Immunocompetent Research Articles

Daylight versus pro yellow laser (577nm) photodynamic therapy mediated with methylene blue (10%) in plane warts: a comparative study.

Warts are small, benign growths caused by human papilloma virus (HPV) infection of the skin or mucous membrane. Photodynamic therapy in dermatology is simplified by the accessibility of the skin to light application and allows using any light source with the appropriate spectrum. This study aimed to compare the efficacy and safety of daylight-PDT versus pro yellow laser (577nm)-PDT mediated by 10% methylene blue (MB) gel in the treatment of plane warts. This prospective comparative study was carried out on 34 patients presented with common warts (≥ 1 warts). Patients were divided into two equal groups by simple randomization process. Group 1: treated with daylight PDT using MB (MB-DL PDT), group 2: treated with Pro yellow laser as PDT using MB. The results of the present study revealed excellent response of warts in 9 patients (52.9%), very good response in 4 patients (23.5%) and poor response in 2 patients (11.8%) of group (1). In group (2), excellent response of the treated warts was observed in 5 patients (29.4%), poor response in 5 patients (29.4%) and no response in 7 patients (41.2%). Daylight-photodynamic therapy (DL-PDT) using MB is an effective treatment, nearly pain free and of convenience to patients. Careful consideration should be given to patient-specific factors such as immune status and previous treatment history. Future research with larger sample sizes, HPV genotyping, and longer follow-up periods is warranted to optimize patient-tailored PDT protocols.

Differential effects of high-fiber and low-fiber diets on anti-tumor immunity and colon tumor progression in a murine model.

The role of dietary fiber in colon cancer prevention remains controversial. We investigated its impact on anti-tumor immunity and the gut microbiota in APCmin/+ mice infected with Enterotoxigenic Bacteroides fragilis. Mice were fed high-fiber, low-fiber, or chow diets, and tumor burden, survival, cytokines, microbiota, and metabolites were analyzed. Contrary to the belief that high fiber inhibits tumor progression, it had no significant impact compared to chow diet. However, the low-fiber diet significantly reduced tumor burden and improved survival. Mechanistically, high fiber increased pro-inflammatory cytokines and CD4+Foxp3+RORγt+IL-17A+ regulatory T cells, while low fiber enhanced anti-inflammatory cytokines and cytotoxic T-cells. High fiber enriched microbial taxa associated with IL-17A+RORγt+ Tregs and altered metabolites, including reduced tryptophan and increased short-chain fatty acids and bile acids. Low fiber produced opposite effects. These findings suggest that dietary fiber's effects on colon cancer depends on microbial infection and immune status, emphasizing the need for personalized dietary interventions in colon cancer management.

Lactiplantibacillus plantarum ameliorated the negative effects of a low-protein diet on growth performance, antioxidant capacity, immune status, and gut microbiota of laying chicks

This experiment was conducted to investigate the effects of adding Lactiplantibacillus plantarum to a low-protein diet on the growth performance, ability immune status, and intestinal microbiota of 0–21-day-old layer chickens. A total of 180 one-day-old healthy Hy-line brown laying chicks were randomly divided into three groups with three replicates each of 20 chicks. The control group was fed a basal diet containing 19% protein, the low-protein (LP) group was fed a diet containing 17% protein, and the probiotic (LPL) group was fed with the 17% protein diet supplemented with L. plantarum (1.0 × 109 CFU/kg). The growth performance, antioxidant capacity, immune status, and gut microbiota of laying chickens were detected. We found that L. plantarum supplementation increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and levels of immunoglobulin (Ig) A, IgG, and interleukin-10 (IL-10) in serum of 17% protein +1.0 × 109 CFU/kg L. plantarum (LPL) compared to the 19% protein group (control). Furthermore, L. plantarum supplementation increased the liver index, GSH-Px and T-AOC activity in serum, and changed the microflora structure, diversity, and polyketose unit bioanabolic metabolism of 17% protein +1.0 × 109 CFU/kg L. plantarum (LPL) compared to the 17% protein group (LP). In conclusion, L. plantarum supplementation could compensate for the adverse effects of low-protein diets in chicks, and the combination of a low-protein diet and L. plantarum is a feasible way to reduce protein in the diet.

Uncovering potential molecular markers and pathological mechanisms of Parkinson's disease and myocardial infarction based on bioinformatics analysis

Background The direct association between Parkinson's disease (PD) and Myocardial infarction (MI) has been the subject of relatively limited research. Objective The purpose of this study was to identify the genes most associated with PD and MI to explore their common pathogenesis. Methods The gene expression profiles of PD and MI were downloaded from GEO database. Differential expression analysis was performed to identify the common differential expression genes (DEGs) of PD and MI, followed by functional annotation. Subsequently, protein-protein interaction network were constructed, and hub DEGs were identified based on CytoHubba plugin and LASSO regression analysis. To explore the potential molecular mechanism of hub DEGs, GSEA analysis, immune correlation analysis, drug prediction and molecular docking were performed, and transcription factors (TF) and lncRNA-miRNA-mRNA (ceRNA) regulatory networks were constructed. Results A total of 48 DEGs with the same expression trend were identified in the MI vs. normal control (NC) and PD vs. NC groups. Functional annotation results showed that the common DEGs were significantly enriched in immune and inflammation-related pathways. RPS4Y1 and UTY were the most relevant hub DEGs for PD and MI, and may be involved in the HALLMARK_MYC_TARGETS_V1 and HALLMARK_PROTEIN_SECRETION pathways. TP63 was a common TF of RPS4Y1 and UTY. The PVT1/KCNQ1OT1-hsa-miR-31-5p-RPS4Y1 and KCNQ1OT1-hsa-let-7a-5p/hsa-miR-19b-3p-UTY axes may play an important role in regulating PD and MI. CYCLOHEXIMIDE and ATALAREN may be potential drugs for the treatment of PD and MI comorbidity. In addition, PD and MI exhibit different patterns of immune cell infiltration and immune function status, which may be related to the specific pathological processes of the disease. Conclusions This study revealed for the first time that RPS4Y1 and UTY may be common biomarkers of PD and MI and may be potential therapeutic targets. This study provides new perspective on the common molecular mechanisms between PD and MI.

EDF1 accelerates ganglioside GD3 accumulation to boost CD52-mediated CD8+ T cell dysfunction in neuroblastoma

BackgroundHeterogeneous clinical features and prognosis in neuroblastoma (NB) children are frequently dominated by immune elements. Dysfunction and apoptosis in immune cells result from the exposure to continuous tumor-related antigen stimulation and coinhibitory signals. To date, key factors pointing to the restriction of NB-specific CD8+ T cells remain elusive.MethodsWe performed bulk-RNA sequencing and lipidomic analyses of children with mediastinal NB. Bioinformatics analysis and biological validation were applied to uncover the underlying mechanism.ResultsThree subtypes were identified using nonnegative matrix factorization (NMF), among which we highlighted an apoptotic status of infiltrated CD8+ T cells, along with the highest CD52 and EDF1 expression in Cluster3 (C3) subtypes. It was verified that high EDF1 expression in NB cells led to Lactosylceramide (LacCer) accumulation, as well as downstream ganglioside-GD3, which subsequently increased the expression of CD52 and immune checkpoint genes, chemotaxis, and apoptosis-related events in activated CD8+T cells. Mechanistically, EDF1 was recruited as a coactivator to form the NF-κB/RelA/EDF1 complex, which further prevented the promoter region methylation of ST8SIA1, to elevate its transcription.ConclusionThese findings characterize abundant GD3 in NB cells, which regulated by the EDF1/RelA/ST8SIA1 axis, is responsible for CD8+ T cell dysfunction. Inhibition of EDF1 may reduce suppressive factors and prevent immune escape of NB cells. Modulating NB-associated GD3 levels through metabolic intervention is beneficial for tuning the depth and duration of responses to current NB therapies. The integration of transcriptomic and lipidomic data offers a more comprehensive understanding of the interaction between LacCer metabolites and the immune status in NB.Graphical

Exploring the Role of Lower Genital Tract Microbiota and Cervical–Endometrial Immune Metabolome in Unknown Genesis of Recurrent Pregnancy Loss

Recurrent pregnancy loss (RPL) of unknown genesis is a complex condition with multifactorial origins, including genetic, hormonal, and immunological factors. However, the specific mechanisms underlying endocervical cell proliferation disorders in women with RPL remain inadequately understood, particularly concerning the role of microbiota and viral infections. The aim of this study was to investigate the mechanisms of endocervical cell proliferation disorders in women with RPL of unknown genesis by examining microbiota, human papillomavirus (HPV) typing, and the expression levels of key molecular biological markers, including p16/Ki-67, BCL-2, miR-145, and miR-34a. A prospective observational comparative study was executed on women with RPL and healthy pregnant controls with full ethical approval. Samples were collected for HPV typing and immunocytochemical analysis to evaluate the expression of p16, Ki-67, BCL-2, and the anti-oncogenic microRNAs (miR-145 and miR-34a). The expression of mRNA for the progesterone receptor (PGR-A) was also assessed, alongside local immune status markers, including proinflammatory T-lymphocytes (Th17/Th1) and regulatory CD4+ Tregs. Overexpression of p16, Ki-67, and BCL-2 was observed in 52.5% of women with RPL who had an ASC-US/LSIL cytogram, with the average double expression of p16/Ki-67 being three times higher than in the healthy pregnant group. A significant decrease in PGR-A mRNA expression in the endocervix of women with RPL was noted, accompanied by a dysregulated local immune status characterized by an increased prevalence of Th17/Th1 cells and a reduction in regulatory CD4+ Tregs. Additionally, the expression of miR-145 and miR-34a in the endocervix and endometrium of women with RPL significantly differed from the physiological pregnancy group, particularly in the context of high-risk HPV infection. The findings describe that disorders of endocervical cell proliferation in women with RPL of unknown genesis are associated with overexpression of specific molecular markers, impaired immune regulation, and altered microRNA profiles. These alterations may contribute to the pathophysiology of RPL, highlighting the need for further research into targeted interventions that could improve reproductive outcomes in affected individuals.

A comprehensive analysis of molecular characteristics of hot and cold tumor of gastric cancer

BackgroundThe advent of immunotherapy has revolutionized the treatment paradigm for gastric cancer (GC), offering unprecedented clinical benefits. However, a detailed molecular characterization of the tumor immune microenvironment in GC is essential to further optimize these therapies and enhance their efficacy.MethodsConsensus clustering was utilized to classify GC patients into distinct immune states, followed by an in-depth analysis of differences in mutation profiles, copy number variations, and DNA methylation patterns. Weighted gene co-expression network analysis (WGCNA) and correlation analysis were applied to identify gene modules underlying the classification of immune “hot” and “cold” tumors. Subsequently, 101 machine learning algorithm combinations were employed to construct a prognostic model based on the identified gene modules. Single-cell analysis was conducted to investigate cellular interactions associated with the immune-determinant gene module. Finally, immunofluorescence staining for CD8, CD45, and CXCR4 was performed on human GC tissue samples.ResultsA total of 1,298 GC patients were included in this comprehensive analysis. For the first time, we identified and characterized immune “hot” and “cold” tumors in GC patients, revealing distinct molecular features associated with these tumor types. Immune “hot” tumor-related genes were identified, and their functional roles were validated through biological behavior analysis. A prognostic signature, termed the hot tumor top regulators (HTTR), was developed using 101 machine learning algorithm combinations. The HTTR signature emerged as an independent prognostic factor, effectively stratifying patients into low- and high-risk groups with significant differences in overall survival. High-risk groups demonstrated strong associations with immune checkpoint regulation, antigen presentation, and inhibitory pathways. Notably, single-cell analysis revealed that HTTR genes were highly active in CD8 + T cells, with the CXCL12-CXCR4 axis playing a critical role in mediating interactions between CD8 + T cells and endothelial cells.ConclusionIn conclusion, the HTTR signature served as a robust prognostic biomarker for GC patients and effectively identified those with immune “hot” tumors. This finding provided valuable insights into the molecular mechanisms of tumor immunity in GC, offering potential avenues for targeted therapeutic interventions.

Effect of Plant-Derived Feed Additives on Enteric Methane Emission, Nutrient Digestibility and Immune Status of Adult Male Goats.

Ruminal methanogenesis reduces animal feed utilizing efficiency and is a potent greenhouse gas contributing to climate change. The present study aimed to study the effect of plant secondary metabolites on methane emission, nutrient digestibility and immune status of adult male goats. To fulfil the goal, 20 adult male goats (2.5-3 years of age, body weight [BW] 25.90 ± 1.46 kg) were divided into four groups of five animals. The control was fed a basal diet containing wheat straw and concentrate in a 50:50 ratio without additives. In groups T1, T2 and T3, the basal diet was supplemented with ajwain (Trachyspermum ammi) oil @ 0.06% dry matter intake (DMI), bahera (Terminalia belirica) @ 0.8% DMI and combination of ajwain oil and bahera @ 0.06% and 0.8% DMI, respectively. The DMI, nutrient digestibility, nitrogen intake, outgo and nitrogen balance were similar (p > 0.05) in all four groups. Methane emissions (g/kg DDMI) reduced (p < 0.05) by 22.16%, 23.88% and 33.49% in T1, T2 and T3 compared to control. Both cell-mediated immunity and humoral immune response significantly improved in T3 than other supplemented groups and control. In conclusion, the combination of behera and ajwain oil effectively reduced methane emissions and improved the immune status of adult male goats without affecting nutrient digestibility.

The Urgency of Express Consent to Waive State Immunity in an International Commercial Arbitration Agreement: Indonesia’s Practice

Indonesian State-owned enterprises’ participation in the international commercial transactions have become a prime example which affects the increasing need for international commercial arbitrations today and in the future. However, the State immunity that Indonesian State-owned enterprise owns may potentially give rise to issue on the implementation of the whole arbitration process, inclusive of the recognition and enforcement of the arbitral award. This issue alone has been hotly debated from the perspective of State-owned enterprises and the foreign private parties. On that account, Indonesian State-owned enterprises are still in need of a legal solution to settle the State immunity matter, whereas express consent to waive State immunity here is in question. Through the normative and comparative juridical research, the writer has found that it is urgent for Indonesian State-owned enterprises to provide express consent to waive State immunity since, inter alia, it paves a way to prevent further procedural hindrance in the whole arbitration process. The recommendation to fortify such practice is strengthened by how solely depending on other exceptions to State immunity, which have their own complexities and uncertainties, is going to bring the parties to procedural barrier that prolong the dispute settlement itself

Preventing bloodborne pathogen transmission in community nursing practice.

Community nurses face challenges while caring for patients with complex conditions, post-hospital recovery needs, or palliative care requirements, which increases their exposure to bloodborne pathogens. Inoculation injuries can transmit viruses such as hepatitis B (HBV), hepatitis C (HCV), and HIV. The risk of transmission depends on several factors, including the healthcare worker's immune status and vaccination history. Despite the high incidence of these injuries, the majority of those exposed do not develop serious illnesses. However, the financial impact of these injuries on the healthcare system is substantial, including both direct costs (such as treatment and testing) and indirect costs like staff absenteeism. Preventive measures, such as proper use of personal protective equipment, prompt reporting and post-exposure prophylaxis are essential to minimise the risk of transmission.

Development of Novel Peptide-Based Radiotracers for Detecting FGL1 Expression in Tumors.

A novel immune checkpoint, FGL1, is a potentially viable target for tumor immunotherapy. The development of FGL1-targeted PET probes could provide significant insights into the immune system's status and the evaluation of treatment efficacy. A ClusPro 2.0 server was used to analyze the interaction between FGL1 and LAG3, and the candidate peptides were identified by using the Rosetta peptide derivate protocol. Three candidate peptides targeting FGL1, named FGLP21, FGLP22, and FGLP23, with a simulated affinity of -9.56, -8.55, and -8.71 kcal/mol, respectively, were identified. The peptides were readily conjugated with p-NCS-benzyl-NODA-GA, and the resulting compounds were successfully labeled with 68Ga in approximately 70% yields and radiochemical purity greater than 95%. In vitro competitive cell-binding assay demonstrated that all probes bound to FGL1 with IC50 ranging from 100 nM to 160 nM. Among the probes, PET imaging revealed that 68Ga-NODA-FGLP21 exhibited the best tumor imaging performance in mice bearing FGL1 positive Huh7 tumor. At 60 min p.i., the tumor uptake of 68Ga-NODA-FGLP21 was significantly higher than those of 68Ga-NODA-FGLP22 and 68Ga-NODA-FGLP23, respectively (2.51 ± 0.11% ID/g vs 1.00 ± 0.16% ID/g and 1.49 ± 0.05% ID/g). Simultaneously, the tumor-to-muscle uptake ratios of the former were also higher than those of the latter, respectively (19.40 ± 2.30 vs 9.65 ± 0.62 and 12.45 ± 0.72). In the presence of unlabeled FGLP21, the uptake of 68Ga-NODA-FGLP21 in Huh7 xenograft decreased to 0.81 ± 0.09% ID/g at 60 min p.i., which is similar to that observed in the FGL1 negative U87 MG tumor (0.46 ± 0.03% ID/g). The results were consistent with the immunohistochemical analysis and ex vivo autoradiography. No significant radioactivity was accumulated in normal organs, except for kidneys. In summary, a preclinical study confirmed that the tracer 68Ga-NODA-FGLP21 has the potential to specifically detect FGL1 expression in tumors with good contrast to the background.

Viral Infections in HSCT Recipients with Post-Transplant Lymphoproliferative Disorder: The Role of Torque Teno Virus as a Marker of Immune Functions

Monitoring immune function in post-transplant patients is crucial to reduce the risk of viral infections (e.g., cytomegalovirus [CMV] or Epstein–Barr virus [EBV]), which can lead to serious complications such as post-transplant lymphoproliferative disorder (PTLD). Recently, Torque Teno virus (TTV) has attracted interest as a marker of immune function. Thus, we studied the kinetics of common post-transplant viral infections (TTV, EBV, CMV, human herpesvirus-6 [HHV-6], and adenovirus [AdV]) and their association with clinical parameters in 23 HSCT recipients who developed PTLD (PTLD-HSCT) and 25 post-HSCT patients without PTLD (Non-PTLD-HSCT) at three different timepoints: at the time of the transplant (T0), 3 months (T1), and 6 months (T2) post-HSCT. Additionally, 25 healthy donors (HD) were used as the control. EBV, CMV, HHV-6, or AdV infections were found in a few samples, while TTV was found in all of our samples. The highest TTV levels (4.61 [T0], 6.24 [T1] and 6.70 [T2] log10 copies/mL) were seen in PTLD-HSCT patients compared to Non-PTLD-HSCT (3.39 [T0], 4.86 [T1], and 3.75 [T2] log10 copies/mL) and HD (2.25 log10 copies/mL) at all timepoints. Higher TTV levels were also seen in patients with a destructive type of PTLD and in surviving PTLD-HSCT patients compared to deceased ones. TTV kinetics in PTLD patients post-HSCT showed that TTV levels increase with the fall in the host immunocompetence and that by monitoring TTV kinetics, the immune status of the patient can be monitored.

Habitat radiomics based on CT images to predict survival and immune status in hepatocellular carcinoma, a multi-cohort validation study.

Though several clinicopathological features are identified as prognostic indicators, potentially prognostic radiomic models are expected to preoperatively and noninvasively predict survival for HCC. Traditional radiomic models are lacking in a consideration for intratumoral regional heterogeneity. The study aimed to establish and validate the predictive power of multiple habitat radiomic models in predicting prognosis of hepatocellular carcinoma (HCC). A total of 232 HCC patients were retrospectively included, including a training/validation cohort and two external testing cohorts from 4 centers. For habitat radiomics, intratumoral habitat partitioning based on CT images was first performed by using Otsu thresholding method. Second, a total of 350 habitat radiomic models were constructed to select the optimal model. Then, both ROC curve analyses and Kaplan-Meier survival curve analyses were applied to assess the predictive performances. Ultimately, an immune status profiling was conducted based on bioinformatic analyses and multiplex immunohistochemistry (mIHC) assays to reveal the potential mechanisms. A total of 4 habitats were segmented, and the corresponding habitat radiomic models were constructed based on each habitat and an integration of all the four habitats. Generally, habitat radiomic models outperformed traditional radiomic models in stratifying prognosis for HCC. The habitat radiomic model based on the segmented habitat 4 involving decision tree (DT) screening and random forest (RF) classifier was identified as the optimal model with an AUCmean of 0.806. Distinct resting natural killer (NK) cell infiltrations significantly contributed to the prognosis stratification of HCC by the optimal habitat radiomic model. The habitat radiomic model based on CT images was potentially predictive of overall survival for HCC, with a superiority over the traditional radiomic model. The prognostic power of the habitat radiomic model was partly attributed to the distinct immune status captured in the CT images.

Seroprevalence of SARS-CoV-2 antibodies in children with nephrotic syndrome and chronic kidney disease: a cross-sectional study from India.

There is a paucity of literature on the seroprevalence of SARS-CoV-2 antibodies among pediatric patients with underlying kidney disorders; few serosurveys among healthy children have shown seropositivity of 20-65% after different waves of infections. The study had a cross-sectional design and was conducted between January 2023 and July 2023; 163 children and adolescents (1-18years) with nephrotic syndrome and chronic kidney disease (CKD) were screened for Anti-Spike SARS-COV-2 IgG antibodies as detected by a quantitative chemiluminescence immunoassay. Children with nephrotic syndrome, both steroid sensitive (SSNS) and steroid resistant (SRNS) were enrolled during disease remission. Correlation of SARS-CoV-2 seropositivity status was done with age, gender, disease type, treatment duration, immunosuppressants, previous SARS-CoV-2 infection, and immunization status. Of 163 children (63.8% boys) with median age of 9years; 101 (62%) had underlying nephrotic syndrome (61 SSNS and 40 SRNS), and 62 (38%) children had CKD. Seroprotective titers for SARS-COV2 antibodies were present in 100 (61.3%) children. The median titers for all patients were 37.1 BAU/mL; for nephrotic syndrome they were 27.1 BAU/mL and for CKD they were 76.7 BAU/mL (p = 0.0033). A total of 43 (26.4%) children had high positive antibody levels (> 200 BAU/ml). Among those with nephrotic syndrome 60.7% with SSNS and 43.5% SRNS had seropositive titers. Only 4 (2.5%) children had a history of previous COVID infection and 6 (3.7%) were vaccinated. In a largely unvaccinated population of children with nephrotic syndrome and CKD, 61.3% were seropositive for SARS-CoV-2 IgG antibody indicating a past asymptomatic infection; titers were significantly higher in CKD compared to nephrotic syndrome.

Nodular-bronchiectatic pattern in pulmonary nocardiosis: Immune status and treatment outcomes in a multicenter retrospective study.

Pulmonary nocardiosis is a rare opportunistic infection, with approximately 15% of patients being immunocompetent. The isolation rate of Nocardia spp. has recently increased, indicating rising clinical concern. This study aimed to summarize computed tomography (CT) findings, evaluate treatment outcomes, and improve disease recognition. We retrospectively analyzed 12 pulmonary nocardiosis cases recorded over 10 years in three hospitals, excluding two unclear cases. All pathogens were detected on smears and isolated from respiratory specimens. The mean age was 73.0±12.9 years, with 9 men and 6 smokers. Among the included patients, 8 had underlying pulmonary diseases, 4 had non-pulmonary diseases, and 3 were on steroids. The most common species were N. cyriacigeorgica and N. nova. CT findings included cavitary, consolidation/infiltrative, and nodular-bronchiectatic (NB) patterns. The NB pattern, particularly common in immunocompetent patients, was associated with significantly better treatment outcomes than non-NB patterns (Fisher's exact test, p=0.0476). All isolates were susceptible to trimethoprim/sulfamethoxazole. Eight patients recovered with appropriate antimicrobial therapy, while two patients died. Pulmonary nocardiosis presented three CT patterns, with the NB pattern being the most frequent and showing favorable treatment outcomes, especially in immunocompetent patients. While Nocardia spp. can develop in patients with preexisting bronchiectasis, it may also independently cause bronchiectasis. Nocardia infection should be considered as a differential diagnosis in patients exhibiting the NB pattern, resembling that of nontuberculous mycobacterial pulmonary diseases.

Effectiveness and Immunogenicity of the MMR Vaccine Against SARS-CoV-2 Among Healthcare Workers

The purpose of this study was to evaluate the effectiveness and immunogenicity of the measles–mumps–rubella (MMR) vaccine against SARS-CoV-2 in healthcare workers at one medical institution. The effectiveness of the MMR vaccine against SARS-CoV-2 was evaluated in overall healthcare workers (HCWs). In addition, neutralizing antibodies to SARS-CoV-2 were measured according to the subjects’ measles immunity status with serum samples collected before the coronavirus disease 2019 pandemic period. The effectiveness of the MMR vaccine for SARS-CoV-2 in all HCWs and measles IgG-positive subjects was 34% (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 0.53–2.70) and 34% (aOR = 0.66, CI = 0.38–18.4), respectively. The neutralizing antibody levels for SARS-CoV-2 were low in all groups regardless of the measles immune status. The MMR vaccine alone may not provide sufficient protection against SARS-CoV-2.

Impact of microbial diversity on inflammatory cytokines and respiratory pattern measured in whole-body plethysmography in guinea pig models.

This study investigates the breathing patterns and immune status of guinea pigs raised under specific pathogen-free (SPF) conditions compared to conventionally bred (CON). Breathing pattern parameters were assessed using whole-body plethysmography (WBP) during quiet breathing and saline nebulisation. Blood and bronchoalveolar lavage fluid (BALF) were analysed for white blood cell, neutrophil and eosinophil counts, and cytokine levels (TNF-α, IL-1β, IL-4). SPF guinea pigs exhibited higher tidal volume, expired volume, minute volume, and airflow parameters than CON guinea pigs. The immune analysis revealed lower white blood cell counts and IL-4 levels in SPF guinea pigs. These findings indicate that SPF guinea pigs have different respiratory and immune responses than CON guinea pigs. The study highlights that the maturation processes affecting breathing pattern parameters in SPF guinea pigs differ significantly from those in CON guinea pigs. This suggests potential limitations of SPF animals in respiratory physiology research due to their different immune and respiratory responses.

Impact of SARS-CoV-2 inactivated vaccine on symptoms following omicron variant breakthrough infection.

The SARS-CoV-2 Omicron variant and its sublineages continue to circulate widely. Clinical outcomes with this variant differ among individuals, primarily influenced by host immunity. Previous studies have explored the relationship between immune responses and severe diseases in infected or convalescent patients. However, the impact of vaccine-induced immune responses on disease severity, especially in cases of mild infection following breakthrough infection, remains unclear. This is primarily due to the lack of assessment of immune status in vaccinated individuals before infection. In this study, we aimed to elucidate the causality between virus-specific cellular and humoral immune responses and the severity of symptoms in breakthrough infected patients from a long-term follow-up post-vaccination cohort. A questionnaire survey was conducted to collect general symptoms upon breakthrough infection with the Omicron variants. Plasma levels of specific antibodies (neutralizing antibodies, anti-S IgG, and anti-N IgG) and T cell responses induced by inactivated SARS-CoV-2 vaccine were evaluated. The findings revealed that individuals with milder symptoms, particularly lower peak fever temperatures, exhibited higher antibody levels and enhanced T cell activation and responses prior to infection. This suggests that cellular and humoral immunity induced by inactivated vaccines may provide protection against severe clinical symptoms following breakthrough infection.

High expression of ARPC1B promotes the proliferation and apoptosis of clear cell renal cell carcinoma cells, leading to a poor prognosis.

ARPC1B has been identified as a key regulator of malignant biological behavior in various tumors. However, its specific role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. This study aims to evaluate the influence of ARPC1B on the prognosis and disease progression in ccRCC patients. Multi-omics data and clinical information from public databases were analyzed to determine the associations between ARPC1B and prognosis, clinical features, immune microenvironment, and drug sensitivity in ccRCC. Co-expression and gene set enrichment analyses were conducted to elucidate the potential role of ARPC1B in ccRCC pathogenesis. Functional assays, including RT-qPCR, CCK8 assays, colony formation assays, immunofluorescence, immunohistochemistry, and xenograft tumor formation in nude mice, were performed to assess ARPC1B's impact on cell proliferation and apoptosis. Flow cytometry and Western blotting were further employed to investigate the underlying molecular mechanisms of ARPC1B in ccRCC. ARPC1B expression was significantly elevated in ccRCC and associated with an unfavorable prognosis. Both independent and meta-analyses confirmed that ARPC1B is an independent prognostic risk factor in ccRCC. Furthermore, ARPC1B expression significantly correlated with the immune microenvironment and drug sensitivity. In vitro, experiments demonstrated that ARPC1B knockdown suppressed ccRCC cell proliferation and induced apoptosis through the BAX-Bcl-2/c-caspase3/c-PARP axis, which was further validated by in vivo studies. ARPC1B overexpression is associated with poor prognosis, altered immune status, and drug sensitivity in ccRCC. Furthermore, ARPC1B promotes the malignant behavior of ccRCC cells and holds potential as a prognostic biomarker and therapeutic target for ccRCC.

Gelatin methacryloyl hydrogel encapsulating molybdenum-inspired macrophage-derived exosomes accelerates wound healing via immune regulation and angiogenesis.

Clinically, abnormal or delayed wound healing leads to functional disorders and disfiguring scars. A well-vascularized environment and an anti-inflammatory immune state are crucial during the healing process. Molybdenum (Mo) is an essential element for the human body in modulating metabolism, immune function and tissue repair. In this study, we found that Mo-inspired macrophages significantly promoted the proliferation, migration, tube formation, and the expression of angiogenic factors (VEGF, PDGF, CD31) in human umbilical vein endothelial cells (HUVECs). We then successfully isolated and characterized Mo-inspired macrophage-derived exosomes (Mo-Exo) and demonstrated their internalization by HUVECs, leading to enhanced proliferation, migration, tube formation, and angiogenic factor expression. Moreover, we proved that Mo-Exo could promote the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. In terms of application, Mo-Exo encapsulated gelatin methacryloyl hydrogel (GelMA) exhibited notable potential in wound healing in rat skin defects, as evidenced by the reduced wound area and increased epidermal thickness observed in H&E and Masson's staining. Mechanically, Mo-Exo promoted angiogenesis through the activation of the ERK1/2 signaling pathway. In general, this research introduced a novel immunoregulatory and pro-angiogenic exosome hydrogel for clinical wound healing.