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INTRODUCTION: Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immune function, consequently enhancing overall therapeutic efficacy. AIM: We aimed to evaluate the effect of metronomic capecitabine as adjuvant therapy on immune function and survival in cases of LA-NPC. SUBJECTS AND METHODS: 28 patients with LA-NPC were enrolled in the study and equally assigned to two groups of 14 each: experimental and control group. The experimental group received induction chemotherapy + concurrent chemotherapy + adjuvant chemotherapy as well as oral capecitabine at a dose of 650 mg/m² of body surface area twice daily for 1 year, with the option to discontinue in case of intolerance. The control group did not receive additional chemotherapy or targeted drugs after the induction chemotherapy + concurrent chemoradiotherapy; however, they were followed up regularly. Changes in immune function and survival were compared between the two groups. RESULTS: The median follow-up time was 43.5 months. One year after adjuvant chemotherapy, the experimental group showed higher levels of CD8 + cells, CD28 + CD8 + cells, and activated CD8 + cells compared to the control group (P < 0.05). The CD4/CD8 ratio and proportion of monocyte-derived dendritic cells were also higher in the experimental group than in the control group, but the difference was not statistically significant (P ≥ 0.05). Comparisons of 3-year overall survival, local-regional recurrence-free survival, progression-free survival, and distant metastasis-free survival between the two groups showed percentages of 92.9% vs. 78.6%, 92.9% vs. 92.9%, 78.6% vs. 71.4%, and 85.7% vs. 0.78 0.6% respectively, but these differences were not significant (P > 0 0.05 ). CONCLUSION: Metronomic capecitabine chemotherapy was observed to induce an immunomodulatory effect in LA-NPC. TRIAL REGISTRATION: NCT02958111, date of registration 04-11-2016.
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Administração Metronômica , Capecitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Masculino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/mortalidade , Feminino , Pessoa de Meia-Idade , Adulto , Quimioterapia Adjuvante/métodos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/imunologia , Linfócitos T CD8-Positivos/imunologia , Idoso , Estadiamento de Neoplasias , Resultado do Tratamento , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , SeguimentosRESUMO
Sickle cell anaemia (SCA) patients display elevated levels of circulating pro-inflammatory cytokines and endothelial activation markers compared to healthy peers. The impact of exercise on the pro-inflammatory state in SCA remains unclear. This study aimed to characterize the whole-blood transcriptome profile in response to an acute bout of exercise in paediatric SCA patients. Twenty-three SCA participants (13 ± 3 years, 52% girls) and 17 healthy controls (14 ± 3 years, 29% girls) performed eight 2-min bouts of cycle ergometry interspersed with 1-min rest intervals. Whole-blood transcriptome profile (RNA-seq) was performed before and after exercise. At baseline, gene pathways associated with gas transport in erythrocytes were up-regulated in SCA patients compared to controls. Following exercise, gene pathways associated with innate immunity were altered in both groups. Interaction analyses revealed 160 annotated genes (101 up- and 59 down-regulated) that differentially altered by exercise in SCA patients. Moreover, genes that exhibited a blunted response to exercise in SCA patients were enriched in the IL-17 signalling pathway, suggesting an impaired innate immune response to exercise. This data will contribute to the development of evidence-based exercise prescription guidelines for this patient population.
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Anemia Falciforme , Exercício Físico , Perfilação da Expressão Gênica , Transcriptoma , Humanos , Anemia Falciforme/sangue , Anemia Falciforme/genética , Anemia Falciforme/terapia , Feminino , Masculino , Criança , Exercício Físico/fisiologia , Adolescente , Imunidade Inata , Estudos de Casos e ControlesRESUMO
In this article for the Highlights of 2023 Series, we consider the growing understanding of mast cell heterogeneity and interactions that has developed from single cell RNA sequencing studies. We also discuss novel concepts concerning mast cell interactions with the central nervous system and evidence for their role in host defense against SARS-CoV-2 infection.
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COVID-19 , Mastócitos , SARS-CoV-2 , Animais , Humanos , Sistema Nervoso Central/imunologia , COVID-19/imunologia , COVID-19/virologia , Mastócitos/imunologia , SARS-CoV-2/imunologia , Análise de Célula ÚnicaRESUMO
BACKGROUND: IgE-mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. METHODS: We performed detailed immune cell phenotyping of peripheral blood mononuclear cells and determined in vitro cytokine responses following allergen specific and non-specific immune stimulation. To determine if unique immune profiles were linked to early-life egg sensitisation, we compared 92 infants at 4-6 months of age, with (EggCAP+, n = 41) and without (EggCAP-, n = 51) early egg sensitisation. Additionally, 47 cord blood samples were analysed. For a subset of participants (n = 39), matching cord blood mononuclear cells were assessed by flow cytometry to establish the impact of IgE sensitisation on immune developmental trajectories. RESULTS: EggCAP+ infants were found to exhibit a unique immune phenotype characterised by increased levels of circulating CD4+ T regulatory cells (Treg), CD4+ effector memory (EM) Treg and increased expression of the IgE receptor, FcεR1, on basophils. The increased CD4+ EM Treg profiles were already present in cord blood samples from EggCAP+ infants. A general Th2-skewing of the immune system was observed based on increased IL-13 production following phytohemagglutinin stimulation and by comparing immune developmental trajectories, EggCAP+ infants displayed an expansion of basophils and reduced levels of CD4- T cells compared to EggCAP- infants. CONCLUSIONS: Immunological profiles associated with egg sensitisation are detectable in infant circulation at 4-6 months of age and at birth. Understanding the immune mechanisms underlying early-life sensitisation could provide important insights for future food allergy prevention strategies.
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Leucócitos Mononucleares , Linfócitos T , Recém-Nascido , Lactente , Humanos , Alérgenos , Linfócitos T CD4-Positivos , Imunoglobulina E , Linfócitos T ReguladoresRESUMO
BACKGROUND: Obesity is often associated with impaired immune responses, including enlarged spleen, increased inflammation, and impaired T cell-mediated function, which may lead to increased susceptibility to infections. Bioactive compounds found in various fruits and vegetables (F&V) have been shown to have strong anti-inflammatory effects. However, few prospective studies have examined the effects of F&V on preventing obesity-associated dysregulation of immune and inflammatory responses. OBJECTIVE: To determine the impact of different levels of a mixture of F&V incorporated in a high-fat diet (HFD) on immune function changes in a diet-induced obesity animal model. METHODS: Six-week-old male C57BL/6J mice were randomly assigned to one of five groups (n = 12/group): matched low-fat control (LF, 10% kcal fat) or high-fat diet (HFD, 45% kcal fat) supplemented with 0%, 5%, 10%, or 15% (wt/wt) freeze-dried powder of the most consumed F&V (human equivalent of 0, 3, 5-7, 8-9 servings/d, respectively) for 20 weeks. Spleen weight was recorded, and the immunophenotype of splenocytes was evaluated by flow cytometry. Ex vivo splenic lymphocyte proliferation was assessed by thymidine incorporation and serum cytokines were measured by Meso Scale Discovery. RESULTS: Mice fed the HFD had significantly higher spleen weight, decreased splenic CD8+ lymphocytes, suppressed T lymphocyte proliferation, and reduced serum IL-1ß and IFN-γ levels compared to those fed the LF diet. Feeding mice with the HFD supplemented with 10% or 15% F&V restored HFD-associated changes of these affected biomarkers compared to those fed HFD only. Further, a significant correlation was found between immunological markers and F&V level. CONCLUSIONS: These results suggest that increased consumption of F&V has beneficial effects in preventing HFD-associated dysregulation of immune function.
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BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. CASE PRESENTATION: A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. CONCLUSION: While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.
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Infecções Fúngicas Invasivas , Afogamento Iminente , Scedosporium , Humanos , Feminino , Adulto , Afogamento Iminente/complicações , Voriconazol/uso terapêutico , EncéfaloRESUMO
BACKGROUND: The research aims to explore the characteristics of intestinal flora, nutritional status and immune function in patients with different types of obese colon cancer. METHODS: A retrospective analysis is conducted on 64 cases of obese colon cancer diagnosed from June 2018 to January 2020. According to the histological staging of the cancer, they are classified into adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma, with corresponding cases of 24, 22 and 18, respectively. The intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI), immune function (IgG, IgM, IgA, CD4+, CD8+, and CD4+/CD8+) are analyzed in the different groups of patients. Survival curves are evaluated by Kaplan-Meier method and log-rank test for tumour death, local recurrence, and distant metastasis. RESULTS: There were no statistically significant differences in intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI) and immune function (IgG, IgM, IgA, CD4+, CD8+, and CD4+/CD8+) between different groups. There was a significant correlation between intestinal flora, nutritional status and immune function for all three. The survival curves of tumour death, local recurrence and distant metastasis in different groups of obese colon cancer patients were statistically significant. The tumor mortality rate, local recurrence, and distant metastasis rate in adenocarcinoma were 78.65%, 54.25% and 48.26% respectively. CONCLUSION: There are differences in intestinal flora, nutritional status and immune function among different types of obese colon cancer patients, but adenocarcinoma has the least benefit in intestinal flora, poor nutritional status, and weakest immune function.
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Neoplasias do Colo , Microbioma Gastrointestinal , Estado Nutricional , Obesidade , Humanos , Microbioma Gastrointestinal/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Colo/imunologia , Neoplasias do Colo/microbiologia , Neoplasias do Colo/patologia , Obesidade/complicações , Obesidade/imunologia , Idoso , Adenocarcinoma/imunologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , AdultoRESUMO
Although the prevalence of lead poisoning in southern Africa's Gyps vultures is now well-established, its finer physiological effects on these endangered species remain poorly characterised. We evaluated the sub-lethal impact of acute lead exposure on Cape and White-backed Vulture chicks from two breeding colonies in South Africa, by analysing its possible effects on key blood biochemistry parameters, immune function, packed cell volume and δ-aminolevulinic acid dehydratase (δ-ALAD) activity. All 37 White-backed Vulture nestlings sampled displayed elevated lead levels (>10 µg/dL), and seven had blood [Pb] >100 µg/dL. Eight of 28 Cape Vulture nestlings sampled had blood [Pb] exceeding background exposure, with one showing blood [Pb] >100 µg/dL. Delta-aminolevulinic acid dehydratase (δ-ALAD) activity was significantly and negatively related to blood [Pb] in nestlings from both species, with 50% inhibition of the enzyme predicted to occur at blood [Pb] = 52.8 µg/dL (White-backed Vulture) and 18.8 µg/dL (Cape Vulture). Although no significant relationship was found between % packed cell volume (PCV) and blood [Pb], the relatively lower mean PCV of 32.9% in White-backed Vulture chicks, combined with normal serum protein values, is likely indicative of depression or haemolytic anaemia. The leukogram was consistent in both species, although the presence of immature heterophils suggested an inflammatory response in White-backed Vulture chicks with blood [Pb] >100 µg/dL. Values for cholesterol, triglycerides, total serum protein, albumin, globulin, albumin/globulin ratio, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) were consistent with values previously reported. Calcium and phosphorus concentrations suggested no adverse effects on bone metabolism. A significant decrease in urea: uric acid (U:UA) ratio at blood [Pb] >100 µg/dL in White-backed Vulture chicks, brought about by a decrease in urea production, raises the possibility of hepatic abnormality. These results suggest that δ-ALAD activity may serve as a sensitive biomarker of lead toxicity in both species, while highlighting the need to better understand the significant variability in sensitivity that is observed, even between closely related members of the same genus.
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Falconiformes , Globulinas , Intoxicação por Chumbo , Animais , Chumbo , Sintase do Porfobilinogênio , Falconiformes/metabolismo , Intoxicação por Chumbo/veterinária , Galinhas/metabolismo , Proteínas Sanguíneas/metabolismo , Albuminas/metabolismo , Globulinas/metabolismo , Ureia/metabolismo , ImunidadeRESUMO
BACKGROUND: Numerous previous reports have demonstrated the efficacy of Lactic acid bacteria (LAB) in promoting growth and preventing disease in animals. In this study, Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were isolated from the feces of healthy rabbits, and both strains showed good probiotic properties in vitro. Two strains (108CFU/ml/kg/day) were fed to weaned rabbits for 21 days, after which specific bacterial infection was induced to investigate the effects of the strains on bacterial diarrhea in the rabbits. RESULTS: Our data showed that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 interventions reduced the incidence of diarrhea and systemic inflammatory response, alleviated intestinal damage and increased antibody levels in animals. In addition, Enterococcus faecium ZJUIDS-R1 restored the flora abundance of Ruminococcaceae1. Ligilactobaciiius animalis ZJUIDS-R2 up-regulated the flora abundance of Adlercreutzia and Candidatus Saccharimonas. Both down-regulated the flora abundance of Shuttleworthia and Barnesiella to restore intestinal flora balance, thereby increasing intestinal short-chain fatty acid content. CONCLUSIONS: These findings suggest that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were able to improve intestinal immunity, produce organic acids and regulate the balance of intestinal flora to enhance disease resistance and alleviate diarrhea-related diseases in weanling rabbits.
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Infecções Bacterianas , Enterococcus faecium , Microbioma Gastrointestinal , Lactobacillales , Probióticos , Coelhos , Animais , Enterococcus faecium/fisiologia , Probióticos/uso terapêutico , Probióticos/farmacologia , Diarreia/prevenção & controle , Diarreia/veterinária , Infecções Bacterianas/veterinária , ImunidadeRESUMO
One carbon (1C) metabolism is critical for cellular viability and physiological homeostasis. Starting from its crucial involvement in purine biosynthesis to posttranslational modification of proteins, 1C metabolism contributes significantly to the development and cellular differentiation through methionine and folate cycles that are pivotal for cellular function. Genetic polymorphisms of several genes of these pathways are implicated in disease pathogenesis and drug metabolism. Metabolic products of 1C metabolism have significant roles in epigenetic modifications through DNA and histone protein methylation. Homocysteine is a product that has clinical significance in the diagnosis and prognosis of several critical illnesses, including chronic immune diseases and cancers. Regulation of the function and differentiation of immune cells, including T-cells, B-cells, macrophages, and so forth, are directly influenced by 1C metabolism and thus have direct implications in several immune disease biology. Recent research on therapeutic approaches is targeting nuclear, cytoplasmic, and mitochondrial 1C metabolism to manage and treat metabolic (i.e., type 2 diabetes), neurodegenerative (i.e., Alzheimer's disease), or immune (i.e., rheumatoid arthritis) diseases. 1C metabolism is being explored for therapeutic intervention as a common determinant for a spectrum of immune and metabolic diseases. Identifying the association or correlation between essential metabolic products of this pathway and disease onset or prognosis would further facilitate the clinical monitoring of diseases.
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Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Humanos , Homeostase , Carbono , ImunidadeRESUMO
BACKGROUND: Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol. METHODS: This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient's immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient's liver function and adverse events. RESULTS: Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3+, CD4+, CD8+, and NK cells and the CD4+/CD8+ ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05). CONCLUSION: The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety. TRIAL REGISTRATION: The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022).
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Hemodinâmica , Hepatectomia , Laparoscopia , Propofol , Humanos , Masculino , Feminino , Hepatectomia/métodos , Pessoa de Meia-Idade , Hemodinâmica/efeitos dos fármacos , Laparoscopia/métodos , Propofol/administração & dosagem , Propofol/farmacologia , Benzodiazepinas/administração & dosagem , Anestésicos Intravenosos/farmacologia , Anestésicos Intravenosos/administração & dosagem , Adulto , Idoso , Hipnóticos e Sedativos/administração & dosagemRESUMO
PURPOSE: This study aimed to examine changes in salivary immunoglobulin A (s-IgA) secretion at different intensities or durations of acute exercise. METHODS: Twelve healthy untrained young males were included in randomized crossover trials in Experiment 1 (cycling exercise for 30 min at a work rate equivalent to 35%, 55%, and 75% maximal oxygen uptake [ V Ë O2max]) and Experiment 2 (cycling exercise at 55% V Ë O2max intensity for 30, 60, and 90 min). Saliva samples were collected at baseline, immediately after, and 60 min after each exercise. RESULTS: Experiment 1: The percentage change in the s-IgA secretion rate in the 75% V Ë O2max trial was significantly lower than that in the 55% V Ë O2max trial immediately after exercise (- 45.7%). The percentage change in the salivary concentration of cortisol, an s-IgA regulating factor, immediately after exercise significantly increased compared to that at baseline in the 75% V Ë O2max trial (+ 107.6%). A significant negative correlation was observed between the percentage changes in saliva flow rate and salivary cortisol concentration (r = - 0.52, P < 0.01). Experiment 2: The percentage change in the s-IgA secretion rate in the 90-min trial was significantly lower than that in the 30-min trial immediately after exercise (-37.0%). However, the percentage change in salivary cortisol concentration remained the same. CONCLUSION: Our findings suggest that a reduction in s-IgA secretion is induced by exercise intensity of greater than or equal to 75% V Ë O2max for 30 min or exercise duration of greater than or equal to 90 min at 55% V Ë O2max in healthy untrained young men.
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BACKGROUND: Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. METHODS: Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h- 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. RESULTS: Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. CONCLUSION: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg- 1. h- 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).
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Gastrectomia , Laparoscopia , Naloxona , Complicações Pós-Operatórias , Neoplasias Gástricas , Humanos , Naloxona/administração & dosagem , Gastrectomia/métodos , Masculino , Feminino , Laparoscopia/métodos , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/farmacologia , Assistência Perioperatória/métodos , Interleucina-6 , Receptor 4 Toll-LikeRESUMO
Lung adenocarcinoma exhibits high incidence and mortality rates, presenting a significant health concern. Concurrently, the COVID-19 pandemic has emerged as a grave global public health challenge. Existing literature suggests that T cells, pivotal components of cellular immunity, are integral to both antiviral and antitumor responses. Yet, the nuanced alterations and consequent functions of T cells across diverse disease states have not been comprehensively elucidated. We gathered transcriptomic data of peripheral blood mononuclear cells from lung adenocarcinoma patients, COVID-19 patients, and healthy controls. We followed a standardized analytical approach for quality assurance, batch effect adjustments, and preliminary data processing. We discerned distinct T cell subsets and conducted differential gene expression analysis. Potential key genes and pathways were inferred from GO and Pathway enrichment analyses. Additionally, we implemented Mendelian randomization to probe the potential links between pivotal genes and lung adenocarcinoma susceptibility. Our findings underscored a notable reduction in mature CD8 + central memory T cells in both lung adenocarcinoma and COVID-19 cohorts relative to the control group. Notably, the downregulation of specific genes, such as TRGV9, could impede the immunological efficacy of CD8 + T cells. Comprehensive multi-omics assessment highlighted genetic aberrations in genes, including TRGV9, correlating with heightened lung adenocarcinoma risk. Through rigorous single-cell transcriptomic analyses, this investigation meticulously delineated variations in T cell subsets across different pathological states and extrapolated key regulatory genes via an integrated multi-omics approach, establishing a robust groundwork for future functional inquiries. This study furnishes valuable perspectives into the etiology of multifaceted diseases and augments the progression of precision medicine.
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Adenocarcinoma de Pulmão , COVID-19 , Neoplasias Pulmonares , Humanos , Leucócitos Mononucleares , Análise da Randomização Mendeliana , Pandemias , COVID-19/genética , Linfócitos T CD8-Positivos , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genéticaRESUMO
Since its discovery, Aire has been the topic of numerous studies in its role as a transcriptional regulator in the thymus where it promotes the "promiscuous" expression of a large repertoire of tissue-restricted antigens (TRAs) that are normally expressed only in the immune periphery. This process occurs in specialized medullary thymic epithelial cells (mTECs) and mediates the elimination of self-reactive T cells or promotes their conversion to the Foxp3+ regulatory T cell lineage, both of which are required for the prevention of autoimmunity. In recent years, there has been increasing interest in the role of extrathymic Aire expression in peripheral organs. The focus has primarily been on the identification of the cellular source(s) and mechanism(s) by which extrathymic AIRE affects tolerance-related or other physiological processes. A cadre of OMICs tools including single cell RNA sequencing and novel transgenic models to trace Aire expression to perform lineage tracing experiments have shed light on a phenomenon that is more complex than previously thought. In this chapter, we provide a deeper analysis of how extrathymic Aire research has developed and progressed, how cellular sources were identified, and how the function of AIRE was determined. Current data suggests that extrathymic AIRE fulfills a function that differs from what has been observed in the thymus and strongly argues that its main purpose is to regulate transcriptional programs in a cell content-dependent manner. Surprisingly, there is data that also suggests a non-transcriptional role of extrathymic AIRE in the cytoplasm. We have arrived at a potential turning point that will take the field from the classical understanding of AIRE as a transcription factor in control of TRA expression to its role in immunological and non-immunological processes in the periphery.
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Regulação da Expressão Gênica , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Timo , Autoimunidade , Antígenos , Células Epiteliais/metabolismoRESUMO
BACKGROUND: The alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients is still unclear. METHODS: Postsurgical tissues from the enrolled luminal A BCs were divided into five categories: primary BC lesion at stage N0 (PL1), primary BC lesion at stage N1 (PL2), negative axillary lymph node at stage N0 BC (LN1), negative axillary lymph node at stage N1 BC (LN2), and positive axillary lymph node at stage N1 BC (LN3). The frequencies of positive immune markers (CD4, CD8, PD1, PD-L1, T-cell immunoglobulin and mucin domain 3 (TIM3), and forkhead box protein 3 (Foxp3)) in the above tissues were quantified by AKOYA Opal Polaris 7 Color Manual IHC Detection Kit. RESULTS: A total of 50 female patients with luminal A BC were enrolled in this study. Among these patients, 23 had stage N1 disease, and 27 had stage N0 disease. Compared with that in the PL2 subgroup, the frequency of PD-1-positive cells was significantly greater in the PL1 subgroup, whether at the stromal or intratumoral level (P value < 0.05). Both the frequency of CD8 + T cells in LN1 and that in LN2 were significantly greater than that in LN3 (P value < 0.05). The frequency of TIM3 + T cells in LN1 was significantly greater than that in PL1 (P value < 0.05). The frequency of CD8 + TIM3 + T cells was significantly greater in both the LN2 and LN3 groups than in the PL2 group (P value < 0.05). The frequency of CD4 + Foxp3 + T cells was significantly greater in LN1 than in PL1 (P value < 0.05), which was the same for both LN3 and PL2 (P value < 0.05). CONCLUSION: Increased frequencies of CD8 + PD1+, CD8 + TIM3 + and CD4 + Foxp3 + T cells might inhibit the immune microenvironment of axillary metastatic lymph nodes in luminal A breast cancer patients and subsequently promote lymph node metastasis.
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Axila , Neoplasias da Mama , Linfonodos , Metástase Linfática , Microambiente Tumoral , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/cirurgia , Microambiente Tumoral/imunologia , Pessoa de Meia-Idade , Linfonodos/patologia , Linfonodos/imunologia , Linfonodos/cirurgia , Adulto , Prognóstico , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/imunologia , Idoso , Seguimentos , Estadiamento de Neoplasias , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Receptor de Morte Celular Programada 1/metabolismoRESUMO
BACKGROUND: Minimal access breast surgery (MABS) is commonly employed in the management of breast cancer, but there is limited research on the postoperative immune function associated with MABS. OBJECTIVE: This study aimed to assess the postoperative immune function in breast patients who underwent MABS or conventional open breast surgery (COBS). METHODS: We retrospectively analyzed the medical records of 829 breast cancer patients treated with either MABS or COBS at a single hospital between January 2020 and June 2023. Among them, 116 matched pairs were obtained through 1:1 propensity score matching (PSM). Flow cytometry was used to measure the percentages of CD3+, CD4+, and CD8+ cells, as well as the CD4+/CD8+ ratio, on three different time points: preoperative day 1 (PreD1), postoperative day 1 (PostD1), and postoperative day 7 (PostD7). RESULTS: Both the MABS and COBS groups demonstrated a significant reduction in the percentages of CD3+, CD4+, and CD8+ cells, along with the CD4+/CD8+ ratio, from PreD1 to PostD1. Interestingly, the MABS group showed a reversal of these parameters, returning to preoperative levels by PostD7. Conversely, the COBS group showed an increase in these parameters from PostD1 to PostD7, but they still remained significantly lower than preoperative levels at PostD7. CONCLUSION: MABS treatment may result in reduced postoperative immune suppression and faster recovery of preoperative immune function compared to COBS in patients.
Assuntos
Neoplasias da Mama , Mastectomia , Pontuação de Propensão , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Seguimentos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Período Pós-Operatório , Adulto , IdosoRESUMO
Lung squamous cell carcinoma (LUSC) kills more than four million people yearly. Creating more trustworthy tumor molecular markers for LUSC early detection, diagnosis, prognosis, and customized treatment is essential. Cuproptosis, a novel form of cell death, opened up a new field of study for searching for trustworthy tumor indicators. Our goal was to build a risk model to assess drug sensitivity, monitor immune function, and predict prognosis in LUSC patients. The 19 cuproptosis-related genes were found in the literature, and patient genomic and clinical information was collected using the Cancer Genomic Atlas (TCGA) database. The LUSC patients were grouped using unsupervised clustering techniques, and 7626 differentially expressed genes were identified. Using univariate COX analysis, LASSO regression analysis, and multivariate COX analysis, a prognostic model for LUSC patients was developed. The tumor immune escape was evaluated using the Tumor Immune Dysfunction and Exclusion (TIDE) method. The R packages 'pRRophetic,' 'ggpubr,' and 'ggplot2' were utilized to examine drug sensitivity. For modeling, a 6-cuproptosis-based gene signature was found. Patients with high-risk LUSC had significantly worse survival rates than those with low-risk conditions. The possibility of tumor immunological escape was increased in patients with higher risk scores due to more immune cell inactivation. For patients with high-risk LUSC, we discovered seven potent potential drugs (AZD6482, CHIR.99021, CMK, Embelin, FTI.277, Imatinib, and Pazopanib). In conclusion, the cuproptosis-based genes predictive risk model can be utilized to predict outcomes, track immune function, and evaluate medication sensitivity in LUSC patients.
RESUMO
Throughout life, animals must maintain homeostasis while coping with challenging events. The period after reproduction can be challenging for oviparous females to maintain homeostasis since they direct most of their energy stores to vitellogenesis, possibly increasing the vulnerability to stressors. Changes in glucocorticoids' (GC) secretion promote various behavioural and physiological adjustments daily and to restore balance after facing stressors. However, when GC are elevated for extended periods, which usually occurs in response to chronic exposure to stressors, they can affect feeding behaviour and suppress the immune function. We aim to elucidate the effects of chronic corticosterone (CORT) exposure on feeding behaviour, body condition and immune function in female lizards, Tropidurus catalanensis, in the post-reproductive period. Thirty animals were divided into three groups: 1. Control (no experimental procedure performed); 2. Empty Implant (animals implanted with empty silastic tube); and 3. CORT Implant (animals implanted with silastic tube filled with CORT, with a chronic continuous release for at least a week). CORT plasma levels feeding behaviour, body condition (body index [BI] and fat index [FI]), leukocyte count, and several immune function variables (bacterial killing ability [BKA], hemagglutination titer, phytohemagglutinin [PHA] immune challenge and leukocyte count) were evaluated. After implantation, CORT treated animals maintained stable body mass through the experiment, while Control and Empty Implant groups displayed weight loss. In the CORT treated animals, there was also a positive relation between BI and FI, and higher FI when compared to groups 1 and 2. No effects of CORT were observed on feeding behaviour nor on the immune function.
RESUMO
OBJECTIVE: To investigate the effects of dexmedetomidine combined with intraoperative thermal insulation on postoperative cognitive function, cellular immune status and inflammatory markers in patients undergoing radical resection for colorectal cancer. METHODS: Fifty patients who underwent radical resection of colorectal cancer in our hospital from March 2020 to September 2021 were selected and divided into observation group (26 cases with dexmedetomidine combined with intraoperative thermal insulation intervention) and control group (24 cases with conventional anesthesia management). The evaluation measures included the mini-mental state scale (MMSE) score, CD4+ T cell, CD8+ T cell ratio and CD4+/CD8+ ratio, the level of inflammatory markers (IL-6, TNF-α, CRP), and the incidence of postoperative complications. RESULTS: The MMSE score of the observation group was significantly higher than that of the control group on the 3rd day after operation (p < 0.001). After treatment, the proportion of CD4+ T cells, the proportion of CD8+ T cells and the ratio of CD4+/CD8+ in observation group were higher than those in control group (p < 0.01), while the inflammatory markers IL-6, TNF-α and CRP were lower than those in control group (p < 0.01). The incidence of postoperative cognitive dysfunction (POCD) in the observation group (7.69%) was significantly lower than that in the control group (33.33%) (p = 0.010), and the postoperative infection rate was also significantly decreased (p = 0.042). CONCLUSION: Dexmedetomidine combined with intraoperative insulation can significantly improve postoperative cognitive function, maintain immune balance, reduce inflammatory response, and reduce the incidence of POCD and other postoperative complications in patients with radical resection of colorectal cancer.