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At least 19 recordsLinked to original sources

Overweight consumers' salient beliefs on omega-3-enriched functional foods in Australia's Illawarra region.

OBJECTIVE: To determine consumer salient beliefs toward functional foods enriched with omega-3 fatty acids. DESIGN: Focus group interviews with adult consumers using the Theory of Planned Behavior (TPB) as a theoretical framework. SETTING: Community-based residents living in the Illawarra region of New South Wales, Australia. PARTICIPANTS: Forty-two overweight participants (29 female, 13 male) aged 30 to 80 years recruited by advertisement and attending 1 of 6 focus groups, which were recorded and transcribed verbatim. ANALYSIS: Content analysis was carried out, and subcategories were developed to capture the emerging themes according to the TPB model. RESULTS: Most participants were aware of a range of potential benefits of omega-3 fatty acids, but they had reservations about the ability of omega-3-enriched foods to deliver a health benefit. They were concerned about whether these foods were labeled clearly and about the possibility of overdosing. Family and friends were viewed as important in introducing participants to novel foods on the market. Participants regarded dietitians as a credible source and were least trusting of food companies and scientists. Overall, participants reported that cost was a major barrier, and that they would not necessarily trade taste for health benefits. Adding omega-3 fatty acids to foods regarded as less healthful was viewed more as a gimmick rather than a real health benefit. CONCLUSIONS AND IMPLICATIONS: The consumer attitudes and purchase intentions identified in this study will be helpful to educators as they plan messages and strategies to guide dietary choices related to products enriched with omega-3 fatty acids.

Adult↗

GeneFEAST: the pivotal, gene-centric step in functional enrichment analysis interpretation.

SUMMARY: GeneFEAST, implemented in Python, is a gene-centric functional enrichment analysis summarization and visualization tool that can be applied to large functional enrichment analysis (FEA) results arising from upstream FEA pipelines. It produces a systematic, navigable HTML report, making it easy to identify sets of genes putatively driving multiple enrichments and to explore gene-level quantitative data first used to identify input genes. Further, GeneFEAST can juxtapose FEA results from multiple studies, making it possible to highlight patterns of gene expression amongst genes that are differentially expressed in at least one of multiple conditions, and which give rise to shared enrichments under those conditions. Thus, GeneFEAST offers a novel, effective way to address the complexities of linking up many overlapping FEA results to their underlying genes and data, advancing gene-centric hypotheses, and providing pivotal information for downstream validation experiments. AVAILABILITY AND IMPLEMENTATION: GeneFEAST GitHub repository: https://github.com/avigailtaylor/GeneFEAST; Zenodo record: 10.5281/zenodo.14753734; Python Package Index: https://pypi.org/project/genefeast; Docker container: ghcr.io/avigailtaylor/genefeast.

Software↗

Enrichment and functional characterization of Sca-1+WGA+, Lin-WGA+, Lin-Sca-1+, and Lin-Sca-1+WGA+ bone marrow cells from mice with an Ly-6a haplotype.

Approximately 4% to 5% of all bone marrow (BM) cells and 8% to 9% of low density BM cells from FVB/N and BALB/c mice (Ly-6a haplotype) show high to intermediate expression of Ly-6E.1 antigen, recognized by the Sca-1 antibody. Functional properties of enriched cells expressing Ly-6E.1-allelic form of Sca-1 antigen were analyzed and correlated with the properties of cells expressing the carbohydrate binding sites for the lectin wheat-germ agglutinin (WGA). Using equilibrium density centrifugation and fluorescence-activated cell sorting, Sca-1+WGA+, Lin-WGA+, Lin-Sca-1+, and Lin-Sca-1+WGA+ cells were isolated and their splenic colony-forming unit (CFU-S) cell content, radioprotection ability, and long-term reconstitution capacity determined. Enriched Sca-1+WGA+, Lin-WGA+, Lin-Sca-1+ and Lin-Sca-1+WGA+ cells gave rise to 1 CFU-S12 cell out of 26, 20, 21, and 15 sorted cells, respectively. When transplanted into lethally irradiated recipients (100 to 500 cells/mouse) all populations rescued 70% to 100% of recipients in a 30-day radioprotection assay and mediated survival of 40% to 80% of recipients 6 months after transplantation. Using transgenic mice as cell donors we have shown that 12 to 16 weeks after transplantation of 100 Sca-1+WGA+, Lin-WGA+, Lin-Sca-1+, and Lin-Sca-1+WGA+ cells, 40% to 80% of recipients had donor cells in BM, spleen, thymus, and lymph nodes. These results indicate that the population of cells expressing Ly-6E.1 form of Sca-1 antigen in two analyzed mouse strains with Ly-6a haplotype contains CFU-S and long-term repopulating cells. Furthermore, the data suggest that, at least in FVB/N mice, day-12 CFU-S cells and cells with long-term repopulating capacity simultaneously express Ly-6E.1 form of Sca-1 antigen and WGA-binding molecules.

Animals↗

S100P as a Shared Biomarker in Inflammatory Bowel Disease, Colorectal Cancer, and Pancreatic Adenocarcinoma: An Integrated Transcriptomic Analysis.

Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC) and pancreatic adenocarcinoma (PAAD), yet the molecular features shared among these diseases remain incompletely understood. This study aimed to identify common genes and biological pathways associated with IBD, CRC, and PAAD through integrated transcriptomic analysis and experimental validation. Gene expression datasets for IBD, CRC, and PAAD were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Weighted gene co-expression network analysis and differential expression analysis were performed to identify disease-associated and shared genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (analyses were used to explore enriched biological functions and pathways. Immune cell infiltration was evaluated using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts. Receiver operating characteristic analysis was performed to assess the diagnostic performance of common genes. Single-cell RNA sequencing analysis was conducted to examine the cellular distribution of S100P. In addition, the effects of S100P downregulation were evaluated in lipopolysaccharide (LPS)-stimulated colonic epithelial cells. A total of 162 disease-associated genes and four common genes were identified. Functional enrichment analyses indicated significant enrichment of immune- and inflammation-related pathways, including the interleukin-17 signaling pathway. Immune infiltration analysis revealed similar trends in several immune cell populations across IBD, CRC, and PAAD. Single-cell analysis showed elevated S100P expression in epithelial cells from all three diseases. Downregulation of S100P restored the proliferative capacity of LPS-stimulated colonic epithelial cells and reduced inflammatory cytokine expression. Integrated transcriptomic analysis identified S100P as a biomarker associated with IBD, CRC, and PAAD and highlighted shared immune-related features across these diseases.

Humans↗

Selection-by-function: efficient enrichment of cathepsin E inhibitors from a DNA library.

A method for efficient enrichment of protease inhibitors out of a DNA library was developed by introducing SF-link technology. A two-step selection strategy was designed consisting of the initial enrichment of aptamers based on binding function while the second enrichment step was based on the inhibitory activity to a protease, cathepsin E (CE). The latter was constructed by covalently linking of a biotinylated peptide substrate to each of the ssDNA molecule contained in the preliminarily selected DNA library, generating 'SF-link'. Gradual enrichment of inhibitory DNAs was attained in the course of selection. One molecule, SFR-6-3, showed an IC(50) of around 30 nM, a K(d) of around 15 nM and high selectivity for CE. Sequence and structure analysis revealed a C-rich sequence without any guanine and possibly an i-motif structure, which must be novel to be found in in vitro-selected aptamers. SF-link technology, which is novel as the screening technology, provided a remarkable enrichment of specific protease inhibitors and has a potential to be further developed.

Amino Acid Sequence↗

Animal and plant fats selectively modulate oxidizability of rabbit LDL and LDL-mediated disruption of endothelial barrier function.

Enrichment of lipoproteins with fatty acids derived from animal and/or plant fats may modify the oxidizability of lipoproteins and their effects on endothelial barrier function. To test this hypothesis, rabbits were fed for 30 days diets containing 2 g corn oil/100 g diet (low fat diet) or low fat supplemented with 16 g/100 g diet of corn oil, corn oil with added cholesterol, milk fat, chicken fat, beef tallow or lard. Compared with those fed the low fat, serum and LDL cholesterol concentrations were significantly lower in rabbits fed corn oil and greater in animals fed corn oil with added cholesterol or chicken fat. In contrast to the cholesterol data, lipid hydroperoxide levels were highest in oxidized LDL derived from rabbits fed corn oil or lard. LDL vitamin E levels were highest in rabbits fed corn oil with added cholesterol. The significant elevations in linoleic acid [18:2(n-6)] in serum and LDL may partially explain the high oxidizability of LDL in rabbits fed corn oil. LDL isolated from animals fed corn oil, lard or milk fat had significantly greater albumin transfer across cultured endothelial monolayers compared with those of the low fat diet group. Their oxidative modification further contributed to endothelial barrier dysfunction. Dietary cholesterol supplementation to the corn oil diet decreased oxidizability of LDL and partially protected the oxidized LDL-mediated endothelial cell dysfunction as compared with the corn oil diet group. These data suggest that beef tallow and chicken fat are the least atherogenic fats if oxidative modification of LDL is a critical issue in atherosclerosis.

Animals↗

Research on identification of key genes and immune-metabolic mechanisms in atrial fibrillation through integrated multi-cohort transcriptomic analysis and machine learning.

This study aimed to integrate multiple datasets for the identification of atrial fibrillation (AF)-related differentially expressed genes (DEGs), analyze their underlying mechanisms through functional enrichment and machine learning, construct diagnostic models, and explore immune-metabolic interactions to provide novel biomarkers and theoretical foundations. Gene expression datasets were integrated and normalized, with batch effects removed using principal component analysis. Differential expression analysis, functional enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways), and machine learning-based feature gene selection and model construction were performed. Shapley additive explanations analysis was utilized to interpret the constructed models, while gene set enrichment analysis, gene set variation analysis, and immune cell infiltration analysis were conducted to investigate the associations between feature genes and immune infiltration. After integrating and normalizing gene expression data and eliminating batch effects via principal component analysis, 6 DEGs were identified, including 4 upregulated and 2 down-regulated ones. Functional enrichment analysis showed these DEGs were significantly enriched in neuro-related biological processes and pathways, indicating their key roles in AF pathogenesis. Five key feature genes were selected using LASSO, random forest, and support vector machine-recursive feature elimination algorithms. They had significant expression differences between the AF and control groups (P&#x2005;<&#x2005;.001) and were located on distinct chromosomes. The constructed random forest and support vector machine models performed excellently (area under the curve&#x2005;&#x2265;&#x2005;0.85). Shapley additive explanations analysis revealed TNNI1 contributed most to model prediction, with its expression significantly positively correlated with immune cell infiltration. Gene set enrichment analysis and gene set variation analysis analyses further showed feature genes participated in AF pathogenesis by regulating immune modulation, metabolic pathways, and autophagy. Immune cell infiltration analysis found altered proportions of T-cell subsets and M0 macrophages in the AF group, along with complex links between feature gene expression and immune cell function. This study systematically elucidated the unique gene expression patterns and key regulatory pathways associated with AF, clarifying the crucial roles of feature genes in immune regulation, metabolic imbalance, and cellular dysfunction. These findings provide a theoretical basis and potential therapeutic targets for understanding AF pathogenesis and developing targeted treatment strategies.

Atrial Fibrillation↗

[The effect of Siwu Tang on EPO and G-CSF gene expression in bone marrow of irradiated blood deficiency mice].

OBJECTIVE: To observe the blood enriching function of Siwu Tang and its effect on Epo and G-CSF gene expressions in bone marrow of blood deficiency mice, and thus provide the basis for understanding the molecular mechanism of blood enriching function of Siwu Tang. METHOD: The animal model of blood deficiency were established in the mice by using 3.5 Gy60Co gamma-ray. Peripheral blood cells were analyzed and CFU-GM, BFU-E, CFU-E and CFU-mix were counted in bone marrow colony cultured. Both Epo and G-CSF gene expressions in bone marrow were measured with RT-PCR. RESULT: Siwu Tang significantly increased the number of peripheral blood cells and the amount of CFU-GM, BFU-E, CFU-E and CFU-mix in bone marrow and enhanced Epo and G-CSF gene expression in bone marrow in the mice with blood deficiency. CONCLUSION: The promotion of Epo and G-CSF gene expressions in bone marrow may be one of the mechanisms underlying the blood enriching function of Siwu Tang decoction.

Animals↗

Why high-error-rate random mutagenesis libraries are enriched in functional and improved proteins.

The fraction of proteins that retain wild-type function after mutation has long been observed to decline exponentially as the average number of mutations per gene increases. Recently, several groups have used error-prone polymerase chain reactions (PCR) to generate libraries with 15 to 30 mutations per gene, on average, and have reported that orders of magnitude more proteins retain function than would be expected from the low-mutation-rate trend. Proteins with improved or novel function were isolated disproportionately from these high-error-rate libraries, leading to claims that high mutation rates unlock regions of sequence space that are enriched in positively coupled mutations. Here, we show experimentally that error-prone PCR produces a broader non-Poisson distribution of mutations consistent with a detailed model of PCR. As error rates increase, this distribution leads directly to the observed excesses in functional clones. We then show that while very low mutation rates result in many functional sequences, only a small number are unique. By contrast, very high mutation rates produce mostly unique sequences, but few retain function. Thus an optimal mutation rate exists that balances uniqueness and retention of function. Overall, high-error-rate mutagenesis libraries are enriched in improved sequences because they contain more unique, functional clones. Our findings demonstrate how optimal error-prone PCR mutation rates may be calculated, and indicate that "optimal" rates depend on both the protein and the mutagenesis protocol.

Data Interpretation, Statistical↗

Enrichment and functional reconstitution of glutathione transport activity from rabbit kidney mitochondria: further evidence for the role of the dicarboxylate and 2-oxoglutarate carriers in mitochondrial glutathione transport.

In previous studies, we provided evidence for uptake of glutathione (GSH) by the dicarboxylate and the 2-oxoglutarate carriers in rat kidney mitochondria. To investigate further the role of these two carriers, GSH transport activity was enriched from rabbit kidney mitochondria and functionally reconstituted into phospholipid vesicles. Starting with 200 mg of mitoplast protein, 2 mg of partially enriched proteins were obtained after Triton X-114 solubilization and hydroxyapatite chromatography. The reconstituted proteoliposomes catalyzed butylmalonate-sensitive uptake of [(14)C]malonate, phenylsuccinate-sensitive uptake of [(14)C]2-oxoglutarate, and transport activity with [(3)H]GSH. The initial rate of uptake of 5 mM GSH was approximately 170 nmol/min per mg protein, with a first-order rate constant of 0.3 min(-1), which is very close to that previously determined in freshly isolated rat kidney mitochondria. The enrichment procedure resulted in an approximately 60-fold increase in the specific activity of GSH transport. Substrates and inhibitors for the dicarboxylate and the 2-oxoglutarate carriers (i.e., malate, malonate, 2-oxoglutarate, butylmalonate, phenylsuccinate) significantly inhibited the uptake of [(3)H]GSH, whereas most substrates for the tricarboxylate and monocarboxylate carriers had no effect. GSH uptake exhibited an apparent K(m) of 2.8 mM and a V(max) of 260 nmol/min per mg protein. Analysis of mutual inhibition between GSH and the dicarboxylates suggested that the dicarboxylate carrier contributes a somewhat higher proportion to overall GSH uptake and that both carriers account for 70 to 80% of total GSH uptake. These results provide further evidence for the function of the dicarboxylate and 2-oxoglutarate carriers in the mitochondrial transport of GSH.

Animals↗

Identification of thymocyte progenitors in hemopoietic tissues of the rat. II. Enrichment of functional prothymocytes on the fluorescence-activated cell sorter.

A quantitative thymocyte regeneration assay was used to monitor the isolation of functional prothymocytes from rat bone marrow on the FACS. Two prothymocyte subpopulations were tentatively identified on the basis of their relative resistance to dexamethasone. Both populations were comprised of undifferentiated, medium-size cells that displayed large amounts of Thy-1 antigen. Simultaneous sorting of bone marrow cells according to relative low angle light scatter (size) and relative fluorescence intensity for Thy-1 resulted in enrichments of 112-fold and 260-fold, respectively, in prothymocyte activity in untreated and dexamethasone-treated bone marrow. These prothymocyte-enriched cell fractions contained or approximately 75% of total functional prothymocyte activity in bone marrow, and represented 1.1 and 0.35% of total untreated and dexamethasone-treated bone marrow cells. Using these enriched cell fractions, significant thymocyte regeneration is possible with as few as 2 X 10(4) and 1 X 10(4) bone marrow cells, respectively. The possible relationship of these functional prothymocyte subpopulations with CFU-S and with TdT-positive cells is discussed.

Animals↗

Improved enrichment of functionally intact anterior pituitary cells by sequential centrifugal elutriation and density gradient sedimentation.

By centrifugal elutriation and subsequent Percoll density gradient centrifugation, we obtained highly enriched cell populations of the anterior pituitary of ovariectomized adult rats. Enrichment of somatotrophs, gonadotrophs and mammotrophs was 90%, 80% and 77%, respectively (determined by immunocytochemistry). 41% of the GH-cells showed a medium cell size and the highest density. 52% of the LH-cells and 44% of the FSH-cells were found within the population of the large and medium-dense cells. 69% of the prolactin-cells belonged to the small-sized cells with low density. Thyrotrophs were found within all of the size ranges. The majority of the corticotrophs (82%) showed a small cell size. The enriched somatotrophs, LH-gonadotrophs, and mammotrophs responded to GRF, LRH and TRH. Before and after enrichment, somatotrophs and mammotrophs showed the same responsiveness to releasing hormones. In contrast, enriched LH-gonadotrophs exhibited a higher responsiveness to LRH than unfractionated LH-gonadotrophs.

Animals↗

IGF1R deficiency mitigates acute lung injury by promoting anti-inflammatory transcriptional profiles.

BACKGROUND: Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and COVID-19 are characterized by hyperinflammation, commonly referred to as "cytokine storm". The insulin-like growth factor (IGF) pathway, particularly the type 1 receptor (IGF1R), plays a critical role in lung homeostasis and has been implicated in the pathogenesis of pulmonary inflammatory diseases. In mice, widespread Igf1r deficiency attenuates lung inflammation and alveolar damage in bleomycin (BLM)-induced ALI. METHODS: We analyzed single-cell RNA sequencing datasets from lung tissue of COVID-19 cases and control donors as well as mouse lungs to determine Igf1r and IGF family expression across pulmonary cell types. Furthermore, we conducted bulk RNA sequencing on lungs from Igf1r-deficient mice three days after BLM or saline instillation, followed by differential expression and functional enrichment analyses. Findings were further tested through protein detection, assessment of DNA damage and methylation in lung tissues, and functional assays using Igf1r-deficient primary mouse embryonic fibroblasts (MEFs). RESULTS: IGF1R was broadly expressed across multiple cell types in both human and mouse lungs under normal and pathological conditions. Other IGF family members showed cell-type-specific expression, which was modulated by lung injury. Transcriptomic profiling revealed differentially expressed genes between BLM-challenged and control mouse lungs, detecting biological processes and signaling pathways involved in ALI pathobiology. Igf1r deficiency in BLM-challenged mice reversed a large fraction of the transcriptional changes triggered by BLM, including "cytokine storm"-related gene expression. Functional enrichment analysis additionally revealed significant modulation of pathways related to DNA damage, metabolic reprogramming, mitochondrial homeostasis, and epigenetic regulation. In vitro, Igf1r-deficient MEFs exhibited decreased mitochondrial respiration and glycolysis, protection against BLM-induced nuclear damage and mitochondrial accumulation, and decreased histone H3 acetylation. Moreover, Igf1r-deficient mouse lungs displayed increased global DNA methylation following BLM challenge. CONCLUSIONS: IGF1R is a key modulator of the inflammatory and molecular response to ALI pathogenesis. IGF1R deficiency dampens the "cytokine storm", modifies transcriptional and epigenetic profiles and promotes protective cellular responses. These findings highlight IGF1R signaling as a potential therapeutic target in ARDS and related lung injuries.

Animals↗

Prognostic value of genes associated with metastasis and propionate metabolism in rectal cancer.

BACKGROUND: Research indicates that alterations in propionate metabolic pathways play a critical role in cancer development and invasion. Postoperative metastatic recurrence remains a major cause of mortality in patients with rectal cancer. However, propionate metabolism-related genes (PMRGs) in rectal cancer remain insufficiently characterized. Therefore, this study aimed to identify prognostic biomarkers associated with lymph node metastasis and propionate metabolism and construct a risk&#x2011;prediction model for rectal cancer via bioinformatic analyses. METHODS: The Cancer Genome Atlas-Rectum Adenocarcinoma (TCGA-READ) and GSE87211 datasets, together with a curated PMRGs gene set, were used in this study. Pearson correlation analysis was performed to assess associations between overlapping genes (differentially expressed genes between READ and normal tissues, as well as between N0 and N1-N2 stages) and PMRGs, leading to the identification of candidate genes. Functional enrichment analyses were subsequently conducted to characterize the biological roles of these candidates. Prognostic biomarkers were identified using univariate Cox regression combined with least absolute shrinkage and selection operator (LASSO) regression, and a prognostic model was constructed accordingly. Independent prognostic validation was then performed. In addition, immune checkpoint profiling and immunotherapy response analyses were conducted across risk subgroups. Single-gene Gene Set Enrichment Analysis (GSEA) was applied to elucidate the pathways associated with the identified biomarkers. Finally, drug sensitivity analyses were performed. RESULTS: A total of 157 candidate genes were identified through the analytical pipeline. Functional enrichment analysis indicated that these genes were primarily involved in inflammatory response regulation and tumor necrosis factor (TNF) signaling pathways. Five prognostic biomarkers were subsequently identified and incorporated into a predictive model. External validation using the GSE87211 cohort confirmed the robustness of the model. Risk score and disease status were identified as independent prognostic factors. Six immune checkpoint molecules exhibited differential expression between risk groups. Correlation analyses revealed that the risk score was positively associated with most immune checkpoint genes. Single-gene GSEA demonstrated that the biomarkers were mainly enriched in ribosomal biogenesis and cell adhesion molecule-related pathways. Furthermore, 51 therapeutic agents exhibited significantly different half-maximal inhibitory concentration (IC50) values between risk subgroups. CONCLUSIONS: This study identified five biomarkers (CCL24, IGFBP3, ODC1, PYGM, and VKORC1) associated with lymph node metastasis and propionate metabolism pathways, providing a potential foundation for prognostic prediction in patients with rectal cancer.

Rectal cancer↗

MAL, a proteolipid in glycosphingolipid enriched domains: functional implications in myelin and beyond.

The myelin and lymphocyte protein MAL (VIP17/MVP17) is a proteolipid of 17 kD with a hydrophobicity pattern that indicates a four transmembrane domain structure. The MAL cDNA has been cloned from human T-cells, rat oligodendrocytes and the Madin-Darby canine kidney (MDCK) cell line. In the nervous system both myelinating cells, oligodendrocytes and Schwann cells, express MAL protein. MAL expression parallels myelin formation, and MAL is predominantly localized in compact myelin. Prior to myelin formation MAL is also found in immature Schwann cells. Outside the nervous system MAL expression is found in T-cells and in distinct epithelial cells, e.g. in kidney, stomach and thyroid gland, where MAL is localised in the apical plasma membrane. Specific glycosphingolipids, e.g. galactosylceramide and sulfatide, are enriched in such apical kidney and stomach membranes as well as in myelin. MAL copurifies with these glycosphingolipids in detergent insoluble domains, indicating a close association and possible functional interactions of MAL with glycosphingolipids in these tissues. Moreover, recent reports point to additional functions of MAL-glycosphingolipid complexes in signalling, cell differentiation and apical sorting. The role of MAL in the formation, stabilisation and maintenance of glycosphingolipid-enriched membrane microdomains and its contribution to specific membrane properties in myelin and epithelial cells are discussed.

Amino Acid Sequence↗

The relationship between vitamin D levels and depression: a genetically informed study.

BACKGROUND: Low vitamin D (vitD) levels are consistently associated with an increased risk of depression. However, the biological mechanisms underlying this relationship and potential shared genetic overlap remain elusive. METHODS: We investigated the genetic overlap and causal relationships between depression (N&#x2009;=&#x2009;589,356) and vitD levels (N&#x2009;=&#x2009;417,580) using genome-wide association study (GWAS) summary statistics. We performed genome-wide and local genetic correlation analyses, followed by quantification of polygenic overlap variants. Shared genetic loci were identified and mapped to genes, which were further analyzed through gene expression and lifespan brain expression trajectory analyses. Bidirectional causal relationships were examined using multiple Mendelian randomization approaches. RESULTS: We observed significant negative genetic correlations (rg = -0.079) and identified genetic overlap (N&#x2009;=&#x2009;410 variants). Genes mapped to the 13 shared loci showed opposing expression patterns. Tissue- and cell-specific functional enrichment analyses revealed significant signals related to brain development, with distinct patterns emerging between fetal development and adulthood. Shared genes (TRMT61A, ITIH4, RASGRP1, CTNND1, HERC1, IP6K1, FURIN ESR1, ZMYND and GRM5) exhibited notable expression variation in the brian throughout the lifespan, aligning with functional enrichment findings. CONCLUSIONS: Our findings elucidate the shared biological mechanisms underlying the relationship between vitD and depression, suggesting that vitD play an important role in the development of depression through altered early neurodevelopmental processes.

Humans↗

Enrichment and function of urushiol (poison ivy)-specific T lymphocytes in lesions of allergic contact dermatitis to urushiol.

The frequencies of urushiol (poison ivy)-specific T cells were determined in the lesional skin and peripheral blood of patients with allergic contact dermatitis to urushiol. Lesions of urushiol dermatitis were biopsied and the T cells retrieved. Frequencies of Ag-specific cells were determined by limiting dilution assay. Enrichment of urushiol specific T cells was detected in lesional skin or blister fluid of five of five of these donors as well as seven of seven donors with urushiol patch tests. There was also enrichment relative to tetanus toxoid specific T cells in blood and skin of six of seven donors. The frequency of lesional T cells specific for urushiol was less than 1/100 and generally less than 1/1000. Furthermore, the frequency of urushiol specific T cells was often less than 1/10,000 in the peripheral blood during an acute eruption. Autoreactive T cells that proliferated to autologous irradiated PBMC were also enriched in skin lesions relative to blood in 5/5 urushiol patch tests. These autoreactive T cells were expanded and found to be CD4+. It has been proposed that such autoreactive T cells recognize autologous DR and may have a role in immunoregulation. Urushiol-specific T cells were expanded from limiting dilution wells of two donors and characterized. The majority of the urushiol-specific cells were CD8+, and 13/43 lines were suppressive for PWM-induced IgG synthesis.

Antigens, Differentiation, T-Lymphocyte↗

The Mechanism of Celosiae Semen in the Treatment of Diabetic Cataract: Based on Network Pharmacology.

INTRODUCTION: Diabetes mellitus can be complicated by a variety of ocular diseases, among which the postoperative complications of diabetic cataract (DC) are significantly higher than those of non-DC patients. Therefore, finding drugs with natural active ingredients is an urgent challenge in the prevention and treatment of DC. Discovering the potential molecular mechanism of celosiae semen (CS) for the treatment of DC and providing new ideas and programs for the treatment and prevention of DC. METHODS: In this study, network pharmacology, molecular docking, and molecular dynamics simulations were utilized to predict the binding and functional enrichment of the main active ingredients of CS with DC-related targets, and to explore the potential pathways and mechanisms of CS for the treatment of DC. RESULTS: Through database searching and screening, a total of 45 potential targets of CS for the treatment of DC were identified, functionally enriched, and a protein-protein interaction network was constructed, and the key target, SRC, was finally found. The results of molecular docking and molecular dynamics simulation showed that the main active ingredient of CS, stigmasterol, could bind stably to the key target SRC protein. DISCUSSION: This study not only elucidates the phyto-pharmacological basis of CS in DC management but also provides a framework for developing natural product-derived targeted therapies against diabetic ocular complications. The integration of modern genomics and computational chemistry to deconstruct the therapeutic effects of traditional Chinese herbal medicines has great clinical significance in expanding the scope of traditional Chinese medicines for the treatment of DC and promoting precision targeting. However, this requires verification through basic experiments. CONCLUSION: These computational findings suggest that CS may exert its anti-cataract effects through the multi-target modulation of diabetic metabolic pathways and SRC-mediated signaling cascades.

Humans↗