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Keywords = hepatitis C viral infection

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68 pages, 2838 KiB  
Review
Unravelling the Viral Hypothesis of Schizophrenia: A Comprehensive Review of Mechanisms and Evidence
by Mădălina Georgeta Sighencea and Simona Corina Trifu
Int. J. Mol. Sci. 2025, 26(15), 7429; https://doi.org/10.3390/ijms26157429 - 1 Aug 2025
Viewed by 374
Abstract
Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a [...] Read more.
Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article
(This article belongs to the Special Issue Schizophrenia: From Molecular Mechanism to Therapy)
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13 pages, 931 KiB  
Article
Ultrasensitive and Multiplexed Target Detection Strategy Based on Photocleavable Mass Tags and Mass Signal Amplification
by Seokhwan Ji, Jin-Gyu Na and Woon-Seok Yeo
Nanomaterials 2025, 15(15), 1170; https://doi.org/10.3390/nano15151170 - 29 Jul 2025
Viewed by 273
Abstract
Co-infections pose significant challenges not only clinically, but also in terms of simultaneous diagnoses. The development of sensitive, multiplexed analytical platforms is critical for accurately detecting viral co-infections, particularly in complex biological environments. In this study, we present a mass spectrometry (MS)-based detection [...] Read more.
Co-infections pose significant challenges not only clinically, but also in terms of simultaneous diagnoses. The development of sensitive, multiplexed analytical platforms is critical for accurately detecting viral co-infections, particularly in complex biological environments. In this study, we present a mass spectrometry (MS)-based detection strategy employing a target-triggered hybridization chain reaction (HCR) to amplify signals and in situ photocleavable mass tags (PMTs) for the simultaneous detection of multiple targets. Hairpin DNAs modified with PMTs and immobilized loop structures on magnetic particles (Loop@MPs) were engineered for each target, and their hybridization and amplification efficiency was validated using native polyacrylamide gel electrophoresis (PAGE) and laser desorption/ionization MS (LDI-MS), with silica@gold core–shell hybrid (SiAu) nanoparticles being employed as an internal standard to ensure quantitative reliability. The system exhibited excellent sensitivity, with a detection limit of 415.12 amol for the hepatitis B virus (HBV) target and a dynamic range spanning from 1 fmol to 100 pmol. Quantitative analysis in fetal bovine serum confirmed high accuracy and precision, even under low-abundance conditions. Moreover, the system successfully and simultaneously detected multiple targets, i.e., HBV, human immunodeficiency virus (HIV), and hepatitis C virus (HCV), mixed in various ratios, demonstrating clear PMT signals for each. These findings establish our approach as a robust and reliable platform for ultrasensitive multiplexed detection, with strong potential for clinical and biomedical research. Full article
(This article belongs to the Special Issue Synthesis and Application of Optical Nanomaterials: 2nd Edition)
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22 pages, 1616 KiB  
Article
Genetic Correlates of Presenile Dementia and Cognitive Decline in the Armenian Population Following COVID-19: A Case-Control Study
by Yekaterina Hovhannisyan, Hermine Yeritsyan, Gohar Hakobjanyan, Gayane Petrosyan, Hayk Harutyunyan, Armen Muradyan, Allen Azizian and Konstantin Yenkoyan
Int. J. Mol. Sci. 2025, 26(14), 6965; https://doi.org/10.3390/ijms26146965 - 20 Jul 2025
Viewed by 292
Abstract
The presence of cognitive lapses in the post-COVID-19 period, particularly among younger individuals, suggests a potential genetic predisposition. This case–control study aimed to assess the association between neurodegeneration-associated genes and cognitive declines in the post-COVID-19 Armenian population under the age of 65. In [...] Read more.
The presence of cognitive lapses in the post-COVID-19 period, particularly among younger individuals, suggests a potential genetic predisposition. This case–control study aimed to assess the association between neurodegeneration-associated genes and cognitive declines in the post-COVID-19 Armenian population under the age of 65. In addition, we examined other contributing factors, including depressive symptoms, hypovitaminosis D, vitamin B12 and B9 deficiencies, and some viral infections, as potential confounders or effect modifiers. A total of 162 participants (ages 19–65, Med = 43), who were exposed to SARS-CoV-2 in Armenia between 2020 and 2022, participated in this study. Standardized assessments, including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment (MoCA), were used to evaluate cognitive functions and mental status, while the Patient Health Questionnaire-9 (PHQ-9) was utilized to assess depressive symptoms. Clinical interview data, comprising yes/no self-reports regarding the presence of cognitive problems and depressive symptoms, were also included. Genetic analysis identified copy number variations (CNVs) in the APP, PSEN1, PSEN2, MAPT, and GRN genes, while viral infections (HSV-1, HSV-2, CMV, EBV, HIV, SARS-CoV-2, Hepatitis A, B, and C) and vitamin D, B12, and B9 deficiencies were measured. Lower cognitive performance was associated with CNVs in PSEN1 (exons 1, 9, 12), GRN (exons 1, 6, 12), and MAPT (exons 2, 8), along with viral infections (HSV-1, HSV-2, HAV-2). The findings indicate that post-COVID-19 cognitive problems are multifactorial and are linked to genetic mutations, viral infections, age, gender, and folic acid deficiency. Full article
(This article belongs to the Section Molecular Neurobiology)
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22 pages, 1765 KiB  
Review
Polyphenols as Antiviral Agents: Their Potential Against a Range of Virus Types
by Nurten Coşkun, Ranya Demir, Ahmet Alperen Canbolat, Sümeyye Sarıtaş, Burcu Pekdemir, Mikhael Bechelany and Sercan Karav
Nutrients 2025, 17(14), 2325; https://doi.org/10.3390/nu17142325 - 16 Jul 2025
Viewed by 778
Abstract
Polyphenols are structurally diverse plant metabolites that have attracted significant interest. Their compositions are versatile, depending on their structures, including the number of rings in the polyphenol composition. Based on these attributes, polyphenols can be classified as flavanols, anthocyanins, flavones, phenolic acids, stilbenes, [...] Read more.
Polyphenols are structurally diverse plant metabolites that have attracted significant interest. Their compositions are versatile, depending on their structures, including the number of rings in the polyphenol composition. Based on these attributes, polyphenols can be classified as flavanols, anthocyanins, flavones, phenolic acids, stilbenes, and lignans. Polyphenols mainly possess inhibition of viral replication, interference with viral protein synthesis, and modulation of immune responses, providing significant antiviral effects against several viruses, including herpes simplex virus, hepatitis C virus, and influenza. They are crucial for medical compounds in diverse, versatile treatments, namely in diabetes, cardiovascular disorders, cancer, and neurodegenerative problems. Plants are the primary source of bioactive molecules, which are valued for their anti-inflammatory, antioxidant, anticancer, and antiviral activities. Especially, polyphenols are extracted as the most abundant bioactive compounds of plants. Moreover, viral infections are one of the major factors in illnesses and diseases, along with bacteria and fungi. Numerous in vitro and in vivo studies report antiviral activity against SARS-CoV-2, Mayaro virus, dengue virus, herpesvirus, and influenza A virus, though clinical validation remains limited. Additionally, inhibition of viral entry, interference with viral replication, modulation of host immune response, and direct virucidal effects were examined. Full article
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15 pages, 762 KiB  
Article
Evaluating the Linkage Between Resistin and Viral Seropositivity in Psoriasis: Evidence from a Tertiary Centre
by Habeeb Ali Baig, Waseema Sultana, Mohamed Soliman, Dhaifallah Alenizi, Awwad Alenezy, Srinath Mote, Ahmed M. S. Hegazy, Bader Khalid Alanazi, Mansour Srhan Alanazi, Yousef Albedaiwi and Nawal Salama Gouda
Life 2025, 15(7), 1054; https://doi.org/10.3390/life15071054 - 30 Jun 2025
Viewed by 491
Abstract
Psoriasis, a chronic immune-mediated inflammatory skin disorder, presents complex pathogenetic mechanisms potentially influenced by viral infections. This comprehensive study explored the possible interplay of resistance and viral infections among psoriasis patients using serological screening techniques. The investigation involved 90 patients aged 23–45 years, [...] Read more.
Psoriasis, a chronic immune-mediated inflammatory skin disorder, presents complex pathogenetic mechanisms potentially influenced by viral infections. This comprehensive study explored the possible interplay of resistance and viral infections among psoriasis patients using serological screening techniques. The investigation involved 90 patients aged 23–45 years, systematically examining viral seropositivity for HSV (herpes simplex virus), HZ (herpes zoster), HBV (hepatitis B virus), HIV (human immunodeficiency virus), and HCV (hepatitis C virus) through ELISA testing. The findings revealed notable active or recent viral infection rates: 8.9% HSV positivity, 2.2% HZ antibody detection, 4.4% HCV positivity, and 4.4% HIV positivity. The research can contribute to current knowledge gaps, broaden the knowledge regarding the relationship between psoriasis and viral infection, and assess resistance, as it can mediate the interaction. The results can lead to improved diagnosis, treatment, and patient care options. This study emphasizes the importance of thorough viral testing for psoriasis patients, as well as focused therapeutic regimens that take into account viral co-infections. It elucidates the complex networks of biological relationships between immune factors, contributes information that is critical to our understanding of the multifactorial etiology of psoriasis, and concludes with a strong argument for investigating the mechanisms of viral involvement in this chronic-relapsing inflammatory disease. Full article
(This article belongs to the Special Issue Innovative Approaches in Dermatological Therapies and Diagnostics)
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14 pages, 997 KiB  
Article
Evaluation of Treatment Response in Chronic Hepatitis C Patients Receiving Sofosbuvir/Velpatasvir/Voxilaprevir: A Multicenter Real-World Experience from Türkiye
by Umut Devrim Binay, Faruk Karakeçili, Bilgehan Aygen, Ayşin Kılınç Toker, İlhami Çelik, Neşe Demirtürk, Tuğçe Şimşek Bozok, Leyla Dursun, Fethiye Akgül, Güle Çınar, Özgür Günal, Ali Asan, Eyüp Arslan, Fatma Yılmaz Karadağ, Orçun Barkay, İrem Akdemir, Funda Şimşek, Emine Türkoğlu Yılmaz, Zeynep Ravza Eğilmez, Süda Tekin and The Viral Hepatitis Study Group of the Turkish Society of Clinical Microbiology and Infectious Diseases (KLİMİK)add Show full author list remove Hide full author list
Viruses 2025, 17(7), 931; https://doi.org/10.3390/v17070931 - 30 Jun 2025
Viewed by 448
Abstract
The combination of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended as a salvage therapy for treatment-experienced chronic hepatitis C (CHC) patients. However, it is used in our country for treatment-naïve and treatment-experienced patients. This study aims to present real-world data from Türkiye on CHC patients treated [...] Read more.
The combination of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is recommended as a salvage therapy for treatment-experienced chronic hepatitis C (CHC) patients. However, it is used in our country for treatment-naïve and treatment-experienced patients. This study aims to present real-world data from Türkiye on CHC patients treated with SOF/VEL/VOX. The present study was conducted by the Viral Hepatitis Study Group of the Turkish Society of Clinical Microbiology and Infectious Diseases (KLİMİK). It was a multicenter, retrospective, observational study. The data were collected from patients receiving SOF/VEL/VOX therapy at 12 medical centers in Türkiye between 1 June 2022 and 31 December 2024. The patients had received the treatment for 8 to 12 weeks. Of the 139 patients enrolled, 63.3% (n = 88) were male, with a mean age of 54.4 years. Most patients were non-cirrhotic (94.2%, n = 131) and treatment-naïve (92%, n = 128); 49.6% (n = 69) were infected with genotype 1b. Early virologic response (EVR) could be assessed in 126 patients, with an EVR rate of 82.5% (n = 104). End-of-treatment data were available for 113 patients, all achieving an end-of-treatment response. Among the 80 patients for whom week-12 post-treatment data were available, 97.5% sustained virologic response at week 12 (SVR12). Significant improvements were observed in AST, ALT, and platelet levels, along with reductions in APRI and FIB-4 scores (p = 0.001).” No serious adverse events leading to treatment discontinuation were reported. Mild adverse events included pruritus (2.1%, n = 3), fatigue (2.1%, n = 3), and nausea (1.4%, n = 2). The SOF/VEL/VOX combination is a highly effective and well-tolerated treatment option in treatment-naïve CHC patients, achieving an SVR12 rate of 97.5%. Full article
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11 pages, 1335 KiB  
Article
Molecular Epidemiology of Hepatitis C Virus Genotypes in Northern Thailand: A Retrospective Study from 2016 to 2024
by Nang Kham-Kjing, Sirithip Phruekthayanon, Thipsuda Krueyot, Panaddar Phutthakham, Sorasak Intarasoot, Khajornsak Tragoolpua, Kanya Preechasuth, Tanawan Samleerat Carraway, Natedao Kongyai and Woottichai Khamduang
Infect. Dis. Rep. 2025, 17(4), 73; https://doi.org/10.3390/idr17040073 - 23 Jun 2025
Viewed by 735
Abstract
Background: Hepatitis C virus (HCV) remains a significant public health concern in Thailand, with genotype-specific, drug-dependent variations influencing treatment response and disease progression. Despite the availability of pan-genotypic direct-acting antivirals (DAAs), genotype surveillance remains essential for optimizing national elimination strategies. This study thus [...] Read more.
Background: Hepatitis C virus (HCV) remains a significant public health concern in Thailand, with genotype-specific, drug-dependent variations influencing treatment response and disease progression. Despite the availability of pan-genotypic direct-acting antivirals (DAAs), genotype surveillance remains essential for optimizing national elimination strategies. This study thus aims to characterize the molecular distribution of HCV genotypes in northern Thailand. Methods: We conducted a retrospective molecular epidemiological study on 1737 HCV-infected patients who attended the Clinical Microbiology Service Unit (CMSU) Laboratory, Faculty of Associated Medical Sciences, Chiang Mai University between April 2016 and June 2024. HCV genotyping was performed using Sanger sequencing and reverse hybridization line probe assay (LiPA). Results: Genotype 3 was the most prevalent (36.6%), followed by genotype 1 (35.8%) and genotype 6 (27.2%). Subtype 3a (27.2%) predominated, along with 1a (22.1%), 1b (12.6%), and genotype 6 subtypes including 6c to 6l (13.5%) and 6n (6.6%). Males had a higher prevalence of genotype 1, while genotype 3 was more common among females. Temporal analysis revealed a relative increase in genotype 6 prevalence since 2021. Genotype 6 also exhibited significantly higher median viral loads compared to genotypes 1 and 3 (p < 0.0001). Conclusions: This study provides updated evidence on the shifting distribution of HCV genotypes in northern Thailand, particularly the increasing prevalence of genotype 6. These findings underscore the importance of continued molecular surveillance to guide genotype-specific treatment strategies and support Thailand’s 2030 HCV elimination goals. Full article
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21 pages, 1156 KiB  
Review
Renal Involvement in Mixed Cryoglobulinemic Vasculitis: Current Perspectives
by Annalisa Villa, Antonietta Gigante, Chiara Pellicano, Klara Radovic, Konstantinos Giannakakis, Milvia Casato and Marcella Visentini
J. Clin. Med. 2025, 14(12), 4369; https://doi.org/10.3390/jcm14124369 - 19 Jun 2025
Viewed by 900
Abstract
Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from [...] Read more.
Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from immune complexes—typically monoclonal IgM with rheumatoid factor activity and polyclonal IgG (Type II), or polyclonal/oligoclonal IgM and IgG (Type III). These complexes can obstruct small blood vessels, leading to ischemia and leukocytoclastic vasculitis. Renal involvement occurs in about 30% of MC patients and it is a manifestation with poor prognosis. Nowadays, types II and III MC are the most common forms, often linked to autoimmune diseases like Sjögren’s syndrome and systemic lupus erythematosus, or to viral infections such as hepatitis B or persisting despite hepatitis C eradication. This review explores renal involvement in MC, offering a comprehensive perspective on current knowledge, including recent advances in pathophysiological understanding, evolving diagnostic strategies, and novel therapeutic approaches. In this context, “perspectives” refers to the growing recognition of the shifting epidemiology of MC—particularly the changing etiological landscape following hepatitis C virus eradication—as well as the integration of emerging clinical and pathological entities such as cryofibrinogenemia and monoclonal gammopathy of renal significance into diagnostic and management frameworks. Furthermore, the review highlights current therapeutic strategies recognized as most effective, emphasizing the importance of a multidisciplinary and multimodal approach that combines etiological treatment, B-cell–targeted therapy (notably rituximab), plasma exchange in selected cases, and comprehensive supportive care for renal and systemic complications. Moreover, the landscape of management could be enriched in future years, since clinical trials are ongoing to explore novel therapies for refractory or relapsing cases of MC with renal involvement. Full article
(This article belongs to the Section Nephrology & Urology)
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17 pages, 1671 KiB  
Article
IL-1b-Bearing NETs: Bridging Inflammation to Early Cirrhosis in Hepatitis B
by Maria Ntinopoulou, Theocharis Konstantinidis, Anna Chalkidou, Eleni Papagianni, Aikaterini Skeva, Maria Panopoulou and Akrivi Chrysanthopoulou
Int. J. Mol. Sci. 2025, 26(12), 5733; https://doi.org/10.3390/ijms26125733 - 15 Jun 2025
Viewed by 755
Abstract
Hepatitis B virus (HBV) infection is one of the most dangerous viral diseases, with innate immunity representing the first line of defense against the virus. In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication [...] Read more.
Hepatitis B virus (HBV) infection is one of the most dangerous viral diseases, with innate immunity representing the first line of defense against the virus. In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication of neutrophils in the distinct stages of the disease, HBV-infected patients were enrolled in this study and categorized into three groups: patients with acute infection, chronic infection under treatment, and at early cirrhotic stage. To elucidate the role of inflammatory mediators and cellular mechanisms of neutrophilic origin in the course of the infection, both ex vivo and in vitro studies were performed. Increased levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-18, IL-33, and citrullinated histone H3 (CitH3)—an accurate marker of neutrophil extracellular traps (NETs)—were detected in the circulation of patients with acute infection or early cirrhosis. In parallel, sera from the aforementioned patient groups induced the formation of IL-1b-bearing NETs in neutrophils from healthy individuals. These inflammatory NETs affected primary fibroblasts towards acquiring a pro-fibrotic phenotype. These results suggest that NETs could be regarded as mediators in hepatitis B manifestations, while their therapeutic targeting could enhance the management of early-stage cirrhotic patients. Full article
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13 pages, 960 KiB  
Article
Immunological and Virological Responses in Patients with Monoinfection and Coinfection with Hepatitis B and C Viruses in the Brazilian Amazon
by Joseane R. Silva, Regiane M. A. Sampaio, Patrícia F. Nunes, Vanessa S. Guimarães, Camila Carla da Silva Costa, Evelen da Cruz Coelho, Micheline Vale de Souza, Luana Wanessa Cruz Almeida, Hellen T. Fuzii, Aldemir Branco Oliveira Filho and Luisa C. Martins
Trop. Med. Infect. Dis. 2025, 10(6), 166; https://doi.org/10.3390/tropicalmed10060166 - 13 Jun 2025
Viewed by 828
Abstract
Infections with the Hepatitis B (HBV) and Hepatitis C (HCV) viruses share some transmission routes, which is why coinfection with these viruses becomes common, especially in endemic areas. This study evaluated the immunological response profile, viral load, and liver damage in groups monoinfected [...] Read more.
Infections with the Hepatitis B (HBV) and Hepatitis C (HCV) viruses share some transmission routes, which is why coinfection with these viruses becomes common, especially in endemic areas. This study evaluated the immunological response profile, viral load, and liver damage in groups monoinfected with HBV or HCV and in those co-infected with HBV/HCV. The groups were composed of 22 patients monoinfected by HCV, 22 patients monoinfected by HBV, and 34 co-infected by HBV/HCV, according to serological markers and molecular biology tests. The study was carried out from December 2017 to October 2019. Virus detection employed enzyme immunoassay, Enzyme-Linked Immunosorbent Assay (ELISA), and real-time PCR, while liver function and fibrosis were assessed using biochemical tests and Fibroscan. To research the immunological profile, cytokines were quantified using the BIO-Plex Pro Human Cytokine. Comparing the groups, both mono- and co-infected patients exhibited a Th1 immune response profile. HCV monoinfection notably showed significantly elevated serum levels of INF-γ (p < 0.01) and TNF-α (p < 0.01). The viral load was significantly higher in the HCV monoinfected group when compared to the other groups. Regarding liver damage, patients with a high level of fibrosis (F4) presented significant levels of cytokines INF-γ (p < 0.001), IL-17 (p < 0.0001), and TNF-α (p < 0.0001). Full article
(This article belongs to the Section Infectious Diseases)
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14 pages, 514 KiB  
Article
Renal Function in Chronic Hepatitis C Patients in Mongolia
by Gantogtokh Dashjamts, Amin-Erdene Ganzorig, Yumchinsuren Tsedendorj, Ankhzaya Batsaikhan, Dolgion Daramjav, Enkhmend Khayankhyarvaa, Bolor Ulziitsogt, Otgongerel Nergui, Nomin-Erdene Davaasuren, Ganchimeg Dondov, Tegshjargal Badamjav, Tulgaa Lonjid, Chung-Feng Huang, Tzu-Chun Lin, Batbold Batsaikhan and Chia-Yen Dai
Diagnostics 2025, 15(12), 1471; https://doi.org/10.3390/diagnostics15121471 - 10 Jun 2025
Viewed by 547
Abstract
Background: According to a study conducted among a relatively healthy population of Mongolia (2017), the prevalence of hepatitis C virus (HCV) infection is 8.5%, which is considered a high prevalence of this infection. In addition to inflammation of the liver, other organ systems [...] Read more.
Background: According to a study conducted among a relatively healthy population of Mongolia (2017), the prevalence of hepatitis C virus (HCV) infection is 8.5%, which is considered a high prevalence of this infection. In addition to inflammation of the liver, other organ systems are affected by HCV infection, according to research. Our study aimed to evaluate renal dysfunction in patients with HCV infection. Methods: In the study, 111 people with chronic hepatitis C virus infection were included in the study group, and 111 relatively healthy people were included in the control group. Laboratory parameters were analyzed. Liver fibrosis score was assessed and evaluated by renal function. Results: There were 22.9% (51) men and 77.1% (171) women among the 222 participants, and the average age was 40.7 ± 11.1 years. The glomerular filtration rate was 105.3 ± 24.5 in the chronic hepatitis C virus-infected group and 118.7 ± 18.5 in the control group, or the statistically significant difference in the case group compared to the control group was p < 0.01. The liver fibrosis score was higher in the case group than in the control group. According to logistic regression analysis, patients with hepatitis C virus infection are 25 times more likely to have a decrease in glomerular filtration rate than those without viral infection (OR 24.91, 95% CI 3.13–198.38, p = 0.002). Conclusions: Our study showed that HCV infection leads to kidney function loss. In addition, older age, obesity, and severe liver fibrosis contribute to kidney function decline. Full article
(This article belongs to the Special Issue Diagnosis of Hepatitis)
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19 pages, 3372 KiB  
Article
iDNS3IP: Identification and Characterization of HCV NS3 Protease Inhibitory Peptides
by Hui-Ju Kao, Tzu-Hsiang Weng, Chia-Hung Chen, Chen-Lin Yu, Yu-Chi Chen, Chen-Chen Huang, Kai-Yao Huang and Shun-Long Weng
Int. J. Mol. Sci. 2025, 26(11), 5356; https://doi.org/10.3390/ijms26115356 - 3 Jun 2025
Viewed by 598
Abstract
Hepatitis C virus (HCV) infection remains a significant global health burden, driven by the emergence of drug-resistant strains and the limited efficacy of current antiviral therapies. A promising strategy for therapeutic intervention involves targeting the NS3 protease, a viral enzyme essential for replication. [...] Read more.
Hepatitis C virus (HCV) infection remains a significant global health burden, driven by the emergence of drug-resistant strains and the limited efficacy of current antiviral therapies. A promising strategy for therapeutic intervention involves targeting the NS3 protease, a viral enzyme essential for replication. In this study, we present the first computational model specifically designed to identify NS3 protease inhibitory peptides (NS3IPs). Using amino acid composition (AAC) and K-spaced amino acid pair composition (CKSAAP) features, we developed machine learning classifiers based on support vector machine (SVM) and random forest (RF), achieving accuracies of 98.85% and 97.83%, respectively, validated through 5-fold cross-validation and independent testing. To support the accessibility of the strategy, we implemented a web-based tool, iDNS3IP, which enables real-time prediction of NS3IPs. In addition, we performed feature space analyses using PCA, t-SNE, and LDA based on AAindex descriptors. The resulting visualizations showed a distinguishable clustering between NS3IPs and non-inhibitory peptides, suggesting that inhibitory activity may correlate with characteristic physicochemical patterns. This study provides a reliable and interpretable platform to assist in the discovery of therapeutic peptides and supports continued research into peptide-based antiviral strategies for drug-resistant HCV. To enhance its flexibility, the iDNS3IP web tool also incorporates a BLAST-based similarity search function, enabling users to evaluate inhibitory candidates from both predictive and homology-based perspectives. Full article
(This article belongs to the Section Molecular Informatics)
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34 pages, 2408 KiB  
Review
Multidrug-Resistant Infections and Metabolic Syndrome: An Overlooked Bidirectional Relationship
by Carlo Acierno, Riccardo Nevola, Fannia Barletta, Luca Rinaldi, Ferdinando Carlo Sasso, Luigi Elio Adinolfi and Alfredo Caturano
Biomedicines 2025, 13(6), 1343; https://doi.org/10.3390/biomedicines13061343 - 30 May 2025
Cited by 2 | Viewed by 738
Abstract
Over the past two decades, metabolic syndrome (MetS) and infections caused by multidrug-resistant (MDR) pathogens have emerged as converging global health challenges. Traditionally investigated as separate entities, accumulating evidence increasingly supports a bidirectional relationship between them, mediated by chronic inflammation, immune dysregulation, gut [...] Read more.
Over the past two decades, metabolic syndrome (MetS) and infections caused by multidrug-resistant (MDR) pathogens have emerged as converging global health challenges. Traditionally investigated as separate entities, accumulating evidence increasingly supports a bidirectional relationship between them, mediated by chronic inflammation, immune dysregulation, gut microbiota alterations, and antibiotic-driven expansion of the resistome. This narrative review examines the complex immunometabolic interplay linking MetS and MDR infections, focusing on molecular mechanisms, clinical implications, and prospective research directions. A systematic literature search was conducted using major databases, including PubMed and Scopus, targeting studies from the last 15 years that explore the interface between metabolic dysfunction and antimicrobial resistance. Particular attention is given to key immunometabolic pathways such as the IRS–PI3K–AKT–mTOR axis; the contribution of visceral adiposity and Toll-like receptor (TLR)-mediated inflammation; and the role of gut dysbiosis in augmenting both susceptibility to infections and metabolic derangements. Evidence is presented supporting the hypothesis that MetS increases host vulnerability to MDR pathogens, while chronic MDR infections may reciprocally induce systemic metabolic reprogramming. Viral infections with established metabolic sequelae (e.g., HIV, hepatitis C virus [HCV], and cytomegalovirus [CMV]) are also considered to broaden the conceptual framework. Although current data remain largely associative and fragmented, the emerging MetS–MDR syndemic model poses substantial challenges for translational research, antimicrobial stewardship, and personalized therapeutic strategies. Recognizing this reciprocal relationship is pivotal for refining infection risk stratification, optimizing treatment, and informing public health policies. Further investigations are warranted to elucidate the magnitude and directionality of this association and to identify predictive immunometabolic biomarkers that may guide targeted interventions in high-risk populations. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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12 pages, 430 KiB  
Article
Long-Term Outcomes of Ledipasvir/Sofosbuvir Treatment in Hepatitis C: Viral Suppression, Hepatocellular Carcinoma, and Mortality in Mongolia
by Amgalan Byambasuren, Buyankhishig Gyarvuulkhasuren, Byambatsogt Erdenebat, Khurelbaatar Nyamdavaa and Oidov Baatarkhuu
Viruses 2025, 17(6), 743; https://doi.org/10.3390/v17060743 - 22 May 2025
Viewed by 586
Abstract
(1) Background: Hepatitis C virus (HCV) infection poses a significant health burden, particularly in Mongolia, where the HCV prevalence is notably high. This study evaluates the long-term outcomes of HCV treatment with ledipasvir/sofosbuvir, focusing on mortality, viral relapse, and hepatocellular carcinoma (HCC) development. [...] Read more.
(1) Background: Hepatitis C virus (HCV) infection poses a significant health burden, particularly in Mongolia, where the HCV prevalence is notably high. This study evaluates the long-term outcomes of HCV treatment with ledipasvir/sofosbuvir, focusing on mortality, viral relapse, and hepatocellular carcinoma (HCC) development. (2) Methods: This prospective, longitudinal cohort study initially enrolled patients with chronic HCV in Mongolia between 2016 and 2017, focusing on those who completed the five-year follow-up (n = 303). The study measured long-term mortality, HCC development, and viral relapse, employing non-invasive methods to assess liver fibrosis and liver function. (3) Results: At the outset, 98.2% of the patients achieved undetectable HCV RNA levels. Over five years, 6.27% experienced viral relapse and 3.30% developed hepatocellular carcinoma (HCC), with a mortality rate of 5.94%. In a multivariable analysis, the significant predictors for HCC occurrence included age (OR = 1.081, 95% CI = 1.021–1.145), liver cirrhosis (OR = 5.866, 95% CI = 1.672–22.577), and GGT level (OR = 1.011, 95% CI = 1.004–1.018). The independent predictors of mortality included age (OR = 1.083, 95% CI = 1.024–1.147), liver cirrhosis (OR = 6.529, 95% CI = 1.913–22.281), and GGT (OR = 1.011, 95% CI = 1.004–1.017). (4) Conclusions: This study demonstrates that ledipasvir/sofosbuvir effectively suppresses HCV initially and maintains low viral relapse rates over the long term. However, it emphasizes the need for continued management to reduce the long-term risk of HCC and mortality, especially in patients with severe liver fibrosis or cirrhosis. Full article
(This article belongs to the Special Issue Viral Hepatitis and Liver Diseases)
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Article
Utilization of Flow Cytometry, Metabolomic Analyses and a Feline Infectious Peritonitis Case Study to Evaluate the Physiological Impact of Polyprenyl Immunostimulant
by Irene Lee, Amar Desai, Akshay Patil, Yan Xu, Kelley Pozza-Adams and Anthony J Berdis
Cells 2025, 14(10), 752; https://doi.org/10.3390/cells14100752 - 21 May 2025
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Abstract
Measles, hepatitis C, and COVID-19 are significant human diseases caused by RNA viruses. While vaccines exist to prevent infections, there are a small number of currently available therapeutic agents that can effectively treat these diseases after infection occurs. This study explores a new [...] Read more.
Measles, hepatitis C, and COVID-19 are significant human diseases caused by RNA viruses. While vaccines exist to prevent infections, there are a small number of currently available therapeutic agents that can effectively treat these diseases after infection occurs. This study explores a new therapeutic strategy using a small molecule designated polyprenyl immunostimulant (PI) to increase innate immune responses and combat viral infections. Using a multi-disciplinary approach, this study quantifies the effects of PI in mice and THP-1 cells using flow cytometry to identify immune phenotypic markers and mass spectroscopy to monitor the metabolomic profiles of immune cells perturbed by PI treatment. The metabolomic studies identified that sphinganine and ceramide, which are precursors of sphingosine-1-phosphate (S1P), were the common metabolites upregulated in THP-1 and mice blood. Sphingosine-1-phosphate can mediate the trafficking of T cells, whereas ceramide can signal the activation and proliferation of T cells, thereby modulating the mammalian host’s immunity. To demonstrate proof-of-principle, a case study was conducted to examine the benefit of administering PI to improve the outcomes of a feline co-infected with two distinct RNA viruses—feline leukemia virus and feline infectious peritonitis virus. Both viruses produce deadly symptoms that closely resemble RNA viruses that infect humans. The results identify quantifiable cellular and metabolic markers arising from PI treatment that can be used to establish a platform measuring the efficacy of PI in modulating the innate immune system. Full article
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