Search Results (12,372)

Background/Objectives: Restored CD4 absolute counts (CD4AC) and CD4/CD8 ratio in the setting of continuous antiretroviral treatment (ART) do not exclude a low-level immune activation associated with HIV reservoirs, microbial translocation, or the side effects of ART itself, which accelerates the aging of people living with HIV (PLHIV). To delineate biomarkers of incomplete immune restoration in PLHIV on successful ART, we evaluated T-lymphocyte mitochondrial parameters in relation to phenotypic markers of immune exhaustion and senescence. Methods: PLHIV with sustained viral suppression, CD4AC >500 and CD4/CD8 ratio >0.9 on ART (n = 39) were compared to age-matched ART-naïve donors (n = 27) and HIV(–) healthy controls (HC, n = 35). CD4 and CD8 differentiation and effector subsets (CCR7/CD45RA and CD27/CD28), activation, exhaustion, and senescence markers (CD38, CD39 Treg, CD57, TIGIT, and PD-1) were determined by flow cytometry. Mitochondrial mass (MM) and membrane potential (MMP) of CD8 and CD4 T cells were evaluated with MitoTracker Green and Red flow cytometry dyes. Results: ART+PLHIV differed from HC by increased CD4 TEMRA (5.3 (2.1–8.8) vs. 3.2 (1.6–4.4), p < 0.05), persistent TIGIT+CD57–CD27+CD28– CD8+ subset (53.9 (45.5–68.9) vs. 40.1 (26.7–58.5), p < 0.05), and expanding preapoptotic TIGIT–CD57+CD8+ effectors (9.2 (4.3–21.8) vs. 3.0 (1.5–7.3), p < 0.01) in correlation with increased CD8+ MMP (2527 (1675–4080) vs.1477 (1280–1691), p < 0.01). These aberrations were independent of age, time to ART, or ART duration, and were combined with increasing CD4 T cell MMP and MM. Conclusions: In spite of recovered CD4AC and CD4/CD8 ratio, the increased CD8+ MMP, combined with elevated markers of exhaustion and senescence in ART+PLHIV, signals a malfunction of the CD8 effector pool that may compromise viral reservoir latency. Full article

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis. Full article

This study aimed to explore the effects of dietary supplementation with soy isoflavones (SI) in the later stages of pregnancy on the antioxidant capacity of sows and intestinal health of newborn piglets. Forty sows with similar body weights and parity (average of 1–2 parity) were randomly divided into two groups (n = 20): the control group and SI group (dose: 100 mg/kg of feed). Feeding was started on day 85 of gestation and continued until farrowing. SI supplementation significantly increased the antioxidant levels in the serum of the sows and newborn piglets, placental tissue, and the intestinal tract of the piglets. This observation was indicated by a decreased activity of the oxidative stress marker malondialdehyde (MDA); increased activity of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase; and enhanced total antioxidant capacity. The organ indices of the intestine and liver and the villus height/crypt depth of the jejunum of newborn piglets significantly increased. SI supplementation activated the Nrf2 signaling pathway in the jejunum of neonatal piglets and the expression of placental antioxidant proteins, and it downregulated the expression of the Bax and Caspase 3 apoptotic proteins in the placenta and neonatal piglets. Intestinal and placental barrier integrity was strengthened. For example, ZO-1, Occludin, and Claudin 1 exhibited elevated expression. In conclusion, dietary supplementation with SI enhanced the antioxidant capacity of sows and piglets and improved the health of the placenta and intestinal tract of newborn piglets. Full article

Targeted radioligand therapy (RLT) is an emerging field in anticancer therapeutics with great potential across tumor types and stages of disease. While much progress has focused on agents targeting somatostatin receptors and prostate-specific membrane antigen (PSMA), the same advanced radioconjugation methods and molecular targeting have spurred the development of numerous theranostic combinations for other targets. A number of the most promising agents have progressed to clinical trials and are poised to change the landscape of positron emission tomography (PET) imaging. Here, we present recent data on some of the most important emerging molecular targeted agents with their exemplar clinical images, including agents targeting fibroblast activation protein (FAP), hypoxia markers, gastrin-releasing peptide receptors (GRPrs), and integrins. These radiopharmaceuticals share the promising characteristic of being able to image multiple types of cancer. Early clinical trials have already demonstrated superiority to ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) for some, suggesting the potential to supplant this longstanding PET radiotracer. Here, we provide a primer for practicing radiologists, particularly nuclear medicine clinicians, to understand novel PET imaging agents and their clinical applications, as well as the availability of companion targeted radiotherapeutics, the status of their regulatory approval, the potential challenges associated with their use, and the future opportunities and perspectives. Full article

Background: Gastric cancer (GC) represents a significant global health burden with considerable heterogeneity in clinical and molecular behavior. The anatomical site of tumor origin—proximal versus distal—has emerged as a determinant of prognosis and response to therapy. The aim of this paper is to elucidate the transcriptional and regulatory differences between proximal gastric cancer (PGC) and distal gastric cancer (DGC) through master regulator (MR) analysis. Methods: We analyzed RNA-seq data from TCGA-STAD and microarray data from GEO (GSE62254, GSE15459). Differential gene expression and MR analyses were performed using DESeq2, limma, corto, and RegEnrich pipelines. A harmonized matrix of 4785 genes was used for MR inference following normalization and batch correction. Functional enrichment and survival analyses were conducted to explore prognostic associations. Results: Among 364 TCGA and 492 GEO patients, PGC was associated with more aggressive clinicopathological features and poorer outcomes. We identified 998 DEGs distinguishing PGC and DGC. PGC showed increased FOXM1 (a key regulator of cell proliferation), STAT3, and NF-κB1 activity, while DGC displayed enriched GATA6, CDX2 (a marker of intestinal differentiation), and HNF4A signaling. Functional enrichment highlighted proliferative and inflammatory programs in PGC, and differentiation and metabolic pathways in DGC. MR activity stratified survival outcomes, reinforcing prognostic relevance. Conclusions: PGC and DGC are governed by distinct transcriptional regulators and signaling networks. Our findings provide a biological rationale for location-based stratification and inform targeted therapy development. Full article

The development of scalable, non-invasive tools to assess tumor responsiveness to structurally active immunoformulations remains a critical unmet need in solid tumor immunotherapy. Here, we introduce a real-time, ex vivo functional system to classify tumor cell lines exposed to a phospholipoproteomic platform, without relying on cytotoxicity, co-culture systems, or molecular profiling. Tumor cells were monitored using IncuCyte^® S3 (Sartorius) real-time imaging under ex vivo neutral conditions. No dendritic cell components or immune co-cultures were used in this mode. All results are derived from direct tumor cell responses to structurally active formulations. Using eight human tumor lines, we captured proliferative behavior, cell death rates, and secretomic profiles to assign each case into stimulatory, inhibitory, or neutral categories. A structured decision-tree logic supported the classification, and a Functional Stratification Index (FSI) was computed to quantify the response magnitude. Inhibitory lines showed early divergence and high IFN-γ/IL-10 ratios; stimulatory ones exhibited a proliferative gain under balanced immune signaling. The results were reproducible across independent batches. This system enables quantitative phenotypic screening under standardized, marker-free conditions and offers an adaptable platform for functional evaluation in immuno-oncology pipelines where traditional cytotoxic endpoints are insufficient. This approach has been codified into the STIP (Structured Traceability and Immunophenotypic Platform), supporting reproducible documentation across tumor models. This platform contributes to upstream validation logic in immuno-oncology workflows and supports early-stage regulatory documentation. Full article

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

Chronic inflammatory response syndrome (CIRS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are debilitating multisystem illnesses that share overlapping symptoms and molecular patterns, including immune dysregulation, mitochondrial impairment, and vascular dysfunction. This review provides a chronological synthesis of biomarker development in CIRS, tracing its evolution from early functional tests such as visual contrast sensitivity (VCS) to advanced transcriptomic profiling. Drawing on peer-reviewed studies spanning two decades, we examine the layered integration of neuroendocrine, immunologic, metabolic, and genomic markers that collectively support a multisystem model of innate immune activation specific to environmentally acquired illness. Particular focus is given to the Gene Expression: Inflammation Explained (GENIE) platform’s use of transcriptomics to classify disease stages and distinguish CIRS from other fatiguing conditions. While ME/CFS research continues to explore overlapping pathophysiologic features, it has yet to establish a unified diagnostic model with validated biomarkers or exposure-linked mechanisms. As a result, many patients labeled with ME/CFS may, in fact, represent unrecognized CIRS cases. This review underscores the importance of structured biomarker timelines in improving differential diagnosis and guiding treatment in complex chronic illness and highlights the reproducibility of the CIRS framework in contrast to the diagnostic ambiguity surrounding ME/CFS. Full article

Background: Obesity is associated with insulin resistance (IR) and characterized by impaired activation of the PI3K/AKT route and glucose uptake. Elevated plasma levels of palmitic acid (PA) diminish insulin signaling in vitro and in vivo. Origanum vulgare L. essential oil (OVEO) is rich in monoterpenes with protective effects against IR. Objective: The study aimed to assess total phenols content and antioxidant activity of OVEO and its cytotoxicity, as well as its effect on insulin signaling and glucose uptake in PA-treated adipocytes. Methods: The quantification of total phenolic content was determined using the Folin–Ciocalteu method, while the antioxidant capacity of OVEO was assessed by DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) methods. The cytotoxicity of OVEO (0.1–10 µg/mL) was assessed using the MTS assay. SW872 adipocytes were incubated with 0.4 mM PA for 24 h, with or without a 2 h preincubation of OVEO, and then stimulated with insulin (100 nM, 10 min) or a vehicle. Phosphorylation of Tyr-IRS-1, Ser-AKT, and Thr-AS160 was analyzed by Western blot, and glucose uptake was measured using 2-NBDG. Results: OVEO contained phenols and exhibits antioxidant capacity. All the concentrations of OVEO assessed were not cytotoxic on SW872 adipocytes. PA decreased basal phospho-AS160 as well as insulin-stimulated phospho-IRS1, phospho-AKT, phospho-AS160 and glucose uptake, while OVEO co-treatment enhanced these markers. Conclusions: These findings suggest a beneficial effect of OVEO on the PA-impaired insulin pathway and glucose uptake, which might be explained by its phenolic content and antioxidant capacity, highlighting its potential as a complementary therapeutic agent for IR and related metabolic disorders. Full article

Hodgkin lymphoma (HL) is a common neoplasm in adolescents and young adults, primarily treated with doxorubicin (DOX) and bleomycin (BLM), which may cause severe adverse effects. The cure rate decreases to 75% in advanced-stage disease, highlighting the need for improved treatment strategies. Pentoxifylline (PTX), an NF-κB pathway inhibitor, enhances chemotherapy-induced apoptosis in cancer cells, making it a promising candidate for HL therapy. This study assessed the effects of PTX, DOX, and BLM on apoptosis, proliferation, and senescence in Hs-445 HL cells. Cell viability and clonogenicity were measured by spectrophotometry and spectrofluorimetry, while apoptosis, caspase activity, cell cycle, mitochondrial membrane potential (ΔΨm), proliferation, and senescence were analyzed via flow cytometry. Gene expression was assessed by qPCR. PTX significantly induced apoptosis, especially when combined with BLM or BLM+DOX (triple therapy), and modulated gene expression by upregulating proapoptotic and downregulating antiapoptotic markers. PTX increased caspase-3, -8, and -9 activity and disrupted the ΔΨm, particularly with BLM or triple therapy. Furthermore, PTX abolished DOX-induced G2 cell cycle arrest, reduced proliferation, and clonogenicity, and reversed DOX- and BLM-induced senescence. In conclusion, PTX induces apoptosis in HL cells, enhances DOX and BLM cytotoxicity synergistically, and reverses senescence, suggesting its potential as an adjunct therapy for HL. Full article

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), represent a spectrum of systemic disorders characterized by necrotizing inflammation of small- to medium-sized vessels. Nailfold videocapillaroscopy (NVC) is a validated, non-invasive technique routinely employed in the assessment of microvascular involvement in systemic sclerosis and in the differential diagnosis of Raynaud’s phenomenon; its application in the context of AAV, particularly EGPA, has not been investigated yet. The present study aims to assess the presence and the possible pattern of microcirculatory abnormalities detected by NVC in EGPA patients, and to explore potential correlations between capillaroscopic findings and disease activity status. Methods: A total of 29 patients with EGPA (19 women and 10 men), aged between 51 and 73 years, and 29 age- and sex-matched healthy controls were retrospectively enrolled between October 2023 and April 2025, after providing informed consent and meeting the inclusion and exclusion criteria. NVC was conducted in both groups to assess various morphological parameters, and mean capillary density was also calculated. Results: This study observed the presence of capillaroscopic alterations in the EGPA group, including decreased capillary density (38%), neoangiogenesis (72%), rolling (100%), pericapillary stippling (66%), and inverted capillary apex (52%). Overall, when comparing healthy controls with EGPA patients, microcirculatory abnormalities were significantly more prevalent in the latter. Specifically, scores for neoangiogenesis, capillary rolling, pericapillary stippling, and inverted capillary apex showed p-values < 0.001. Conclusions: Our study demonstrates a higher prevalence of four nailfold videocapillaroscopic abnormalities in patients with EGPA compared to healthy controls. However, the identification of these capillaroscopic alterations as specific to EGPA requires further confirmation. Ongoing studies aim to explore the potential role of NVC as a diagnostic marker and to investigate its correlation with the clinical manifestations of EGPA. Full article

Background/Objectives: Digital food-related videos significantly influence cravings, appetite, and weight outcomes; however, the dynamic neural mechanisms underlying appetite fluctuations during naturalistic viewing remain unclear. This study aimed to identify neural activity patterns associated with moment-to-moment appetite changes during naturalistic food-cue video viewing and to examine their relationships with cravings and weight-related outcomes. Methods: Functional magnetic resonance imaging (fMRI) data were collected from 58 healthy female participants as they viewed naturalistic food-cue videos. Participants concurrently provided continuous ratings of their appetite levels throughout video viewing. Hidden Markov Modeling (HMM), combined with machine learning regression techniques, was employed to identify distinct neural states reflecting dynamic appetite fluctuations. Findings were independently validated using a shorter-duration food-cue video viewing task. Results: Distinct neural states characterized by heightened activation in default mode and frontoparietal networks consistently corresponded with increases in appetite ratings. Importantly, the higher expression of these appetite-related neural states correlated positively with participants’ Body Mass Index (BMI) and post-viewing food cravings. Furthermore, these neural states mediated the relationship between BMI and food craving levels. Longitudinal analyses revealed that the expression levels of appetite-related neural states predicted participants’ BMI trajectories over a subsequent six-month period. Participants experiencing BMI increases exhibited a significantly greater expression of these neural states compared to those whose BMI remained stable. Conclusions: Our findings elucidate how digital food cues dynamically modulate neural processes associated with appetite. These neural markers may serve as early indicators of obesity risk, offering valuable insights into the psychological and neurobiological mechanisms linking everyday media exposure to food cravings and weight management. Full article

Background/Objectives: Lactobacillus kefiranofaciens HL1, isolated from kefir, exhibits antioxidant and anti-aging activities, defined here as improved cognitive function and reductions in oxidative stress and inflammatory markers. However, its poor milk viability limits application. This study developed a novel fermented milk by co-culturing HL1 with Lactococcus lactis subsp. cremoris APL015 (APL15) to enhance fermentation and health benefits. Methods: HL1 and APL15 were co-cultured to produce fermented milk (FM), and fermentation performance, microbial viability, texture, and syneresis were evaluated. A D-galactose-induced aging BALB/c mouse model was used to assess cognitive function, oxidative stress, inflammation, antioxidant enzyme activity, and gut microbiota after 8 weeks of oral administration. Results: FM reached pH 4.6 within 16 h, with high viable counts (~10⁹ CFU/mL) for both strains. HL1 viability and texture were maintained, with smooth consistency and low syneresis. In vivo, FM improved cognitive behavior (Y-maze, Morris water maze), reduced oxidative damage (MDA), lowered IL-1β and TNF-α, and enhanced brain SOD levels. FM-fed mice exhibited increased short-chain fatty acid producers, higher cecal butyrate, and reduced Clostridium perfringens. Conclusions: The co-cultured fermented milk effectively delivers HL1 and provides antioxidant, anti-inflammatory, and anti-aging effects in vivo, likely via gut–brain axis modulation. It shows promise as a functional food for healthy aging. Full article

Lonicera japonica Thunb. is a traditional Chinese medicinal herb whose floral buds are the primary source of pharmacological compounds that require manual harvesting. As a result, its floral bud duration, determined by the opening time, is a key determinant of both quality and economic value. However, the genetic mechanisms controlling floral bud duration remain poorly understood. In this study, we employed population structure analysis and molecular experiments to identify candidate genes associated with this trait. The improved cultivar Beihua No. 1 (BH1) opens its floral buds significantly later than the landrace Damaohua (DMH). Exogenous application of methyl jasmonate (MeJA) to BH1 indicated that jasmonate acts as a negative regulator of floral bud duration by accelerating floral bud opening. A genome-wide selection scan across 35 germplasms with varying floral bud durations identified the transcription factor LjWRKY50 as the causative gene influencing this trait. The dual-luciferase reporter assay and qRT-PCR experiments showed that LjWRKY50 activates the expression of the jasmonate biosynthesis gene, LjAOS. A functional variant within LjWRKY50 (Chr7:24636061) was further developed into a derived cleaved amplified polymorphic sequence (dCAPS) marker. These findings provide valuable insights into the jasmonate-mediated regulation of floral bud duration, offering genetic and marker resources for molecular breeding in L. japonica. Full article

Motor imagery (MI) electroencephalograms (EEGs) are pivotal cortical potentials reflecting cortical activity during imagined motor actions, widely leveraged for brain-computer interface (BCI) system development. However, effectively decoding these MI EEG signals is often overshadowed by flawed methods in signal processing, deep learning methods that are clinically unexplained, and highly inconsistent performance across different datasets. We propose BCINetV1, a new framework for MI EEG decoding to address the aforementioned challenges. The BCINetV1 utilizes three innovative components: a temporal convolution-based attention block (T-CAB) and a spectral convolution-based attention block (S-CAB), both driven by a new convolutional self-attention (ConvSAT) mechanism to identify key non-stationary temporal and spectral patterns in the EEG signals. Lastly, a squeeze-and-excitation block (SEB) intelligently combines those identified tempo-spectral features for accurate, stable, and contextually aware MI EEG classification. Evaluated upon four diverse datasets containing 69 participants, BCINetV1 consistently achieved the highest average accuracies of 98.6% (Dataset 1), 96.6% (Dataset 2), 96.9% (Dataset 3), and 98.4% (Dataset 4). This research demonstrates that BCINetV1 is computationally efficient, extracts clinically vital markers, effectively handles the non-stationarity of EEG data, and shows a clear advantage over existing methods, marking a significant step forward for practical BCI applications. Full article