine hesitancy continue to hamper control of Covid-19. It is therefore crucial to find alternative methods that can prevent disease symptoms. Evidence-based efficacy of certain probiotics (Lactobacillus and Bifidobacterium) that may be useful in viral infections was shown with immunomodulatory properties (pro-inflammatory mediators reduction), promoting antiviral immunity (antibodies production, virus titers) and controlling inflammation (anti-inflammatory effect), as well as viral clearance and antimicrobial potential against opportunistic bacteria (anti-dysbiosis effect). But, available data about clinical application of probiotics in Covid-19 context remain limited and relevant scientific investigation is still in its early stages. Also, evidence for prebiotics potential in this field is limited, since the exact mechanism involved in systemic immune modulation by these compounds is till now unknown. Thus, further research is necessary to explore in the viral infection context the mechanism by which gut and lung interact in the presence of probiotics and prebiotics through more animal and clinical experiments.

Acute Disseminated Encephalomyelitis (ADEM) following viral infections: Investigating triggers, immune response and management

ADEM is diagnosed as an acute disseminated demyelinating disease of the CNS. It is normally initiated by viral infections. The objective of the current research was to elucidate the etiology, immunologic characteristics and management of ADEM in 430 subjects in Hayatabad Medical Complex, Peshawar. Of the viral causes the most commonly identified were influenza, 25%; measles, 20%; and varicella, 18%. Perhaps this may show how distribution of the infective agents common in this region may explain the occurrence of ADEM. They have similarly given out high cytokine concentration particularly IL-6 and TNF-α and similar to past findings they might not only be biomarkers of disease severity but may also be a site of immunomodulation. As for the reaction to the treatment the favorable responses are 80% of the times on corticosteroids and the IVIG and plasmapheresis are great for severe cases or if the prior one failed. Datalocalized at six months follow-up, the majority of the patients had positively improved in seventy percent with the other ten percent patients’ symptoms nearly dropped down. Therefore, the present research suggests that diagnosis of ADEM should be done early and patients ought to be put on working on formulation of tailor made treatment plans that might improve prognosis of ADEM. Findings regarding genetic profile identifying high risk patients who must be prescribed special medicine are still lacking. Therefore, this study will therefore complement information on Immune defenses and therapeutic approaches in ADEM in a region of the world where viral diseases are common.

Features of hyperinflammation link the biology of EBV infection and cytokine storm syndromes

BackgroundOvert immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). ObjectiveWe aim to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes. MethodsWe recruited children who presented to the emergency room with fever for ≥ 3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C). ResultsWe enrolled 352 febrile patients and studied 110 cases with confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, tumor necrosis factor, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH / MAS, but less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38+HLA-DR+ T lymphocytes, which are pathogenic cells responsible for IFN-γ production in HLH / MAS, are vastly expanded in patients with acute EBV infection. Cell sorting identified CD38+HLA-DR+ T cells as atypical lymphocytes that are classically associated with acute EBV infection. ConclusionThis work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH / MAS.

Potential therapeutic and ameliorative effects of ramipril alone and in combination with methylprednisolone for the cytokine releasing syndrome in mice: An in vivo study.

Cytokine-releasing syndrome (CRS) is a special form of systemic inflammatory response syndrome provoked by factors like viral infections and certain immunomodulatory drugs like monoclonal antibodies and adoptive T therapy. To elucidate the potential role of ramipril (RM) and its combination with methylprednisolone (MP) against the development and progression of CRS in mice. This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5mg/kg lipopolysaccharide (LPS) without intervention. The other groups received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 3 mg/kg RM, and a combination of 1.5 mg/kg RM with 25 mg/kg MP). The second part of the study involves the therapeutic potential; all groups received similar doses of drugs in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RM and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with ramipril and its combination with MP ameliorate the tissue damage in both lung and liver tissues following LPS induction. Ramipril showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms.

SECOND SOUTHERN SCIENCE CONFERENCE: HEALTH SESSIONS

The Second Southern Science Conference brought together international researchers focused on health and diseases. The event featured expert lectures across various fields, including cell biology, neurobiology, immunology, and pharmacology. Notable presentations covered new tools for cell biology research, such as the RUSH and RUCH systems, which enable studying protein trafficking in cells. In microbiology, key topics included antibiotic resistance and bacterial and viral infections. In neurobiology, researchers presented advances in treating neurodegenerative diseases, including the use of nanoparticles for drug delivery. The conference also addressed immunology issues, such as COVID-19 vaccination effects, and aspects of diet in cell physiology. The event concluded with a lecture on academic entrepreneurship, demonstrating how research can be transformed into commercial products. The conference, hosted at the Universidad de Mendoza, provided a unique opportunity for sharing scientific knowledge and advances in healthcare, with the next edition scheduled for 2026.

Optimal control analysis applied to the transmission dynamics of Hepatitis B to primary liver cancer

Infection with hepatitis virus, especially hepatitis B virus causes an irritation to the liver. Ranked among the top ten diseases with high mortality rate, viral hepatitis poses a great health challenges worldwide, with threat to chronic infection, hepatitis-related liver cancer and cirrhosis. Hence, a mathematical model to study the dynamics of hepatitis B virus infection from progressing into primary liver cancer was developed for analysis. We aimed at obtaining the optimal control strategies needed to reduce the number of new cases of this disease, and also reducing the deterioration rate of people living with this disease from sliding into primary liver cancer. We introduced four distinct control variables at each point in the model, and assumed that all the controls are set of Lebesque Measurable functions. The Pontryagin’s maximum principle (PMP) is employed to establish the optimal effect of these controls on the disease under study. Existence of model solution was established using the appropriate theorem. The model with control strategies was analytically solved using PMP and numerically simulated for each compartments, to establish the effect of the control variables on the dynamics of transmission of this infection within the compartment, and their overall effect on the entire population. Differential transform method (DTM) was later adopted as a semi-analytic scheme to solve the developed model. The series solution of DTM was numerically plotted for each compartment and compared with Runge-Kutta order 4 (RK4) numerical scheme. Analysis of the model with control pinpoint the importance of sensitization and vaccination on the overall dynamics of the infection, while the numerical plot of DTM and RK4 established the efficacy of the adopted semi-analytic method (DTM) to accurately solve the system of equations of the model.

Deep Learning-Assisted Design of de novo Protein Binders Targeting Hepatitis C Virus E2 Protein

Hepatitis C virus is a grievous disease with an increased mortality rate worldwide. Chemical-based medications possess deleterious side effects and are considered inefficient in combating viral infections. Advanced therapeutic strategies are being examined with increased specificity against viral proteins such as designing highly regular proteins facilitating the development of highly effective inhibitors. Here, we present for the first time, the use of deep learning-based large language protein model ProtGPT2 with a unique strategy to design novel therapeutic binders that have the potential to mimic host receptors and inhibit the viral protein, especially the HCV envelope glycoprotein E2 for clinically relevant genotype 1a and 1b. We generated five de novo proteins for each host receptor that mimic the human receptors, based on the interacting residues which were identified by the tools of the PDBSum database in the docked host-E2 complexes generated with the ClusPro web server. The Root Mean Square Deviation score revealed that each de novo designed binder exhibited high similarity with the human receptors indicating a successful generation. Furthermore, multiple interactions were observed between these de novo designed proteins and E2 protein, emphasizing the potential of these de novo designed proteins as significant inhibitors. A comparative analysis of molecular docking between human interacting partners and de novo designed proteins revealed that de novo proteins, such as CD81-D1 and CLDN-D4, are the most effective inhibitors having the lowest binding energy when interacting with the most conserved regions of the E2 protein. These generated proteins may inhibit the interaction of E2 with CD81 and CLDN host receptors.

Andrographolide attenuates SARS-CoV-2 infection via an up-regulation of glutamate-cysteine ligase catalytic subunit (GCLC)

BackgroundAndrographolide is a medicinal compound which possesses anti-SARS-CoV-2 activity. A number of cellular targets of andrographolide have been identified by target predictions and computational studies. PurposeHowever, a potential cellular target of andrographolide has never been explored in SARS-CoV-2 infected lung epithelial cells. We aimed to identify cellular pathways involved in andrographolide-mediated anti-SARS-CoV-2 activity. MethodsThe viral infection was determined by immunofluorescence staining, enzyme-linked immunosorbent assay and focus-forming assay. Proteomic analysis was employed to identify cellular pathways and key proteins controlled by andrographolide in the human lung epithelial cells Calu-3 infected by SARS-CoV-2. Immunofluorescence staining was used to test protein expression and localization. Western blot and realtime PCR were utilized to elucidate gene expression. Cellular glutathione level was examined by a reduced/oxidized glutathione assay. An ectopic gene expression was delivered by plasmid transfection. ResultsGene ontology analysis indicates that proteins involved in nuclear factor erythroid 2-related factor 2 (NRF2)-regulated pathways were differentially expressed by andrographolide. Notably, andrographolide increased expression and nuclear localization of the transcription factor NRF2. In addition, transcriptional expression of GCLC and glutamate-cysteine ligase modifier subunit (GCLM), which are NRF2 target genes, were induced by andrographolide. We further find that infection of SARS-CoV-2 resulted in a reduction of glutathione level in Calu-3; the effect that was rescued by andrographolide. Moreover, andrographolide also induced expression of the glutathione producing enzyme GCLC in SARS-CoV-2 infected lung epithelial cells. Importantly, an ectopic over-expression of GCLC or treatment of N-acetyl-L-cysteine in Calu-3 cells led to a decrease in SARS-CoV-2 infection. ConclusionCollectively, our findings suggest the interplay between GCLC-mediated glutathione biogenesis induced by andrographolide and the anti-SARS-CoV-2 activity. The glutathione biogenesis and recycling pathways should be further exploited as a targeted therapy against SARS-CoV-2 infection.

State‐of‐the‐art in food safety: The potential of CRISPR/Cas‐based lateral flow assay technology in the field of food analysis

AbstractFood safety is essential for public health, with key hazards including microbial and chemical contamination and pesticide residues. Therefore, food testing is integral to ensuring food safety. Combining CRISPR/Cas with lateral flow assays (LFAs) leverages CRISPR's robust trans‐acting activity, specific target recognition, and high enzymatic efficiency while retaining LFA's advantages of direct visualization, low cost, and simple operation. This combination enhances food safety detection capabilities. In this paper, we review the CRISPR‐based lateral flow combined detection technology, summarize its basic principles and features, and focus on its integrated applications. The technology is fast, accurate, and cost‐effective in detection, and is thus widely used in various testing fields, especially in food pathogen and viral infection detection. Finally, we highlight the technology's potential to improve various aspects, such as detection strength, and discuss the barriers and pre‐commercialization issues of CRISPR/Cas detection platforms. We also provide solutions to increase the likelihood of its commercialization. Currently, CRISPR lateral flow assays are anticipated for broad detection applications. Researchers are investigating Cas protein properties to enhance assay stability and accuracy, promising enhanced food and bioassay safety in the future.

The Epidemiology, Clinical, and Economic Burdens of Respiratory Syncytial Virus Infections Amongst Hospitalized Children Under 5 Years of Age in Jordan: A National Multi-Center Cross-Sectional Study

Respiratory syncytial virus (RSV) has been recognized as a highly important cause of morbidity and mortality among children and adults. A cross-sectional study at representative sites in Jordan was undertaken to provide an assessment of the epidemiology and health and economic burdens of RSV and influenza infections in Jordan amongst hospitalized children under 5 years old for the period between 15 November 2022 and 14 April 2023. This study involved 1000 patients with a mean age of 17.10 (SD: 16.57) months. Of these, half (n = 506, 50.6%) had positive results for RSV. Furthermore, 33% and 17.4% of the participants had positive results for RSV-B and RSV-A, respectively. The findings underscore the severity of RSV infections, where a significant proportion of the children experienced severe respiratory distress, which led to bronchiolitis and pneumonia. This study meticulously documented the clinical outcomes, including the need for intensive care, mechanical ventilation, and prolonged hospital stays. There was no statistically significant difference in the financial burdens between the RSV-positive and RSV-negative patients. This study revealed the urgent need for preventive measures to control the substantial burden of RSV among children under 5 years old in Jordan.

Wild Brazilian Yellow Fever Virus infection in Syrian hamsters (Mesocricetus auratus): Clinical and histopathological analyses

The Yellow Fever virus (YFV) wild-type strains studied until now have little or no ability to evade the Syrian hamster interferon antiviral response. Thus, evaluating the susceptibility of this model to new YFV isolates is paramount to aid in the understanding of their viscerotropic phenotype. To this end, Syrian hamsters were inoculated intraperitoneally with two Brazilian wild-type YFV isolates originated from dying or dead howler monkeys obtained during outbreaks in the states of Rio Grande do Sul in 2008 (PR4408) and Rio de Janeiro in 2019 (RJ155). The results were compared with a YFV experimental vaccine strain (17DDexp). The main findings observed for animals infected with the PR4408 strain were progressive weight loss and persistent viremia (at least up to day seven post-infection), associated with viral RNA detection in the liver, and hepatic, splenic, and pancreatic histological alterations consistent with YF. The infection was eliminated seven days post-infection in animals inoculated with the RJ155 strain. No changes were observed for animals infected with 17DDexp virus. The findings indicate that both Brazilian isolates are able to infect Syrian hamsters, resulting in histopathological changes compatible with the YF pathology observed in humans. Furthermore, the PR4408 strain exhibited increased virulence in this mammalian model, despite causing a non-fatal infection.

Multi-protomics analysis identified host cellular pathways perturbed by tick-borne encephalitis virus infection

Tick-borne encephalitis virus (TBEV) represents a pivotal tick-transmitted flavivirus responsible for severe neurological consequences in Europe and Asia. The emergence of TBEV genetic mutations and vaccine-breakthrough infections, along with the absence of effective vaccines and specific drugs for other tick-borne flaviviruses associated with severe encephalitis or hemorrhagic fever, underscores the urgent need for progress in understanding the pathogenesis and intervention strategies for TBEV and related flaviviruses. Here we elucidate cellular alterations in the proteome, phosphoproteome, and acetylproteome upon TBEV infection. Our findings reveal a substantial impact of TBEV infection on the innate immune response, ribosomal biogenesis, autophagy, and DNA damage response (DDR). Mechanically, the non-structural protein NS5 of TBEV impedes DNA damage repair by interacting with SIRT1 to suppress the deacetylation of KAP1 and Ku70. Additionally, the precursor membrane protein prM induces autophagy via associating with AKT1 while constrains autolysosome formation through binding to VPS11. Inhibitors targeting DDR, as well as specific kinases, exhibit potent antiviral activity, suggesting the dysregulated pathways and kinases as potential targets for antiviral intervention. These results from our study contribute to elucidating the pathogenesis and offers insights for developing effective antiviral drugs against TBEV and other tick-borne flaviviruses.

TRICOMONÍASE COMO UM FATOR DE RISCO PARA INFECÇÃO PELO HIV EM MULHERES: REVISÃO DA LITERATURA

This paper addresses trichomoniasis as a risk factor for HIV infection in women, highlighting the relevance of this topic in public health. The main objective is to investigate the association between Trichomonas vaginalis infection and the increased risk of HIV infection, contributing to the understanding of the dynamics involving these infections. To achieve this objective, we utilized a qualitative research methodology, consisting of a literature review in databases such as PubMed, SciELO, and Google Scholar, analyzing articles published between 1999 and 2024. The results indicate a significant prevalence of co-infection by Trichomonas vaginalis and HIV among women, revealing geographical differences and worrying rates, especially in vulnerable populations, such as those with multiple sexual partners or without access to adequate health services. The evidence suggests that trichomoniasis not only facilitates the transmission of HIV but can also complicate the treatment of the virus infection, as inflammation and lesions caused by trichomoniasis increase susceptibility to HIV infection. We conclude that trichomoniasis worsens public health issues, emphasizing the need for integrated prevention and treatment strategies. It is essential for health policies to address co-infection comprehensively, promoting awareness, early diagnosis, and effective treatment, as well as ensuring access to health services, especially for vulnerable populations. The paper highlights the importance of a multidisciplinary approach to tackle these challenges and improve outcomes for affected women.

Molecular characterization of circulating infectious bursal disease viruses in chickens from different Egyptian governorates during 2023

Infectious bursal disease virus (IBDV) induces severe immunosuppression in chickens, leading to significant economic losses in the global poultry industry. This study investigated 52 chicken flocks, including commercial broilers, layers, and baladi, from various Egyptian governorates in 2023. These flocks exhibited symptoms of depression, along with kidney and bursa lesions, indicative of IBDV infection. Pooled Bursal homogenates were tested using RT-PCR with VP2-specific primers, revealing that 20 flocks tested positive for IBDV. Six representative samples were selected from 20 positive flocks for isolation in embryonated chicken eggs. The embryonic lesions observed included haemorrhage, skull swelling, and liver necrosis with a pale-yellow appearance, in addition to congestion and thickening in the chorioallantoic membrane (CAM). Partial amplification of the VP2 gene from the harvested embryo suspensions of the six IBDV isolates was performed for sequencing. Phylogenetic analysis of the sequences revealed that five IBDV isolates (VV4, VV5, VV6, VV10, and VV16) belonged to the very virulent strain group A3 cluster, whereas one isolate (VV2) clustered with Chinese Variant strains in the A2d group. Sequence analysis of the hypervariable region (HVR) of VP2 compared to that of Egypt-USC-IBD-1-2019 and vvIBDV/Beh21/Egypt/18 highly virulent IBDV strains revealed several amino acid mutations. The VP2 HVR of all isolates maintained the serine-rich heptapeptide sequence SWSASGS, which is adjacent to the major hydrophilic peak B and serves as a virulence marker. Histopathological examination revealed that bursae from chickens infected with vvIBDV exhibited marked interlobular oedema and lymphoid depletion. In contrast, bursae from chickens infected with Variant IBDV showed massive lymphoid depletion, with hyperplasia of the bursal capsule. These findings highlight the circulation of both virulent and Variant IBDV strains in Egyptian chicken flocks, complicating disease control. Consequently, there is a need to update vaccination programs and vaccine strains for IBDV in Egypt.

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. To address this gap, gain insights into vLRTI pathophysiology, and test a novel diagnostic approach, we assayed 1,305 proteins in tracheal aspirate (TA) and plasma from 62 critically ill children using SomaScan. We performed differential expression (DE) and pathway analyses comparing vLRTI (n = 40) to controls with non-infectious acute respiratory failure (n = 22), developed a diagnostic classifier using LASSO regression, and analyzed matched TA and plasma samples. We further investigated the impact of viral load and bacterial coinfection on the proteome. The TA signature of vLRTI was characterized by 200 DE proteins (Padj <0.05) with upregulation of interferons and T cell responses and downregulation of inflammation-modulating proteins including FABP and MIP-5. A nine-protein TA classifier achieved an area under the receiver operator curve (AUC) of 0.96 (95% CI: 0.90-1.00) for identifying vLRTI. In plasma, the host response to vLRTI was more muted with 56 DE proteins. Correlation between TA and plasma was limited, although ISG15 was elevated in both compartments. In bacterial coinfection, we observed increases in the TNF-stimulated protein TSG-6, as well as CRP, and interferon-related proteins. Viral load correlated positively with interferon signaling and negatively with neutrophil-activation pathways. Taken together, our study provides fresh insights into the lower airway and systemic proteome of severe pediatric vLRTI and identifies novel protein biomarkers with diagnostic potential.IMPORTANCEWe describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated a positive correlation with interferon-related protein expression and a negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insights into the lower airway and systemic proteome of severe pediatric vLRTI.

The emerging role of photodynamic therapy in the treatment of cutaneous infections.

Cutaneous infections pose ongoing challenges to standard treatments due to resistance and limited efficacy. Photodynamic therapy (PDT) emerges as a promising supplement or an alternative to address complicated cases. In this review, we comprehensively review PDT's safety and efficacy in treating cutaneous infections. A PubMed systematic review with search terms for PDT treatment, hair, skin, and nail infections. There were a total of 43 studies on the use of PDT in cutaneous infections which discussed the treatment of viral (N.=20), bacterial (N.=11), fungal (N.=9), and protozoal (N.=3) infections. There is evidence for using PDT, mostly 5-aminolevulinic acid (5-ALA) and methyl aminolevulinate (MAL), in the treatment of cutaneous infections. Most evidence for viral infections involved treatment with 5-ALA PDT in condyloma acuminatum (CoAc), verruca vulgaris, and molluscum contagiosum. In bacterial infections, 5-ALA and MB PDT have been used to achieve complete remission in refractory Pseudomonas and atypical mycobacteria infections without recurrence. In onychomycosis, MAL PDT achieved a 40.9% cure rate and MB PDT showed a 77.8-100% cure rate with no reports of recurrence. Parasitic infections, such as leishmaniasis have also been successfully treated with both 5-ALA and MAL PDT. PDT is a promising treatment option for cutaneous infections, with growing evidence for its utility in treating cutaneous bacterial, viral, fungal, and parasitic infections, particularly those that fail standard treatments. Side effects were mostly limited to localized pain with good outcomes and low recurrence rates.

TMBIM6/BI-1 is an intracellular environmental regulator that induces paraptosis in cancer via ROS and Calcium-activated ERAD II pathways.

Transmembrane B cell lymphoma 2-associated X protein inhibitor motif-containing (TMBIM) 6, also known as Bax Inhibitor-1 (BI-1), has been heavily researched for its cytoprotective functions. TMBIM6 functional diversity includes modulating cell survival, stress, metabolism, cytoskeletal dynamics, organelle function, regulating cytosolic acidification, calcium, and reactive oxygen species (ROS). Clinical research shows TMBIM6 plays a key role in many of the world's top diseases/injuries (i.e., Alzheimer's, Parkinson's, diabetes, obesity, brain injury, liver disease, heart disease, aging, etc.), including cancer, where TMBIM6 expression impacts patient survival, chemoresistance, cancer progression, and metastasis. We show TMBIM6 is activated by, and undergoes, different conformational changes that dictate its function following a significant change in the cell's IntraCellular Environment (ICE). TMBIM6 agonism, following ICE change, can help the cell overcome multiple stresses including toxin exposure, viral infection, wound healing, and excitotoxicity. However, in cancer cells TMBIM6 agonism results in rapid paraptotic induction irrespective of the cancer type, sub-type, genotype or phenotype. Furthermore, the level of TMBIM6 expression in cancer did not dictate the level of paraptotic induction; however, it did dictate the rate at which paraptosis occurred. TMBIM6 agonism did not induce paraptosis in cancer via canonical routes involving p38 MAPK, JNK, ERK, UPR, autophagy, proteasomes, or Caspase-9. Instead, TMBIM6 agonism in cancer upregulates cytosolic Ca2+ and ROS, activates lysosome biogenesis, and induces paraptosis via ERAD II mechanisms. In xenograft models, we show TMBIM6 agonism induces rapid cancer cell death with no toxicity, even at high doses of TMBIM6 agonist (>450 mg/kg). In summary, this study shows TMBIM6's functional diversity is only activated by severe ICE change in diseased/injured cells, highlighting its transformative potential as a therapeutic target across various diseases and injuries, including cancer.

Advancements in the Study of the Immune Molecule NKp46 in Immune System-related Diseases.

NKp46 is a natural killer cell activating receptor primarily expressed on NK cells and non-NK innate lymphoid cells. In the context of anti-infection, NKp46 activates NK cells by binding to ligands on pathogens or infected cells, enabling NK cells to kill the infected cells. In antitumor activities, NKp46 plays a pivotal role in combating tumor growth through mechanisms such as directly killing tumor cells, inhibiting tumor immune escape, and reducing tumor growth rate through immune editing. The expression levels of NKp46 are closely associated with the progression of immune-related diseases, viral infections, leukemia, tumors, and reproductive failure, affecting diagnosis and prognosis. However, the functionality and mechanistic actions of NKp46, as well as the identification of additional NKp46 ligands, require further investigation. This review provides a comprehensive understanding of NKp46, offering a theoretical foundation for the research and development of diagnostic and therapeutic approaches for related diseases.

RNA-seq and Ribosome Profiling Reveal the Translational Landscape of Rice in Response to Rice Stripe Virus Infection

Rice is a crucial staple food for over half the global population, and viral infections pose significant threats to rice yields. This study focuses on the Rice Stripe Virus (RSV), which is known to drastically reduce rice productivity. We employed RNA-seq and ribosome profiling to analyze the transcriptional and translational responses of RSV-infected rice seedlings. Our results reveal that translational reprogramming is a critical aspect of the plant’s defense mechanism, operating independently of transcriptional changes. Notably, less than half of the differentially expressed genes showed concordance between transcription and translation. Furthermore, RSV infection led to significant alterations in translational efficiency for numerous genes, suggesting that the virus selectively manipulates translation to enhance its pathogenicity. Our findings underscore the necessity of examining both transcriptional and translational landscapes to fully understand plant responses to viral infections.

Overview of Pediatric Respiratory Syncytial Virus (RSV) infections: has risk perception for RSV changed in children with comorbid conditions?

Respiratory syncytial virus (RSV) is the primary etiology of lower respiratory tract infection in children. The fluctuating incidence of RSV, particularly in light of the COVID-19 pandemic, has shifted the spotlight onto preventive strategies. Our study aims to investigate both the risk factors and clinical symptoms of RSV. From February 2015 to February 2023, samples were analyzed during all seasons to identify viral respiratory infections. RSV was identified in a total of 835 individuals. In 2021, following the easing of limitations after the COVID-19 pandemic, the largest number of identified cases was recorded. January was the most commonly used month. The median age were 5 months (min-max: 1-204 months) and 128 (17.7%) cases had a history of prematurity. Around 24.7% of the patients had a preexisting medical condition. Neurological disease patients were followed up in the intensive care unit more often than others (53.3 vs. 35.8% p = 0.036). While the hospital stay of pediatric patients born under the 29th week of gestation is almost twice as long compared to other groups, the hospital stay is almost twice as long as that of patients between 29 and 32 weeks. (p = 0.046, p = 0.012 respectively). RSV was a powerful companion during the pandemic and a persistent reminder of its severity. Our initial data suggest that RSV prevention is difficult for children with pre-existing diseases, notably neurological abnormalities, who are not advised for preventive treatments. Given this outcome, late-premature newborns and children with medical issues should receive RSV prophylaxis first.