Search Results (361)

The global obesity epidemic and associated metabolic disorders present urgent public health challenges. This study employed a multi-omics approach (lipidomics, metabolomics, and gut microbiome analysis) to investigate how Bletilla striata polysaccharides (BSPs) and composite polysaccharides modulate liver lipid metabolism and gut microbiota in high-fat diet (HFD)-induced obese mice. HFD elevated hepatic phosphatidylcholines, cholesteryl esters (CEs), and acylcarnitines (CARs), alongside increased cecal choline and trimethylamine. BSP interventions reduced hepatic CEs, free fatty acids (FAs), CARs, and cecal sarcosine while restoring gut microbial diversity. Notably, BSP enriched beneficial genera, including Jeotgalicoccus and Atopostipes, and the network analysis revealed negative correlations between these genera and hepatic triglycerides (TGs), implicating the gut–liver axis in lipid metabolism regulation. These findings elucidate the anti-obesity mechanisms of polysaccharides through gut microbiota remodeling and cross-tissue metabolic interactions, providing a foundation for leveraging plant polysaccharides in developing safer, effective obesity therapies. Full article

Background: The evaluation of antiviral or vaccination strategies for the prevention of dengue infections in a traveler population would require extensive and complex studies. This prospective study aimed to identify a cohort of dengue naïve participants living in Medellín, a dengue endemic area, as a proxy for travelers and to determine the incidence of primary dengue virus (DENV) infection (symptomatic and asymptomatic) in this cohort. In Colombia, epidemic dengue waves occur every 3–4 years, with infected Aedes mosquitoes present in ~80% of the territory, including Medellín. Methods: Participants > 16 years of age, living in Medellín, were screened for anti-DENV immunoglobulin G (IgG). DENV seronegative participants were enrolled in this study. A serological anti-DENV survey was performed, with semiannual sample collections for up to 2 years. Acute DENV infections were evaluated by monitoring fever and testing for DENV nonstructural protein 1 and/or RNA. Results: Of the 4885 screened participants, 3008 participants (62%) were DENV seronegative and enrolled. Among them, 2263 (75%) completed this study, and 2644 (88%) had at least one serosurvey visit after baseline. Of those, 52 (2%) had laboratory-confirmed DENV seroconversion, and 19 (<1%) had febrile illness, but none had laboratory-confirmed DENV infection. Conclusions: This study identified a cohort of predominantly students, seronegative at study start, living in Medellín and serving as a proxy for a prospective DENV infection traveler population. Laboratory-confirmed primary DENV infection was found in 2% of participants, with <1% reporting febrile illnesses, meeting the WHO criteria for probable clinical dengue cases. Full article

Background/Objectives: Respiratory syncytial virus (RSV) is a leading cause of respiratory infections across all age groups, with the greatest burden observed in young children and older adults. The COVID-19 pandemic significantly disrupted RSV circulation, resulting in an immunity gap and altered transmission dynamics. This study aimed to assess the seroprevalence of anti-RSV IgG antibodies in the Polish population during the 2023/2024 epidemic season. To our knowledge, this is the first study to characterize RSV seroprevalence at the population level in Poland. Methods: A total of 700 serum samples from individuals across different age groups were analyzed using a commercial assay to detect anti-RSV IgG antibodies. Seroprevalence and antibody levels, expressed as the index of positivity (IP), were examined by age and sex. Results: The overall seroprevalence of anti-RSV IgG antibodies was 91.4%. Antibody positivity increased markedly from 35.5% in infants aged 0–1 years to over 90% in children aged 4–5 years, reaching nearly universal levels in older age groups, including 99.1% in adults aged ≥60 years. Median IP values also rose with age, peaking in individuals aged ≥60 years. No significant differences in seroprevalence were observed between sexes, though older men showed slightly higher median IP values, potentially reflecting greater cumulative RSV exposure. Conclusions: This study provides key insights into the post-pandemic landscape of RSV immunity in Poland. The high seroprevalence across most age groups underscores widespread prior exposure, while the lower rates in infants highlight a continued vulnerability. These findings support the development and implementation of targeted immunization strategies, particularly for infants and older adults. Full article

The aim of this study was to determine the level of anti-hemagglutinin antibodies using the hemagglutination inhibition test (HAI) in the blood sera of patients collected during the 2023/2024 epidemic season in Poland. This data is valuable for assessing the level of population immunity to influenza viruses circulating in Poland during this epidemic season. The study material consisted of serum samples collected across the country and divided into seven age groups. The test results confirmed the presence of anti-hemagglutinin antibodies for the antigens included in the quadrivalent influenza vaccine recommended by the World Health Organization (WHO) for the 2023/2024 epidemic season: A/Victoria/4897/2022 (H1N1)pdm09, A/Darwin/9/2021 (H3N2), B/Austria/1359417/2021 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage). The highest values of the geometric mean (GMT = 121.0 [95% CI: 108.5–134.9]) and protective factor (70 [95% CI: 67–74]%) were recorded for the A/H3N2/influenza virus antigen. In Poland, the vaccination rate of the general population in the discussed season was only 5.52%. The obtained results can therefore be interpreted as a response of the immune system, consisting of the production of anti-hemagglutinin antibodies in patients who had previously had an infection caused by the influenza virus. Full article

Porcine epidemic diarrhea (PED), a highly contagious enteric disease caused by the porcine epidemic diarrhea virus (PEDV), is characterized by vomiting, diarrhea, and dehydration, leading to high mortality in newborn piglets and significant economic losses in the swine industry. The shortage of effective PED vaccines emphasizes the need to explore potent natural compounds for therapeutic intervention. It has been shown that glycerol monolaurate (GML) effectively inhibits PEDV replication in vivo and in vitro. Further investigation is needed to assess whether complex medium-chain triglycerides (CMCTs), composed of glyceryl tricaprylate/caprate (GTCC) and GML, offer an efficient anti-PEDV activity. In this study, piglets were orally infected with PEDV and exhibited typical clinical signs, including diarrhea and vomiting, accompanied by intestinal inflammation, oxidative stress, and tissue damage. CMCTs were administered orally twice daily for one week. In vivo findings indicate that CMCT treatment alleviated clinical signs and prevented weight loss. It significantly increased serum immunoglobulins (IgG, IgM, and IgA) and intestinal mucosal sIgA and MUC-2 levels, while reducing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-17) and increasing antiviral interferons (IFN-α and IFN-γ), anti-inflammatory cytokines (IL-4 and IL-10), and IL-22. Antioxidant enzyme activities (T-AOC, SOD, GSH-Px, and CAT) were elevated, whereas oxidative stress markers (iNOS, NO, and MDA) were decreased. Expression of intestinal tight junction proteins claudin-1 and ZO-1 was restored. Moreover, CD4⁺ and CD8⁺ T cell populations increased, and the functions of regulatory T cells (Tregs) were restored. Gut microbiota analysis showed increased beneficial genera (Streptococcus and Ligilactobacillus) and decreased pathogenic Escherichia-Shigella. These results demonstrate that CMCTs mitigate PEDV infection by enhancing anti-inflammation, antioxidation, and intestinal barrier function, as well as modulating gut microbiota composition. This study improves the understanding of the pathogenesis of PEDV and highlights CMCTs as a promising therapeutic candidate for PED. Full article

Porcine epidemic diarrhea (PED) remains a persistent threat to global swine production, necessitating urgent development of targeted interventions. Our previous research established that Hypericum japonicum Thunb. ex Murray (HJT) extract exhibited significant anti-porcine epidemic diarrhea virus (PEDV) activity both in vivo and in vitro. Nevertheless, the principal bioactive constituents mediating this antiviral activity remained uncharacterized. In this study, it was demonstrated that ethanol eluates with 20% (v/v) and 60% (v/v) ethanol exhibited activity against PEDV. Phytochemical characterization revealed 66 distinct compounds, including 36 flavonoids and 13 organic acids identified as possible antiviral constituents. Among these, taxifolin-7-O-rhamnoside and quercetin-7-rhamnoside were identified as the most potent anti-PEDV components. Notably, neither compound exhibited significant antiviral efficacy as monotherapy. However, co-administration produced a reduction in PEDV-G2 titers. This study mechanistically links taxifolin-7-O-rhamnoside and quercetin-7-rhamnoside as core anti-PEDV phytochemicals in HJT extract. These findings support the further development of HJT as a potential therapeutic for PED. Full article

Aim. This study aimed to assess the SARS-CoV-2 herd immunity in the Republic of Armenia (RA) by late 2022. Materials and Methods. A randomized study was conducted from 28 November to 2 December (2022) by the Saint Petersburg Pasteur Institute (Russia) in collaboration with the National Center for Disease Control and Prevention (Armenia). This study was approved by the ethics committees at both organizations. A volunteer cohort (N = 2974) was formed and grouped by participant age, region, or activity. Antibodies (Abs) to viral nucleocapsid antigen (Nc) and receptor-binding domain (RBD) in plasma were determined by ELISA. The statistical significance of differences was calculated using a p < 0.05 threshold, unless noted. Results. At the end of 2022, estimated SARS-CoV-2 seroprevalence (Nc and/or RBD Abs) among the Armenian population was 99% (95%CI: 98.5–99.3). It was evenly distributed throughout the cohort without any significant differences by age, region, or activity. Volunteers with low (32–124 BAU/mL) or medium (125–332 BAU/mL) anti-Nc Ab levels prevailed: 32.4% (95%CI: 30.7–34.1) and 25.5% (95% CI: 24.0–27.1), respectively. Regarding anti-RBD Abs, maximum levels (>450 BAU/mL) were detected in 40% of children. The share of individuals with high anti-RBD Abs levels increased with age, reaching 65% among those aged 70⁺ years. The important contribution to the formation of herd immunity to coronavirus infection was made by vaccination in the preceding period (1 April 2021 to 1 May 2022). The contribution from individuals with post-vaccination immunity was estimated to be above 80%. Hybrid immunity, formed after vaccination of those who had earlier experienced COVID-19, was characterized by greater effectiveness than post-vaccination immunity alone. Conclusions. Within the context of mass prophylactic vaccination, effective herd immunity to SARS-CoV-2 was formed, which helped to stop epidemic spread in the Republic. Full article

The mRNA vaccine has protected humans from the Coronavirus disease 2019 (COVID-19) and has taken the lead in reversing the epidemic efficiently. However, the Centre of Disease Control (CDC) reported and raised the alarm of allergic or acute inflammatory adverse reactions after vaccination with mRNA-LNP vaccines. Meanwhile, the US Food and Drug Administration (FDA) has added four black-box warnings in the instructions for mRNA-LNP vaccines. Numerous studies have proven that the observance of side effects after vaccination is indeed positively correlated to the level of anti-PEG antibodies (IgM or IgG), which are enhanced by PEGylated preparations like LNP vaccine and environmental exposure. After literature research and review in the past two decades, it was found that the many clinical trial failures (BIND-014, RB006 fell in phase II) of PEG modified delivery system or PEGylated drug were related to the high expression of anti-PEG IgM and IgG. In the background of shooting multiple mRNA-LNP vaccines in billions of people around the world in the past three years, the level of anti-PEG antibodies in the population may have significantly increased, which brings potential risks for PEG-modified drug development and clinical safety. This review summarizes the experience of using mRNA-LNP vaccines from the mechanism of the anti-PEG antibodies generation, detection methods, clinical failure cases of PEG-containing products, harm analysis of abuse of PEGylation, and alternatives. In light of the increasing prevalence of anti-PEG antibodies in the population and the need to avoid secondary injuries, this review article holds greater significance by offering insights for drug developers. It suggests avoiding the use of PEG excipients when designing PEGylated drugs or PEG-modified nano-formulations and provides references for strategies such as utilizing PEG-free or alternative excipients. Full article

The influenza A virus (IAV) is a major cause of recurrent seasonal epidemics and global pandemics, posing a significant threat to public health. Although lycorine has demonstrated broad-spectrum antiviral activity, its specific mechanisms of action against IAV remain incompletely understood. In this study, we characterized the potent inhibitory effects of lycorine on seasonal and drug-resistant IAV subtypes (H1N1/H3N2) as well as the influenza B virus, showing its ability to suppress viral mRNA, viral titers, and M2 protein expression across multiple cell lines. Time-of-addition and time-course assays revealed that lycorine exerts multiphasic interference, and the critical late stage of the IAV life cycle aroused our interest to study this further. Mechanistically, we discovered that lycorine specifically interferes with the de novo synthesis of nucleoporin Nup93, thereby disrupting the nuclear export of viral nucleoprotein (NP). These findings not only establish lycorine as a promising broad-spectrum anti-influenza candidate but also provide new insights for developing host-targeted antiviral strategies. Full article

The detection of “silent” poliovirus (PV) circulation among clinically healthy populations is an important component of supplementary surveillance for poliomyelitis. Migrants from countries or regions where polio is endemic, affected by outbreaks, or at risk may contribute to the introduction of PVs of epidemic significance: wild poliovirus type 1, vaccine-derived polioviruses (VDPVs), or poliovirus type 2 into polio-free countries. Migrant children, refugees under 5 years of age, are considered a “risk group” in Russia and are subject to testing for PVs. During 2014–2023, guided by the algorithm of virological and molecular investigation of acute flaccid paralysis cases recommended by the WHO, 51,548 migrant children, arriving from 40 countries, were examined. Among 4% of children excreting various cytopathogenic viruses, polio excretors accounted for 20.8%. Among the PVs, PV3 was predominant (41.7%), and PV types 2, 1, and a mixture of PVs accounted for, respectively, 28.2%, 18.8%, and 11.3%. All isolates of PVs 1 and 3 were identified as Sabin-like. The detection of five children excreting epidemically significant PV2 (four VDPV2 and one Sabin-like) required an assessment of the risk of dissemination and additional immunization activities. Among 580 identified isolates of NPEV, the most abundant was the E. betacoxsakie species at 73.8% (CVB1–6, E11, E6, E13, E7). Information on NPEVs expands our knowledge of the spectrum of NPEVs circulating among healthy children worldwide, but its prognostic significance is still unclear. The detection of PVs in children from the “risk group” allows targeted anti-epidemic measures and is a significant advantage of this type of supplementary surveillance for polio. Full article

Feline panleukopenia (FPL), caused by the feline panleukopenia virus (FPLV), is a severe and highly contagious viral disease with high morbidity and mortality. Vaccination remains the gold standard for preventing and controlling this debilitating condition. The viral protein VP2 serves as the major immunogen of FPLV and represents the key target antigen in the development of a novel FPLV vaccine. Virus-like particle (VLP)-based vaccines have emerged as next-generation vaccine candidates due to their high immunogenicity and safe profile. In this study, a baculovirus expression vector system (BEVS) was employed to generate FPLV-VLPs through recombinant expression of the VP2 protein of a Chinese epidemic strain (Ala91Ser, Ile101Thr) of FPLV. The resulting FPLV-VLPs demonstrated markedly enhanced antigenicity and hemagglutination activity, achieving a hemagglutination titer of up to 1:2¹⁶. Following vaccination, immunized cats developed high titers of anti-FPLV hemagglutination inhibition (HI) antibodies (1:2¹⁶) and exhibited 100% protection against challenge with a virulent epidemic FPLV variant (Ala91Ser, Ile101Thr). These findings demonstrate that FPLV-VLPs hold strong potential as candidates for a novel subunit vaccine against FPLV infection. Full article

Melanoma is one of the deathliest cancers worldwide and its incidence is reaching epidemic proportions. It is characterized by intrinsic chemo-resistance, low response rates to treatment and high metastatic potential. Because of this, new therapeutic options are permanently required. Tessaria absinthioides (Hook. & Arn.) DC. is a traditional medicinal plant, with antioxidant, selective cytotoxicity and anti-colorectal cancer evidence-based properties. This study aims to demonstrate the antitumoral and antimetastatic effects of T. absinthioides decoction (DETa), correlating in vitro and in vivo activities in a murine melanoma model. DETa was assayed on B16F0 murine non-metastatic cells to determine cytotoxicity and clonogenicity; while, in the B16F10 metastatic siblings, adhesion, wound healing migration and Boyden chamber invasion were studied. The ex vivo intestinal-sac model was used to quantify DETa bioavailability. Meanwhile, in C57BL6/wt mice, DETa was orally administered to evaluate its antitumoral and antimetastatic activities. DETa induced cytotoxicity in a dose- and time-dependent manner, affecting the long-term clonogenic survival, as well as the processes of adhesion and migration. Then, the intestinal absorption of DETa phenolics was proven, while the systemic anti-tumoral and anti-metastatic activities of DETa were confirmed. Results demonstrated that DETa has antimelanoma activity promoting this botanical compound as a relevant agent for cancer research and treatment. Full article

Obesity is a metabolic condition of epidemic scale. Previously, we showed that antioxidant extracts from Ribes nigrum had antioxidant and anti-adipogenic effects in mature adipocytes (AD). Here, we evaluated an aqueous extract from Peumus boldus (Boldo) in AD and studied its effect on reactive oxygen species (ROS) and lipid production. We analyzed the antioxidant activity (AA) of the Boldo extract using the DPPH technique and polyphenol (Pph) content via Folin’s reagent. In AD, we evaluated ROS production, catalase (CAT) activity, intracellular triglyceride (Tg) and cholesterol (Chol) contents, nitric oxide (NO) production via Griess reagent, and the levels of glycerol (Gly) and TNF-α released in the culture medium. We showed that the Boldo extract has high AA. In vitro, Boldo treatment decreased ROS intracellular production and CAT activity. In addition, the Boldo extract was effective in reducing Tg and Chol levels and NO production. We did not identify significant differences in Gly released or TNF-α secreted. We suggest that the Boldo extract has antioxidant and anti-adipogenic effects, but we did not observe lipolytic effects. Boldo did not modify inflammatory markers. Full article

Seasonal influenza epidemics caused by influenza A viruses (IAV) and influenza B viruses (IBV) pose a substantial public health burden. Despite the significant impact of IBV, its restricted host range and the absence of documented pandemics have resulted in limited research attention relative to IAV. Understanding the viral infection mechanisms of both IAV and IBV is crucial for controlling seasonal epidemics. Previously, we demonstrated that 3′-O-sulfated galactosylceramide sulfatide binds to IAV and enhances viral replication, a finding with potential therapeutic implications. However, the role sulfatide plays in other influenza virus infections, including those caused by IBV, remains unknown. Accordingly, in this paper, we investigate the function of sulfatide during IBV infection. We demonstrate that sulfatide binds to IBV hemagglutinin (HA), and that sulfatide overexpression significantly enhances IBV replication, whereas treatment with sulfatase or an anti-sulfatide antibody markedly suppressed IBV replication. Moreover, further tests involving the inhibition of sulfatide biosynthesis resulted in the suppression of viral replication with impaired nuclear export of viral ribonucleoproteins (vRNPs). These findings establish that sulfatide is a critical regulator of IBV replication, which parallels its role in IAV infection, and suggest that targeting sulfatide-virus interactions can lead to broad-spectrum therapeutic strategies against influenza virus. Full article

(1) Background: Overconsumption of processed meats, fats, and carbohydrates drives the obesity epidemic in the USA. Associated with this epidemic are increases in metabolic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. In this study, protein levels of adipocytokines isolated from visceral fat in mice fed high-fat diets with proteins modified through ammonium supplementation were analyzed to determine changes that occur as a result of dietary protein source and its modification based on age or sex. (2) Methods: Male and female C3H/HeJ mice were randomized into six customized diets—Group 1: CCN = Control Chow (CC) + Ammonium Hydroxide Enhancement (AHE); Group 2: CC = Control Chow; Group 3: HFBN = High Fat (HF) AHE Dietary Beef; Group 4: HFB = HF Beef; Group 5: HFCN = HF AHE Dietary Casein; Group 6: HFC = HF Dietary Casein. Mice were censored at six-month intervals, and visceral fat was collected for analysis. This study highlights sex- and age-related changes in cellular adipocytokine protein expression from 12 to 18 months. (3) Results: When compared to dietary casein, dietary-beef-fed mice showed increased expression of adiponectin, leptin, and MCP-1. In dietary casein protein diets, high fat content was correlated with the expression of pro-inflammatory adipocytokines leptin, MCP-1, resistin, VEGF-A, and TIMP-1. Sex-related differences were observed in adiponectin, leptin, and MCP-1 expression levels. AHE of dietary protein decreased the expression of adiponectin, leptin, MCP-1, and TIMP-1. Age-related changes in expression were observed in leptin, MCP-1, and VEGF-A. (4) Conclusions: Our results indicate that the source of dietary protein plays a critical role in determining adipocytokine expression in WAT. Furthermore, this study shows that in addition to dietary protein type (beef or casein), AHE and fat content also impact the relative expression of both pro-inflammatory and anti-inflammatory adipocytokines based on sex over time, with leptin and MCP-1 identified as the most frequently affected. Full article