Carbohydrate antigen 125 on epicardial fat and its association with local inflammation and fibrosis-related markers.

BACKGROUND: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis. METHODS: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively. RESULTS: The median age was 71 (63-74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels. CONCLUSION: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis).

Production and performance evaluation of chitosan/collagen/honey nanofibrous membranes for wound dressing applications.

Persistent bacterial infections are the leading risk factor that complicates the healing of chronic wounds. In this work, we formulate mixtures of polyvinyl alcohol (P), chitosan (CH), collagen (C), and honey (H) to produce nanofibrous membranes with healing properties. The honey effect at concentrations of 0 % (PCH and PCHC), 5 % (PCHC-5H), 10 % (PCHC-10H), and 15 % (PCHC-15H) on the physicochemical, antibacterial, and biological properties of the developed nanofibers was investigated. Morphological analysis by SEM demonstrated that PCH and PCHC nanofibers had a uniform and homogeneous distribution on their surfaces. However, the increase in honey content increased the fiber diameter (118.11-420.10) and drastically reduced the porosity of the membranes (15.79-92.62 nm). The addition of honey reduces the water vapor transmission rate (WVTR) and the adsorption properties of the membranes. Mechanical tests revealed that nanofibers were more flexible and elastic when honey was added, specifically the PCHC-15H nanofibers with the lowest modulus of elasticity (15 MPa) and the highest elongation at break (220 %). Also, honey significantly improved the antibacterial efficiency of the nanofibers, mainly PCHC-15H nanofibers, which presented the best bacterial reduction rates against Staphylococcus aureus (59.84 %), Pseudomonas aeruginosa (47.27 %), Escherichia coli (65.07 %), and Listeria monocytogenes (49.58 %). In vitro tests with cell cultures suggest that nanofibers were not cytotoxic and exhibited excellent biocompatibility with human fibroblasts (HFb) and keratinocytes (HaCaT), since all treatments showed higher or similar cell viability as opposed to the cell control. Based on the findings, PVA-chitosan-collagen-honey nanofibrous membranes have promise as an antibacterial dressing substitute.

A Minimally Invasive Surgical Procedure to Harvest Palate Periosteum as a Source of Mesenchymal Stromal/Stem Cells for Bone Tissue Engineering.

The aim of this study is to validate a minimally invasive surgical procedure to harvest palate periosteum as a source of tissue for mesenchymal stromal/stem cells. We performed a standardized procedure to harvest the palate periosteum in ten subjects, which consisted of a 3 mm disposable punch and a Molt periosteal elevator to harvest a small full-thickness fragment of soft tissue at the hard palate area, between the upper bicuspids, 3 to 4 mm apical to the cement enamel junction. The one-third inner portion was fragmented, and following standard cell culture procedures, the adherent cells were cultured for three passages, after obtaining 70-90% confluence. Cell morphology analysis, flow cytometry analysis, and viability and osteogenic differentiation assays were performed. In all 10 cases, uneventful healing was observed, with no need for analgesic intake. The evaluation of cell morphology showed elongated spindle-shaped cells distributed in woven patterns. A high viability range was verified as well as an immunophenotype compatible with mesenchymal stem cell lineage. The differentiation assay showed the potential of the cells to differentiate into the osteogenic lineage. These results demonstrate that the minimally invasive proposed surgical technique is capable of supplying enough periosteum source tissue for stem cell culture and bone tissue engineering.

Hematoxylin and Eosin Architecture Uncovers Clinically Divergent Niches in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the only cancers with an increasing incidence rate and is often associated with intra- and peri-tumoral scarring, referred to as desmoplasia. This scarring is highly heterogeneous in extracellular matrix (ECM) architecture and plays complex roles in both tumor biology and clinical outcomes that are not yet fully understood. Using hematoxylin and eosin (H&E), a routine histological stain utilized in existing clinical workflows, we quantified ECM architecture in 85 patient samples to assess relationships between desmoplastic architecture and clinical outcomes such as survival time and disease recurrence. By utilizing unsupervised machine learning to summarize a latent space across 147 local (e.g., fiber length, solidity) and global (e.g., fiber branching, porosity) H&E-based features, we identified a continuum of histological architectures that were associated with differences in both survival and recurrence. Furthermore, we mapped H&E architectures to a CO-Detection by indEXing (CODEX) reference atlas, revealing localized cell- and protein-based niches associated with outcome-positive versus outcome-negative scarring in the tumor microenvironment. Overall, our study utilizes standard H&E staining to uncover clinically relevant associations between desmoplastic organization and PDAC outcomes, offering a translatable pipeline to support prognostic decision-making and a blueprint of spatial-biological factors for modeling by tissue engineering methods.

MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes.

The lysosomal degradation of macromolecules produces diverse small metabolites exported by specific transporters for reuse in biosynthetic pathways. Here we deorphanized the major facilitator superfamily domain containing 1 (MFSD1) protein, which forms a tight complex with the glycosylated lysosomal membrane protein (GLMP) in the lysosomal membrane. Untargeted metabolomics analysis of MFSD1-deficient mouse lysosomes revealed an increase in cationic dipeptides. Purified MFSD1 selectively bound diverse dipeptides, while electrophysiological, isotope tracer and fluorescence-based studies in Xenopus oocytes and proteoliposomes showed that MFSD1-GLMP acts as a uniporter for cationic, neutral and anionic dipeptides. Cryoelectron microscopy structure of the dipeptide-bound MFSD1-GLMP complex in outward-open conformation characterized the heterodimer interface and, in combination with molecular dynamics simulations, provided a structural basis for its selectivity towards diverse dipeptides. Together, our data identify MFSD1 as a general lysosomal dipeptide uniporter, providing an alternative route to recycle lysosomal proteolysis products when lysosomal amino acid exporters are overloaded.

Orthogonal-view microscope for the biomechanics investigations of aquatic organisms.

Microscopes are essential for the biomechanical and hydrodynamical investigation of small aquatic organisms. We report a prototype of a do-it-yourself microscope that enables the visualization of organisms from two orthogonal imaging planes - top and side views. Compared to conventional imaging systems, this approach provides a comprehensive visualization strategy of organisms, which could have complex shapes and morphologies. The microscope was constructed by combining custom 3D-printed parts and off-the-shelf components. The system is designed for modularity and reconfigurability. Open-source design files and build instructions are provided in this report. Additionally, proof-of-use experiments (particularly with Hydra) and other organisms that combine the imaging with an analysis pipeline were demonstrated to highlight the system's utility. Beyond the applications demonstrated, the system can be used or modified for various imaging applications.

Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study.

OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.

mitoBKCa is functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming.

Alterations in the function of K+ channels such as the voltage- and Ca2+-activated K+ channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCa splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBKCa). Through a combination of genetic knockdown and knockout along with a cell permeable BKCa channel blocker, we show that mitoBKCa modulates overall cellular and mitochondrial energy production, and mediates the metabolic rewiring referred to as the 'Warburg effect', thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBKCa and BKCa transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBKCa could represent a treatment strategy for selected BC patients in future.

Assessing the Role of Asthma on the Relationship between Neurodevelopmental Disabilities and Adverse Birth Outcomes.

BACKGROUND: Investigating asthma as an effect modifier between adverse birth outcomes and neurodevelopmental disabilities (NDDs) across different races is crucial for tailored interventions and understanding variable susceptibility among diverse populations. METHODS: Data were collected through the National Survey of Children's Health. This cross-sectional study included 131,774 children aged 0 to 17 years. Study exposures comprised adverse birth outcomes including preterm birth and low birth weight. Weighted prevalence estimates and odds ratios with 95% confidence intervals (CIs) among children with and without adverse birth outcomes were calculated for NDDs including attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, seizure, and several others including behavior problems. Adjusted odds ratios were stratified by asthma status and separate interactions were assessed for each outcome. RESULTS: Of 131,774 participants, 10,227 were born low birth weight (9.12%; 95% CI: 8.77% to 9.49%), 14,058 were born preterm (11.35%; 95% CI: 10.94% to 11.76%), and 16,166 participants had asthma (11.97%; 95% CI: 11.58% to 12.37%). There were 68,100 males (51.11%), 63,674 females (48.89%), 102,061 non-Hispanic Whites (NHW) (66.92%), 8,672 non-Hispanic Blacks (NHB) (13.97%), and 21,041 participants (19.11%) categorized as other. NHB children with adverse birth outcomes had higher prevalence of several NDDs compared to NHW children. CONCLUSIONS: Asthma was not shown to be an effect modifier of the association between adverse birth outcomes and NDDs. Nevertheless, these results suggest that NDDs are more prevalent within US children with adverse birth outcomes, with higher rates among NHB compared to NHW children. These findings support screening for NDDs in pediatric health care settings among patients with adverse birth outcomes, particularly among those from ethnic minority backgrounds.

Force Production and Electromyographic Activity during Different Flywheel Deadlift Exercises.

This study aimed to characterize and compare force production and muscle activity during four flywheel deadlift exercises (bilateral [Bi] vs. unilateral [Uni]) with different loading conditions (vertical [Ver] vs. horizontal [Hor]). Twenty-three team-sport athletes underwent assessments for exercise kinetics (hand-grip force), along with surface electromyography (sEMG) of the proximal (BFProx) and medial biceps femoris (BFMed), semitendinosus (ST), and gluteus medius (GM). Mean and peak force were highest (p < 0.001) in Bi + Ver compared with Bi + Hor, Uni + Ver, and Uni + Hor. Although no significant differences were observed between Bi + Hor and Uni + Ver, both variants showed higher (p < 0.001) average force and peak eccentric force when compared with Uni + Hor. The presence of eccentric overload was only observed in the vertically loaded variants. Bi + Ver and Uni + Ver showed higher (p < 0.05) sEMG levels in BFProx and BFMed compared with the Uni + Hor variant. In addition, Uni + Ver registered the largest GM and ST sEMG values. In conclusion, the vertical variants of the flywheel deadlift exercise led to higher muscle force production and sEMG compared with their horizontal counterparts. Both Bi + Ver and Uni + Ver may be effective in promoting an increase in hamstring muscles activity and muscle force at long muscle length, while the Uni + Ver variant may be more effective in promoting GM and ST involvement.

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review.

Cancer remains one of the global leading causes of death and various vaccines have been developed over the years against it, including cell-based, nucleic acid-based, and viral-based cancer vaccines. Although many vaccines have been effective in in vivo and clinical studies and some have been FDA-approved, there are major limitations to overcome: (1) developing one universal vaccine for a specific cancer is difficult, as tumors with different antigens are different for different individuals, (2) the tumor antigens may be similar to the body's own antigens, and (3) there is the possibility of cancer recurrence. Therefore, developing personalized cancer vaccines with the ability to distinguish between the tumor and the body's antigens is indispensable. This paper provides a comprehensive review of different types of cancer vaccines and highlights important factors necessary for developing efficient cancer vaccines. Moreover, the application of other technologies in cancer therapy is discussed. Finally, several insights and conclusions are presented, such as the possibility of using cold plasma and cancer stem cells in developing future cancer vaccines, to tackle the major limitations in the cancer vaccine developmental process.

Advances in the Production of Sustainable Bacterial Nanocellulose from Banana Leaves.

Interest in bacterial nanocellulose (BNC) has grown due to its purity, mechanical properties, and biological compatibility. To address the need for alternative carbon sources in the industrial production of BNC, this study focuses on banana leaves, discarded during harvesting, as a valuable source. Banana midrib juice, rich in nutrients and reducing sugars, is identified as a potential carbon source. An optimal culture medium was designed using a simplex-centroid mixing design and evaluated in a 10 L bioreactor. Techniques such as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) were used to characterize the structural, thermal, and morphological properties of BNC. Banana midrib juice exhibited specific properties, such as pH (5.64), reducing sugars (15.97 g/L), Trolox (45.07 µM), °Brix (4.00), and antioxidant activity (71% DPPH). The model achieved a 99.97% R-adjusted yield of 6.82 g BNC/L. Physicochemical analyses revealed distinctive attributes associated with BNC. This approach optimizes BNC production and emphasizes the banana midrib as a circular solution for BNC production, promoting sustainability in banana farming and contributing to the sustainable development goals.

Near-infrared hyperspectral imaging and robust statistics for in vivo non-melanoma skin cancer and actinic keratosis characterisation.

One of the most common forms of cancer in fair skinned populations is Non-Melanoma Skin Cancer (NMSC), which primarily consists of Basal Cell Carcinoma (BCC), and cutaneous Squamous Cell Carcinoma (SCC). Detecting NMSC early can significantly improve treatment outcomes and reduce medical costs. Similarly, Actinic Keratosis (AK) is a common skin condition that, if left untreated, can develop into more serious conditions, such as SCC. Hyperspectral imagery is at the forefront of research to develop non-invasive techniques for the study and characterisation of skin lesions. This study aims to investigate the potential of near-infrared hyperspectral imagery in the study and identification of BCC, SCC and AK samples in comparison with healthy skin. Here we use a pushbroom hyperspectral camera with a spectral range of ≈ 900 to 1600 nm for the study of these lesions. For this purpose, an ad hoc platform was developed to facilitate image acquisition. This study employed robust statistical methods for the identification of an optimal spectral window where the different samples could be differentiated. To examine these datasets, we first tested for the homogeneity of sample distributions. Depending on these results, either traditional or robust descriptive metrics were used. This was then followed by tests concerning the homoscedasticity, and finally multivariate comparisons of sample variance. The analysis revealed that the spectral regions between 900.66-1085.38 nm, 1109.06-1208.53 nm, 1236.95-1322.21 nm, and 1383.79-1454.83 nm showed the highest differences in this regard, with <1% probability of these observations being a Type I statistical error. Our findings demonstrate that hyperspectral imagery in the near-infrared spectrum is a valuable tool for analyzing, diagnosing, and evaluating non-melanoma skin lesions, contributing significantly to skin cancer research.

Assessing Antigen-Specific T Cell Responses Through IFN-γ Enzyme-Linked Immune Absorbent Spot (ELISpot).

T cells are instrumental in protecting the host against invading pathogens and the development of cancer. To do so, they produce effector molecules such as granzymes, interleukins, interferons, and perforin. For the development and immunomonitoring of therapeutic applications such as cell-based therapies and vaccines, assessing T cell effector function is paramount. This can be achieved through various methods, such as 51Cr release assays, flow cytometry, and enzyme-linked immune absorbent spot (ELISpot) assays. For T cell ELISpots, plates are coated with antibodies directed against the effector molecule of interest (e.g., IFN-g). Subsequently, peripheral blood mononuclear cells (PBMCs) or isolated T cells are cultured on the plate together with stimuli of choice, and the production of effector molecules is visualized via labeled detection antibodies. For clinical studies, ELISpot is currently the gold standard to determine antigen-specific T cell frequencies. In contrast to 51Cr release assays, ELISpot allows for the exact enumeration of responding T cells, and compared to flow cytometry, ELISpot is more cost-effective and high throughput. Here, we optimize and describe, in a step-by-step fashion, how to perform a controlled IFN-γ ELISpot experiment to determine the frequency of responding or antigen-specific T cells in healthy human volunteers. Of note, this protocol can also be employed to assess the frequency of antigen-specific T cells induced in, e.g., vaccination studies or present in cellular products.

Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits.

In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are advanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2-10CaO-5P2O5-x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rabbits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the osteostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteostatin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice. STATEMENT OF SIGNIFICANCE: Treatment of bone defects without the capacity for self-repair is a global problem in the field of Orthopedic Surgery, as evidenced by the fact that in the U.S alone it affects approximately 100,000 patients per year. The gold standard of treatment in these cases is the autograft, but its use has limitations both in the amount of graft to be obtained and in the morbidity produced in the donor site. In the field of materials engineering, there is a growing interest in the development of a bone substitute equivalent. Mesoporous bioactive glass (MBG´s) scaffolds with three-dimensional architecture have shown great potential for use as a bone substitutes. The osteostatin-enriched Sr-MBG used in this long bone defect in rabbit radius bone in vivo study showed an increase in bone formation close to autograft, which makes us think that it may be an option to consider as bone substitute.

Practical RGB-to-XYZ Color Transformation Matrix Estimation under Different Lighting Conditions for Graffiti Documentation.

Color data are often required for cultural heritage documentation. These data are typically acquired via standard digital cameras since they facilitate a quick and cost-effective way to extract RGB values from photos. However, cameras' absolute sensor responses are device-dependent and thus not colorimetric. One way to still achieve relatively accurate color data is via camera characterization, a procedure which computes a bespoke RGB-to-XYZ matrix to transform camera-dependent RGB values into the device-independent CIE XYZ color space. This article applies and assesses camera characterization techniques in heritage documentation, particularly graffiti photographed in the academic project INDIGO. To this end, this paper presents COOLPI (COlor Operations Library for Processing Images), a novel Python-based toolbox for colorimetric and spectral work, including white-point-preserving camera characterization from photos captured under diverse, real-world lighting conditions. The results highlight the colorimetric accuracy achievable through COOLPI's color-processing pipelines, affirming their suitability for heritage documentation.

Weekly Programming of Hamstring-Related Training Contents in European Professional Soccer.

Hamstring injuries in soccer continue to be a challenge for professionals who work with soccer players daily. Although its origin is multifactorial, the proper management of neuromuscular fatigue during the training microcycle is a very important factor to consider. There are no clear guidelines regarding the weekly distribution of certain exercises that demand the hamstrings. The main objective of this study was to describe the usual training practices of professional European soccer teams. An international observational survey design was applied to some of the strength and conditioning coaches of professional soccer teams. The survey included different neuromuscular demanding exercises for the hamstrings. For each exercise, the strength and conditioning coaches had to respond in relation to their frequency of use and timepoint depending on the day of the weekly microcycle. Although there is no strong consensus in this regard, there does seem to be a trend when applying certain exercises, especially on the days matchday-4 and matchday-3.

Role of human Kallistatin in glucose and energy homeostasis in mice.

OBJECTIVE: Kallistatin (KST), also known as SERPIN A4, is a circulating, broadly acting human plasma protein with pleiotropic properties. Clinical studies in humans revealed reduced KST levels in obesity. The exact role of KST in glucose and energy homeostasis in the setting of insulin resistance and type 2 diabetes is currently unknown. METHODS: Kallistatin mRNA expression in human subcutaneous white adipose tissue (sWAT) of 47 people with overweight to obesity of the clinical trial "Comparison of Low Fat and Low Carbohydrate Diets With Respect to Weight Loss and Metabolic Effects (B-SMART)" was measured. Moreover, we studied transgenic mice systemically overexpressing human KST (hKST-TG) and wild type littermate control mice (WT) under normal chow (NCD) and high-fat diet (HFD) conditions. RESULTS: In sWAT of people with overweight to obesity, KST mRNA increased after diet-induced weight loss. On NCD, we did not observe differences between hKST-TG and WT mice. Under HFD conditions, body weight, body fat and liver fat content did not differ between genotypes. Yet, during intraperitoneal glucose tolerance tests (ipGTT) insulin excursions and HOMA-IR were lower in hKST-TG (4.42 ± 0.87 AU, WT vs. 2.20 ± 0.27 AU, hKST-TG, p < 0.05). Hyperinsulinemic euglycemic clamp studies with tracer-labeled glucose infusion confirmed improved insulin sensitivity by higher glucose infusion rates in hKST-TG mice (31.5 ± 1.78 mg/kg/min, hKST-TG vs. 18.1 ± 1.67 mg/kg/min, WT, p < 0.05). Improved insulin sensitivity was driven by reduced hepatic insulin resistance (clamp hepatic glucose output: 7.7 ± 1.9 mg/kg/min, hKST-TG vs 12.2 ± 0.8 mg/kg/min, WT, p < 0.05), providing evidence for direct insulin sensitizing effects of KST for the first time. Insulin sensitivity was differentially affected in skeletal muscle and adipose tissue. Mechanistically, we observed reduced Wnt signaling in the liver but not in skeletal muscle, which may explain the effect. CONCLUSIONS: KST expression increases after weight loss in sWAT from people with obesity. Furthermore, human KST ameliorates diet-induced hepatic insulin resistance in mice, while differentially affecting skeletal muscle and adipose tissue insulin sensitivity. Thus, KST may be an interesting, yet challenging, therapeutic target for patients with obesity and insulin resistance.