Search Results (82)

With new emerging diseases such as COVID-19 and an increasing incidence of cancer, there remains a significant need for investigating new therapeutic options to treat a wide range of ailments and disorders. Peppermint (Mentha × piperita) and white snakeroot (Ageratina altissima) have been used medicinally by native people in the Midwestern United States for centuries. However, the antiproliferative and antimicrobial properties of the aqueous extracts of these plants remain unclear. In this study, we evaluate the therapeutic potential of peppermint and white snakeroot aqueous leaf extracts by examining their activity against mammalian cancer cells, bacteria, and viruses. Both peppermint and snakeroot extracts showed no reductions in viability at concentrations lower than 25 mg/mL and 10 mg/mL, respectively, in two different cancer lines, HEp-2 and DBT-9 cells, in vitro. While treatment with the snakeroot extract resulted in significant disruption to cytoskeletal organization in HEp-2 cells at a concentration of 10 mg/mL, peppermint and snakeroot extracts did not have a major impact on the viability or proliferation of the cancer cell lines tested. Peppermint and snakeroot were then evaluated for antibacterial activity against four different bacterial pathogens. Significant inhibition of bacterial replication was observed for E. coli (at concentrations greater than 0.1 mg/mL) and S. aureus (at concentrations greater than 1 mg/mL) treated with either peppermint or snakeroot extracts. No significant activity was observed against the bacterial strains P. aeruginosa and S. pyogenes. Peppermint (EC₅₀ = 2.36 mg/mL) and snakeroot (EC₅₀ = 2.64 mg/mL) significantly reduce infectivity and replication (at concentrations above 0.2 mg/mL) of the major human pathogen, human respiratory syncytial virus (hRSV). However, testing for antiviral activity against a mouse coronavirus (murine hepatitis virus, MHV) showed no impact on replication at concentrations up to 2.5 mg/mL. Lastly, chemical analysis of the extracts identified several prominent compounds, which were subsequently evaluated for their biological contributions to the observed plant extract phenotypes. Two of the identified compounds, 1,8-cineole (Eucalyptol) and menthol, show significant antimicrobial activity. We report that aqueous extracts of peppermint and white snakeroot exhibit specific antibacterial and antiviral activities that support further investigation for therapeutic potential. Full article

Human respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract infections in infants and immunocompromised populations, causing approximately 160,000 annual deaths globally. Despite recent approvals of prefusion F (pre-F) protein-based vaccines (Arexvy, Abrysvo) for older adults and pregnant women, pediatric vaccine development faces unique challenges including enhanced respiratory disease (ERD) risks, maternal antibody interference, and immature infant immune responses. Meanwhile, G protein glycosylation variability and NS1/NS2-mediated interferon suppression remain the outstanding difficulties in structure-based vaccine design. Additionally, current animal models demonstrate notable constraints in virus replication, host susceptibility, immune responses, clinical symptoms, and ERD phenomena. This review synthesizes current obstacles and innovative strategies, highlighting that the selection of multi-antigen strategies, appropriate adjuvants, and the development of more precise preclinical animal models are critical elements that will determine the efficacy and safety of future RSV vaccines. Full article

Background/Objectives: Human Respiratory Syncytial Virus (HRSV) is a major global cause of acute lower respiratory infections in children. With recent approval of pre-fusion F protein-based vaccines and monoclonal antibodies, ongoing molecular surveillance is critical. This study examined HRSV molecular epidemiology and evolution in Riyadh, focusing on mutations in the attachment (G) and fusion (F) glycoproteins and their potential impact on vaccine efficacy. Methods: Nasopharyngeal aspirates (NPAs) (200 samples) were collected from pediatric patients. HRSV-positive samples were typed, and the G gene hypervariable region and F gene were sequenced. Sequence and phylogenetic analyses were performed to identify circulating genotypes and amino acid substitutions. Results: HRSV was detected in 15% of samples, with HRSV-B slightly predominant over HRSV-A. Infants aged 2–5 months had the highest incidence rate of infection. The ON1 subgenotype remained dominant. The duplicated region of the G gene showed constrained evolution, with 18 variable and 6 conserved residues over 13 years. In the F protein, HRSV-A isolates exhibited high conservation, with only three amino acid substitutions in antigenic sites (Ø and II). Sites III, IV, and V remained fully conserved. In contrast, HRSV-B isolates displayed eight substitutions in antigenic sites, including six in site II (palivizumab-binding epitope). Conclusions: Given the highly effective HRSV prophylactics, including the approved vaccines and monoclonal antibodies, these mutations raise critical concerns regarding vaccine efficacy against HRSV-B. These findings underscore the necessity of sustained, seasonal molecular surveillance to monitor the emergence of variants and provide a molecular basis for further clinical studies. Full article

The 14-3-3 protein family, which includes the isoforms η, γ, ε, θ, β, and ζ, is essential for controlling a number of pathways linked to DNA and RNA viruses, including HIV, influenza A virus (IAV), measles virus, HRSV, and double-stranded DNA viruses. TRIM32, an E3 ubiquitin ligase, has been reported to target IAV’s PB1 polymerase for species-specific degradation via ubiquitination. Notably, 14-3-3η binds to phosphorylated TRIM32, preventing its autoubiquitylation and forming soluble but inactive cytoplasmic aggregates that regulate TRIM32 levels. However, the functional link between 14-3-3η, TRIM32, and PB1 during viral infection remains unclear. In this study, we establish a mechanistic connection between 14-3-3η–TRIM32 and TRIM32–PB1 interactions in IAV (H1N1) infection. We demonstrate that 14-3-3η directly interacts with PB1, influencing viral replication. Using transient knockdown models, we show that 14-3-3η deficiency alters influenza virus-induced cytotoxicity, cell death, immune responses, and reactive oxygen species (ROS) production. Additionally, we observe a significant reduction in the soluble TRIM32 levels in 14-3-3η-deficient cells, which leads to increased PB1 accumulation and thus suggests a critical regulatory role for 14-3-3η in PB1 stability. Our findings reveal a novel function of 14-3-3η in influenza virus infection, demonstrating its role in PB1 regulation via TRIM32 and its impact on innate immune activation. This study highlights 14-3-3η as a possible target for antiviral treatments against influenza and offers fresh insights into the host–virus relationship. Full article

Background: This study investigated the epidemiology of Mycoplasma pneumoniae (MP) in children with acute respiratory tract infections (ARTIs) and explored the risk factors for severe mycoplasma pneumoniae pneumonia (SMPP) in children. Methods: A retrospective analysis was conducted on 36,380 children with acute respiratory infections who underwent multiplex real-time polymerase chain reaction (RT-PCR) assays for nine respiratory pathogens from September 2021 to November 2024. Results: A total of 36,380 children with ARTIs were enrolled in this study. The co-detection rate of MP with other pathogens was significantly higher in the post-NPIs period than in the NPIs period (36.5% vs. 25.7%, p < 0.01). Multivariate regression identified the detection of influenza A virus (InfA), InfB, human parainfluenza virus (HPIV), human bocaparvovirus (HBoV), human rhinovirus (HRV), adenovirus (ADV), human respiratory syncytial virus (HRSV), and human metapneumovirus (HMPV) as protective factors against MP epidemics (p < 0.01); meanwhile, older age, the cancellation of NPIs, and summer–autumn seasons were found to be risk factors. After adjusting for sex, age, period, season, and pathogens, InfB (OR: 3.009, 95%CI: 1.041–8.697, p = 0.042), HPIV (OR: 2.226, 95%CI: 1.170–4.235, p = 0.015), and ADV (OR: 2.035, 95%CI: 1.105–3.750, p = 0.023) were identified as independent risk factors for SMPP. Conclusions: These findings highlight post-NPI shifts in MP epidemiology and identify ADV, InfB, and HPIV as early warning markers for SMPP. Full article

The increasing prevalence of antibiotic resistance and the limited availability of antiviral therapeutics for pathogens such as human respiratory syncytial virus (hRSV) underscore the need for novel, plant-derived antimicrobial substances. In this study, we evaluated the antiproliferative, antibacterial, and antiviral activities of aqueous leaf extracts from two plants commonly found in North America, Osage orange (M. pomifera) and spearmint (M. spicata). Both extracts exhibited no significant cytotoxic or morphologic impact on HEp-2 human cancer cells up to 25 mg/mL. However, both extracts demonstrated strong dose-dependent antibacterial activity, significantly inhibiting replication of E. coli and S. aureus at concentrations ≥ 1 mg/mL. Antiviral assays revealed that both extracts inhibited hRSV infectivity, with spearmint extract showing higher potency (EC₅₀ = 1.01 mg/mL) compared to Osage orange (EC₅₀ = 3.85 mg/mL). Gas chromatography–mass spectrometry (GC-MS) identified three major extract constituents: 3-hydroxybenzyl alcohol, 4-hydroxybenzyl alcohol (Osage orange), and R-(-)-carvone (spearmint). Among these, only carvone significantly inhibited hRSV in vitro, suggesting its key role in spearmint’s antiviral activity. These findings highlight the therapeutic potential of Osage orange and spearmint leaf extracts, particularly as sources of water-soluble compounds with antimicrobial properties, and support further investigation into their mechanisms of action and broader clinical relevance. Full article

Background/Objectives: Spontaneous intraparenchymal hemorrhage (sIPH) accounts for a significant proportion of strokes and is associated with an estimated 30-day mortality between 35 and 52%. Subsequent hematoma progression (HP) occurs in up to 30% of patients and is associated with blood pressure variability, increasing poor outcomes. This study evaluates systolic blood pressure and heart rate variability in the emergency department (ED) and HP in the first 24 h of admission. Methods: This retrospective study analyzed patients with sIPH presenting to the ED and transferred to a resuscitation unit between 2017 and 2020. Outcomes included the occurrence of HP. Variables included blood pressure variability as measured by the standard deviation in systolic blood pressure (SBP-SD), successive variation of systolic blood pressure (SBP-SV), standard deviation of heart rate (HR-SD), and successive variation of heart rate (HR-SV). Bivariate analysis and machine learning algorithms were used to identify ED predictors for HP. Results: Of the 142 records analyzed, 41 (29%) patients experienced HP. The medians [interquartile (IQR)] for baseline characteristics were similar between groups. In the group with no HP (control), the median [IQR] for SBP-SD was 17.6 [11–26] compared with 20.5 [13.9–26.1, p = 0.25]. The median [IQR] for standard deviation in SBP-SV was 18 [11.4–25.4] for the control group and 19.8 [15.2–27.3, p = 0.19] for the HP group. While bivariate analysis did not show statistical difference for SBP-SD, SBP-SV, HR-SD, or HR-SV, machine learning algorithms identified SBP-SD, HR-SD, and HR-SV as clinically impactful on HP with good accuracy (92.59% and 79.31%). Conclusions: This study suggests that there are factors in hyperacute hemodynamic management in the ED associated with HP among patients with sIPH. Full article

Human respiratory syncytial virus (HRSV) is a highly contagious RNA virus that causes respiratory infections, especially in children. This study evaluated the impact of COVID-19 control measure changes on HRSV infection patterns in Hangzhou by comparing epidemiological and clinical characteristics. We conducted a retrospective analysis of 12,993 pediatric nasopharyngeal swab samples from children with acute respiratory infections at The Children’s Hospital of Zhejiang University School of Medicine. These samples, collected between February 2022 and January 2024, were screened for HRSV and 12 other respiratory pathogens using capillary electrophoresis technology. From February 2022 to January 2023, the HRSV positivity rate was 7.06%. In 2023, it increased to 9.26%. The highest positivity rates were in infants aged 0–6 months and children aged 6 months to 1 year. Coinfections were most common with rhinovirus in 2022 and Mycoplasma pneumoniae in 2023. HRSV positivity rates were low from April to September 2022, peaking in December. In 2023, the peak occurred from April to September. Symptoms ranged from mild to severe pneumonia, with higher hospitalization rates in children with underlying conditions. The study revealed significant changes in HRSV infection rates following pandemic restriction relaxations, emphasizing the need for the early identification and prevention of severe cases. Full article

The results of this study, which involved treating cotton fabrics with three fluorescent hyperbranched polymers modified with 1,8-naphthalamide (P1), acridine (P2), and dansyl (P3) groups, could have applications in the development of antimicrobial textiles with self-disinfecting ability. The polymers, dissolved in DMF/water solution, were deposited on the cotton fabric using the exhaustion method. The fabrics were thoroughly analyzed by reflection spectra, CIEL*a*b* coordinates, and color difference (∆E). The release of the polymers from the cotton surface was studied in a phosphate buffer with pH = 7.4 and an acetate buffer with pH = 4.5 at 37 °C for 10 h. It is shown that at pH = 7.4, the release of the three polymers occurs slowly (about 4–5%). In contrast, in an acidic medium, due to protonation of the tertiary amino group of 1,8-naphthalimide, P1 passes significantly more readily into the aqueous solution (35%). The possibility of singlet oxygen (¹O₂) generation by the polymers and the cotton fabrics treated with them under sunlight irradiation was followed using an iodometric method. The microbiological activity was investigated against Gram-positive Bacillus cereus and Gram-negative Pseudomonas aeruginosa as model bacterial strains in the dark and after irradiation with sunlight. The antimicrobial activity of the polymers increased after light irradiation, as ¹O₂ attacks and destroys the bacterial cell membrane. Scanning electron microscopy showed that a stable bacterial biofilm had formed on the untreated cotton surface, but treatment with hyperbranched polymers prevented its formation. However, many bacteria were still observed on the fiber surface when the microbial test was performed in the dark, whereas only a few single bacteria were noticed after the illumination. A virucidal effect against respiratory viruses HRSV-2 and AAdV-5 was observed only after irradiation with sunlight. Full article

In Cabo Verde, Acute Respiratory Infection caused by various pathogens was the most reported condition in children under 5 years old between 2014–2020, and the fourth leading cause of mortality in this age group, with Human Respiratory Syncytial Virus (HRSV) being one of the main etiological agents. However, limited literature on the subject hinders the study of its epidemiology and the evaluation of potential implications for public health. In this work, we developed and validated a primer collection for the amplification and sequencing of the G and F genes of HRSV, using a sequential workflow including conventional and semi-nested PCR, followed by Sanger sequencing. This strategy not only allowed for the identification of HRSV linages but also facilitated the detection of mutants in the HRSV F protein, a critical step towards evaluating and ensuring the continued efficacy of Nirsevimab or Palivizumab as prophylactic therapies. Our analysis revealed the presence of the HRSV lineages A.D.2.2.1, A.D.3, B.D.4.1.1, and B.D.E.1, corresponding to the globally circulating lineages during the study period (years 2019 and 2022). No previously described mutations in the F protein that confer resistance to Palivizumab and Nirsevimab were found. However, continuous monitoring of HRSV genotypes is crucial to promptly identifying resistant viruses, considering their potential impact on public health. Full article

Human respiratory syncytial virus (HRSV) is a leading cause of severe respiratory infections among children, older adults, and immunocompromised individuals. The COVID-19 pandemic and the non-pharmacological interventions to mitigate it resulted in significant changes in HRSV epidemiology and seasonality patterns. Worldwide, there was a considerable reduction in the number of HRSV infections during that period, and the impact of those changes on genotype distribution is still not fully understood. In this work, we analyzed the genotypic characteristics of HRSV strains detected between 2021 and 2024 in Mexico with the aim of identifying changes in circulating lineages. HRSV positive samples collected in five states in Mexico were used. The complete viral attachment glycoprotein gene was sequenced, and phylogenetic inference was performed using datasets including all sequences available at GenBank and GISAID until 30 June 2024. We obtained 114 HRSV sequences (63.2% HRSV-A and 36.8% HRSV-B); 19 were from the 2021–2022 season, 53 from 2022–2023, and 42 from 2023–2024. All HRSV-A sequences clustered with sequences from other countries within A.D lineages, including A.D.1, A.D.3, A.D.5.1, and A.D.5.2 lineages. All HRSV-B sequences clustered in the B.D.E.1 lineage with sequences collected between 2020 and 2024. In conclusion, the characterization of HRSV viruses circulating in Mexico during and after the SARS-CoV-2 pandemic and comparison to all available sequences reported to date corroborates that, on a global scale, HRSV-A viruses of several A.D lineages circulate simultaneously, while HRSV-B viruses are restricted to the B.D.E.1 lineage. Full article

Pneumonia virus of mice (PVM) infection is a reference animal model for human respiratory syncytial virus (hRSV), a leading cause of lower respiratory tract disease in children under 5 years of age and in the elderly. This longitudinal study employed necropsy to examine macroscopic lesions, histological slides to assess microscopic lesions, and qRT-PCR to measure lung viral load and cytokine expression in PVM-infected mice from three different genetic backgrounds, spanning from day 1 to day 6 post-infection. Our analysis reveals a strong correlation between viral load and microscopic lesions across the 129/Sv, BALB/c, and SJL/J mouse lines, indicating that PVM pathogenicity is partially driven by the virus itself. Additionally, a significant correlation between cytokine levels and lesion severity was observed in 129/Sv and BALB/c mice, suggesting an important role of cytokines in disease progression. This study emphasizes the interplay between viral load and cytokine-driven tissue damage, with genetic background significantly influencing disease outcomes. Full article

In a previous outbreak of the human respiratory syncytial virus (HRSV), we identified a variant strain of genotype BA9 with a seven-amino-acid extension (Q-R-L-Q-S-Y-A) at the C-terminus of the attachment protein (G). To assess the impact of this extension on the virulence of HRSV, two full-length infectious clones using the wild strain of genotype BA9 as a backbone, one containing the seven-amino-acid extension (rRSV BA9 WT), and the other deleting this extension (rRSV BA9 Δ7AA), were successfully rescued using a reverse genetics system. The biological properties and virulence of the two rescued viruses were then compared and analyzed in vitro and in vivo. Compared to the rRSV BA9 Δ7AA, the rRSV BA9 WT exhibited a larger plaque size and a more pronounced suppression of the host cell innate immune response in vitro (IFN-β levels: 154.33 pg/mL vs. 11.27 pg/mL). The rRSV BA9 WT demonstrated increased adaptability in mice, with a 10-fold higher lung viral load and a stronger inflammatory response following intranasal exposure. Our study primarily demonstrated that the C-terminal extension of the G protein of the HRSV can enhance viral virulence, underscoring the importance of virological surveillance in the prevention and treatment of severe HRSV-related disease. Full article

The respiratory syncytial virus (RSV) matrix protein plays key roles in the virus life cycle and is essential for budding, as it stimulates the optimal membrane curvature necessary for the emergence of viral particles. Resveratrol, a polyphenol (3,4′,5-trihydroxy-trans-stilbene) produced by plants, exhibits pharmacological effects, including anti-inflammatory and antiviral activities. In this study, resveratrol was tested in HEp-2 (Epidermoid carcinoma of the larynx cell) cells for its post-infection effects, and recombinant M protein was produced to characterize the biophysical mechanisms underlying this interaction. The CC50 (Cytotoxic concentration 50%) value for resveratrol was determined to be 297 μM over 48 h, and the results from the HEp-2 cell cultures demonstrated a viral inhibition of 42.7% in the presence of resveratrol, with an EC50 (Half maximal effective concentration) of 44.26 μM. This mechanism may occur through interaction with the M protein responsible for the budding of mature viral particles. Biophysical assays enabled us to characterize the interaction of the M/resveratrol complex as an entropically driven bond, guided by hydrophobic interactions at the dimerization interface of the M protein, which is essential for the stabilization and formation of the oligomers necessary for viral budding. These findings suggest that one of the targets for resveratrol binding is the M protein, indicating a potential site for blocking the progression of the infection. Full article

Background: Human respiratory syncytial virus (HRSV) imposes a significant disease burden on infants and the elderly. Intranasal immunization using attenuated live vaccines and certain vector vaccines against HRSV has completed phase II clinical trials with good safety and efficacy.Recombinant protein vaccines for mucosal immunization require potent mucosal adjuvants. Type I interferon (IFN), as a natural mucosal adjuvant, significantly enhances antigen-presenting cell processing and antigen presentation, promoting the production of T and B cells. Methods: This study utilized human α2b interferon (IFN-human) and mouse α2 interferon (IFN-mouse) as nasal mucosal adjuvants in combination with fusion protein (F). Intranasal immunization was performed on BALB/c mice to evaluate the immunogenicity of the formulation in vivo. Results: Compared to the F protein immunization group, mice in the F + IFN-Human and F + IFN-Mouse experimental groups exhibited significantly increased neutralizing antibody titers and augmented secretion of IFN-γ and IL-4 by lymphocytes,  and both of them could induce the production of high-titer specific IgA antibodies in mice (p < 0.001).The F + IFN-Human immunization induced the highest IgG and IgG1 antibody titers in mice; however, the F + IFN-Mouse immunization group elicited the highest neutralizing antibody titers (598), lowest viral loads in the lungs (Ct value of 31), and fastest weight recovery in mice. Moreover, mice in the F + IFN-Mouse immunization group displayed the mildest lung pathological damage (Total score of pathological injury was 2). Conclusions: In conclusion, IFN-Mouse, as a mucosal adjuvant for HRSV recombinant protein vaccines, demonstrated superior protective effects in mice compared to IFN-Human adjuvants. Full article