Local Immune Status Research Articles

The role of probiotics in correction of microbiocenosis and cytokine balance of the oral cavity of patient with chronic inflammatory disease of periodont

Relevance. A long-term inflammation in the oral cavity, unreasonable treatment of periodontal patients with antibiotics cause imbalance between certain types of fungal-bacterial associations accompanied by oral dysbiosis and change of local immune status. So, development and application of new comprehensive diagnosis and treatment techniques in periodontal patients, use of products for correction of microbiota and local immunity are a current and a long-term task. Purpose is to optimize the comprehensive treatment protocol of inflammatory periodontal diseases by introducing probiotics and evaluation of oral microbiome and cytokine profile.Materials and methods. 140 patients were examined. Of these 60 patients had chronic generalized plaque-induced gingivitis and 60 patients suffered from moderate chronic generalized periodontitis. Bacterial and fungal microbiome was assessed and the host immune response was evaluated in all patients before and after the treatment. Half of the patients were treated conventionally and the other half were treated according to a modified scheme: probiotic “Bifidumbacterin Forte” was added.Results. A large number of yeast-like fungi Candida and commensal bacteria were detected in periodontal pockets of patients with chronic generalized plaque-induced gingivitis and moderate chronic generalized periodontitis. That correlates with a significant increase of pro-inflammatory cytokines (TNF-α, IL—8), decrease of concentration of INF-γ and increase of antiinflammatory cytokine IL-4.Conclusion. Changes in clinical, microbiological and immunological values during a modified combination therapy with a probiotic and during a conventional treatment demonstrated that effectiveness of treatment of chronic gingivitis and chronic periodontitis increased by 40% and 37% respectively.

КЛИНИКО-ЛАБОРАТОРНАЯ ОЦЕНКА ПРИМЕНЕНИЯ БАЛЬЗАМА ДЛЯ ДЕСЕН «ЛЕСНОЙ БАЛЬЗАМ» ПРИ ЛЕЧЕНИИ ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ ПАРОДОНТА

Subject. Microorganisms are a fundamental factor in the development of inflammation. The choice of a medicinal composition in the form of a gel can provide a prolonged introduction of dosage forms into the focus of inflammation. For our research, the herbal medicine Gum balm "Forest Balm" was selected. The main components are aloe juice, bisabolol, panthenol and ginger extract, which have an anti-inflammatory and wound-healing effect; troxerutin, which helps reduce gum bleeding; fir extract, which blocks the growth of pathogenic oral microbiota.
 Purpose ― to assess the effectiveness of the use of gum balm "Forest Balsam" in the treatment of inflammatory periodontal diseases 
 Methodology. A survey of 30 volunteer patients aged 20 to 22 years was conducted. Dental examinations were performed at the following time intervals: before application, after the 1st application, after 3 days, after 5 days and 7 days of application. The prevalence of the inflammatory process was assessed using the papillary-marginal-alveolar index and the Muhlemann bleeding index (modified by Cowell). Qualitative and quantitative study of microbiological material was performed by measuring the buccal epithelial colonization index to determine the status of local immunity.
 Results. Changes in the cytological picture in the direction of normocenosis are determined on the third day of applying the gum balm "Forest balm". On the 7th day of application, it eliminates all visible symptoms of gum disease (bleeding, inflammation, swelling).
 Conclusions. Gum balm "Forest balm" improves the protective function of the oral cavity by activating cellular defense mechanisms, strengthens local immunity, activates its own immune defense of the oral cavity to fight opportunistic microorganisms, increases the colonization resistance of the oral mucosa to opportunistic microorganisms.

Interleukin-35 has a tumor-promoting role in hepatocellular carcinoma.

Hepatic inflammatory response is a risk factor for liver cancer initiation and progression. Interleukin (IL)-35 is the newest member of the IL-12 cytokine family, and has been reported to play an essential role in the immunosuppressive liver microenvironment. Herein we focus on the expression profiles of IL-35 in hepatocellular carcinoma (HCC) and effects on local immune status. HCC transcriptome array data were downloaded from Gene Expression Omnibus (GEO). Analysis was performed by BRB-Array Tools and Ingenuity Pathway Analysis (IPA) software. Serum IL-35 level was detected by AimPlet bead-based immunoassay. In-situ IL-35 detection was performed by immunohistochemical staining and Western blot. The n-vitro effect of IL-35 on CD4+ or CD8+ T cell function was detected by flow cytometry. Our results showed that there were large amounts of IL-35 expressed in HCC serum and tumor tissues. IL-35 expression affects the transcript of thousands of genes, most differentially expressed genes (DEGs), in tumor tissues correlated with T cell immunity. The IL-35 high-expression group exhibited enhancement of regulatory T cells (Tregs ) and impairment of cytolytic T cells. In-vitro experiments proved that exogenous IL-35 stimulated the expression of programmed cell death 1 (PD-1) and lymphocyte activation gene-3 (LAG3) in CD4+ and CD8+ T cells. In addition, the stimulating effect was time-dependent. Furthermore, IL-35 inhibited interferon (IFN)-γ secretion by CD4+ and CD8+ T cells. Elevated IL-35 had an immune suppressive role in HCC tumor microenvironments through affecting inhibitor receptor expression and cytokine secretion of CD4+ and CD8+ T cells. Dissection of the precise targets and underlying molecular mechanisms would mean alternative treatments for HCC patients.

Results of integrated treatment of herpetic stomatitis with the inclusion of lipid concentrate of ERYX biomass

Aim. The study of the effectiveness of the use of the biologically active additive Reptin-plant in the complex treatment of patients with herpetic stomatitis.Materials and methods. We examined 189 patients with a diagnosis of herpetic stomatitis, which were divided into 2 groups depending on the receipt of complex antiviral therapy with the inclusion of ERYX biomass lipid concentrate in the treatment regimen and without it. The following were assessed: clinical status, index assessment of the state of the oral cavity, state of local immunity, frequency of relapses and duration of the latency period.Results. 57 (30.2%) patients were identified with a mild form of herpetic stomatitis (HS), the average severity of HS was determined in 93 (49.2%) and a severe course of the disease was diagnosed in 39 (20.6%) patients. Analysis of the index assessment of the state of the oral cavity (OHIS, PMA), molecular genetic parameters, immunological studies (lysozyme titer, phagocytosis, concentration of sIg A in saliva) showed a statistically significant difference when included in the complex treatment of Reptin-plant, demonstrating the benefits of using it.Conclusions. The use of ERYX biomass lipid concentrate in the complex treatment of herpetic stomatitis effectively affects the dynamics of the course of the disease, improves the quality of life of patients.

Effect of mare’s milk prebiotic supplementation on the gut microbiome and the immune system following antibiotic therapy

Abstract. Nurgaziyev M, Atenov Y, Khassenbekova Z, Akpanova S, Rysbekov K, Kozhakhmetov S, Nurgozhina A, Sergazy S, Chulenbayeva L, Ospanova Z, Tuyakova A, Mukhambetganov N, Sattybayeva R, Urazova S, Galymgozhina N, Zhumadilova A, Gulyaev A, Kushugulova A. 2020. Effect of mare’s milk prebiotic supplementation on the gut microbiome and the immune system following antibiotic therapy. Biodiversitas 21: 5065-5071. Antibiotic treatment can severely affect the gut microbiome for short-term and long-term consequences. Probiotic and prebiotic supplements are widely prescribed to modulate the composition and function of the human gut microbiome. The current study aims to determine the impacts of mare’s milk prebiotics on the diversity of gut bacterial communities and the local immune system when administered during and after a course of antibiotic therapy. Six children aged 4 to 5 years diagnosed with bilateral bronchopneumonia were prescribed cephalosporin (cefuroxime) antibiotics. During the 60 days of the study, three children consumed mare’s milk prebiotics, while the other three did not. Fecal samples were collected daily during antibiotic therapy and every five days after the last day of antibiotic treatment. Total DNA was isolated, and the taxonomic composition of the gut microbiome was analyzed by sequencing the 16S rRNA gene (V1-V3 region). The MULTIPLEX MAP platform was used to evaluate the local immune status. The relative abundance of 11 genera was reduced and did not recover until the last day of the study. The abundance of Bacteroides was not significantly altered in either group. Christensenella, Rothia, Abiotrophia, Acinetobacter, Anaerotruncus, Holdemania, and Turicibacter numbers were significantly increased on day five and remained at the same level during the study period. Cephalosporin administration also reduced the levels of pro-inflammatory and anti-inflammatory cytokines/chemokines (MIP1α, TNFα, GMCSF, GCSF, sCD40L, FGF2, TGFα, IL1α, and IP10).

Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype.

The link between a lung tumor and the lung microbiome is a largely unexplored issue. To investigate the relationship between a lung microbiome and the phenotype of an inflammatory stromal infiltrate, we studied a cohort of 89 patients with non-small cell lung cancer. The microbiome was analyzed in tumor and adjacent normal tissue by 16S rRNA amplicon sequencing. Characterization of the tumor stroma was done using immunohistochemistry. We demonstrated that the bacterial load was higher in adjacent normal tissue than in a tumor (p = 0.0325) with similar patterns of taxonomic structure and alpha diversity. Lung adenocarcinomas did not differ in their alpha diversity from squamous cell carcinomas, although the content of Gram-positive bacteria increased significantly in the adenocarcinoma group (p = 0.0419). An analysis of an inflammatory infiltrate of tumor stroma showed a correlation of CD68, iNOS and FOXP3 with a histological type of tumor. For the first time we showed that high bacterial load in the tumor combined with increased iNOS expression is a favorable prognostic factor (HR = 0.1824; p = 0.0123), while high bacterial load combined with the increased number of FOXP3+ cells is a marker of poor prognosis (HR = 4.651; p = 0.0116). Thus, we established that bacterial load of the tumor has an opposite prognostic value depending on the status of local antitumor immunity.

Therapy of recurrent herpetic stomatitis in childrens with bronchial asthma

The work presents the results of a study of the effectiveness of the use of an immunomodulating agent for the treatment of recurrent herpetic stomatitis in children with bronchial asthma. The therapy of recurrent herpetic stomatitis was carried out in 67 children aged 1 to 16 years with bronchial asthma according to the scheme proposed by the authors using an immunomodulator. The immune status of patients before and after the therapy was assessed using the following indicators: the content of immunoglobulin (SIgA) in saliva, salivary lysozyme, an integrated indicator, the balance coefficient (Ksb). The results of the study showed that after the therapy, the incidence rates of recurrent herpetic stomatitis improved, the state of local immunity approached the group of healthy children. It is concluded that the proposed therapy for recurrent herpetic stomatitis in children with bronchial asthma gave a positive result and can be recommended for the treatment of this category of patients.

The effect of low intensity ultrasound on neutrophil granulocytes of the mucous membranes and other factors of local immunity of women with Mycoplasma of urogenital system

Local and systemic physiotherapeutic effects using low intensity ultrasound for inflammatory diseases of the genitourinary system caused by M. genitalium are based on the stimulating effect of ultrasonic waves which allows to restore local immune status, eliminate the imbalance of neutrophil activity in the focus of the inflammatory reaction, and normalize the state of mucosal immunity factors of the mucous membranes in women with Mycoplasma infection of the genitourinary system.

The effect of local immunity on gastric cancer prognosis

Aim. To study the state of local immunity in patients with gastric adenocarcinoma.
 Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 with stage IIII, 20 with stage IV) received surgical/combined treatment or chemotherapy, respectively, at the Blokhin Scientific Research Center of Oncology. Tumor tissue was taken before treatment. By using flow cytometry there were evaluated the percentage of tumor tissue infiltration by lymphocytes (CD45+CD14-TIL); T cells (CD3+CD19-TIL); B cells (CD3-CD19+TIL); NK cell (CD3-CD16+CD56+TIL); effector cells CD16 (CD16+Perforin+TIL) and CD8 (CD8+Perforin+TIL) with their cytotoxic potential active CD16TIL and active CD8TIL; subpopulations of regulatory T cells NKT cells (CD3+CD16+CD56+TIL), regulatory cells CD4 (CD4+CD25+CD127-TIL) and CD8 (CD8+CD11b-CD28-TIL). The prognostic value of immune cells for overall survival (OS) and progression-free survival (PFS) was assessed.
 Results. A favorable prognosis factor for progression-free survival in patients with local and locally advanced forms of gastric cancer was an increase in the number of CD3-CD19+TIL (HR 0.862, 95% CI 0.7820.957, p=0.005), and an unfavorable prognosis was an increase in NK cells (CD3-CD16+CD56+TIL); HR 1.382, 95% CI 1.0871.758, p=0.008. The negative effect of the relative content of NK cells (CD3-CD16+CD56+TIL) and NKT cells (CD3+CD16+CD56+TIL) on OS of patients with metastatic gastric cancer noted (HR 1.249, 95% CI 0.9971.564, p=0.053; HR 1.127, 95% CI 1.0251.239, p=0.013). At the same time, an increase in the percentage of tumor tissue infiltration by lymphocytes (CD45+CD14-TIL) and an increase in the age of patients (HR 1.005, 95% CI 1.0021.008, p=0.003; HR 1.098, 95% CI 1.0311.170, p=0.004) reduce the incidence of PFS in patients with metastatic gastric carcinoma.
 Conclusion. Indices of local immunity can serve as additional prognostic factors for gastric carcinoma.

The local interferon-corrective therapy in children with congenital cleft lip and palate, suffering from the recurrent respiratory infections

It is known that children with congenital cleft lip and palate are suffering from recurrent respiratory infections, which worsen the state of their health, and also complicate the results of reconstructive surgical treatment. The aim of the study was to detect defects of mucosal immunity in children with congenital cleft lip and palate, suffering from recurrent respiratory infections, and to create the program of local interferon corrective therapy with an assessment of its effectiveness. The studies included 56 children from the age of 1 to 3 years. Three groups of children were formed: group 1 – 26 children with congenital cleft lip and palate (antibiotic therapy); group 2 — 30 children with congenital cleft lip and palate (antibiotic therapy + local interferon therapy), group 3 — the control group. The clinical examination included a medical history, an assessment of the symptoms of recurrent episodes of acute respiratory infections and exacerbations of chronic infections. Microbiological studies were performed using standard methods. The status of local immunity was detected: the concentrations of secretory IgA, cytokines IL-17, IL-4, IL-6, IL-1β, IFNγ in the oral fluid were tested by ELISA. Results of the study established that in group 1 and group 2 clinical criteria of immunodeficiency with an infectious syndrome were revealed: repeated acute respiratory viral infections from 10 or more times a year, complicated by frequent exacerbations of chronic bacterial infection (up to 10 or more per year). Assessment of the state of local immunity in children with congenital cleft lip and palate revealed a lack of sIgA compared with the control group. Before treatment in group 2 oral fluid level of IL-17, IL-6 were statistically significant increase (p 0.05); the results of the study also established increase in the level of IL-1β and a decrease in anti-inflammatory IL-4 and regulatory IFNγ relative to the control group (p 0.05). After complex treatment with the inclusion of local interferon therapy in group 2 the appearance of sIgA, increase in the concentration of IL-4, IL-1β and a decrease IL-17 in oral fluid were observed (p 0.05). The concentrations of IL-6, IFNγ did not change (p 0.05). After treatment in group 2 there were a decrease in exacerbations of chronic upper respiratory tract infection and in frequency of acute respiratory viral infections compared with group 1 (p 0.05). Positive clinical efficacy of local interferon therapy (the gel of recombinant IFNα2b in combination with oxidants — Viferon gel) in the process of staged rehabilitation of children with congenital cleft lip and palate has a protective clinical effect in reducing the frequency of acute respiratory viral infections, reducing the number of postoperative complications, reducing hospital stay, duration of antibacterial therapy and the number of exacerbations of chronic bacterial infection.

ОЦЕНКА НЕСПЕЦИФИЧЕСКОЙ РЕЗИСТЕНТНОСТИ СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА У КУРИЛЬЩИКОВ

Object. The article presents an assessment of the effect of smoking on factors of non-specific resistance of oral mucosa by the reaction of adsorption of microorganisms by epithelial cells. Purpose. is to detect and evaluate changes in non-specific oral mucosa resistance in smoking patients. Methodology. A clinical examination of the oral cavity 120 volunteers (58 women and 62 men) aged 18 to 44 years (average age: 22, 50 ± 2.59) was conducted. Three groups 2 participants have been formed: the main group (75 people) ― smokers and the comparison group (45 people) - non-smoking volunteers. The material taken twice: in smokers - before and 15 minutes after smoking, in non-smokers (for reliability) ― initially and after 15 minutes. A sterile instrument used to cut epithelium off the mucosa portion of the inner surface of the cheek, transfer it to a slide, dry, stain and microscopy the preparations. The integrity of the epithelial cell structure, their size, the intensity of the core staining and the cytoplasm evaluated. Depending on the number of microorganisms adsorbed on their surface, the viewed epithelial cells divided into 4 categories. Results. A change in the adsorption response of microorganisms by epithelial cells indicates a negative influence of tobacco on the oral mucosa. Conclusions. Smoking negatively affects the state of local immunity ― non-specific resistance of oral mucosa. Changes in the adsorption response of microorganisms by oral mucosa epithelial cells can be used in the diagnosis and prevention of diseases of oral organs arising from smoking.

Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma.

The relationship between the local immune status and cancer metabolism regarding 18F‐FDG and 18F‐FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty‐one ESCC patients who underwent 18F‐FDG PET and 18F‐FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD‐1), CD8, Ki‐67, CD34, GLUT1 (18F‐FDG transporter) and LAT1 (18F‐FAMT transporter). ESCC specimens with high tumoral PD‐L1 and high CD8‐positive lymphocytes were considered to have “hot tumor immune status.” High PD‐L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8‐positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki‐67 labelling index (P = 0.009) and CD34‐positive vessel counts (P < 0.001). SUVmax of 18F‐FDG was significantly higher in high PD‐L1 cases than in low PD‐L1 cases (P = 0.009). SUVmax of 18F‐FAMT was significantly higher in high PD‐L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18F‐FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.

Reprograming the tumor immunologic microenvironment using neoadjuvant chemotherapy in osteosarcoma.

Tumor‐infiltrating immune cells play a crucial role in tumor progression and response to treatment. However, the limited studies on infiltrating immune cells have shown inconsistent and even controversial results for osteosarcoma (OS). In addition, the dynamic changes of infiltrating immune cells after neoadjuvant chemotherapy are largely unknown. We downloaded the RNA expression matrix and clinical information of 80 OS patients from the TARGET database. CIBERSORT was used to evaluate the proportion of 22 immune cell types in patients based on gene expression data. M2 macrophages were found to be the most abundant immune cell type and were associated with improved survival in OS. Another cohort of pretreated OS samples was evaluated by immunohistochemistry to validate the results from CIBERSORT analysis. Matched biopsy and surgical samples from 27 patients were collected to investigate the dynamic change of immune cells and factors before and after neoadjuvant chemotherapy. Neoadjuvant chemotherapy was associated with increased densities of CD3+ T cells, CD8+ T cells, Ki67 + CD8+ T cells and PD‐L1+ immune cells. Moreover, HLA‐DR‐CD33+ myeloid‐derived suppressive cells (MDSC) were decreased after treatment. We determined that the application of chemotherapy may activate the local immune status and convert OS into an immune “hot” tumor. These findings provide rationale for investigating the schedule of immunotherapy treatment in OS patients in future clinical trials.

Influence of Short-Term Inhalations of High-Concentrated Oxygen Adding of Chamomile Oil to the State of Local Immunity at Sore Throat in Adults

Influence of Short-Term Inhalations of High-Concentrated Oxygen Adding of Chamomile Oil to the State of Local Immunity at Sore Throat in Adults

Various surgical techniques influence on the local immunity state in the postoperative period in children's tonsils hypertrophy

Topicality: There are many conflicting opinions in the literature regarding the best surgical technique for the treatment of OSAS related to palatine hypertrophy – partial (tonsillotomy) or complete (tonsillectomy) removal of lymphoid tissue of the tonsils. Also, there are many opinions about the use of a variety of traditional and modern surgical instruments to reduce the volume of the tonsils, including using a laser, a radiofrequency knife, an ultrasonic knife, a shaver (microdebrider) and a coblator. Aim of the study: The aim of the study was to compare the surgical methods effectiveness of tonsils hypertrophy treatment which the based on the restoration of the mucous membrane's local immunity function. Materials and methods: Children who undergoing surgical treatment for palatine tonsils hypertrophy 2-3 degrees according to the Brodsky classification and the presence of OSAS took part in the study. The patients were randomized and divided into four comparison groups using different surgical techniques. The first group, which used the surgical technique of classical tonsillotomy (TT) included 28 patients, the second group, which used the surgical technique of intracapsular shavertonsillotomy(STT) included 18 patients, the third group, which used surgical technique of intracapsular coblationtonsillotomy (CTT), and groups which using surgical technique of tonsilloplasty included 12 patients (TP). Determined the state of local immunity before surgery and 1 month after surgery by concentration levels of sIgA, α-IFN, IL-1β, TGF-1β and general-purpose immune complexes. Results: Recovery of the concentration of the major marker of local immunity sIgA occurs significantly (P&lt;0.05) faster when using the surgical technique of CTT and STT. Recovery of the concentration of the major marker of antiviral immunity α-IFN occurs significantly (P &lt;0.05) faster when using the surgical technique of CTT, STT and TP. Recovery of the concentration of the anti-inflammatory cytokine IL-1β occurs significantly (P&lt;0.05) faster with the use of the surgical technique of STT and TP. Indicators of the regeneration factor TGF-1β are significantly the highest when using the surgical techniques of STT, TT and TP. The concentration of immune complexes in the oropharyngeal secretions of patients with tonsil hypertrophy at 1 month after surgery significantly decreased with the use of surgical techniques TT and TP. Significant (P &lt;0.05) increase in IgG level was de- termined in all comparison groups except the group where tonsilloplasty was used. Conclusions: The safety surgical technique of palatine tonsils volume reduction – TP and STT promotes significantly (P&lt;0,05) faster restoration of concentration of the main mucous membrane's local immunity markers.

The response of phenoloxidase to cadmium-disturbed hepatopancreatic immune-related molecules in freshwater crayfish Procambarus clarkii

There has been extensive research on local and systemic oxidative stress and immunosuppression in cadmium exposed crustaceans, but the underlying mechanisms remain to be elucidated. Because of multiple functions of epithelial cells, such as storing and detoxifying heavy metals, producing and secreting immune-related molecules (i.e. hemocyanin, NF-κB and CBS/H2S et al.), hepatopancreas may play an important role in immune system. In the present study, as an indication of systemic and local immune status in crayfish Procambarus clarkii, the relationship between PO activities in haemolymph and levels of CBS/H2S/NF-κBp65 in hepatopancreas was evaluated following a 96 h exposure to sub-lethal Cd2+ concentrations (1/40, 1/8 and 1/4 of the 96 h LC50). The results indicated that there was a significant increase in ROS contents accompanied by markedly decreased THC and PO levels (P < 0.01) in a dose- and time- dependent manner. The evolutionarily conserved CBS and NF-κB p65 showed obvious difference (P < 0.01) (including cellular distribution and expression level) between the healthy and pathological conditions based on IHC analysis. Even small change of endogenous H2S content may be closely related to NF-κB p65 level and PO activity (P < 0.01). There was significantly negative correlation (P < 0.05) between PO activity and expression levels of CBS and NF-κB p65. Obviously, crayfish innate immunity was a highly complex network of various cells, molecules, and signaling pathways which operate, at least partly, through small signaling molecules such as H2S. ROS-mediated CBS/H2S/NF-κB pathway probably allowed hepatopancreas to inhibit PO activity under cadmium stress.

An Immune-Related Signature Predicts Survival in Patients With Lung Adenocarcinoma.

We investigated the local immune status and its prognostic value in lung adenocarcinoma. In total, 513 lung adenocarcinoma samples from TCGA and ImmPort databases were collected and analyzed. The R package coxph was employed to mine immune-related genes that were significant prognostic indicators using both univariate and multivariate analyses. The R software package glmnet was then used for Lasso Cox regression analysis, and a prognosis prediction model was constructed for lung adenocarcinoma; clusterProfiler was selected for functional gene annotations and KEGG enrichment analysis. Finally, correlations between the RiskScore and clinical features or signaling pathways were established. Sixty-four immune-related genes remarkably correlated with patient prognosis and were further applied. Samples were hierarchically clustered into two subgroups. Accordingly, the LASSO regression algorithm was employed to screen the 14 most representative immune-related genes (PSMD11, PPIA, MIF, BMP5, DKK1, PDGFB, ANGPTL4, IL1R2, THRB, LTBR, TNFRSF1, TNFRSF17, IL20RB, and MC1R) with respect to patient prognosis. Then, the prognosis prediction model for lung adenocarcinoma patients (namely, the RiskScore equation) was constructed, and the training set samples were incorporated to evaluate the efficiency of this model to predict and classify patient prognosis. Subsequently, based on functional annotations and KEGG pathway analysis, the 14 immune-related genes were mainly enriched in pathways closely associated with lung adenocarcinoma and its immune microenvironment, such as cytokine–cytokine receptor interaction and human T-cell leukemia virus 1 infection. Furthermore, correlations between the RiskScore and clinical features of the training set samples and signaling pathways (such as p53, cell cycle, and DNA repair) were also demonstrated. Finally, the test set sample data were employed for independent testing and verifying the model. We established a prognostic prediction RiskScore model based on the expression profiles of 14 immune-related genes, which shows high prediction accuracy and stability in identifying immune features. This could provide clinical guidance for the diagnosis and prognosis of different immunophenotypes, and suggest multiple targets for precise advanced lung adenocarcinoma therapy based on subtype-specific immune molecules.

Dickkopf-related protein 1, a new biomarker for local immune status and poor prognosis among patients with colorectal liver Oligometastases: a retrospective study

BackgroundIt was reported that tumor-expressed dickkopf-related (DKK) proteins affect micro-environment. However, the influence of DKK1 on colorectal cancer (CRC) liver oligometastases (CRCLOM) remains unclear.MethodsCRC cases after resection of liver oligometastases were enrolled in Sun Yat-Sen University Cancer Center with intact clinical data. Serum DKK1 was detected by ELISA assay. Immunofluorescent staining examination for CD3 and CD8 in slices were also conducted.ResultsAmong 65 patients included, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the low serum DKK1 group (RFS: P = 0.021; OS: P = 0.043). DKK1 was overexpressed in stage IV CRC patients in TCGA data. The number of CD8+ tumor-infiltrating lymphocytes (TILs) in invasive margin of CRC liver oligometastases was significantly higher in low serum DKK1 group (P = 0.042).ConclusionElevated serum DKK1 level was associated with poorer RFS and OS, and less CD8+ TILs in invasive margin in CRC liver oligometastases. DKK1 might serve as a supplementalprognostic factor for clinical risk score and a potential target for immunotherapy.

Systematic construction and validation of an immune prognostic model for lung adenocarcinoma.

Lung adenocarcinoma (LUAD), the most common non‐small‐cell lung cancer, is characterized by a dense lymphocytic infiltrate, which indicates that the immune system plays an active role in the development and growth of this cancer. However, no investigations to date have proposed robust models for predicting survival outcome for patients with LUAD in terms of tumour immunology. A total of 761 LUAD patients were included in this study, in which the database of The Cancer Genome Atlas (TCGA) was utilized for discovery, and the Gene Expression Omnibus (GEO) database was utilized for validation. Bioinformatics analysis and R language tools were utilized to construct an immune prognostic model and annotate biological functions. Lung adenocarcinoma showed a weakened immune phenotype compared with adjacent normal tissues. Immune‐related gene sets were profiled, an immune prognostic model based on 2 immune genes (ANLN and F2) was developed with the TCGA database to distinguish cases as having a low or high risk of unfavourable prognosis, and the model was verified with the GEO database. The model was prognostically significant in stratified cohorts, including stage I‐II, stage III‐IV and epidermal growth factor receptor (EGFR) mutant subsets, and was considered to be an independent prognostic factor for LUAD. Furthermore, the low‐ and high‐risk groups showed marked differences in tumour‐infiltrating leucocytes, tumour mutation burden, aneuploidy and PD‐L1 expression. In conclusion, an immune prognostic model was proposed for LUAD that is capable of independently identifying patients at high risk for poor survival, suggesting a relationship between local immune status and prognosis.

Metabolic syndrome attenuates ulcerative colitis: Correlation with interleukin-10 and galectin-3 expression.

BACKGROUNDUlcerative colitis (UC) is a chronic disease characterized by inflammation of intestinal epithelium, primarily of the colon. An increasing prevalence of metabolic syndrome (MetS) in patients with UC has been documented recently. Still, there is no evidence that MetS alters the course of the UC.AIMTo test the influence of the MetS on the severity of UC and the local and systemic immune status.METHODSEighty nine patients with de novo histologically confirmed UC were divided in two groups, according to ATP III criteria: Group without MetS (no MetS) and group with MetS.RESULTSClinically and histologically milder disease with higher serum level of immunosuppressive cytokine interleukin-10 (IL-10) and fecal content of Galectin-3 (Gal-3) was observed in subjects with UC and MetS, compared to subjects suffering from UC only. This was accompanied with predomination of IL-10 over pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17) in the sera as well as Gal-3 over TNF-α and IL-17 in feces of UC patients with MetS. Further, the patients with both conditions (UC and MetS) had higher percentage of IL-10 producing and Gal-3 expressing innate and acquired immune cells in lamina propria.CONCLUSIONLocal dominance of Gal-3 and IL-10 over pro-inflammatory mediators in patients with MetS may present a mechanism for limiting the inflammatory process and subsequent tissue damage in UC.