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Adipose tissue is a dynamic and metabolically active organ that plays a crucial role in energy homeostasis and endocrine function. Recent advancements in lipidomics techniques have enabled the study of the complex lipid composition of adipose tissue and its role in metabolic disorders such as obesity, diabetes, and cardiovascular disease. In addition, adipose tissue lipidomics has emerged as a powerful tool for understanding the molecular mechanisms underlying these disorders and identifying bioactive lipid mediators and potential therapeutic targets. This review aims to summarize recent lipidomics studies that investigated the dynamic remodeling of adipose tissue lipids in response to specific physiological changes, pharmacological interventions, and pathological conditions. We discuss the molecular mechanisms of lipid remodeling in adipose tissue and explore the recent identification of bioactive lipid mediators generated in adipose tissue that regulate adipocytes and systemic metabolism. We propose that manipulating lipid-mediator metabolism could serve as a therapeutic approach for preventing or treating obesity-related metabolic diseases. Metabolic disorders: lipid dynamics as biomarkers and therapeutic targets Large-scale analyses of lipid composition and distribution in body fat (adipose tissue) have the potential to revolutionize the treatment and prevention of metabolic disorders associated with obesity. Yun-Hee Lee from Seoul National University, South Korea, and colleagues review the intricate molecular mechanisms underlying lipid synthesis, breakdown, and redistribution, both in healthy and diseased states. Advances in ‘lipidomics’, the analysis of the complete set of lipids and their reactions, have helped to illuminate the complex interactions between bioactive lipids and lipid-modifying enzymes. Such interactions play a critical roles in insulin sensitivity, energy expenditure, and other metabolic processes. The authors propose that the signaling pathways involved, along with the bioactive lipid mediators themselves, could serve as biomarkers or therapeutic targets for type 2 diabetes, cardiovascular disease, and various obesity-related conditions.

The mammalian gastrointestinal tract accommodates trillions of bacteria, many of which provide beneficial effects to the host, including protection from pathogenic microorganisms and essential metabolites. However, the intestinal immune system needs to adapt to the constantly fluctuating microbial environment at mucosal surfaces in order to maintain homeostasis. In particular, the gut microbiota induces the differentiation of effector Th17 cells and regulatory T cells (Tregs) that express RORγt, the master regulator of antimicrobial type 3 immunity. RORγt + Tregs constitute a major population of colonic Tregs that is distinct from thymusderived Tregs and require bacterial antigens for differentiation. The balance between Th17 cells and RORγt + Tregs, that is, the tone of the local type 3 immune response, is regulated by the vitamin A metabolite retinoic acid produced by the host. Furthermore, Th17 cells and RORγt + Tregs regulate intestinal type 2 immune responses, explaining how bacteria block allergic reactions. Here, we review the cellular and molecular mechanisms involved in the differentiation, regulation and function of RORγt + (type 3) Tregs, and discuss the multiple equilibria that exist between effector T cells and Tregs, as well as between different types of immune responses, which are necessary to maintain homeostasis and health.

To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events. First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis. Contrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, and its higher taxonomic ranks were enriched in the DSS-treated mice. , and exerted anti-arthritic effects. Propionate production deficiency further prevented the protective effect of on arthritis. We suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producing species examined in this study may be a potential candidate for developing effective treatments for inflammatory arthritis.

Faecalibacterium prausnitzii , a dominant member of healthy human gut microbiota, exhibits a strong positive correlation with fecal fructose levels, suggesting fructose as a key energy source for its colonization and persistence. This study explores the regulatory mechanisms governing the fru operon in F. prausnitzii , responsible for fructose uptake and metabolism. Here, we demonstrate that FruR, a DeoR family transcriptional regulator, orchestrates fru operon expression through interactions with fructose-1-phosphate (F1P) and HPr2, the histidine-containing phosphocarrier protein. The F1P-HPr2(Ser-P)-FruR complex enhances RNA polymerase binding to the fru promoter, with stronger affinity for specific operator motifs compared to apo-FruR. F1P induces structural modifications in FruR that strengthen its interaction with HPr2 and alter its DNA recognition pattern, facilitating RNA polymerase access to the promoter. In vivo experiments in mice demonstrate increased F. prausnitzii abundance alongside upregulated fru operon expression in fructose-rich environments. This study provides new insights into how fructose availability modulates fru operon regulation and promotes F. prausnitzii colonization in the host intestine. Fructose availability promotes bacterial colonization in the human gut via regulation of the fructose operon in Faecalibacterium prausnitzii , governed by the transcription factor FruR and its interactions with fructose-1-phosphate and HPr2(Ser-P).

Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (TH17) cells and regulatory T cells (Tregs) in the intestine. Here, we report that microbiota-induced Tregs express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to TH17 cells. In the absence of RORγt+ Tregs, TH2-driven defense against helminths is more efficient, whereas TH2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt+ Tregs and TH17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.

ABCG2 is a member of the ATP binding cassette (ABC) transmembrane proteins that plays an important role in stem cell biology and drug resistance of cancer cells. In this study, we investigated how expression of human ABCG2 gene is regulated in lung cancer A549 cells. Binding of Sp1 and Sp3 transcription factors to the ABCG2 promoter in vitro and in vivo was elucidated by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. The ABCG2 promoter activity was impaired when Sp1 sites were mutated but was enhanced by overexpression of Sp1 or Sp3 proteins. Knockdown of Sp1 or Sp3 expression by short interfering RNA significantly decreased the expression of ABCG2 mRNA and protein, resulting in attenuated formation of the side population in A549 cells. In addition, Sp1 inhibition in vivo by mithramycin A suppressed the percentage of the side population fraction and sphere forming activities of A549 cells. Moreover, inhibiting Sp1- or Sp3-dependent ABCG2 expression caused chemosensitization to the anticancer drug cisplatin. Collectively, our results demonstrate that Sp1 and Sp3 transcription factors are the primary determinants for activating basal transcription of the ABCG2 gene and play an important role in maintaining the side population phenotype of lung cancer cells.

Our guts harbor trillions of microbial inhabitants, some of which regulate the types of immune cells that are present in the gut. For instance, Clostridium species of bacteria induce a type of T cell that promotes tolerance between the host and its microbial contents. Ohnmacht et al. and Sefik et al. characterized a population of gut regulatory T cells in mice, which required gut microbiota to survive. Multiple bacterial species of the microbiota could induce transcription factor-expressing regulatory T cells that helped maintain immune homeostasis. Mice engineered to lack these transcription factors exhibited enhanced susceptibility to colonic inflammation and had elevated amounts of proinflammatory molecules associated with allergies (see the Perspective by Hegazy and Powrie). Science, this issue pp. 989 and 993 Changes to the symbiotic microbiota early in life, or the absence of it, can lead to exacerbated type 2 immunity and allergic inflammations. Although it is unclear how the microbiota regulates type 2 immunity, it is a strong inducer of proinflammatory T helper 17 (TH17) cells and regulatory T cells (Tregs) in the intestine. Here, we report that microbiota-induced Tregs express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to TH17 cells. In the absence of RORγt+ Tregs, TH2-driven defense against helminths is more efficient, whereas TH2-associated pathology is exacerbated. Thus, the microbiota regulates type 2 responses through the induction of type 3 RORγt+ Tregs and TH17 cells and acts as a key factor in balancing immune responses at mucosal surfaces.

Perfusion culture with microcarriers was conducted to produce cell-associated and cell-free Varicella-Zoster virus (VZV) with human embryonic lung cells. After the cells were infected with VZV infected cells, glucose in the medium decreased rapidly, suggesting that VZV propagation was related closely to the use of glucose. While the yield of cell-associated VZV in microcarriers was 9,350 PFU/cm2, almost two-thirds of that in T-80 flask and cell factory, the yield of cell-free VZV in microcarriers was only about 10% of that in T-80 flask and cell factory.[PUBLICATION ABSTRACT]

Microbe-associated molecular patterns (MAMPs) are recognized by pattern recognition receptors (PRRs) of the innate immune system. Flagellin, the primary component of bacterial flagella, is recognized by membrane TLR5 and cytoplasmic NLRC4 receptors, which promote a vigorous pro-inflammatory response typically associated with bacterial infection. However, herein, we report that the nature of the flagellin-induced response is highly dependent on the physiological state of the tissue. Specifically, in the steady state, epithelial cell detection of flagellin orchestrates an anti-inflammatory response mediated by IL-33-dependent type 2 regulatory T cells while, in the context of injury, it induces a proinflammatory response mediated by myeloid cells, IL-18 and Th17 cells. Likewise, in the absence of infection, bacterial symbionts expressing high levels of flagellin induce a type 2 response. These data demonstrate that, depending on the inflammatory state of the milieu, MAMPs can function both as immunogens or tolerogens.

In contrast to other existing terrestrial surveying instruments, there are not many benchmark tests available for Terrestrial Laser Scanner (TLS) data quality specifications. This paper presents two possible approaches to the standardization of a TLS point data set. Firstly, the ranging accuracy from an instrument to the object is investigated by comparing measured distances by TLS with those of Total Station (TS). In this case, we use two different slope distances with one being about 25 m and the other, about 50 m in range. Secondly, the comparison of data intensity with six different materials, such as aluminum, a sheet of plywood, resin (black & white), steel (black), and laminate (yellow) is carried out. When comparing the distances measured by TS and those scanned by TLS, the standard deviations (Std.) of differences were found to be about 7 mm (50 m range) and 3 mm (25 m range). In the case of plane-fitting of point clouds, aluminum with white color gave better result than that of others, suggesting that the color of an object affects the intensity value of point clouds. It is expected that these results will contribute to the quality evaluation of TLS point clouds and the selection of standard targets.