Search Results (888)

Background: Mixed infections can worsen disease symptoms. This study investigated the impact of mixed infections with viral and bacterial pathogens in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Using the in-house multiplex PCR method, we tested 337 SARS-CoV-2 positive samples for co-infections with three bacterial and 14 other viral pathogens. Results: Between August 2021 and May 2022, 8% of 337 SARS-CoV-2-positive patients had bacterial co-infections, 5.6% had viral co-infections, and 1.4% had triple mixed infections. The most common causes of mixed infections were Haemophilus influenzae (5.93%) and respiratory syncytial virus (RSV) (1.18%). Children < 5 years old had more frequent co-infections than adults < 65 years old (20.8% vs. 16.4%), while adults showed a more severe clinical picture with a higher C-reactive protein (CRP) level (78.1 vs.16.2 mg/L; p = 0.033), a lower oxygen saturation (SpO2) (89.5 vs. 93.2%), and a longer hospital stay (8.1 vs. 3.1 days; p = 0.025) (mean levels). The risk of a fatal outcome was 41% in unvaccinated patients (p = 0.713), which increased by 2.66% with co-infection with two pathogens (p = 0.342) and by 26% with three pathogens (p = 0.005). Additionally, 50% of intensive care unit (ICU) patients had a triple infection, compared with only 1.3% in the inpatient unit (p = 0.0029). The risk of death and/or ICU admission was 12 times higher (p = 0.042) with an additional pathogen and increased by 95% (p = 0.003) with a third concomitant pathogen. Conclusions: Regular multiplex testing is important for prompt treatment and targeted antibiotic use. Full article

Lung cancer is among the most clinically challenging tumors because of its aggressive proliferation, metastasis, and the presence of cancer stem cells (CSCs). Natural bioactive substances have been used for cancer prevention, and, in particular, resveratrol (RSV), a stilbene-based compound with wide biological properties, has been proposed for chemoprevention. Its lesser-known analogue 4,4’-dihydroxy-trans-stilbene (DHS) has demonstrated superior activity both in cell-based assays and in mouse and zebrafish in vivo models. The present study analyzed the effects of DHS and RSV on A549 lung cancer cells, with a particular focus on stemness features and CSCs, isolated by sorting of the side population (SP). The results show that both stilbenes, especially DHS, strongly inhibited cell cycle progression. A reduction in the S phase was induced by DHS, whereas an increase in this phase was obtained with RSV. In addition, 50% reductions in the clonogenicity and soft agar colony formation were observed with the DHS treatment only. Finally, both stilbenes, especially DHS, reduced stemness marker expression in A549 cells and their sorted SP fraction. Spheroid formation, higher in SP cells than in the main population (MP), was significantly reduced after pretreatment with DHS, which was found to decrease SOX2 levels more than RSV. These findings indicate that stilbenes, and particularly DHS, affect stemness features of A549 cells and the SP fraction, suggesting their potential utility as anticancer agents, either alone or combined with chemotherapeutic drugs. Full article

Background: Colorectal cancer is one of the leading and most lethal neoplasms. Standard chemotherapy is ineffective, especially in metastatic cancer, and does not target cancer stem cells. A promising approach to improve cancer treatment is the combination therapy of standard cytostatic drugs with natural compounds. Several plant-derived compounds have been proven to possess anticancer properties, including the induction of apoptosis and inhibition of cancer invasion. This study was focused on investigating in vitro the combination of camptothecin (CPT) with celastrol (CEL) or resveratrol (RSV) as a potential strategy to target metastatic (LOVO) and stem-like (LOVO/DX) colon cancer cells. Methods: The genotoxic effects that drive cancer cells into death-inducing pathways and the ability to inhibit the migratory properties of cancer cells were evaluated. The γH2AX+ assay and Fast-Halo Assay (FHA) were used to evaluate genotoxic effects, the annexin-V apoptosis assay to rate the level of apoptosis, and the scratch test to assess antimigratory capacity. Results: The results showed that both combinations CPT-CEL and CPT-RSV improve general genotoxicity of CPT alone on metastatic cells and CSCs. However, the assessment of specific double-stranded breaks (DSBs) indicated a better efficacy of the CPT-CEL combination on LOVO cells and CPT-RSV in LOVO/DX cells. Interestingly, the combinations CPT-CEL and CPT-RSV did not improve the pro-apoptotic effect of CPT alone, with both LOVO and LOVO/DX cells suggesting activation of different cell death mechanisms. Furthermore, it was found that the combinations of CPT-CEL and CPT-RSV improve the inhibitory effect of camptothecin on cell migration. Conclusions: These findings suggest the potential utility of combining camptothecin with celastrol or resveratrol in the treatment of colon cancer, including more aggressive forms of the disease. So far, no studies evaluating the effects of combinations of these compounds have been published in the available medical databases. Full article

Background: In-home palivizumab administration programs (PH) have shown promise in reducing RSV-associated infections. These programs may be particularly beneficial for children with medical complexity (CMC) by limiting their exposure to healthcare-associated infections (HAIs) from non-RSV-related pathogens during transportation and visits to medical facilities. Methods: In this prospective study, 41 children with CMC less than 2 years of age were randomized by their health insurance to receive PH or in the clinic (PC) during the RSV season (October 2018–April 2019). Patients were stratified by home ventilation. The primary outcome was the total number of face-to-face encounters. Secondary outcomes were unscheduled clinic visits and hospitalizations secondary to the non-RSV LRTIs. Standard frequentist and Bayesian analyses were performed. Results: All demographic factors and strata were matched between PH (“n” = 13, mean age 22 mo. SD ± 1), and PC (“n” = 28, mean age: 18 mo. SD ± 1). There was a decrease in the number of total face-to-face encounters (adjusted for mechanical ventilation and baseline diagnosis) [(4.5 vs. 8.8), (RR: 1.8, 95% CI: 1.3–2.5, p = 0.001)], and hospitalizations [(0.3 vs. 1.25), (RR: 3.8, 95% CI: 1.3–11.3, p = 0.016)], in the PH vs PC groups. Bayesian analysis showed a 93% probability of benefit in favor of fewer face-to-face encounters in the PH group. Conclusions: This study suggests that PH administration may reduce healthcare utilization in CMC. Minimizing exposure to healthcare facilities and supporting home-based interventions are promising strategies for this population. Full article

Viral respiratory diseases place a heavy burden on the healthcare system, with children making up a significant portion of related hospitalizations. While comorbidities increase the risk of complications and poor outcomes, many hospitalized children lack clear risk factors. As new vaccines for respiratory viral diseases emerge, this study examined pediatric respiratory hospitalizations, focusing on viral etiology, complication rates, and the impact of comorbidities to guide future policy. Data were analyzed from eight pre-COVID influenza seasons (2011/2012–2018/2019) involving patients under 18 years hospitalized with respiratory complaints across 4–10 hospitals in Valencia, Spain. Respiratory specimens were tested for eight viral targets using multiplex real-time reverse-transcription polymerase chain reaction. Demographics, clinical outcomes, discharge diagnoses, and laboratory results were examined. Among the hospitalized children, 26% had at least one comorbidity. These children had higher rates of pneumonia, asthma exacerbation, and pneumothorax, and were twice as likely to require ICU admission, though mechanical ventilation and length of stay were similar to those without comorbidities. Respiratory syncytial virus (RSV) was the most common virus detected (23.1%), followed by rhinovirus/enterovirus (9.5%) and influenza (7.2%). Viral codetection decreased with age, occurring in 4.6% of cases. Comorbidities increase the risk of complications in pediatric respiratory illnesses, however, healthcare utilization is driven largely by otherwise healthy children. Pediatric viral vaccines could reduce this burden and should be further evaluated. Full article

Respiratory diseases (RDs) constitute a common public health problem both in industrialized and developing countries. The comprehension of the pathophysiological mechanisms underlying these conditions and the development of new therapeutic strategies are critical for improving the quality of life of affected patients. β2-adrenergic receptor (β2AR) and transient receptor potential vanilloid 1 (TRPV1) are both involved in physiological responses in the airways. β2AR is implicated in bronchodilation, mucociliary clearance, and anti-inflammatory effects, while TRPV1 is involved in the mediation of pain and cough reflexes. In RDs, such as respiratory infections, asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, the concentration and expression of these receptors can be altered, leading to significant consequences. In this review, we provided an update on the literature about the role of β2AR and TRPV1 in these conditions. We reported how the diminished or defective expression of β2AR during viral infections or prolonged therapy with β2-agonists can increase the severity of these pathologies and impact the prognosis. Conversely, the role of TRPV1 was pivotal in neuroinflammation, and its modulation could lead to innovative treatment strategies in specific patients. We indicate future perspectives and potential personalized treatments in RDs through a comprehensive analysis of the roles of these receptors in the physiological and pathological mechanisms of these pathologies. Full article

Circular RNAs (circRNAs) are a class of circular non-coding RNAs that play essential roles in the intricate and dynamic networks governing cell growth, development, and apoptosis. Resveratrol (RSV), a non-flavonoid polyphenol, is known to participate in follicular development and ovulation. In our previous research, we established a model using porcine ovarian granulosa cells (POGCs) treated with resveratrol, which confirmed its regulatory effects on long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) within these cells. However, the influence of resveratrol on circRNA expression has not been thoroughly investigated. To explore how resveratrol affects circRNA levels in POGCs, we designed an experiment with three groups: a control group (CON, n = 3, 0 μM RSV), a low-dose RSV group (LOW, n = 3, 50 μM RSV), and a high-dose RSV group (HIGH, n = 3, 100 μM RSV) for circRNA sequencing. We identified a total of 10,045 candidate circRNAs from POGCs treated with different concentrations of resveratrol (0, 50, and 100 μM). Differential expression analysis indicated that 96 circRNAs were significantly altered in the LOW vs. CON group, while 109 circRNAs showed significant changes in the HIGH vs. CON group. These circRNAs were notably enriched in biological processes associated with cell metabolism, apoptosis, and oxidative stress. Functional enrichment analysis of the host genes revealed their involvement in critical signaling pathways, including mTOR, AMPK, and apoptosis pathways. Additionally, we identified potential miRNA sponge candidates among the differentially expressed circRNAs, particularly novel_circ_0012954 and novel_circ_0004762, which exhibited strong connectivity within miRNA-target networks. Our findings provide valuable insights into the regulatory mechanisms of circRNAs in the context of resveratrol-induced apoptosis in POGCs, highlighting their potential as innovative therapeutic targets in reproductive biology. Full article

Respiratory infections with respiratory syncytial virus (RSV) account for an important part of hospital admissions for acute respiratory infections. Nirsevimab has been developed to reduce the hospital burden of RSV infections. Compared with the product previously used, it has a stronger binding capacity to RSV F protein and a high affinity for FcRn (neonatal receptor for the Fc fragment of IgG), which extends its lifespan. Nirsevimab has been shown to be highly effective in reducing hospitalization rates of RSV infections but a large or unknown number of treated subjects have been excluded in clinical and post-marketing studies. However, analysis of these studies cannot exclude that, in rare cases, nirsevimab facilitates and worsens RSV infection (or other respiratory infections). This could be attributable to antibody-dependent enhancement (ADE) which has been observed with RSV F protein antibodies in inactivated vaccine trials. This risk has been incompletely assessed in pre-clinical and clinical trials (incomplete exploration of nirsevimab effector functions and pharmacokinetics). ADE by disruption of the immune system (not studied and due to FcRn binding) could explain why there is no reduction in all-cause hospital admissions in treated age groups. Given the high price of nirsevimab, the cost-effectiveness of mass immunization campaigns may therefore be debated from an economic as well as a scientific point of view. Full article

Background: After the removal of the three-year epidemic control restrictions, Chinese children were confronted with heightened risks of respiratory infections. We aimed to investigate the post-pandemic (2023) epidemiology of respiratory infections among pediatric inpatients in a tertiary hospital in Shanghai, China, and compare it with the pre-pandemic (2019) levels. Methods: A total of 2644 pediatric inpatients were enrolled based on discharge time and divided into group 2019 (n = 1442) and group 2023 (n = 1202). Information on the demographic characteristics, diagnoses, and pathogen test results (Mycoplasma pneumoniae, MP; Chlamydia pneumoniae, CP; Legionella pneumophila, LP; Influenza A, IFA; Influenza B, IFB; Parainfluenza virus, PIV; respiratory syncytial virus, RSV; Coxsackie virus, COX; Adenovirus, ADV; Epstein–Barr virus, EBV) was collected and analyzed. Results: Significant increases were found in the overall test positivity rates (64.6% vs. 46.7%), mixed infection rates (17.4% vs. 9%), and proportion of severe cases (25.5% vs. 3.7%) after the pandemic than those before it. Compared with 2019, the incidences of MP, IFA, LP, RSV, and ADV remarkably increased, while those of IFB and COX decreased, with no obvious differences noted for CP, PIV, and EBV in 2023. A significantly higher MP-positive detection rate was noticed in children aged 1–6 years in 2023 than in 2019. The incidence of RSV infection began to rise in August 2023, earlier than the conventional epidemic season. Conclusions: Compared with the pre-pandemic levels, the overall test positivity rates of atypical pathogens and viruses among pediatric inpatients significantly increased, and alterations in the disease spectrum, epidemic season, and age of prevalence were observed after the COVID-19 pandemic. Full article

Respiratory Syncytial Virus (RSV) is responsible for a considerable burden of respiratory disease among children and older adults. Several prophylactic strategies have recently been introduced. We review the available evidence on the interplay between RSV infection and HIV, looking at the specific role of RSV prophylactic strategies in individuals affected by or exposed to HIV. We conducted a systematic review on the association between HIV infection and RSV incidence and severity. We searched in PubMed/MEDLINE for clinical epidemiological studies covering outcomes such as RSV-associated illness, severity, and mortality in individuals affected by or exposed to HIV. A total of 36 studies met the inclusion criteria and were included, the majority conducted in sub-Saharan Africa. There was no compelling evidence suggesting a higher incidence of RSV illness among HIV-infected people. A higher risk of severe disease was consistent among both HIV-positive and HIV-exposed but uninfected (HEU) children. Case fatality rates were also higher for these groups. Evidence on a differing risk among adults was scarce. HIV-positive pregnant women should be given priority for recently approved RSV vaccination, for protection of their newborns. HIV-infected and HEU infants should be considered risk groups for nirsevimab prophylaxis in their first year of life and possibly beyond. Full article

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such as infants under two years old, the elderly, and immunocompromised individuals. Although newly approved vaccines and treatments have substantially reduced RSV hospitalizations, accessibility remains limited, and response to treatment varies. This underscores the importance of comprehensive studies on host–RSV interactions. tRNA-derived RNA fragments (tRFs) are recently discovered non-coding RNAs, notable for their regulatory roles in diseases, including viral infections. Our prior work demonstrated that RSV infection induces tRFs, primarily derived from the 5′-end of a limited subset of tRNAs (tRF5), to promote RSV replication by partially targeting the mRNA of antiviral genes. This study found that tRFs could also use their bound proteins to regulate replication. Our proteomics data identified that PABPC1 (poly(A)-binding protein cytoplasmic 1) is associated with tRF5-GluCTC, an RSV-induced tRF. Western blot experimentally confirmed the presence of PABPC1 in the tRF5-GluCTC complex. In addition, tRF5-GluCTC is in the anti-PABPC1-precipitated immune complex. This study also discovered that suppressing PABPC1 with its specific siRNA increased RSV (-) genome copies without impacting viral gene transcription, but led to less infectious progeny viruses, suggesting the importance of PABPC1 in virus assembly, which was supported by its interaction with the RSV matrix protein. Additionally, PABPC1 knockdown decreased the production of the cytokines MIP-1α, MIP-1β, MCP-1, and TNF-α. This is the first observation suggesting that tRFs may regulate viral infection via their bound proteins. Full article

Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and older adults. This virus is responsible for one-third of pneumonia deaths in the pediatric population; however, there are currently only a few effective vaccines. A better understanding of the RSV–host relationship at the molecular level may lead to a more effective management of RSV-related symptoms. The fractalkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and diverse immune cells. RSV G protein binds to the CX3CR1 receptor via a highly conserved amino acid motif (CX3C motif), which is also present in CX3CL1. The CX3CL1-CX3CR1 axis is involved in the activation and infiltration of immune cells into the infected lung. The presence of the RSV G protein alters the natural functions of the CX3CR1-CX3CL1 axis and modifies the host’s immune response, an aspects that need to be considered in the development of an efficient vaccine and specific pharmacological treatment. Full article

Background/Objectives: Despite being the leading cause of acute lower respiratory tract infections in infants, the impact of respiratory syncytial virus (RSV) on the caregivers of infected children remains largely unexplored. This study is the first in Japan to examine the psychological, social, and economic burdens on caregivers of infants infected with RSV. Methods: An online questionnaire survey was used to understand the circumstances surrounding RSV infection and the psychological, social, and economic burdens on caregivers. Equal numbers of infants aged either <6 or ≥6 months were enrolled. Results: A total of 606 caregivers were included in the final analysis. Notably, 36.1% of the infants were hospitalized. Most caregivers (91.4%) felt anxious about their infants’ RSV infection, and more than half (55.8%) answered that their anxiety interfered with their daily lives. Caregivers whose daily routines were disrupted due to concerns about RSV infection were more likely to hospitalize infants, particularly for extended stays. Infection significantly affected family dynamics, hindering normal daily activities and escalating stress, which in turn led to conflicts and arguments among family members (30.4%). Regarding the financial burden, most caregivers incurred medical expenses (34.2%). Additionally, 76.9% of caregivers expressed interest in the hypothetical RSV vaccination. Conclusions: In Japan, caregivers of infants with RSV experience had significant psychological burden regardless of whether the treatment is outpatient or inpatient. In addition, a non-negligible proportion of caregivers suffer from societal and economic burdens. This study lays the groundwork for all stakeholders to fully comprehend the comprehensive disease burden of child RSV infections. Full article

Traditional approaches employing natural plant products to treat a wide array of ailments have been documented and described for thousands of years. However, there remains limited scientific study of the therapeutic potential or effectiveness of ethnobotanical applications. Increases in the incidence of cancer and emerging infectious diseases demonstrate a growing need for advances in the development of therapeutic options. In this study, we evaluate the therapeutic potential of aqueous extracts prepared from four plants, purple aster (Symphyotrichum novae-angliae (L.) Nemsom), common sage (Salvia lyrata (L.)), northern spicebush (Lindera benzoin (L.) Blume), and lamb’s ear (Stachys byzantina (K.) Koch)) traditionally used in Native American medicine in Indiana, USA. Using a combination of cytotoxicity assays, immunofluorescence microscopy, and antiviral assays, we found that sage and spicebush extracts exhibit cytotoxic and antiproliferative effects on HeLa cell proliferation and that sage, spicebush, and aster extracts were capable of significantly inhibiting human respiratory syncytial virus (hRSV), a major respiratory pathogen of infants and the elderly. Chemical analysis of the four extracts identified four major compounds which were subsequently evaluated to identify the responsible constituents in the extracts. While none of the identified compounds were shown to induce significant impacts on HeLa cell proliferation, two of the compounds, (1S)-(-)-Borneol and 5-(hydroxymethyl)-furfural, identified in sage and spicebush, respectively, were shown to have antiviral activities. Our data suggest that several of the extracts tested exhibited either anti-proliferative or antiviral activity supporting future further analysis. Full article

Background: Respiratory syncytial virus (RSV) is a significant cause of illness in adults, especially older adults and those with underlying conditions. This study aimed to assess the incidence of RSV hospitalizations in adults and identify risk factors for hospitalization and poor outcomes. Methods: A retrospective cohort study was conducted using data from two hospitals in southern Israel from 2016–2022. We calculated incidence rates of RSV and influenza hospitalizations. Risk factors for hospitalization were analyzed using Poisson regression. We evaluated poor outcomes (death, ICU admission, or mechanical ventilation) among RSV-hospitalized patients. Results: The median annual incidence of RSV hospitalization was 28.2/100,000 population, increasing with age to 199/100,000 in those ≥75 years. Significant risk factors for RSV hospitalization included pulmonary diseases (RR 4.2, 95% CI 3.4–5.2), cardiovascular diseases (RR 3.3, 95% CI 2.6–4.2), and chronic renal failure (RR 2.9, 95% CI 2.3–3.7). Among hospitalized RSV patients, 13.9% had poor outcomes. Renal failure (RR 1.81, 95% CI 1.23–2.66), neutropenia (RR 2.53, 95% CI 1.19–5.35), neutrophilia (RR 1.66, 95% CI 1.81–2.34), and lymphopenia (RR 2.03, 95% CI 1.37–3.0) were associated with poor outcomes. Conclusions: RSV causes a substantial burden of hospitalizations in adults, particularly among older adults and those with comorbidities. Identifying high-risk groups can help target prevention and treatment strategies, including vaccination. Full article