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At least 937 records · Page 52Linked to original sources
PubMed2026

Breathing carcinogens: PM2.5 air pollution and lung cancer in never-smokers, a narrative review.

BACKGROUND AND OBJECTIVE: Lung cancer in never-smokers (LCINS) disproportionately affects women and younger individuals, and its incidence has increased over recent decades. Environmental respiratory hazards, such as particulate matter ≤2.5 µm (PM2.5), are associated with lung cancer incidence and mortality, but the mechanisms by which PM2.5 increases lung cancer susceptibility remain incompletely understood. This review summarizes the current evidence linking PM2.5 exposure to LCINS and identifies priorities for future research. METHODS: A narrative review was conducted using PubMed/MEDLINE to identify English-language studies published from 2000 through May 2026 using combinations of the terms "PM2.5", "fine particulate matter", "air pollution", "lung cancer", "never-smokers", "environmental respiratory hazards", "genomic alterations", and "tumor microenvironment". Additional relevant studies were identified through manual review of the reference lists of included articles. Studies were selected based on their relevance to the epidemiology, biological mechanisms, genomic and immune landscape, and clinical implications of PM2.5-associated LCINS, with emphasis on original investigations, high-quality reviews, and landmark publications. KEY CONTENT AND FINDINGS: PM2.5 exposure promotes inflammatory signaling, metabolic reprogramming, and tumor progression. Emerging evidence suggests that PM2.5 functions primarily as a tumor promoter rather than a direct mutagen and is associated with genomic and epigenetic alterations, more advanced disease, and worse survival following lung cancer diagnosis and surgical resection. LCINS also exhibits distinct molecular and immunologic characteristics with important implications for screening, molecular profiling, and targeted therapies. CONCLUSIONS: PM2.5 is an increasingly recognized contributor to lung carcinogenesis in never-smokers. Improved understanding of the biologic mechanisms linking environmental respiratory hazards to LCINS may inform future screening strategies, precision oncology approaches, and novel therapeutic targets for this growing and understudied patient population.

Fine particulate matter ≤2.5 µm in dia↗
PubMed2006

Identification of novel Th2-associated genes in T memory responses to allergens.

Atopic diseases are associated with hyperexpression of Th2 cytokines by allergen-specific T memory cells. However, clinical trials with recently developed Th2 inhibitors in atopics have proven disappointing, suggesting underlying complexities in atopy pathogenesis which are not satisfactorily explained via the classical Th1/Th2 paradigm. One likely possibility is that additional Th2-associated genes which are central to disease pathogenesis remain unidentified. The aim of the present study was to identify such novel Th2-associated genes in recall responses to the inhalant allergen house dust mite. In contrast to earlier human microarray studies in atopy which focused on mitogen-activated T cell lines and clones, we concentrated on PBMC-derived primary T cells stimulated under more physiological conditions of low dose allergen exposure. We screened initially for allergen-induced gene activation by microarray, and validated novel genes in independent panels of subjects by quantitative RT-PCR. Kinetic analysis of allergen responses in PBMC revealed an early wave of novel atopy-associated genes involved in signaling which were coexpressed with IL-4 and IL-4R, followed by a later wave of genes encoding the classical Th2 effector cytokines. We further demonstrate that these novel activation-associated Th2 genes up-regulate in response to another atopy-associated physiological stimulus bacterial superantigen, but remain quiescent in nonphysiological responses in primary T cells or cell lines driven by potent mitogens, which may account for their failure to be detected in earlier microarray studies.

Administration, Inhalation↗
PubMed2003

[Role of cytokines in pathomechanism of otitis media].

Otitis media is one of the most common diseases in children. A variety if cytokines, potent inflammatory mediators, play a crucial role in the initiation and maintenance of the immunological response in otitis media. We discussed a profile of cytokines in various forms of otitis media (otitis media acute, chronic otitis media with effusion) and we underlined the differences between these types. We also described the influence of the most common pathogens of otitis media (S. pneumoniae and H. influenzae) on the cytokine panel in middle ear effusion. We discussed the current data supporting the hypothesis that in some cases the middle ear may act as a target organ for allergic inflammation. Since numerous authors demonstrated that the cytokine profiles are relevant for the evolution of otitis media it has been proposed that measurement of some proinflammatory cytokines in the middle ear effusion may be used in order to monitor the inflammatory process. It has been also proposed using cytokines as a target for pharmacological manipulation in the treatment of otitis media.

Child↗
PubMed1989

[Selective effect of personality markers and psychosocial stress on T lymphocyte subpopulations].

Measurements were made of cellular immune system parameters in a group of healthy medical students. On the basis of psychosocial stress encountered during a five-day topic-centered self-awareness course, we investigated modulation in immunity in relation to personality characteristics. 6 days before the beginning of the seminar personality profiles were drawn and blood samples taken. Further immunological measurements were made on day four of the seminar and three weeks after its conclusion. On the fourth day of the seminar we observed throughout the group higher lymphocyte and suppressor/cytotoxic T lymphocyte counts in comparison with counts one week earlier, and likewise a heightened responsiveness to PHA- and IL-2 stimulation. The T lymphocyte counts had dropped. In subjects with a higher need for succorance/nurturance, the depression of the immune system was manifested in a drop in the helper/inducer T lymphocyte counts, and in the more achievement- and order-oriented subjects in a downregulation as observed by higher suppressor/cytotoxic T lymphocyte counts. Our results show that under psychosocial stress, healthy people experience on the one hand an activation of the immune system, and on the other hand an immunodepression bearing a specific relation to personality characteristics.

Adult↗
PubMed1985

Assessment by a two-site enzyme immunoassay of human epidermal growth factor (urogastrone) in the urine of patients with various gastrointestinal diseases including malignant tumors.

By using our two-site enzyme immunoassay (EIA) system, the levels of human epidermal growth factor (hEGF) in the urine of patients with various gastrointestinal diseases including malignant tumors were measured. Urinary excretion of hEGF in patients having undergone gastric resection, expressed as a function of creatinine, was found to be somewhat decreased. While the levels of hEGF in patients with gastric cancer were significantly increased. Then, the molecular features of hEGF in the urine of patients with gastric cancer were examined by gel filtration. The elution profile demonstrated that high molecular weight components, which immunologically cross-reacted with hEGF, were considerably increased. On the other hand, the level of normal EGF with a molecular weight of 6500 was decreased to some extent. These results suggest that processing of the EGF precursor into an active EGF molecule is partially suppressed in patients with gastric cancer.

Epidermal Growth Factor↗
PubMed2026

Proteomic profiling of plasma extracellular vesicles reveals a therapeutically targetable liver-heart axis in cardiac transplantation.

Extracellular vesicle-mediated interorgan communication represents a promising frontier in transplant immunology; however, its role in cardiac allograft rejection remains poorly characterized. We performed proteomic profiling of plasma-derived extracellular vesicles in a rat heterotopic heart transplantation model and identified a distinct liver-predominant protein signature during acute rejection, with antithrombin III (ATIII) emerging as a top candidate. Functional validation revealed that pharmacological extracellular vesicle inhibition intensified systemic and intragraft inflammation, whereas adeno-associated virus-mediated silencing of hepatic ATIII directly accelerated allograft rejection. Conversely, adeno-associated virus-mediated hepatocyte-specific ATIII overexpression attenuated rejection pathology, reduced immune cell recruitment, and markedly prolonged median graft survival. This protective effect was achieved without evidence of coagulopathic complications, indicating an immunomodulatory mechanism beyond ATIII's canonical anticoagulant function. Mechanistically, ATIII overexpression was associated with upregulation of heme oxygenase-1 (HO-1) in the liver and suppression of proinflammatory cytokine expression in the graft. These findings highlight hepatocyte-derived extracellular vesicles as important mediators of a liver-heart signaling axis in transplant rejection and further implicate the protein ATIII as a contributor to this axis. Our study reveals a therapeutically targetable liver-heart signaling axis in transplant rejection, whereby enhancing liver-derived ATIII or its downstream pathways (such as HO-1) could attenuate acute cardiac allograft rejection.

Animals↗
PubMed1976

Comparison of histocompatibility antigens on cultured human tumor cells and fibroblasts by quantitative antibody absorption and sensitivity to cell-mediated cytotoxicity.

Human tumor and febroblast tissue culture cells were compared to determine the suitability of fibroblasts as control cells in experiments on human tumor serology and cellular immunology. Fibroblasts expressed the same HL-A antigen profile as did melanoma cells. Furthermore, the quantitative expression of the determinants was similar on both cell types. In four of five pairs tested, the fibroblasts displayed similar sensitivity to effector cells generated by mixed lymphocyte culture as did the tumor cells from the same donor, but there were some differences in the effects of specific alloimmune effector cells at high and low effector-to-target ratios on the two types of target cells. Results indicated that fibroblasts are legitimate control target cells for studies in human tumor immunology, if screening assays are done to verify their antigenicity and sensitivity to cell-mediated cytolysis.

Antigen-Antibody Reactions↗
PubMed2006

Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection.

CMVs are beta herpesviruses that establish lifelong latent infection of their hosts. Acute infection of C57BL/6 mice with murine CMV elicits a very broad CD8 T cell response, comprising at least 24 epitopes from 18 viral proteins. In contrast, we show here that the CD8 T cell response in chronically infected mice was dominated by only five epitopes. Altogether, four distinct CD8 T cell kinetic patterns were evident. Responses to some epitopes, including M45, which dominates the acute response, contracted sharply after day 7 and developed into stable long-term memory. The response to m139 underwent rapid expansion and contraction, followed by a phase of memory inflation, whereas the response to an M38 epitope did not display any contraction phase. Finally, responses against two epitopes encoded by the immediate early gene IE3 were readily detectable in chronically infected mice but near the limit of detection during acute infection. CD8 T cells specific for the noninflationary M45 epitope displayed a classic central memory phenotype, re-expressing the lymph node homing receptor CD62L and homeostatic cytokine receptors for IL-7 and IL-15, and produced low levels of IL-2. Responses to two inflationary epitopes, m139 and IE3, retained an effector memory surface phenotype (CD62L(low), IL-7Ralpha(-), IL-15Rbeta(-)) and were unable to produce IL-2. We suggest that immunological choices are superimposed on altered viral gene expression profiles to determine immunodominance during chronic murine CMV infection.

3T3 Cells↗
PubMed2004

Molecular cloning and ovarian expression profiles of thrombospondin, a major component of cortical rods in mature oocytes of penaeid shrimp, Marsupenaeus japonicus.

In penaeid shrimp, cortical rods (CRs) are formed in peripheral crypts of the oocyte after completion of yolk accumulation; subsequently the CRs are utilized as a source of jelly materials that surround fertilized eggs. In our previous study, of five major components, three CR proteins displayed quite similar immunological characteristics. In this study, cDNA sequences and developmental expression profiles at both transcriptional and protein levels were examined to elucidate the molecular characteristics of CR proteins and the process of CR formation. Sequencing cDNAs exhibited the presence of three related forms that have identical sequences except for the loss of 246 and 369 bp in medium and short forms, respectively, suggesting that a single gene generates three transcriptional variants corresponding to the three CR proteins. Their deduced amino acid sequences revealed similarities to those of extracellular matrix proteins in a thrombospondin (TSP) 3,4/cartilage oligomeric protein family, and thereby the CR proteins were designated mjTSP. Semiquantitative analysis by real-time polymerase chain reaction revealed the presence of mjTSP transcripts, at similar levels, in immature, vitellogenic, and mature ovaries. Furthermore, in situ hybridization localized the majority of transcripts in previtellogenic oocytes in ovaries at all developmental stages. By the Western blot, on the other hand, mjTSP proteins were undetectable in immature ovaries but became obvious at the early vitellogenic stage. The immunosignals were enhanced during vitellogenic stages and maintained a high intensity in mature ovaries. Thus, transcription, translation of mjTSP, and formation of the CR structure occurred at different stages of ovarian development.

Amino Acid Sequence↗
PubMed2002

Discordance between genotypic and phenotypic drug resistance profiles in human immunodeficiency virus type 1 strains isolated from peripheral blood mononuclear cells.

The aim of the study was to analyze the relationship between genotypic and phenotypic drug resistance profiles of human immunodeficiency virus type 1 (HIV-1) strains isolated from patients during double-analogue nucleoside therapy. A drug-resistant HIV strain was isolated from 20 out of 25 patients, with 16 (64%) subjects carrying a virus with multiple drug resistance mutations. The most frequent resistance mutations were M184V (18 isolates) and M41L (7 isolates). Discordance between the genotypic and phenotypic profile for at least one drug was detected in 16 out of 25 strains. Particularly, eight isolates had a discordant genotypic-phenotypic resistance pattern for two drugs and one isolate had such a pattern for three drugs. A genotypic resistance pattern with a phenotypic sensitivity profile was detected in six isolates (four resistant to zidovudine and two resistant to lamivudine). On the other hand for several strains a genotypic pattern of sensitivity pattern to abacavir (10 strains), didanosine (7 strains), stavudine (3 strains), zidovudine (2 strains), and lamivudine (1 strain) with a phenotypic resistance profile was detected. After a follow-up period of 8 months, an impairment of virological and immunological parameters was detected only in subjects with an HIV-1 isolate with a phenotypic resistance profile in despite of the genotypic results. Predicting resistance phenotype from genotypic data has important limitations. Despite the low number of patients and the short follow-up period, this study suggests that during failing therapy with analogue nucleosides, a phenotypic analysis could be performed in spite of an HIV genotypic sensitivity pattern.

Anti-HIV Agents↗
PubMed2006

Discovery of eight novel divergent homologs expressed in cattle placenta.

Ten divergent homologs were identified using a subtractive bioinformatic analysis of 12,614 cattle placenta expressed sequence tags followed by comparative, evolutionary, and gene expression studies. Among the 10 divergent homologs, 8 have not been identified previously. These were named as follows: cattle cerebrum and skeletal muscle-specific transcript 1 (CSSMST1), cattle intestine-specific transcript 1 (CIST1), hepatitis A virus cellular receptor 1 amino-terminal domain-containing protein (HAVCRNDP), prolactin-related proteins 8, 9, and 11 (PRP8, PRP9, and PRP11, respectively) and secreted and transmembrane protein 1A and 1B (SECTM1A and SECTM1B, respectively). In addition, two previously known divergent genes were identified, trophoblast Kunitz domain protein 1 (TKDP1) and a new splice variant of TKDP4. Nucleotide substitution analysis provided evidence for positive selection in members of the PRP gene family, SECTM1A and SECTM1B. Gene expression profiles, motif predictions, and annotations of homologous sequences indicate immunological and reproductive functions of the divergent homologs. The genes identified in this study are thus of evolutionary and physiological importance and may have a role in placental adaptations.

Amino Acid Sequence↗
PubMed2001

Gene expression profile of herpesvirus-infected T cells obtained using immunomicroarrays: induction of proinflammatory mechanisms.

Herpesvirus infections can frequently lead to acute inflammation, yet the mechanisms regulating this event remain poorly understood. In order to determine some of the immunological mechanisms regulated by human herpesvirus infections, we studied the gene expression profile of lymphocytes infected with human herpesvirus 6 (HHV-6) by using a novel immunomicroarray. Our nylon-based immunomicroarray contained more than 1,150 immune response-related genes and was highly consistent between experiments. Experimentally, we found that independently of the HHV-6 strain used to infect T cells, multiple proinflammatory genes were increased and anti-inflammatory genes were decreased at the mRNA and protein levels. HHV-6 strains A and B increased expression of the genes for interleukin-18 (IL-18), the IL-2 receptor, members of the tumor necrosis factor alpha superfamily receptors, mitogen-activated protein kinase, and Janus kinase signaling proteins. As reported previously, CD4 protein levels were also increased significantly. Specific type 2 cytokines, including IL-10, its receptor, and IL-14, were downregulated by HHV-6 infection and, interestingly, amyloid precursor proteins and type 1 and 2 presenilins. Thus, T cells respond to HHV-6 infection by inducing a type 1 immune response that may play a significant role in the development and progression of diseases associated with HHV-6, including pediatric, hematologic, transplant, and neurologic disorders.

Base Sequence↗
PubMed1998

Combination of peptide profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and immunodetection on single glands or cells.

The combination of two sensitive and powerful analytical techniques on the same biological sample was examined: (i) matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), which gives informative peptide profiling on complex samples such as organs or cells; (ii) immunological tools such as enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry to probe for specific peptides in biological extracts or cells. The cellular expression of the two precursors of the hyperglycemic hormone (cHH) was analyzed in neurosecretory cells (30-micron diameter) from the crayfish Orconectes limosus. Neurohemal organs were used to optimize the sample preparation and to demonstrate that, after peptide fingerprinting by MALDI-TOF MS, the sample can be recovered from the MALDI plate for further immunological analysis by ELISA. It was also established that, after immunocytochemistry following 4% paraformaldehyde fixation of the organ, the stained tissue could be recovered for further MALDI-TOF MS analysis. This dual characterization was successfully scaled down to the level of a single crayfish neurosecretory cell. Direct peptide profiling by MALDI-TOF MS on a single cHH-producing cell previously identified by immunocytochemistry demonstrated that both procHH isoforms were expressed in each cell analyzed.

Animals↗
PubMed2000

Cytokine profiles in immunocompetent persons infected with Mycobacterium avium complex.

To evaluate the immunologic factors that contribute to protection against Mycobacterium avium complex (MAC), cytokine production by peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus-negative persons with pulmonary MAC (MAC patients) and healthy control subjects with a delayed hypersensitivity skin test response to M. avium sensitin (MAS-positive control subjects) was measured. In MAC patients, mycobacterium-stimulated PBMC produced higher concentrations of interleukin (IL)-10 but lower concentrations of interferon (IFN)-gamma, IL-12, and tumor necrosis factor (TNF)-alpha, compared with PBMC from MAS-positive control subjects. Immunolabeling for intracellular IL-10 revealed that this cytokine was produced by both monocytes and T cells. Alveolar macrophages produced TNF-alpha and IL-10 in response to MAC, which suggests that these cytokines are produced in the lungs of patients with pulmonary disease caused by this pathogen. Our findings suggest that IFN-gamma, TNF-alpha, and IL-12 contribute to protection against MAC, whereas IL-10 is immunosuppressive.

Adult↗
PubMed1998

Chemical, metabolic and immunological characterization of gangliosides of human glioma cells.

The patterns of ganglioside profiles were studied in 10 human glioma and one melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1-4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1-1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha 2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant constituents. The activities of the two key enzymes, GM3 synthetase and lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl showed more pronounced difference in the synthetic rate of each ganglioside type, in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines. On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the antibody binding to these gangliosides were examined in native forms in the cell membrane and in chemically-isolated forms. The intensity of reaction against chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and GM2 was more reactive than GM3; however, the reactivities on the cell surface did not correlate with the chemical content indicating other factors to influence their immunoreactivities.

Antibodies, Monoclonal↗