Abstract This study reports about a new ion chromatography method for the detection of chloride ions in sweat as an alternative to the gold standard of the chloridometer. Information about necessary materials, required preparations, reference ranges, advantages and disadvantages of this method is provided. We finally demonstrate that this method is useful to screen for cystic fibrosis in sweat samples. Article Highlights. A new ion chromatography method for detection of chloride ions in sweat is described References ranges for this method are given Advantages and disadvantages are discussed The usefulness of this method is shown in 145 sweat samples

Hintergrund: In Zellkultur, im Tiermodell und auch an humanem Biopsiematerial wurde ein kausaler Zusammenhang zwischen der Leberfibrose und einer erhöhten Expression von tissue inhibitor of metalloproteinases-1 (TIMP-1) belegt. Eine Bindung und Inaktivierung von TIMP-1 würde die natürliche proteolytische Aktivität des fibrotischen Gewebes fördern und so eine weitere Akkumulation von extrazellulärer Matrix verhindern. Ziel unserer Arbeiten ist eine spezifische und maximale Antagonisierung von TIMP-1 durch neue proteolytisch inaktive MMP-9 Mutanten.

INTRODUCTION: Food insecurity, the household-level socio-economic condition of having limited or uncertain ability to acquire adequate and safe food, has affected 13.8 million households in the United States in 2020 and is a cofactor in the onset and worsening of metabolic dysfunction-associated steatotic liver disease (MASLD). AREAS COVERED: To illustrate the epidemiological evidence linking MASLD with food insecurity, and the potential pathobiological mechanisms underlying their association we searched the PubMed, Web of Science, and Scopus database from inception to April 2025 for relevant keywords pertaining to the topic. Finally, we discuss promising areas of future research in this field. EXPERT OPINION: Research on food insecurity contributes to the establishment of the biopsychosocial disease model in the MASLD field. Understanding the broader sociocultural factors influencing food choices, which may disproportionately affect certain vulnerable populations, can help shift the focus from individual responsibility to a more comprehensive approach to addressing obesity-related metabolic dysfunction. Future studies should focus on quantifying descriptors of food insecurity more effectively. Additionally, further research is necessary to determine whether and to what extent global cultural advancements and specific education in food security can prevent and reverse the negative outcomes of food insecurity-associated MASLD.

<br><b> Measurement of % of body weight changes , White blood cells, and clinical chemistry parameters at the4-day in sera of male mice treated with L-asparaginase.</b><br><br>

Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, placing a growing burden on individual health and public health systems worldwide. Here we aim to elucidate how obesity contributes to liver dysfunction and highlight the preventive, diagnostic, and management strategies that are most relevant to healthcare providers, researchers, and policy makers. To this end, a comprehensive literature search using major scientific databases was conducted. Various clinically heterogenous pathophenotypes, such as android, gynoid, sarcopenic, metabolically healthy and unhealthy obesity, exhibit variable associations with liver health in the context of chronic liver disease (CLD), including alcohol-related CLD, viral hepatitis B and C, and, particularly, metabolic dysfunction-associated steatotic liver disease (MASLD), which is the prototypic manifestation of obesity-associated CLD. Regardless of the etiology of CLD, obesity is a major risk factor for the progression to cirrhosis and hepatocellular carcinoma through a variety of lipotoxic, proinflammatory, pro-fibrotic, and carcinogenic pathomechanisms involving genetics and epigenetics, altered adipokine profile, oxidative stress, endoplasmic reticulum stress, apoptosis, intestinal dysbiosis, and altered gut-liver axis. Various strategies are available to address obesity-associated CLD, including lifestyle changes, endoscopic techniques, and metabolic/bariatric surgery. Integrative approaches bringing together clinicians, basic researchers, and public health experts will be crucial in developing a coherent, holistic framework to address, with a precision medicine approach, the rising tide of obesity-related CLD on a global scale.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD). The increasing burden of MASH and its associated complications is challenging to cure. Our study aims to investigate the therapeutic potential of sclareol in MASH pathogenesis. Huh-7 cells were treated with various concentrations of free fatty acids (FFAs; 200–1200 µM), followed by treatment with sclareol (FFAs; 1200 µM + sclareol; 5 µM to 100 µM). An in vivo MASH model was developed using a high-fat diet and carbon tetrachloride (0.16 µg/kg every 15 th days) for 12 weeks, while control animals received a normal pellet diet. After model induction, animals were divided into four groups: Control, MASH, MASH + SLD (5 mg/kg/day, SLD: Sclareol low dose), and MASH + SHD (10 mg/kg/day, SHD: Sclareol high dose). Sclareol treatment was administered intraperitoneally for six weeks. In Huh-7 cells, co-treatment with sclareol, particularly at doses of 20, 40, and 80 µM, reduced reactive oxygen species and nitric oxide production while regulating lipogenic gene expression, thereby mitigating lipotoxicity. In vivo , sclareol alleviated dyslipidemia, hyperglycemia, liver injury, and oxidative stress in MASH animals. Histopathology confirmed that sclareol improved liver morphology by reducing nuclear infiltration, macro- and microsteatosis, hepatocyte ballooning, and fibrosis. GC-MS analysis revealed that sclareol intervention was associated with reduced fecal short-chain fatty acid (SCFA) levels. Interestingly, this reduction was accompanied by improvements in colon health. Furthermore, sclareol upregulated AMP-activated protein kinase and modulated the molecular expression of genes related to lipogenic, gluconeogenic, inflammation, fibrotic, and apoptotic pathways. This study is the first to report that sclareol prevents MASH progression by regulating oxidative stress, dyslipidemia, inflammation, fibrosis, and apoptosis. • MASH is characterized by hepatic steatosis, inflammation, and fibrosis. • Sclareol prevents lipotoxicity in Huh7 cells. • Sclareol mitigates oxidative stress and dyslipidemia in MASH. • Sclareol prevents MASH progression by regulating inflammation, fibrosis, and apoptosis.

ABSTRACT: Interferon alfa (IFN-α) is approved for the therapy of patients with polycythemia vera (PV), a subtype of myeloproliferative neoplasm (MPN). Some patients achieve molecular responses (MRs), but clonal factors sensitizing for MRs remain elusive. We integrated colony formation assays with single-cell RNA sequencing (scRNA-seq) and genotyping in PV-derived cells and healthy controls (HCs) to dissect how IFN-α targets diseased clones during erythroid differentiation. IFN-α significantly decreased colony growth in MPNs and HCs with variable transcriptional responses observed in individual colonies. scRNA-seq of colonies demonstrated more mature erythroid colonies in PV than HCs. JAK2V617F-mutant cells exhibited upregulated STAT5A, heme, and G2M checkpoint pathways compared with JAK2WT cells from the same patients. Subgroup analysis revealed that IFN-α significantly decreased immature erythrocytic cells in PV (basophilic erythroblasts P < .05; polychromatic erythroblasts P < .05) but not in HCs. CD71-/CD235a+ cells from HCs (P < .05) but not PV were inhibited by IFN-α, and the number of reticulocytes was less affected in PV. Robust IFN-α responses persisted throughout differentiation, leading to significant apoptosis in PV. Apoptotic cells displayed downregulation of ribosomal genes. This link between apoptosis and ribosomal genes was corroborated through the analysis of mitochondrial variants, demonstrating IFN-α-induced eradication of specific clones, characterized by elevated expression of ribosomal genes. Our findings indicate that PV-derived clones either undergo apoptosis or pass through differentiation, overall reducing the cycling mutant cells over long-term treatment. Furthermore, the significance of ribosomal genes and clonal prerequisites in IFN-α's therapeutic mechanism is underscored, shedding light on the intricate dynamics of IFN-α treatment in PV.

Lipocalin 2 (LCN2) mediates key roles in innate immune responses. It has affinity for many lipophilic ligands and binds various siderophores, thereby limiting bacterial growth by iron sequestration. Furthermore, LCN2 protects against obesity and metabolic syndrome by interfering with the composition of gut microbiota. Consequently, complete or hepatocyte-specific ablation of the Lcn2 gene is associated with higher susceptibility to bacterial infections. In the present study, we comparatively profiled microbiota in fecal samples of wild type and Lcn2 null mice and show, in contrast to previous reports, that the quantity of DNA in feces of Lcn2 null mice is significantly lower than that in wild type mice (p &lt; 0.001). By using the hypervariable V4 region of the 16S rDNA gene and Next-Generation Sequencing methods, we found a statistically significant change in 16 taxonomic units in Lcn2-/- mice, including eight gender-specific deviations. In particular, members of Clostridium, Escherichia, Helicobacter, Lactococcus, Prevotellaceae_UCG-001 and Staphylococcus appeared to expand in the intestinal tract of knockout mice. Interestingly, the proportion of Escherichia (200-fold) and Staphylococcus (10-fold) as well as the abundance of intestinal bacteria encoding the LCN2-sensitive siderphore enterobactin (entA) was significantly increased in male Lcn2 null mice (743-fold, p &lt; 0.001). This was accompanied by significant higher immune cell infiltration in the ileum as demonstrated by increased immunoreactivity against the pan-leukocyte protein CD45, the lymphocyte transcription factor MUM-1/IRF4, and the macrophage antigen CD68/Macrosialin. In addition, we found a higher expression of mucosal mast cell proteases indicating a higher number of those innate immune cells. Finally, the ileum of Lcn2 null mice displayed a high abundance of segmented filamentous bacteria, which are intimately associated with the mucosal cell layer, provoking epithelial antimicrobial responses and affecting T-helper cell polarization.

Results of dose escalation study using 3 different doses of Oncaspar. <br>

Perilipin 2 (PLIN2) is a lipid droplet protein with various metabolic functions. However, studies investigating PLIN2 in the context of inflammation, especially in systemic and acute inflammation, are lacking. Hence, we assessed the relevance of serum PLIN2 in critically ill patients. We measured serum PLIN2 serum in 259 critically ill patients (166 with sepsis) upon admission to a medical intensive care unit (ICU) compared to 12 healthy controls. A subset of 36 patients underwent computed tomography to quantify body composition. Compared to controls, serum PLIN2 concentrations were elevated in critically ill patients at ICU admission. Interestingly, PLIN2 independently indicated multiple organ dysfunction (MOD), defined as a SOFA score > 9 points, at ICU admission, and was also able to independently predict MOD after 48 h. Moreover, serum PLIN2 levels were associated with severe respiratory failure potentially reflecting a moribund state. However, PLIN2 was neither a predictor of ICU mortality nor did it reflect metabolic dysregulation. Conclusively, the first study assessing serum PLIN2 in critical illness proved that it may assist in risk stratification because it is capable of independently indicating MOD at admission and predicting MOD 48 h after PLIN2 measurement. Further evaluation regarding the underlying mechanisms is warranted.

Obesity is a complex and growing global concern, affecting one in eight individuals and compromising health, quality of life and life expectancy. It carries significant metabolic, cardiovascular, oncological, hepatorenal, skeletal and psychiatric risks, imposing substantial costs on health-care systems. Traditional treatments have often been ineffective or have led to relapse after lifestyle changes. Whereas bariatric surgery is effective, it also involves risks such as mortality and hospitalisation. Semaglutide, licensed in 2018, is a synthetic analogue of glucagon-like peptide 1 which regulates glucose metabolism and gastrointestinal (GI) motility. Studies show that semaglutide, administered either weekly and subcutaneously, or daily orally, induces an average weight loss of -11.62 kg compared to placebo and reduces waist circumference by up to -9.4 cm. It also improves blood pressure, fasting glucose levels, C-reactive protein levels and lipid profiles. The most common adverse events are mild-to-moderate GI complaints occurring more frequently with daily administration than weekly doses; hypoglycaemia is more common without lifestyle intervention. Weight regain often follows semaglutide withdrawal. Furthermore, semaglutide offers cardiovascular benefits for patients with established atherosclerotic cardiovascular disease (CVD), lowers the risk of kidney outcomes and cardiovascular-related death, resolves nonalcoholic steatohepatitis in many cases, and positively impacts mental health and quality of life. In conclusion, semaglutide therapy could significantly benefit many adults regarding CVD and mortality if made widely accessible. Ethical and financial considerations must be addressed for personalised obesity treatment approaches.