Search Results (3,159)

A 9-week experiment investigated the effects of dietary cobalt levels on the growth performance, antioxidant capacity, and immunity of largemouth bass. Six feed groups were designed and each group received different cobalt levels, including 0.129 mg/kg (control group), 0.192 mg/kg, 0.201 mg/kg, 0.233 mg/kg, 0.277 mg/kg, and 0.316 mg/kg. The results show that the control group (0.129 mg/kg diet) had the lowest final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR), and the highest feed conversion ratio (FCR), when compared to the cobalt supplementation groups. Dietary cobalt levels of 0.192 mg/kg increased the body protein content and decreased the body moisture content. Regarding antioxidant capacity, the highest catalase (CAT) activity was found in the 0.277 mg/kg dietary cobalt group, while the malondialdehyde (MDA) content was significantly diminished; the total antioxidant capacity (T-AOC) content and glutathione peroxidase (GSH-Px) activity exhibited the highest values in the 0.192 mg/kg and 0.233 mg/kg dietary cobalt groups, respectively. Regarding gene expression, compared with the control group, the mRNA expression of sod was upregulated in the 0.192 mg/kg, 0.233 mg/kg, and 0.277 mg/kg dietary cobalt groups, while the mRNA expression of gpx was diminished when dietary cobalt levels were below 0.233 mg/kg. In addition, the highest il-10 and tgf-β mRNA expression levels were observed in the 0.201 mg/kg and 0.233 mg/kg dietary cobalt groups, respectively. According to the quadratic regression analysis based on the SGR and FCR, the optimal requirement was 0.24 and 0.26 mg/kg of dietary cobalt, respectively. Full article

Nocardia is an emerging bacterial disease that often affects patients with compromised immune systems. As the number of patients undergoing solid organ transplants continues to rise, and as more cancer survivors are treated with long-term immune-modifying agents, corticosteroids, and immunosuppressive medications, organisms that typically pose no harm are becoming a public health concern. Carbapenems are usually a second-line therapy in the setting of Nocardia infections. We present the case of a patient who had an immunocompromised status and was diagnosed with Nocardia farcinica, which showed in vitro resistance to carbapenems. The symptoms were non-specific and had a common presentation with headache, fatigue, and a nonresponsive cough to usual cough drugs, although the infection was disseminated and had severe CNS and ocular involvement. The clinical course worsened when the carbapenem was withdrawn and markedly improved when it was re-administered, although the initial antibiogram showed resistance to carbapenems. Despite the observed in vitro resistance in the laboratory, the re-administration of carbapenems was beneficial, as both inflammatory markers and clinical status showed improvement. This was based on clinical judgment, which carefully evaluated the associated risks and benefits. Also, this raises the question of potential risks to develop real resistance to carbapenems of some Nocardia species, which could pose a significant challenge to healthcare. It could become a serious healthcare problem in the future and should prompt active environmental testing. Full article

In December 2019, the so-called “coronavirus disease 2019” (COVID-19) began. This disease is characterized by heterogeneous clinical manifestations, ranging from an asymptomatic process to life-threatening conditions associated with a “cytokine storm”. This article (narrative review) summarizes the epidemiologic characteristics and clinical manifestations of COVID-19 and multi-system inflammatory syndrome in children (MIS-C). The effect of the pandemic confinement on vitamin D status and the hypotheses proposed to explain the age-related difference in the severity of COVID-19 are discussed. The role of vitamin D as a critical regulator of both innate and adaptive immune responses and the COVID-19 cytokine storm is analyzed. Vitamin D and its links to both COVID-19 (low levels of vitamin D appear to worsen COVID-19 outcomes) and the cytokine storm (anti-inflammatory activity) are detailed. Finally, the efficacy of vitamin D supplementation in COVID-19 is evaluated, but the evidence supporting vitamin D supplementation as an adjuvant treatment for COVID-19 remains uncertain. Full article

COVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a ¹H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH₃)₃ choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19. Full article

Background: There is limited evidence comparing hepatitis A seroprevalence among HIV-exposed uninfected (HEU), HIV-infected (HIV), and unexposed uninfected (HUU) children. This compromises rational vaccine decision-making. Methods: This study comprised a retrospective health facility-based population of children aged 1 month–12 years. Archival sera were tested for markers of acute (anti-HAV IgM) or past (total anti-HAV) HAV infection. Subgroup analysis was conducted based on perinatal HIV exposure or infection status. Results: Among 513 children, the median age was 10 (IQR: 4–25) months. The median maternal age was 29 (IQR: 25–34) years. An anti-HAV seropositivity of 95.1% (117/122 [95% CI 90.2–98.4]) was found among those ≤6 months of age, indicative of the rate of transplacental antibody transfer. Among 1–12-year-olds, hepatitis A seroprevalence was 19.3% (37/192 [95% CI 14.1–25.7]), while 1.1% (2/188 [95% CI 0.12–2.76]) had evidence of acute infection. Compared to HIV-exposed subgroups (HIV = 60%, 6/10 [95% CI 27.4–86.3] and HEU = 45%, 9/20 [95% CI 23.8–68]), hepatitis A seroprevalence among HUU children was low (29.2%, 47/161 [95% CI 22.4–37.0]). Conclusions: Natural immunity among HIV-exposed and unexposed children in South Africa is insufficient to protect against severe liver complications associated with HAV infection later in adulthood. Full article

Purpose: The neutrophil-to-lymphocyte ratio is a simple biomarker that reflects the balance between the systemic inflammatory and immunity status. Here we investigate the prognostic role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in an Asian cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients. Methods: A retrospective review of OPSCC patients from a tertiary institution was conducted. The NLR was calculated from the haematological specimen taken within a month before treatment. Survival rates were estimated via the Kaplan–Meier method, and Cox proportional hazards regression was performed for univariable and multivariable analyses. The NLR cutpoint was determined using maximally selected log-rank statistics. Results: In a cohort of 148 OPSCC patients, 43% were p16-positive and 44% were p16-negative, with a median follow-up of 24 months. The p16-positive patients were younger (median age 62 vs. 67 years) and exhibited a lower prevalence of heavy smoking (47% vs. 69%). The p16-negative cases frequently presented at an advanced disease stage (74% vs. 41%), with a history of previous radiotherapy (26% vs. 3%). The p16-negative patients displayed a higher median NLR (2.91 vs. 2.49). The 3-year disease-specific survival (DSS) in p16-positive was higher compared to p16-negative patients (89.9% vs. 41.6%). The optimal NLR cutpoint was determined as 3.56 and predicted for decreased DSS (hazard ratio [HR] 2.59, p = 0.004). Multivariable analysis revealed smoking, high NLR ≥ 3.56, and p16-negativity as independent variables associated with poorer DSS and overall survival (OS) across the cohort. Conclusion: A high NLR is independently prognostic of poorer DSS in OPSCC, independent of p16 and smoking status. A NLR of more than 3.56 was highly prognostic for poorer survival and warrants further validation in larger cohorts of OPSCC. Full article

Penile carcinomas are rare tumors in Europe and need further investigations due to their inferior prognosis in late tumor stages. The presence of disparate immune cell infiltrates was observed in these tumors, which were subsequently demonstrated to give rise to divergent tumor prognoses. The objective was to further characterize this immune cell infiltrate with the use of immunohistochemistry and RNA expression. A total of twelve well-characterized cases of penile squamous cell carcinomas with known infection status by human papillomavirus (HPV) and p16 status were assessed. The cases were classified according to their morphological characteristics, including those exhibiting a pronounced peritumoral immune cell infiltrate and those with less peritumoral immune cell infiltration. The generation of RNA expression data was conducted using the nCounter^® PanCancer Immune Profiling Panel. Computational models were employed to calculate the proportions of immune cells. To corroborate the findings, an immunohistochemical analysis was conducted using antibodies against CD20, CD3, CD4, CD8, MUM1, CD68, and CD117. Our cases were clustered according to the immune cell infiltrate detected via histology in a group with less immune cell infiltrate density and in a group with increased immune cell infiltrate density. Generally, all immune cells showed an increased amount in the group with pronounced immune cell infiltrate density. The clusters were found to relate to cell functions, the complement system, cytotoxicity, pathogen defense, regulation, and T-cell functions. In cases exhibiting a pronounced immune cell infiltrate, the top three genes that exhibited the greatest upregulation were GZMA, MICB, and GNLY. No relationship to HPV infection status was demonstrated. Immunohistochemistry validated the data gained via RNA expression and showed a correlation with EPIC and Cibersort. The clustering of cases based on immune cell infiltrate density revealed significant distinctions between groups with lower and higher immune cell infiltrate density. The group with increased immune cel infiltrate density showed a greater abundance of immune cells, aligning with key functions like cytotoxicity, pathogen defense, and T-cell regulation. Among these cases, the genes GZMA, MICB, and GNLY were significantly upregulated, suggesting their involvement in an increased immune response. The role of HPV infection status in our cases with regard to the peritumoral immune cell infiltrate remains inconclusive. Full article

Lumpy skin disease (LSD), caused by the LSD virus (LSDV), a dsDNA virus of the genus Capripoxvirus, represents a significant cross-border infectious threat, particularly impacting cattle and water buffaloes through transmission by blood-feeding insects. Traditionally endemic to Southern Africa, LSD has rapidly spread over the past decade through the Middle East to Eastern Europe and China, reaching Korea in October 2023. This outbreak prompted a nationwide vaccination campaign, addressing both the disease’s severe economic impact and its status as a notifiable disease under the World Organisation for Animal Health. This study assesses the seropositivity of the LSD vaccine in cattle across four Korean provinces 2–3 months post-vaccination, aiming to inform improvements in biosecurity and vaccination strategies. Overall, 30.59% of the cattle tested (1196 out of 3910) exhibited positive antibody responses, comparable to international post-vaccination findings. Analysis further revealed differences in the antibody positivity between farm types and management practices. Specifically, farms where vaccines were administered by veterinarians showed no significant difference in antibody positivity between Korean native cattle and dairy cattle, regardless of the presence of restraint facilities. However, on farms where vaccinations were conducted by the owners, dairy cattle demonstrated a higher seropositivity (43.30 ± 33.39%) compared to Korean native cattle (21.97 ± 20.79%) in the absence of restraint facilities. Further comparisons underscored the impact of restraint facilities on vaccination efficacy, with dairy farms generally achieving higher antibody positivity (29.43 ± 30.61%) than farms with Korean native cattle (23.02 ± 23.33%) (p < 0.05), suggesting that consistent vaccine delivery methods enhance immunogenic responses. Contrarily, no significant difference was noted in antibody positivity between large- and small-scale farms, indicating that farm size did not notably impact the effectiveness of the vaccinator. These findings emphasize that while current vaccines are sufficiently inducing immunity, enhancing vaccination strategies, particularly through trained personnel and improved restraint facilities, is crucial. This study’s insights into the impact of vaccination and farm management practices provide valuable guidance for refining LSD control measures in Korea and potentially other affected regions. Full article

Objectives: This study focused on the presence or absence of vascular invasion and extrahepatic metastasis in hepatocellular carcinoma (HCC) and examined their impact on systemic treatment outcomes. Methods: We retrospectively analyzed 362 patients with unresectable HCC who received first-line systemic therapy. The prognostic evaluation was based on the presence of vascular invasion and extrahepatic metastasis at the time of treatment initiation. Results: Patients with vascular invasion or extrahepatic metastasis (advanced group) had significantly worse outcomes than those without these features (intermediate group), with median survival times of 434 and 658 days, respectively. Further subdivision of the advanced group into three categories—patients with only extrahepatic metastasis (m group, n = 77), patients with only vascular invasion (v group, n = 78), and patients with both vascular invasion and extrahepatic metastasis (vm group, n = 52)—revealed that the m group had significantly better outcomes than those in the other two groups, with median survival times of 649, 323, and 187 days, respectively. A comparison of the clinical backgrounds among the three groups demonstrated that the m group had significantly better liver function at the time of treatment initiation than that in the other two groups. Multivariable analysis, including performance status, Child–Pugh score, and the use of immune checkpoint inhibitors as first-line therapy, identified the m group as an independent and significant prognostic factor (hazard ratio, 0.50). Conclusions: Unresectable HCC with extrahepatic metastasis and no vascular invasion represents a novel staging category for systemic treatment. Full article

Background: Immunotherapy is the cornerstone of treatment for many cancers. The effectiveness of immunotherapy in hospitalized patients is unknown due to the exclusion of this fragile population from clinical trials. This study evaluates the efficacy of immunotherapy in fragile hospitalized patients. Method: We conducted a single-center retrospective study involving 49 patients who started an immunotherapy (IO) during a hospitalization or within 3 months after a hospitalization at the Centre Hospitalier de l’Université de Sherbrooke (CHUS). Efficacy analysis included objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Results: Immunotherapy resulted in 30.6% of all grades combined and 18.4% of grade three to four immune-related adverse events (irAE). Efficacy outcomes were inferior in the fragile cohort of patients with ORR of 38.9%, PFS of 2.8 months (95% CI [2.17–3.35]), and OS of 3.2 months (95% CI [1.60–4.84]). Performance status of ECOG three to four compared to ECOG zero predicts poor OS (HR 5.666 [1.207–26.594]; p = 0.028) and PFS (HR 4.136 [0.867–19.733]; p = 0.075). Fitness to receive four to six cycles (HR 0.335 [0.152–0.0.738]; p < 0.007) or more predicts greater OS compared to one to three cycles of immunotherapy. Low levels of serum albumin (HR 0.917 [0.852–0.987]; p = 0.021) and elevated levels of serum LDH (HR 2.224 [1.469–3.367]; p < 0.001) are associated with a reduced OS. Conclusion: The effectiveness of immunotherapy in fragile hospitalized patients is compromised, although they exhibit significant irAE. Excellent performance status, fitness to receive many IO treatments, and normal levels of serum LDH and albumin may be useful in selecting patients who will benefit from immunotherapy. Full article

Background/Objectives: Neutrophils have recently gained significant attention due to their heterogeneity in tumor settings. The gene expression profiles of neutrophils from different tumor types are of great interest. Murine splenic neutrophils reflect the immune status of the organism and could be a source of tumor-associated neutrophils in tumor-bearing mice. However, information about appropriate reference genes for RT-qPCR analysis of murine neutrophils in the literature is lacking. The aim of this study was to identify stably expressed reference genes in murine splenic neutrophils. Methods: Bone marrow- and spleen-derived neutrophils were isolated from healthy C57Bl/6 and CBA/LacSto mice. Spleen-derived neutrophils were isolated from mice with Lewis lung carcinoma (LLC) and drug-resistant lymphosarcoma (RLS₄₀). RNA was isolated and used for RT-qPCR analysis of 10 selected reference genes. Analysis of reference gene stability was performed using four different algorithms (BestKeeper, NormFinder, geNorm, ΔCt method), and comprehensive ranking was constructed using RefFinder. Results: The Ct values for the reference genes were in the range of 16.73–30.83 with the highest expression levels observed for B2m and the lowest for Sdha. Differences in the stability ranking performed by different algorithms were observed; however, the overall ranking of the studied reference genes was as follows, from most to least stably expressed: Tbp, Hprt1, Ywhaz, B2m, Gapdh, Actb, Sdha, Eef2, Rack1, and Rpl13a. Using Tbp or Rpl13a for RT-qPCR data normalization significantly affected the interpretation of target gene expression. Conclusions: Tbp and Hprt1 are recommended reference genes for murine splenic neutrophils regardless of their activation status. Full article

Enhancing or protecting sperm motility has always been a pivotal approach to improving the ewe pregnancy rate. Sperm motility is highly susceptible to the immune status of the reproductive tract. Neutrophil extracellular traps (NETs) have been demonstrated to capture sperm and impair its motility in human, swine, and goat species. Quercetin is a flavonoid derived from Cuscuta Chinensis Lam., which can protect sperm from oxidative damage. In this study, we investigated whether inflammation decreases sperm motility and tried to clarify the potential protective mechanism of quercetin on goat sperm motility. Sperm-triggered NETs were analyzed by immunofluorescence analysis. Sperm acrosome integrity was detected by using giemsa staining. Quercetin exhibited no cytotoxicity towards sperm and PMNs within the concentration range of 20–80 μM. PMNs impaired both the survival rate and rapid linear motility of sperm, while quercetin significantly enhanced these parameters. PMNs captured sperm through NETs composed of DNA, citrullinated histone 3 (citH3), and neutrophil elastase (NE); however, quercetin effectively inhibited the release of sperm-stimulated NETs. The stimulation of PMNs with sperm resulted in a significant increase in levels of ROS and MDA, which decreased by quercetin. Moreover, PMNs caused integrity violation to both the plasma membrane and acrosome in sperm; this effect was significantly alleviated by quercetin. In conclusion, quercetin effectively ameliorated PMN-reduced sperm motility through the inhibition of NETs and oxidative stress, and preserving sperm plasma membrane and acrosome integrity, thereby providing preliminary insights into the underlying mechanisms and theoretical support for the development of potential sperm protectors. Full article

The oral mycobiome plays a critical role in maintaining oral and systemic health, with its composition and function influenced by various physiological and environmental factors. This descriptive review explores the changes in the oral mycobiome among postmenopausal women, examining how aging and associated inflammatory processes contribute to these alterations. These changes are linked to an increased prevalence of xerostomia, oral dysbiosis, and inflammation, which can negatively impact both oral and systemic health. We discuss the impact of hormonal fluctuations and immune senescence on fungal diversity and abundance, highlighting key species implicated in oral and systemic diseases. The review also examines the role of systemic conditions and medications, which are common in postmenopausal women, in further exacerbating oral mycobiome alterations. Lastly, it highlights the need for future research to better understand these interactions and develop targeted therapeutic strategies. The current literature indicates a significant association between menopausal status, age-related mycobiome shifts, and increased inflammatory responses, suggesting potential pathways for intervention. Full article

Background: Autoantibodies against Desmoglein-2 desmosomal protein (anti-DSG2-ab) were identified in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) by Enzyme-Linked ImmunoSorbent Assay (ELISA); anti-intercalated disk autoantibodies (AIDAs) were identified in myocarditis and (ARVC) by indirect immunofluorescence (IFL). We aim to assess: (1) anti-DSG2-ab specificity in ARVC and myocarditis, (2) accuracy of anti-DSG2-ab detection by ELISA versus AIDA by IFL, and (3) clinical correlates of anti-DSG2-ab in ARVC. Methods: We included 77 patients with ARVC, 91 with myocarditis/dilated cardiomyopathy (DCM), 27 with systemic immune-mediated diseases, and 50 controls. Anti-heart antibodies (AHAs) and AIDAs were assessed by IFL, and anti-DSG2-ab by ELISA (assessed both by optical density, OD, and U/L). Receiving operator curve (ROC) analysis was used to assess ELISA diagnostic accuracy. Results: A relevant proportion (56%) of ARVC patients was anti-DSG2-ab-positive, with higher anti-DSG2-ab levels than controls. Anti-DSG2-ab titer was not different between ARVC and myocarditis/DCM patients (48% anti-DSG-ab positive). Frequency of anti-DSG2 positivity by ELISA was higher in AIDA-positive cases by IFL than AIDA-negative cases (p = 0.039 for OD, p = 0.023 for U/L). In ARVC, AIDA-positive patients were more likely to be AHA-positive (p < 0.001), had pre-syncope (p = 0.025), and abnormalities in cardiac rhythm (p = 0.03) than ARVC AIDA-negative patients, while anti-DSG2-ab positivity did not have clinical correlates. Conclusions: Anti-DG2-ab detection in ARVC and myocarditis/DCM reflects immune-mediated pathogenesis to desmosomal proteins. Higher frequency of anti-DSG2-ab positivity by ELISA by U/L was higher in AIDA-positive cases by IFL than AIDA-negative cases, in keeping with the hypothesis that DSG2 is one of AIDA autoantigens. In ARVC, AIDA status but not anti-DSG2-ab showed distinct clinical correlates, possibly reflecting a wider AIDA autoantigenic spectrum. Full article

Background: Older people are more likely to have poor nutrition and low muscle mass, which leads to poor physical performance and anemia, resulting in a poor quality of life and risks to mobility and mortality. Furthermore, malnutrition may, in part, raise the level of inflammatory biomarkers as well as muscle catabolism. Moreover, a range of indices related to systemic inflammation, obtained from routine complete blood count (CBC) tests, have been applied to inflammation markers. However, these biomarkers remain insufficiently addressed in the evidence supporting the presence of sarcopenia and malnutrition. This study aimed to explore sarcopenia in terms of malnutrition, anemia, and inflammation among Thai community-dwelling older people. Methods: This study enrolled community-dwelling older people aged 60 years and above. All participants were requested to complete a questionnaire assessing for sarcopenia (SARC-F) and nutritional status using the mini nutritional assessment (MNA). In addition, blood samples were obtained for the CBC test. Logistic regression analysis explored the risk of sarcopenia, CBC, and malnutrition status. Results: Of 126 older people (aged 62–88 years) enrolled, 12 individuals (9.52%) had sarcopenia. Furthermore, 34.9% and 5.56% of the participants were demonstrated to have anemia and malnutrition, respectively. Nutrition status was positively associated with hemoglobin levels (r = 0.241, p = 0.007) and negatively related to SARC-F scores (r = −0.190, p = 0.034). Older people with anemia show an increased risk of malnutrition at an odds ratio (OR) of 3.375. Moreover, individuals with anemia were at a higher risk of developing sarcopenia (OR 4.982) than those with no anemia. However, individuals with a high level of inflammatory markers, e.g., a high systemic inflammatory response index (SIRI) and monocyte-to-lymphocyte ratio (MLR), had a higher risk of sarcopenia than those with low SIRI and MLR values. The systemic immune–inflammation index (SII) and platelet-to-lymphocyte ratio (PLR) were also positively associated with SARC-F scores. Conclusions: The association between sarcopenia, malnutrition status, and anemia might overlap in clinical manifestation. In addition, future research directions regarding the utility of routine CBC testing should focus on sarcopenia and malnutrition status. Full article