Search Results (17,981)

Yajiangxue cattle (XF) is three-way crossbred cattle developed specifically for producing high-quality beef in the Tibetan Plateau by introducing the bloods of Tibetan yellow cattle (HF) and Angus cattle into Tibetan yak (MF). In the present study, we mainly focused on fat deposition and metabolism changes and used RNA-seq and LC-MS/MS-based metabolomics to partially explain the meat quality improvement in Yajiangxue cattle. Differential expression analysis revealed 1762, 2949, and 2931 different expression genes in XF vs. HF, XF vs. MF, and XF vs. cattle–yak (PF), respectively, such as BMP2, WISP2, FGF1, IL1B, IL6, and WNT5B. Immune response, oxidation–reduction processes, and fatty acid metabolism were markedly enriched. Furthermore, an initial identification revealed 319 metabolites using positive ion mode and 289 metabolites using negative ion mode in bovine adipose tissue across four breeds/populations. Of these, 143 were differential metabolites in positive ion mode, while 166 were in negative ion mode. The main pathways of metabolism affected by breed/population were unsaturated fatty acid biosynthesis, tryptophan and tyrosine biosynthesis, primary bile acid biosynthesis, cholesterol metabolism, beta-alanine metabolism, etc. Similarly, both the transcriptome and the metabolome results highlighted fatty acid metabolism. These results could help elucidate the biological mechanisms involved in fat deposition and identify valuable biomarkers for specific metabolite accumulation. Full article

Graft-versus-host disease (GVHD) is one of the most prevalent and life-threatening complications that can arise following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD occurs when immune cells—primarily T cells—from the graft recognize host cells as foreign entities and initiate an immune response against host tissues. This immune reaction generally involves a diverse array of cytokines, including interleukins (ILs), which play a pivotal role in modulating the immune response, promoting inflammation, and sustaining immune tolerance. Members of the interleukin family are not only directly involved in the activation, proliferation, and differentiation of T cells but also regulate inflammatory responses and the migration of immune cells. Consequently, they significantly influence both the clinical manifestations and prognosis of GVHD. The objective of this study is to review recent advancements in research concerning interleukins and their role in the pathogenesis of GVHD. This study aims to elucidate how interleukins contribute to immune regulation, inflammatory responses, and clinical manifestations. Furthermore, we will discuss their potential as therapeutic targets, with the intention of providing novel insights and strategies for the clinical management of GVHD. Full article

Detailed analysis of gene expression by real time-quantitative polymerase chain reaction (RT-qPCR) has become a widespread method. To normalize the expression of target genes, this approach relies on constitutively expressed internal controls known as housekeeping genes (HKGs). Their proper selection is a critically important methodological step, since all the studied gene expression will be recalculated based on HKG expression. This concise review aims to discuss the selection of HKGs for endometrial cancer (EC) studies. We draw attention to the fact that the commonly used gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is unsuitable as a HKG for research on the normal endometrium, EC, as well as many other tissues. In contrast, accumulating evidence suggests that GAPDH is a pan-cancer marker and an EC marker. Work on GAPDH overexpression in EC in relation to overall and relapse-free survival is lacking. Both original research and overviews indicate that at least two HKGs should be used for target gene expression recalculations, a rarely applied technical aspect of final data processing. The insufficiently careful selection in many studies of only one HKG, e.g., GAPDH, can be held responsible for broad discrepancies in published results obtained by this RT-qPCR technique. We provide an account of the discrepancies reported for sex hormone receptors expression in EC. Achieving consensus on the selection and validation of HKGs for research on this cancer is of crucial importance. Ideally, this trusted gene combination should be universal for any EC histotype and grade, irrespective of the final anatomopathological result. Full article

Mast cells (MC) are key effector cells in allergic diseases and are increasingly recognized for their roles in the immunopathogenesis of tuberculosis (TB). In allergic conditions, MCs are hyperactivated, driving T-helper Type 2 (Th2)-skewed immune responses that may antagonize the T-helper Type 1 (Th1)-mediated immunity essential for controlling Mycobacterium tuberculosis (Mtb) infection. This immunological imbalance may contribute to increased TB susceptibility, altered granuloma dynamics, and accelerated fibrotic remodeling. Histopathological and in vivo studies have revealed that MCs are recruited to TB lesions, where they release a spectrum of mediators, including histamine, IL-17A, TNF-α, TGF-β, tryptase, and chymase. These mediators can either support initial immune defense or promote chronic inflammation and tissue damage, depending on context and regulation. Moreover, individuals with chronic allergic diseases such as asthma and allergic rhinitis may experience worse TB outcomes due to their baseline immune dysregulation. Environmental exposures (e.g., air pollution, smoking), genetic polymorphisms (e.g., IL-4 −589C/T, IL-13 R130Q), and gut-lung axis disturbances further modulate MC activity and TB pathogenesis. This review synthesizes current findings on MC involvement in TB, particularly in allergic settings, and highlights the need for epidemiological studies and mechanistic research. It also explores the promise of host-directed therapies (HDTs) that target MCs or their mediators, such as antihistamines, MC stabilizers, leukotriene inhibitors, and cytokine modulators, as novel adjuncts to standard TB treatment. Personalized approaches that consider immune profiles, genetic risk, and comorbid allergies may improve TB outcomes and inform future clinical guidelines. Full article

Plant respiratory burst oxidase homolog (Rboh) genes are integral to the production of reactive oxygen species (ROS) and the regulation of stress responses. Here, bioinformatic techniques were employed to identify eight PgRboh genes (PgRbohA–H) in the genome of pomegranate (Punica granatum L.) and conduct a systematic analysis of this family. The findings showed that all PgRbohs proteins possess characteristic NADPH oxidase domains and are predicted to be localized on the cell membrane. Experimental verification confirmed the membrane localization of PgRbohD and PgRbohE proteins. Phylogenetic analysis categorized the PgRbohs proteins into six distinct groups, suggesting potential functional divergence among these groups. Promoter analysis revealed a significant presence of cis-acting elements responsive to low-temperature and methyl jasmonate (MeJA). The expression of PgRboh genes was found to be tissue-specific. Additionally, real-time PCR (RT-qPCR) was used to analyze expression patterns in response to low-temperature stress that involves multiple PgRboh genes in the cold response process. Overall, our results lay an important foundation for subsequent studies on the cold resistance function of pomegranate Rboh genes and provides new ideas for the breeding of new cold-resistant pomegranate varieties. Full article

Aggregation-induced emission (AIE) luminogens are materials that exhibit enhanced light emission in the aggregated state, primarily due to the restriction of intramolecular motions, which reduces energy loss through non-radiative pathways. Tetraphenylethylene (TPE) and its derivatives are prominent examples of AIE-active materials, owing to their ease of synthesis, tuneable photophysical properties, and strong aggregation tendencies. This review provides an overview of the fundamental AIE mechanisms in TPE-based systems, with a focus on the role of restricted intramolecular rotation (RIR) and π-twisting in governing their emission behaviour. It explores the influence of molecular structure, electronic configuration, and intermolecular interactions on fluorescence properties. Furthermore, recent advances in practical applications of TPE-based AIE luminogens are highlighted across a spectrum of biological imaging domains, including cellular imaging, tissue and in vivo imaging, and organelle-targeted imaging. Additionally, their integration into multifunctional and theranostic platforms, along with the development of stimuli-responsive and self-assembled systems, underscores their versatility and expanding potential in biomedical research and diagnostics. This review aims to offer valuable insights into the design principles and functional potential of TPE-based AIE luminogens, guiding the development of next-generation materials for advanced bioimaging technologies. Full article

Malnutrition afflicts millions of the world’s children and predisposes to death from diarrhea and infectious diseases. Children with severe acute malnutrition (SAM) are at highest risk. Our review of the endocrinology and metabolomics of SAM implicates critical roles for white adipose tissue and its regulatory hormones and growth factors in the adaptation to nutritional deprivation and the restoration of metabolic homeostasis: white adipose provides substrates and energy for hepatic glucose production and cardiopulmonary and central nervous system function, and products of fat metabolism inhibit muscle glucose uptake and utilization and spare muscle protein. Collectively, these effects maintain glucose availability for the brain, red blood cells, and renal medulla and conserve muscle mass. White adipose tissue also secretes leptin, which facilitates the immune response and may protect against mortality from infection. Euglycemia and survival in SAM are thereby prioritized over linear growth, which is suppressed owing to inhibition of insulin-like growth factor 1 production and action. Diversion of energy from growth serves to maintain essential bodily functions in critically ill malnourished children, who have limited energy reserves. Thus, short-term reductions in growth rate have adaptive benefits in SAM. Under favorable conditions, clinical and metabolic recovery are accompanied by catch-up growth, which can mitigate, and in many cases reverse, the stunting of growth in childhood. Nevertheless, clinical recovery can be complicated by preferential accrual of central fat and a relative deficiency of lean/skeletal mass, with potential long-term complications including insulin resistance, glucose intolerance, and metabolic syndrome. Full article

Background/Objectives: Radiobiology has shown heterogeneity in the sensitivity of cells to ionizing radiation, depending on a variety of conditions. The presence of an extracellular matrix (ECM) appears to confer a radioprotective effect on cells and can influence the cellular microenvironment by modulating the availability of oxygen and nutrients, which can affect cellular metabolism and stress responses. A three-dimensional cell culture allows the synergistic effect on cell survival to be obtained based not only on the radioprotective properties of the extracellular matrix but also on the stress-resistant endogenous properties of the cell culture. The aim of this study was to investigate the survival of chondrocytes in a 3D cell culture during high-dose ionizing irradiation. Methods: The properties of nasal chondrocytes were evaluated using a pellet culture model in which the cells were surrounded by a de novo synthesized extracellular matrix. Tissue cultures were exposed by gamma radiation at doses of 10, 100, and 1300 Gy. Cell viability was assessed after 2 days of irradiation by live/dead staining using confocal scanning laser microscopy. Results: Tissue-cultured chondrocytes survive after gamma-irradiation of low (10 Gy), medium (100 Gy), and high (1300 Gy) dosages; however, after irradiation of 1300 Gy, the percentage of surviving cells was lower. The average percentages of viable cells were evaluated as 82%, 79%, and 63% in low-, medium-, and high-dose groups, respectively. Conclusions: Under determined conditions, human cells are able to survive at doses of ionizing radiation that are significantly higher than the current limits. Full article

Cysteine-rich polycomb-like protein (CPP) transcription factors (TFs) play critical roles in the process of plant growth and development, as well as stress responses. To date, no reports about CPP TFs have been published for lettuce (Lactuca sativa). In this study, six CPP TFs (LsCPP1-LsCPP6) were identified in lettuce. Phylogenetic analysis showed that LsCPP TFs were classified into two clades (Clade I and Clade II). Six LsCPP genes were distributed across four chromosomes. Cis-elements, which are involved in environmental stress, hormone response, and development processes, were identified in the promoters of LsCPP genes. LsCPP genes were induced by different tissues and the stem enlargement processes of stem lettuce. Plant hormones (SA, ABA) and abiotic stress (salt, drought) induced the expression of LsCPP genes. LsCPP4 was significantly induced after drought stress for 12 h. Notably, the expression level of LsCPP4 increased more than 10 times (12 h) and 150 times (24 h) after salt stress. ABA and SA significantly induced the expression profile of LsCPP6. This study not only provides the basis for future functional research of LsCPP genes, particularly their roles in lettuce stress resistance, but also provides a foundation for molecular breeding to enhance the agricultural traits in lettuce. Full article

Obesity has traditionally been considered a major risk factor for numerous metabolic disorders and diseases. However, a subset of individuals with obesity, classified as having “metabolically healthy obesity” (MHO), display relatively normal metabolic parameters despite excess adiposity. This review critically examines the current knowledge surrounding MHO, including its various definitions, prevalence, clinical characteristics, contributing factors, and long-term outcomes. While MHO carries lower health risks compared to metabolically unhealthy obesity (MUO), evidence consistently demonstrates increased disease risk compared to metabolically healthy normal-weight individuals, particularly for type 2 diabetes, cardiovascular disease, chronic kidney disease, and certain cancers. MHO prevalence ranges from 10 to 30% among individuals with obesity globally, varying by sex, age, BMI, and ethnicity. Multiple factors contribute to the MHO phenotype, including beneficial adipose tissue distribution patterns, enhanced adipocyte function, favorable genetic profiles, and lifestyle factors. Recent single-cell transcriptomic analyses have identified specific cell populations, particularly mesothelial cells, as key drivers of metabolic health in visceral adipose tissue. The discovery of persistent epigenetic memory of obesity provides molecular evidence for why MHO often represents a transient state, with many individuals progressing to MUO over time. Emerging evidence also reveals differential therapeutic responses to GLP-1 receptor agonists between MHO and MUO phenotypes, highlighting the need for precision medicine approaches. The concept of MHO has important clinical implications for risk stratification and personalized treatment approaches. This review synthesizes current evidence while highlighting knowledge gaps and future research directions in this rapidly evolving field. Full article

Staphylococcus aureus is the most common pathogen causing osteomyelitis, a hardly recoverable bone infection that generates significant burden to patients. Osteomyelitis mouse models have long and successfully served to provide phenomenological insights into both pathogenesis and host response. However, direct in situ monitoring of bone microbial pathogenesis and immune response at the cellular level is still conspicuously missing in the published literature. Here, we update a standard pyogenic osteomyelitis in Wistar rat model, in order to investigate bacterial localization and immune response in osteomyelitis of rat tibia upon adding in situ analyses by spectrally resolved Raman spectroscopy. Raman experiments were performed one and five weeks post infections upon increasing the initial dose of bacterial inoculation in rat tibia. Label-free in situ Raman spectroscopy clearly revealed the presence of Staphylococcus aureus through exploiting peculiar signals from characteristic carotenoid staphyloxanthin molecules. Data were collected as a function of both initial bacteria inoculation dose and location along the tibia. Such strong Raman signals, which relate to single and double bonds in the carbon chain backbone of carotenoids, served as efficient bacterial markers even at low levels of infection. We could also detect strong Raman signals from cytochrome c (and its oxidized form) from bone cells in response to infection and inflammatory paths. Although initial inoculation was restricted to a single location close to the medial condyle, bacteria spread along the entire bone down to the medial malleolus, independent of initial infection dose. Raman spectroscopic characterizations comprehensively and quantitatively revealed the metabolic state of bacteria through specific spectroscopic biomarkers linked to the length of staphyloxanthin carbon chain backbone. Moreover, the physiological response of eukaryotic cells could be quantified through monitoring the level of oxidation of mitochondrial cytochrome c, which featured the relative intensity of the 1644 cm⁻¹ signal peculiar to the oxidized molecules with respect to its pyrrole ring-breathing signal at 750 cm⁻¹, according to the previously published literature. In conclusion, we present here a novel Raman spectroscopic approach indexing bacterial concentration and immune response in bone tissue. This new approach enables locating and characterizing in situ bone infections, inflammatory host tissue reactions, and bacterial resistance/adaptation. Full article

Dehydroepiandrosterone (DHEA) and its sulfate ester form DHEAS, are multifunctional steroid hormones primarily produced in the adrenal cortex, with additional synthesis in peripheral tissues. DHEA/DHEAS serve as precursors to sex steroids and exhibit neuroprotective, anti-inflammatory, and immune-modulating effects. DHEA levels decline significantly with age, a phenomenon termed “adrenopause,” prompting interest in supplementation to mitigate age-related symptoms. Particularly in postmenopausal women, DHEA has shown potential benefits in treating genitourinary syndrome of menopause (GSM), including improved vaginal health, lubrication, and sexual function. While intravaginal DHEA appears effective and safer than systemic estrogen therapy, especially for women with estrogen sensitivity, results remain mixed for oral administration. DHEA and DHEAS exhibit diverse neuroactive properties through modulation of GABA-A, NMDA, and sigma-1 receptors. These neurosteroids contribute to neuroprotection, synaptic plasticity, and mood regulation. Altered DHEA/DHEAS levels have been implicated in neurodegenerative disorders and depression, with emerging evidence supporting their potential therapeutic value. In addition, DHEA plays a multifaceted role in aging-related physiological changes. It supports muscle anabolism, bone density maintenance, cardiovascular protection, and immune regulation. Though supplementation shows potential benefits, especially in conjunction with resistance training, results remain discrepant. Current evidence has revealed that the therapeutic effects of DHEA supplementation are inconsistent in different human systems among different studies. The diversity of results is mainly due to heterogeneous receptor distribution, various action pathways, and distinct tissue responses in different systems. Further research is needed to define its efficacy and dosage across various systems. Full article

Oxidative stress is caused by an imbalance between the formation of reactive oxygen species (ROS) and the activity of antioxidant defense system, which disrupts redox signaling and causes molecular damage. While there are numerous methods to measure oxidative stress, the complex and dynamic nature of ROS production and antioxidant reactions requires a multi-faceted approach. Direct methods such as electron spin resonance (ESR) and fluorescent probes measure ROS directly but are limited by the short lifespan of certain species. Indirect methods such as lipid peroxidation markers (e.g., malondialdehyde, MDA), protein oxidation (e.g., carbonyl content), and DNA damage (e.g., 8-oxo-dG) provide information on oxidative damage, but they do not capture the real-time dynamics of ROS. The antioxidant defense system, which includes enzymatic components such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), further complicates assessment, as it responds dynamically to oxidative challenges. Furthermore, the compartmentalized nature of ROS production in organelles and tissues coupled with the temporal variability of oxidative damage and repair underscores the need to integrate multiple assessment methods. This commentary highlights the limitations of using single assays and emphasizes the importance of combining complementary techniques to achieve a comprehensive assessment of oxidative stress. A multi-method approach ensures accurate identification of ROS dynamics, antioxidant responses, and the extent of oxidative damage, providing crucial insights into redox biology and its impact on health and disease. Full article

Background: The COVID-19 pandemic provided a unique opportunity to evaluate how the human immune system responded to a novel pathogen and to determine whether immune responses initiated through natural infection differ from those elicited by vaccination against the same antigen. Here, we provide a comprehensive analysis of SARS-CoV-2 Spike (S-antigen)-reactive memory B cells (B_mem) elicited in previously immunologically naïve subjects following their first infection with the original Wuhan-Hu-1 (WH1)-like strain or their initial COVID-19 mRNA prime-boost regimen encoding the same WH1-S-antigen. In particular, we tested the hypothesis that the primary encounter of SARS-CoV-2 S-antigen in lung mucosal tissues during infection vs. intramuscular COVID-19 mRNA injection would elicit different B_mem responses. Methods: Cryopreserved peripheral blood mononuclear cell (PBMC) samples collected following primary infection with the WH1 strain or completion of the initial prime-boost vaccination regimen were tested in ImmunoSpot^® assays to assess the frequency, Ig class/subclass usage, and cross-reactivity of the S-antigen-reactive B_mem compartment; pre-pandemic blood draws served as naïve controls. Results: The B_mem repertoires generated post-infection vs. post-vaccination were found to be quite similar but with some subtle differences. In both cases, the prevalent induction of IgG1-expressing B_mem in similar frequencies was seen, ~30% of which targeted the receptor binding domain (RBD) of the WH1-S-antigen. Also, the extent of cross-reactivity with the future Omicron (BA.1) RBD was found to be similar for both cohorts. However, IgA⁺ B_mem were preferentially induced after infection, while IgG4⁺ B_mem were detected only after vaccination. Conclusions: B_mem elicited in naïve human subjects following SARS-CoV-2 infection or after WH1-S encoding mRNA vaccination were only subtly different, although the relevance of these differences as it relates to immune protection warrants further investigation. Our findings serve to illustrate the usefulness and feasibility of performing comprehensive monitoring of antigen-specific B cell memory in larger cohorts using the ImmunoSpot^® technique. Full article

This study assessed the impact of untreated wastewater discharge in the Danube River on four native fish species: barbel (Barbus barbus), vimba bream (Vimba vimba), perch (Perca fluviatilis), and white bream (Blicca bjoerkna). Biomarkers of exposure and effect were evaluated, including metal and metalloid bioaccumulation in gills, liver, and gonads, DNA damage (comet assay), chromosomal abnormalities (micronucleus assay), liver enzyme activities (ALT, AST), and erythrocyte maturation. White bream showed the highest genotoxic damage (TI% = 22.57), particularly in liver tissue, indicating high sensitivity to pollution. Perch had elevated DNA damage in blood (TI% = 22.69) and strong biomarker responses, likely due to its predatory behavior. Barbel displayed notable DNA damage in gills (TI% = 30.67) and liver (TI% = 20.35), aligning with sediment exposure due to its benthic habits. Vimba bream had the lowest responses, possibly reflecting reduced exposure or resilience. Element accumulation varied across tissues and species, with perch showing the highest overall levels. Hepatic enzyme activities (highest values: ALT = 105.69 in barbel; AST = 91.25 in white bream) and changes in erythrocyte profiles supported evidence of physiological stress. Integrated Biomarker Response (IBR) analysis identified white bream as the most sensitive species, followed by perch and barbel. These results emphasize the value of multi-species biomonitoring and the importance of species-specific traits in freshwater ecotoxicology. Full article