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PubMed2026

Lipid Metabolism-related lncRNA Model Identifies AC026412.3 as a Driver of Fatty Acid β-oxidation in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Dysregulated lipid metabolism contributes to hepatocellular carcinoma (HCC) progression, but the prognostic value and mechanistic roles of lipid metabolism-related long noncoding RNAs (LRLs) remain insufficiently characterized. This study aimed to construct and validate an LRL-based prognostic model and to investigate the biological function and metabolic mechanism of AC026412.3 in HCC. METHODS: Transcriptomic and clinical data from the The Cancer Genome Atlas Liver Hepatocellular Carcinoma cohort were analyzed to identify LRLs based on their correlation with curated lipid metabolism genes. Differential expression, univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analyses were performed to construct a prognostic signature, which was evaluated using Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses. Functional enrichment analyses Gene Ontology [GO], Kyoto Encyclopedia of Genes and Genomes [KEGG] and gene set enrichment analysis [GSEA], mutation profiling, tumor mutational burden, immune infiltration estimation, and consensus clustering were applied to characterize associated features. A key LRL was identified through integrated bioinformatic screening and prioritization. Its biological role was assessed by quantitative reverse transcription polymerase chain reactionq (RT-PCR), western blotting, BODIPY staining, colony formation, Transwell assays, and xenograft models. RNA sequencing followed by pathway enrichment analysis was conducted to explore underlying mechanisms. RESULTS: A three-LRL signature (AL031985.3, NRAV, and AC026412.3) stratified HCC patients into distinct risk groups with significantly different survival outcomes and demonstrated independent prognostic value. AC026412.3 was markedly upregulated in HCC and associated with poor prognosis. Functional assays demonstrated that AC026412.3 promoted proliferation, invasion, and tumor growth while reducing lipid accumulation. Mechanistically, AC026412.3 upregulated solute carrier family 22 member 5 (SLC22A5), enhanced fatty acid β-oxidation, and increased adenosine triphosphate (ATP) production, thereby driving metabolic reprogramming. CONCLUSIONS: This study establishes a robust LRL-based prognostic model and identifies AC026412.3 as a key regulator of lipid metabolic reprogramming via the SLC22A5-fatty acid β-oxidation axis, highlighting its potential as a biomarker and therapeutic target in HCC.

HCC↗
PubMedDate not supplied

Pathogenetic and diagnostic aspects of siliconosis.

Silicones have an adverse effect on human health well beyond that suggested by the recent superficial public controversy. The evidence for immune responses to injected/implanted silicones is extensive, detailed, often very specific, and not at all new. Comprehending the immunopathogenicity, realized and potential, of silicone has grown as our general understanding of the immune system has developed. Several major issues in furthering this comprehension pertain to the nature of the essential epitope, special risk of silicones to women, and definition of the chronic disease complex so evident clinically, one defying classification within currently traditional disease categories and states. The commentary presented here emphasizes the immunopathic evidence, explores the question of the essential epitope, estimates the minimal threshold of silicone load for immune reactivity, presents a profile of autoantibodies for siliconosis, and calls attention to specific silicone-based female contraceptive modalities. The silicone content of personal care products, not always revealed by retail package labeling, is explored as a potential sensitizing factor in the environment.

Autoantibodies↗
PubMed2006

Impaired regulation of immune responses in cognitive decline and Alzheimer's disease: lessons from genetic association studies.

Altered levels of cytokines and acute-phase proteins have been described in the blood and brain of patients with Alzheimer's disease. Microglia are resident cells of the brain and metabolic upregulation of these cells may play a crucial role in the development of the neurodegeneration associated with Alzheimer's disease. Studies focusing on gene polymorphisms of molecules with immune regulatory function have demonstrated an association with increased risk of the disease and confirmed the pivotal role of immune responses in Alzheimer's disease pathogenesis. Several gene variants may also influence the rate of the cognitive decline associated with the disease. A definite immune-related gene polymorphism profile may be a feature of a limited group of patients with early onset of the disease and fast clinical deterioration. Only this group of patients may benefit from anti-inflammatory treatment.

Alzheimer Disease↗
PubMed2026

Mitochondria related gene signature serves as prognosis prediction and risk stratification of cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CHOL) is a highly aggressive biliary malignancy with poor clinical outcomes and limited effective prognostic biomarkers. Mitochondrial dysfunction participates in multiple oncological processes of CHOL, yet the prognostic roles of mitochondria‑related genes (MRGs) remain poorly understood. This study aimed to characterize MRGs expression in CHOL and develop a molecular prognostic model for predicting patient survival and guiding clinical management. METHODS: RNA sequencing (RNA-seq) and clinical data of CHOL were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) (GSE89748) databases. Differentially expressed MRGs were identified, and 10 machine learning algorithms were used to construct prognostic models. The optimal model (highest average C-index) was selected to establish a mitochondria-related risk score (MRRS), which was validated internally and externally. A nomogram integrating clinical factors and MRRS was developed, and biological mechanisms were explored via functional and immune analyses. RESULTS: A 3-MRG (MAP3K1, MRPL18, PYGB) prognostic signature was constructed, stratifying patients into high- and low-risk groups with significantly different overall survival. The model showed high predictive accuracy, with an area under the curve (AUC) up to 0.845, and MRRS was an independent prognostic factor. The signature was associated with mitochondrial pathways, and the high-risk group had distinct immune infiltration and mutation profiles. CONCLUSIONS: A validated MRG prognostic model effectively stratifies CHOL patients and has potential clinical value for prognosis prediction. Further validation in larger cohorts is needed to confirm its applicability.

Cholangiocarcinoma (CHOL)↗
PubMed1993

PPD-specific IgG and IgG subclasses in the sera of pulmonary tuberculosis patients.

This study was performed to characterize the humoral immune responses with isotype profiles in Mycobacterium tuberculosis infection. PPD-Specific IgG and IgG subclasses were measured using ELISA in 212 patients with pulmonary tuberculosis. The values of PPD-specific IgG were significantly higher in pulmonary tuberculosis patients than those in the control group, and were correlated to the severity of illness (P < 0.01). The specificity and sensitivity of ELISA for IgG antibodies were 1.0 and 0.81, respectively as determined in 212 sera from tuberculosis patients and 44 from healthy controls. The positive predictive value was 1.0 (171/171), while negative predictive value was 0.52 (44/85). The values of PPD-specific IgG were significantly decreased after 2-4 months of treatment. Among the moderately and far advanced pulmonary tuberculosis patients, the values of PPD-specific IgG were significantly decreased in responders after 6 months of treatment. However, PPD-specific IgG in nonresponders was increased (P < 0.01). PPD-specific IgG subclass responses were evident to all four IgG subclasses. No changes of isotype response according to the severity of the disease were observed.

Adolescent↗
PubMed1991

Effect of dietary fats on the fatty acid compositions of serum and immune tissues in chickens.

The purpose of the present study was to measure the effect of dietary fat source on the fatty acid composition of immune cells in chickens. One-day-old female chicks were fed corn and soybean meal-based diets containing 7% of either lard, corn oil, canola oil, linseed oil (LO), or menhaden fish oil (FO). After being fed experimental diets for 3 to 4 wk, samples of serum, thymus glands, bursa of Fabricius glands, and splenocytes were collected. All samples were frozen and stored at -80 C until lipid analysis. Results indicate that the fatty acid composition of the sera and immune tissues of chickens reflected the fat in the diet. The relative content of long-chain polyunsaturated fatty acids varied considerably among immune tissues, with, from greatest to least, spleen, bursa, and thymus. The young chick demonstrated a substantial capacity to elongate and desaturate linoleic (C18:2n-6) and alpha-linolenic acids (C18:3n-3). Feeding chicks fats rich in n-3 fatty acids (e.g., LO or FO) decreased significantly (P less than .05) the level of arachidonic acid (C20:4n-6) present in the serum and immune tissues by 50 to 75%. The levels of eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C20:6n-3) were substantially increased (P less than .05) by FO and LO feeding. However, LO, which is rich in C18:3n-3, was generally only one-half to one-quarter as effective as FO in elevating EPA and DHA levels in immune tissues. The implications for these changes in serum and immune tissue fatty acid profiles are discussed briefly.

Animals↗
PubMed2025

Recent Advances in nccRCC Classification and Therapeutic Approaches.

Non-clear cell renal cell carcinoma (nccRCC) constitutes a biologically diverse category of renal malignancies. The 2022 WHO classification framework has significantly evolved to incorporate molecularly defined entities alongside traditional histologic subtypes, reflecting the growing recognition of distinct pathogenic drivers. Current therapeutic paradigms for advanced disease remain suboptimal, with treatment strategies often extrapolated from clear cell renal cell carcinoma (ccRCC). In this review, we highlight transformative multi-omics approaches to address nccRCC's profound heterogeneity, which enables molecular stratification beyond conventional pathology, identifying novel subtypes characterized by unique immune microenvironment features, metabolic profiles, and genomic instability patterns. This molecular reclassification provides a foundational framework for precision oncology, facilitating patient selection for targeted therapies and immunomodulatory strategies. Advancements in multi-omics subtyping represent a pivotal shift toward biologically guided clinical management and underscore the imperative for biomarker-driven therapeutic development in nccRCC.

Humans↗
PubMed1981

Correlation of circulating immune complexes and complement breakdown products with the severity of the disease in human schistosomiasis mansoni.

Circulating immune complexes and complements compounds were measured in serum and plasma from 66 patients with three different clinical forms of chronic schistosomiasis mansoni: intestinal, hepato-intestinal and hepatosplenic. Three different methods were used: the 125I-C1q-binding assay, conglutinin-binding assay (KgB) and Raji cell-binding assay. Approximately 25% of the patients were positive for circulating immune complexes as measured by the C1q and Raji assays. The levels of complexes increased significantly with the severity of the disease. 60% of the patients were positive for immune complexes as measured by the KgB-assay but the incidence of positive results was not clearly influenced by the stage of the disease. There was no significant correlation between immunoglobulin levels and immune complexes. The complement profile of these patients does not suggest a dramatic activation of the complement system. However, there was a progressive decrease in the plasma levels of C4 and an increase of C3d levels which correlated significantly with the severity of the disease.

Adolescent↗
PubMed2001

Tumor cell lysate-pulsed human dendritic cells induce a T-cell response against pancreatic carcinoma cells: an in vitro model for the assessment of tumor vaccines.

Dendritic cells (DCs) are potent antigen-presenting cells and play a pivotal role in T cell-mediated immunity. DCs have been shown to induce strong antitumor immune responses in vitro and in vivo, and their efficacy is being investigated in clinical trials. Compared with vaccination strategies directed against a single tumor antigen, tumor-cell lysate as the source of antigen offers the potential advantage of inducing a broad T-cell response against multiple known, as well as unknown, tumor-associated antigens expressed by the individual tumor. We used pancreatic carcinoma cell lines to develop an in vitro model for monitoring T-cell responses induced by lysate-pulsed DCs. Monocyte-derived DCs of HLA-A2(+) donors were pulsed with lysate generated from the HLA-A2(+) pancreatic carcinoma cell line Panc-1. In some experiments, the immunogenic protein keyhole limpet hemocyanin (KLH) was added to the lysate. Subsequently, the antigen-loaded DCs were activated with tumor necrosis factor-alpha and prostaglandin E(2). Autologous mononuclear cells were cocultured with DCs in the presence of low-dose interleukin (IL)-2 and IL-7 and were restimulated weekly with new DCs. High levels of IL-12 and IFN-gamma could be detected in the supernatants, indicating a T-helper type 1-type immune response. This cytokine profile was associated with the expression of the activation marker CD69 on both T helper and CTLs and with an antigen-induced proliferative T-cell response. After 4 weeks, CTL-mediated cytotoxicity was assessed. Tumor cell lysis was specific for Panc-1 tumor cells and was MHC class I-restricted. Cytokine secretion, CD69 expression of T cells, and antigen-induced T-cell proliferation correlated with the cytotoxic activity and were more pronounced when KLH was added to the lysate. This is the first study to show that T cells specific for pancreatic carcinoma cells can be generated in vitro by lysate-pulsed DCs and that the T-cell response can be enhanced by KLH. This in vitro model can be applied to compare different strategies in the development of DC-based tumor vaccines.

Antigen Presentation↗
PubMed2003

A randomized controlled trial comparing split and subunit influenza vaccines in adults in Colombia.

In a two-center, comparative trial, 344 adults were randomly assigned to receive a single dose of inactivated split-virion (Imovax Gripe) or sub-unit (Agrippal S1) influenza vaccine (1999-2000 formulations). For analysis, study groups were subdivided into adult (18-60 years old) and elderly (over 60 years) subjects. Blood was drawn immediately before and one month after vaccination, safety was evaluated using a blind-observer design based on reporting of solicited and unsolicited adverse events. Both vaccines were very well tolerated, had similar reactogenicity profiles, and elicited fewer reports of reactions in elderly individuals. Post-vaccination Imovax Gripe induced seroprotective antibody titers against the three vaccine strains in 94-99% of adults and 88-97% of elderly subjects, compared with 88-100% and 88-98%, respectively, of those given Agrippal S1. In conclusion, the split-virion and sub-unit influenza vaccines had similar safety and reactogenicity profiles, and elicited satisfactory immunity in adult and elderly subjects. However, higher post-vaccination geometric mean titer (GMT) values in response to the B strain were seen with the split vaccine Imovax Gripe, giving it a better overall immunogenicity.

Adolescent↗
PubMed2006

[Preliminary study on expression of oviductin in mouse cervix].

In the present study,in order to investigate the pattern of the expression and location of oviductin using RT-PCR and Western blot,a 410bp cDNA fragment was amplified from mouse cervix tissue. Sequencing analysis and homology comparison with BLAST alignment showed that this fragment amplified from mouse cervix was homologous to the region from +310 to +714 of the mouse OGP gene in Genebank by the degree up to 100%. Western blot showed 60 KD and 30 KD components from mouse cervix same as those from mouse oviduct mucosa epithelium. Semi-quantitative RT-PCR analysis showed that expression of OGP was significantly higher at the estrous stage than that of non-estrous stage and almost no expression in the immature mouse. Those results suggest that the mRNA level of mouse cervix oviductin was related to estrous cycle,implied with estrogen-dependence. To further confirm the results,in situ hybridization histochemistry analysis showed that OGP mRNA was expressed at columnar epithelium of mouse cervix. To clarify the possible significance of oviductin expressed at the cervix, the function of oviductin on the mobility of human sperm was studied using "loss-of-function". The VAP, VCL, ALH, VSL showed no significant differences of the mobility of the human sperm in the conditioned medium blocked by the anti-CTP rOGP (rabbit Oviductin) antiserum compared with that in the conditioned medium of the normal rabbit serum. These results suggest that rOGP may not affect the mobility of human sperm in vitro.

Animals↗
PubMedDate not supplied

Cloning and expression in Escherichia coli of Mycoplasma gallisepticum antigens recognized by sera from infected chickens.

A clone bank of Mycoplasma gallisepticum (MG) strain A5969 DNA was prepared in the expression vector phage lambda gt11. Approximately 75% of the resulting phages were recombinants, based upon the insertional inactivation of the lacZ gene of the vector. Clones were screened immunologically with serum prepared from specific-pathogen-free white leghorn chickens that had been infected with aerosolized MG. Approximately 250 clones, or less than 1% of the recombinant phage, reacted positively to various degrees with the test serum and failed to react with serum from uninfected specific-pathogen-free control chickens. A single clone was chosen at random for comparison with a vector control by western immunoblot, revealing a polypeptide of 140,000 molecular weight in the clone profile but not the control profile that reacted with immune serum. Clones expressing MG antigens recognized during infection may provide an improved means for antigen preparation for serologic diagnosis of mycoplasmosis.

Animals↗
PubMed1989

Subclass characterization of IgG anti-S.typhi lipopolysaccharide antibodies with commercial monoclonal antibodies.

We have evaluated several commercial monoclonal antibodies, specific for human IgG subclasses, for their reactivity in an ELISA test for the characterization of subclasses of IgG anti- Salmonella typhi lipopolysaccharide (LPS) antibodies. Four monoclonals, each specific for a single IgG subclass, were chosen for their good reactivity. In 19 typhoid and non-typhoid serum samples, the sum of the ELISA values obtained with the four subclass-specific monoclonals was highly correlated with the ELISA values obtained with a monoclonal anti-total IgG. Moreover, there was no competition among the various IgG subclasses of anti-LPS antibodies. These data indicate that the subclass distribution of IgG anti-LPS antibodies, calculated on the basis of ELISA values in the subclass-specific assays, is likely to reflect the actual distribution of the different subclasses in whole serum. Different subclass patterns of IgG anti-LPS antibodies were observed in serum samples from 11 patients with typhoid fever, with IgG1 and IgG2 being the most represented subclasses. The ELISA method described here will be useful to elucidate the factors that influence the anti-LPS subclass profile during the humoral immune response to Salmonella typhi.

Adolescent↗
PubMed1996

Immunological outcome measures.

The determination of immunoglobulin E (IgE) antibodies by one of several laboratory tests, by skin-prick tests or by appropriate challenge procedures is useful either to identify atopic individuals or as outcome predictors in wheezy children. The determination of allergen specific antibodies of other isotypes, e.g. immunoglobulin G (IgG) and IgG subclass antibodies in serum, secretory immunoglobulin A (IgA) and various immune complexes, have not been confirmed as clinically useful tools for this purpose. Immune responses in atopic and nonatopic individuals differ in several other respects, e.g. they express somewhat different lymphocyte and cytokine profiles, as well as cellular immune responses. At present, none of these differences can be employed clinically, however, and the determinations are still research tools. A reduction in exposure to allergens is associated with fewer symptoms and improved lung function in sensitized individuals. There are also indications that reduced exposure to allergens in early infancy may prevent, or at least delay, sensitization and wheezing in atopic children. Determination of exposure to major indoor allergens, e.g. house dust mite, cat and cockroach allergens, are, therefore, of value in the assessment of the wheezing atopic infant. The relationship between wheezing disorders and the results of most immunological tests remain to be defined. In particular, the sensitivity, positive and negative predictive value and the diagnostic efficiency of recently introduced immunoassays remain to be defined. At present, there are no immunological tests of documented value to identify the severity of disease, or to predict the outcome of a certain therapy.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

Intravenous immunoglobulin preparations as immunomodulatory agents.

Certain immunopathologic conditions, such as hypersensitivity and autoimmune diseases, are characterized by quantitative and/or qualitative alterations of immune reactions. It is now believed that such immunologic disturbances generate from inadequate internal control and regulation of immunologic reactivity. Important member of the complex regulatory network that supervises an immune response are antibodies themselves. Since antibody is bifunctional molecule, its regulatory action deals with two separate molecular structures denoted as Fab and Fc portion. By Fab fragment, antibody interferes with the reaction with antigens, or participates in the regulatory idiotype/antiidiotype interactions. Fc-mediated regulation includes influence on complement activation cascade, formation and clearance of immune complexes, phagocytosis, ADCC activity, T- and B-cell function, cytokine profile, etc. In general, antibody triggers immune reactions, but also has the capacity to suppress them. Exogenous antibodies are likely to elicit similar effects on immune processes. Actually, it has been demonstrated that intravenously given immunoglobulins, particularly high-dose IgG, effectively combat harmful immune response in some chronic inflammatory and autoimmune disorders. Hence, preparations of immunoglobulins for intravenous use (IVIG) can be considered as an immunomodulatory agent. To achieve the property of modulating the immune response, IVIG products must contain intact (7S) IgG molecule and maintain sufficient concentrations in plasma.

Adjuvants, Immunologic↗
PubMed1997

[Indications and results of breast implant replacement with implants pre-filled with silicone gel].

Based on a series of 74 patients, the authors report their experience of reoperation on unsatisfactory breast implants by the implant replacement technique using silicone prefilled implants. In 92 (57.8%) of the 160 cases, the implant was modified because of a peri-implant capsule, with a satisfactory aesthetic result after only a single operation. However, this leaves the problem of repeated surgical operations, especially in the context of Baker stage IV capsules, which are only partially improved after two to three surgical operations. A particular surgical revision technique is required in the cases, while the role of in situ cortivazol is under investigation. This series comprises two patients with auto-immune disease and dysimmune profiles, not exarcerbate by secondary surgery. Analysis of this series clearly argues in favour of reoperation for unsatisfactory breasts implants. Squeezing manoeuvres appear to be dangerous and useless. Textured implants filled with very cohesive silicone gel should be maintened in view of the absence of any reported serious complications.

Breast Implantation↗
PubMed2026

Determinants of pro- and anti-inflammatory cytokine profiles across populations.

BACKGROUND: Cytokine dysregulation contributes to chronic inflammation and immune-mediated diseases, yet population-level determinants of pro- and anti-inflammatory cytokines remain poorly characterized. We aimed to identify demographic and lifestyle determinants of plasma cytokine levels and evaluate reproducibility of inflammatory patterns across European populations. METHODS: In the population-based Rotterdam Study cohort (n&#x2009;=&#x2009;3,456; mean age 57 years; 56% female), we examined associations between plasma levels of nine cytokines (Olink Inflammation Panel) and age, sex, smoking, body mass index (BMI), and alcohol consumption. Linear and non-linear regression models were applied, with stratified analyses where appropriate. Cytokine clustering was assessed using principal component analysis (PCA). Findings were replicated in two independent European cohorts using identical protocols. Additionally, associations between raw IL-6 levels and determinants were meta-analyzed across the two replication cohorts (total n&#x2009;>&#x2009;4,000). RESULTS: Plasma IL-10, IL-6, IL-17&#xa0;A, TNF, IFN-&#x3b3;, IL-18, and IL-17&#xa0;C increased with age; IL-18 and IL-17&#xa0;C followed non-linear trends (P < 0.01). Females had lower IL-18 and IL-17&#xa0;C levels (&#x3b2;: -&#x2009;0.41 and -&#x2009;0.32, respectively) but higher IFN-&#x3b3; (&#x3b2;: 0.17). Smoking was associated with higher IL-10, IL-6, IL-18, and IL-17&#xa0;C (&#x3b2; range: 0.10-0.54) and lower IFN-&#x3b3; (&#x3b2;: -0.15) and IL-13 (&#x3b2;: -&#x2009;0.10). BMI was positively associated with IL-6, IL-18, TNF, and IL-17&#xa0;A levels (P < 0.05), and inversely with IL-10 (P < 0.001). Sex-specific associations were observed for alcohol use. PCA revealed stable pro-inflammatory cytokine clustering, consistent across cohorts. Replication in analyses confirmed a robust, shared pro-inflammatory signature, and meta-analysis supported consistent associations with older age, higher BMI, and current smoking. CONCLUSIONS: Older age, higher BMI, male sex, and current smoking are consistent and reproducible determinants of inflammatory cytokine profiles across European populations. These findings support the use of cytokine profiling in enhancing risk stratification for inflammation-related diseases.

Humans↗