MST1 Negatively Regulates TNFα-Induced NF-κB Signaling through Modulating LUBAC Activity.

The nuclear factor (NF)-κB pathway plays a central role in inflammatory and immune responses, with aberrant activation of NF-κB signaling being implicated in various human disorders. Here, we show that mammalian ste20-like kinase 1 (MST1) is a previously unrecognized component of the tumor necrosis factor α (TNFα) receptor 1 signaling complex (TNF-RSC) and attenuates TNFα-induced NF-κB signaling. Genetic ablation of MST1 in mouse embryonic fibroblasts and bone marrow-derived macrophages potentiated the TNFα-induced increase in IκB kinase (IKK) activity, as well as the expression of NF-κB target genes. TNFα induced the recruitment of MST1 to TNF-RSC and its interaction with HOIP, the catalytic component of the E3 ligase linear ubiquitin assembly complex (LUBAC). Furthermore, MST1 activated in response to TNFα stimulation mediates the phosphorylation of HOIP and thereby inhibited LUBAC-dependent linear ubiquitination of NEMO/IKKγ. Together, our findings suggest that MST1 negatively regulates TNFα-induced NF-κB signaling by targeting LUBAC.

CEP41-mediated ciliary tubulin glutamylation drives angiogenesis through AURKA-dependent deciliation.

The endothelial cilium is a microtubule-based organelle responsible for blood flow-induced mechanosensation and signal transduction during angiogenesis. The precise function and mechanisms by which ciliary mechanosensation occurs, however, are poorly understood. Although posttranslational modifications (PTMs) of cytoplasmic tubulin are known to be important in angiogenesis, the specific roles of ciliary tubulin PTMs play remain unclear. Here, we report that loss of centrosomal protein 41 (CEP41) results in vascular impairment in human cell lines and zebrafish, implying a previously unknown pro-angiogenic role for CEP41. We show that proper control of tubulin glutamylation by CEP41 is necessary for cilia disassembly and that is involved in endothelial cell (EC) dynamics such as migration and tubulogenesis. We show that in ECs responding to shear stress or hypoxia, CEP41 activates Aurora kinase A (AURKA) and upregulates expression of VEGFA and VEGFR2 through ciliary tubulin glutamylation, as well as leads to the deciliation. We further show that in hypoxia-induced angiogenesis, CEP41 is responsible for the activation of HIF1α to trigger the AURKA-VEGF pathway. Overall, our results suggest the CEP41-HIF1α-AURKA-VEGF axis as a key molecular mechanism of angiogenesis and demonstrate how important ciliary tubulin glutamylation is in mechanosense-responded EC dynamics.

Optimal ICG dosage of preoperative colonoscopic tattooing for fluorescence-guided laparoscopic colorectal surgery.

BACKGROUND: Indocyanine green (ICG) is a multifunctional dye used in tumor localization, tissue perfusion, and lymph node (LN) mapping during fluorescence-guided laparoscopic colorectal surgery. PURPOSE: This study aimed to establish the optimal protocol for preoperative endoscopic submucosal ICG injection to perform fluorescence lymph node mapping (FLNM), along with undisturbed fluorescent tumor localization and ICG angiography during a single surgery. METHODS: Colorectal cancer patients (n = 192) were enrolled from May 2017 to December 2019. Colonoscopic submucosal ICG injection was performed 12 to 18 h before surgery. ICG injection protocols were modified based on the total injected ICG (mg) and tattooing site number. The concentrations of ICG were gradually decreased from the standard dose (2.5 mg/ml) to the minimum dose (0.2 mg/ml). Successful FLNM (FLNM-s) was defined as distinct fluorescent LNs observed under NIR camera. The patient's age, sex, body mass index (BMI), stage, cancer location, obstruction, and laboratory findings were compared between the FLNM-s and failed FLNM (FLNM-f) groups to identify clinical and pathological factors that affect FLNM. RESULTS: In the ICG dose section of 0.5 to 1 mg, the success rate was highest within all functions including FLNM, fluorescent tumor localization, and ICG angiography. FLNM-s was related to ICG dose (0.5-1 mg), multiple submucosal injections, location of cancer, camera light source, and lower BMI. In the multivariate analysis, camera light source, non-obesity, and multiple injections were independent factors for FLNM-s). The mean total number of harvested LNs was significantly higher in the FLNM-s group than that in the FLNM-f group (p < 0.001). The number of metastatic lymph nodes was comparable between the two groups (p = 0.859). CONCLUSIONS: Preoperative, endoscopic submucosal ICG injection with dose range 0.5 to 1 mg would be optimal protocol for multifunctional ICG applications during fluorescence-guided laparoscopic colorectal surgery.

MST1 mediates the N-methyl-D-aspartate-induced excitotoxicity in mouse cortical neurons.

Excessive activation of the ionotropic N-methyl-D-aspartate (NMDA) receptor has been shown to cause abnormally high levels of Ca2+ influx, thereby leading to excitotoxic neuronal death. In this study, exposure of mouse primary cortical neurons to NMDA resulted in the cleavage and activation of mammalian sterile 20-like kinase-1 (MST1), both of which were mediated by calpain 1. In vitro cleavage assay data indicated that calpain 1 cleaves out the autoinhibitory domain of MST1 to generate an active form of the kinase. Furthermore, calpain 1 mediated the cleavage and activation of wild-type MST1, but not of MST1 (G339A). Intriguingly, NMDA/calpain-induced MST1 activation promoted the nuclear translocation of the kinase and the phosphorylation of histone H2B in mouse cortical neurons, leading to excitotoxicity. Thus, we propose a previously unrecognized mechanism of MST1 activation associated with NMDA-induced excitotoxic neuronal death.

TRAF6-mediated ubiquitination of MST1/STK4 attenuates the TLR4-NF-κB signaling pathway in macrophages.

Pattern-recognition receptors including Toll-like receptors (TLRs) recognize invading pathogens and trigger an immune response in mammals. Here we show that mammalian ste20-like kinase 1/serine/threonine kinase 4 (MST1/STK4) functions as a negative regulator of lipopolysaccharide (LPS)-induced activation of the TLR4-NF-κB signaling pathway associated with inflammation. Myeloid-specific genetic ablation of MST1/STK4 increased the susceptibility of mice to LPS-induced septic shock. Ablation of MST1/STK4 also enhanced NF-κB activation triggered by LPS in bone marrow-derived macrophages (BMDMs), leading to increased production of proinflammatory cytokines by these cells. Furthermore, MST1/STK4 inhibited TRAF6 autoubiquitination as well as TRAF6-mediated downstream signaling induced by LPS. In addition, we found that TRAF6 mediates the LPS-induced activation of MST1/STK4 by catalyzing its ubiquitination, resulting in negative feedback regulation by MST1/STK4 of the LPS-induced pathway leading to cytokine production in macrophages. Together, our findings suggest that MST1/STK4 functions as a negative modulator of the LPS-induced NF-κB signaling pathway during macrophage activation.

Data-Driven Non-Linear Current Controller Based on Deep Symbolic Regression for SPMSM.

This study designs a simple current controller employing deep symbolic regression (DSR) in a surface-mounted permanent magnet synchronous machine (SPMSM). A novel DSR-based optimal current control scheme is proposed, which after proper training and fitting, generates an analytical dynamic numerical expression that characterizes the data. This creates an understandable model and has the potential to estimate data that have not been seen before. The goal of this study was to overcome the traditional linear proportional-integral (PI) current controller because the performance of the PI is highly dependent on the system model. Moreover, the outer speed control loop gains are tuned using the cuckoo search algorithm, which yields optimal gain values. To demonstrate the efficacy of the proposed design, we apply the control design to different test cases, that is varied speed and load conditions, as well as sinusoidal speed reference, and compare the results with those of a traditional vector control design. Compared with traditional control approaches, we deduce that the DSR-based control design could be extrapolated far beyond the training dataset, laying the foundation for the use of deep learning techniques in power conversion applications.

Cholecalciferol- and α-tocopherol-loaded walnut oil emulsions stabilized by whey protein isolate and soy lecithin for food applications.

BACKGROUND: To overcome the limitations in the use of protein as an emulsifier, soy lecithin, a natural surfactant, was used along with whey protein isolate (WPI) to produce o/w emulsions containing cholecalciferol and α-tocopherol. The physical stability of the emulsions prepared with WPI and varying concentrations of lecithin (0, 1, 2, and 3% w/w) was measured in different heat, pH, and ionic-strength food environmental conditions. RESULTS: All emulsions were shown to be less than 250 nm in size and less than 0.3 in polydispersity index (PDI). The morphology of the emulsions was spherical, and the droplets of the emulsion containing lecithin were thicker and larger than those of the emulsion without lecithin (WPI_L0). After autoclaving, WPI_L0 increased in size from 197.8 ± 1.7 nm to 528.5 ± 28.4 nm, and the retention of cholecalciferol and α-tocopherol decreased to 40.83 ± 0.63% and 49.68 ± 1.84%, respectively. At pH 5.5, near the isoelectric point of WPI, WPI_L0 increased in size due to aggregation, but emulsions containing lecithin remained stable at a PDI under 0.3. Turbiscan stability index of the emulsion prepared with WPI and 3% lecithin was the lowest, indicating good storage stability. In addition, it was confirmed that the higher the lecithin content, the higher the viscosity, and the higher the amount of free fatty acids released in the in vitro digestion model. CONCLUSION: This study can provide theoretical evidence for enhancing the physical stability of protein emulsions by co-stabilization with lecithin, promoting their application in various foods. © 2022 Society of Chemical Industry.

Optimization of indocyanine green angiography for colon perfusion during laparoscopic colorectal surgery.

AIM: This study aims to evaluate the extrinsic effects of conditional factors affecting quantitative parameters and to establish the optimization of indocyanine green (ICG) angiography using in vitro experiments and a prospective observational study. METHOD: In vitro experiments were performed to evaluate the correlation between conditional factors such as camera distance, surrounding lighting, fluorescence emission sources and ICG doses. The fluorescence intensity was measured from the ICG-containing test tube in each condition. In the clinical study, ICG angiography was applied to patients with colorectal cancer (n = 164). The quantitative perfusion parameters were the maximal fluorescence intensity (FMAX ), slope, T1/2MAX and perfusion time ratio (TR). Camera position, distance to colon, fluorescence emission source, surrounding lighting, site of angiography and ICG specific mode were considered as conditional factors and compared with the quantitative parameters to identify the optimal condition of ICG angiography. RESULTS: The fluorescence intensity had an inverse correlation with distance, and the transitional zone was shown at a distance of 4-5 cm by slope differential. FMAX , T1/2MAX and slope were affected significantly by camera distance, site of angiography, fluorescence emission source and ICG mode as conditional factors. On multivariate analysis, FMAX was independently associated with spectral ICG mode with red inversion, laser mode and camera distance. Conversely, TR was not related to any conditional factors. CONCLUSION: Since quantitative parameters of ICG angiography are influenced by various conditions, a standardized protocol is required. The application of ICG specific modes with a constant distance of 4-5 cm can provide optimized fluorescence images.

Amyotrophic lateral sclerosis-related mutant superoxide dismutase 1 aggregates inhibit 14-3-3-mediated cell survival by sequestration into the JUNQ compartment.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron loss in the spinal cord and brain. Mutations in the superoxide dismutase 1 (SOD1) gene have been linked to familial ALS. To elucidate the role of SOD1 mutations in ALS, we investigated 14-3-3, a crucial regulator of cell death that was identified in patients with familial ALS. In a transgenic mouse model (SOD1-G93A) of ALS, 14-3-3 co-localized with mutant SOD1 aggregates and was more insoluble in the spinal cords of mutant SOD1 transgenic mice than in those of wild-type mice. Immunofluorescence and co-immunoprecipitation experiments showed that the 14-3-3ɛ and θ isoforms interact with mutant SOD1 aggregates in the juxtanuclear quality control compartment of N2a neuroblastoma cells. Fluorescence loss in photobleaching experiments revealed that movement of the isoforms of 14-3-3 was markedly reduced in SOD1 aggregates. Bax translocation into and cytochrome c release from the mitochondria were promoted by the sequestration of 14-3-3 into mutant SOD1 aggregates, increasing cell death. Mutant SOD1 aggregates were dissolved by the Hsp104 chaperone, which increased the interaction of 14-3-3 with Bax, reducing cell death. Our study demonstrates that mutant SOD1 inhibits 14-3-3-mediated cell survival. This information may contribute to the identification of a novel therapeutic target for ALS.

Kefir prevented excess fat accumulation in diet-induced obese mice.

Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein-cholesterol concentrations. Overall, kefir has the potential to prevent obesity.

BAT3 negatively regulates lipopolysaccharide-induced NF-κB signaling through TRAF6.

TNF receptor-associated factor 6 (TRAF6) plays a critical role in NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, both of which mediate macrophage activation in response to pathogen-associated molecular patterns such as bacterial endotoxin, lipopolysaccharides (LPS). In this study, we investigated whether HLA-B associated transcript-3 (BAT3) regulates LPS-induced macrophage activation. BAT3 physically interacted with TRAF6 in macrophages, and this interaction was enhanced in the cells after LPS treatment. Furthermore, BAT3 inhibited the homo-oligomerization of TRAF6 as well as the interaction between TRAF6 and its downstream kinase transforming growth factor beta-activated kinase 1 (TAK1), thereby suppressing TRAF6-mediated signaling events. Intriguingly, TRAF6 mediated ubiquitination of BAT3 and this ubiquitination was crucial for its inhibitory effect on TRAF6-mediated signaling. Depletion of BAT3 by RNA interference resulted in enhancement of LPS-induced activation of the NF-κB signaling with increasing expression levels of pro-inflammatory cytokines. These findings suggest that BAT3 functions as the negative regulator of LPS-induced macrophage activation.

Polyphenol-Rich Fraction of Ecklonia cava Improves Nonalcoholic Fatty Liver Disease in High Fat Diet-Fed Mice.

Ecklonia cava (E. cava; CA) is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of the polyphenol-rich fraction of E. cava produced from Gijang (G-CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-fed mice. C57BL6 mice were fed a HFD for six weeks and then the HFD group was administered 300 mg/kg of G-CA extracts by oral intubation for 10 weeks. Body weight, fat mass, and serum biochemical parameters were reduced by G-CA extract treatment. MRI/MRS analysis showed that liver fat and liver volume in HFD-induced obese mice were reduced by G-CA extract treatment. Further, we analyzed hepatic gene expression related to inflammation and lipid metabolism. The mRNA expression levels of inflammatory cytokines and hepatic lipogenesis-related genes were decreased in G-CA-treated HFD mice. The mRNA expression levels of cholesterol 7 alpha-hydroxylase 1 (CYP7A1), the key enzyme in bile acid synthesis, were dramatically increased by G-CA treatment in HFD mice. We suggest that G-CA treatment ameliorated hepatic steatosis by inhibiting inflammation and improving lipid metabolism.

Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress.

Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect. We also show that viral-mediated expression of neuritin in the hippocampus produces antidepressant actions and prevents the atrophy of dendrites and spines, as well as depressive and anxiety behaviors caused by CUS. Conversely, neuritin knockdown produces depressive-like behaviors, similar to CUS exposure. The ability of neuritin to increase neuroplasticity is confirmed in models of learning and memory. Our results reveal a unique action of neuritin in models of stress and depression, and demonstrate a role for neuroplasticity in antidepressant treatment response and related behaviors.

Carbamylated erythropoietin promotes neurite outgrowth and neuronal spine formation in association with CBP/p300.

Both erythropoietin (EPO) and carbamylated EPO (cEPO) have been shown to increase the length of neurites and spine density in neurons. However, the molecular mechanism underlying the EPO- and cEPO-induced neuronal differentiation has yet to be investigated. To address this issue, we investigated epigenetic modifications that regulate gene expression in neurons. Neurons treated with EPO or cEPO display an upregulation of E1A-binding protein (p300) and p300-mediated p53 acetylation, possibly increasing the transactivation activity of p53 on growth-associated protein 43 (GAP43). Treatment of cells with cEPO markedly increases spine formation and potentiates p300-mediated transactivation of PSD95, Shank2 and 3 compared to EPO. These results demonstrate that cEPO controls neuronal differentiation via acetylation of transcription factors and subsequent transactivation of target genes. These findings have important medical implications because cEPO is of interest in the development of therapeutic agents against neuropsychiatric disorders.

Multi-Functional Polymer Nanoparticles with Enhanced Adipocyte Uptake and Adipocytolytic Efficacy.

Multi-functional polymer nanoparticles have been widely utilized to improve cellular uptake and enhance therapeutic efficacy. In this study, it is hypothesized that the cellular uptake of poly(D,L-lactide-co-glycolide) (PLG) nanoparticles loaded with calcium carbonate minerals into adipocytes can be improved by covalent modification with nona-arginine (R9 ) peptide. It is further hypothesized that the internalization mechanism of R9 -modified PLG nanoparticles by adipocytes may be contingent on the concentration of R9 peptide present in the nanoparticles. R9 -modified PLG nanoparticles followed the direct penetration mechanism when the concentration of R9 peptide in the nanoparticles reached 38 µM. Notably, macropinocytosis is the major endocytic mechanism when the R9 peptide concentration is ≤ 26 µM. The endocytic uptake of the nanoparticles effectively generated carbon dioxide gas at an endosomal pH, resulting in significant adipocytolytic effects in vitro, which are further supported by the findings in an obese mouse model induced by high-fat diet. Gas-generating PLG nanoparticles, modified with R9 peptide, demonstrated localized reduction of adipose tissue (reduction of 13.1%) after subcutaneous injection without significant side effects. These findings highlight the potential of multi-functional polymer nanoparticles for the development of effective and targeted fat reduction techniques, addressing both health and cosmetic considerations.

AI-driven automatic compression system for colorectal anastomosis.

Although circular staplers offer technical advancements over traditional hand-sewn techniques, their use remains challenging for unskilled users, necessitating substantial time and experience for mastery. In particular, it is challenging to apply a consistent pressure of an appropriate magnitude. We developed an automated circular anastomosis device using artificial intelligence (AI) to solve this problem. Automation through AI reduces experiential factors during the anastomosis process. We defined damage occurring during the anastomosis process, noting that a greater depth of damage indicated a more severe injury. For automated anastomosis, data at a tissue strain of 40% were used for the AI model, as this strain level showed optimal performance based on the accuracy and cost matrix. We compared the outcomes of automated anastomosis using a trained AI with those of unskilled users. The results were validated using the Shapiro-Wilk test and t tests. Compression damage was verified on collagen sheets. The AI-driven automatic compression system resulted in less damage compared to unskilled users. In particular, a more significant difference in damage was observed in poor-condition collagen than in good-condition collagen. Damage to the collagen under poor conditions was 54.8% when handled by unskilled users, while the AI-driven automatic compression system resulted in 38.9% damage. This study confirmed that novices' use of AI for automated anastomosis reduces the risk of damage, especially for tissues in poor condition.

2,7-Phloroglucinol-6,6'-bieckol from Ecklonia cava ameliorates nanoplastics-induced premature endothelial senescence and dysfunction.

Nanoplastics (NPs), plastic particles ranging from 1 to 100 nm are ubiquitous environmental pollutants infiltrating ecosystems. Their small size and widespread use in various products raise concerns for human health, particularly their association with cardiovascular diseases (CVD). NPs can enter the human body through multiple routes, causing oxidative stress, and leading to the senescence and dysfunction of endothelial cells (ECs). Although there are potential natural compounds for treating CVD, there is limited research on preventing CVD induced by NPs. This study investigates the efficacy of Ecklonia cava extract (ECE) in preventing NPs-induced premature vascular senescence and dysfunction. Exposure of porcine coronary arteries (PCAs) and porcine coronary ECs to NPs, either alone or in combination with ECE, demonstrated that ECE mitigates senescence-associated ß-galactosidase (SA-ß-gal) activity induced by NPs, thus preventing premature endothelial senescence. ECE also improved NPs-induced vascular dysfunction. The identified active ingredient in Ecklonia cava, 2,7'-Phloroglucinol-6,6'-bieckol (PHB), a phlorotannin, proved to be pivotal in these protective effects. PHB treatment ameliorated SA-ß-gal activity, reduced oxidative stress, restored cell proliferation, and decreased the expression of cell cycle regulatory proteins such as p53, p21, p16, and angiotensin type 1 receptor (AT1), well known triggers for EC senescence. Moreover, PHB also improved NPs-induced vascular dysfunction by upregulating endothelial nitric oxide synthase (eNOS) expression and restoring endothelium-dependent vasorelaxation. In conclusion, Ecklonia cava and its active ingredient, PHB, exhibit potential as therapeutic agents against NPs-induced premature EC senescence and dysfunction, indicating a protective effect against environmental pollutants-induced CVDs associated with vascular dysfunction.

Tribological properties of real foods using extended Stribeck curves and their relationship with nutritional and rheological parameters.

The tribological properties of 19 commercial food products, grouped into six categories (yogurt, dressings, spreads, porridges, emulsified sauces, and syrups) were investigated in relation to their rheological (dynamic oscillatory shear test) and nutritional properties (fat, carbohydrate, and protein). A tribological system (a glass ball and three polydimethylsiloxane pins) generated the extended Stribeck curve, monitoring friction factors (f) over an extended range of sliding speed (v) (10-8 to 100 m/s). Tribological parameters (f, v) at four inflection points dividing the frictional regimes (X1, breakaway point between the static and kinetic regimes; X1-X2, boundary; X2-X3, mixed; X3-X4, hydrodynamic regimes) and the slope between X3 and X4 (s) were subjected to principal component analysis and hierarchical clustering on principal components, using rheological and nutritional parameters as quantitative supplementary variables. Tribological patterns were predominantly influenced by viscosity, viscoelasticity, yield stress, fat content, and the presence of particles (e.g., sugar, proteins, and fibers) and pasting materials (e.g., starches and modified starches). The 19 tribological patterns were classified into 3 clusters: low f and s for fat- and/or viscoelastic-dominant foods (Cluster 1), low f and high s for food emulsions and/or those with low extent of shear-thinning (Cluster 2), and high f at the boundary regime either for the most viscous foods or for those in the presence of particulates (Cluster 3). These results suggest that the compositional and rheological properties have a more profound impact on the classification of complex tribological patterns than the categories of food products.

Kefir inhibits 3T3-L1 adipocyte differentiation through down-regulation of adipogenic transcription factor expression.

BACKGROUND: Kefir, a traditional fermented milk composed of microbial symbionts, is reported to have various health benefits such as anti-tumour, anti-inflammatory, anti-neoplastic and pro-digestive effects. In this study, to elucidate the effects of kefir on adipocyte differentiation and lipid accumulation, three fractions were prepared from kefir culture broth. The inhibitory effects of kefir liquid culture broth fraction (Fr-1), soluble fraction (Fr-2) and insoluble fraction (Fr-3), prepared by sonication of kefir solid culture broth, on adipocyte differentiation in 3T3-L1 preadipocytes were examined. RESULTS: Fr-3 (0.1 mg mL(-1)) significantly decreased lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity by 60 and 68% respectively without affecting cell viability. In addition, Fr-3 treatment down-regulated the mRNA expression of adipogenic transcription factors including C/EBPα (32%), PPARγ (46%) and SREBP-1c (34%) during adipocyte differentiation compared with untreated control cells. The mRNA expression of adipocyte-specific genes (aP2, FAS and ACC) was also clearly decreased. CONCLUSION: The results suggest that the insoluble fraction of kefir (Fr-3) mediates anti-adipogenic effects through the inhibition of adipocyte differentiation, partly via suppression of the C/EBPα-, SREBP-1c- and PPARγ-dependent pathways.

Case Report: Single-port laparoscopic total gastrectomy for gastric cancer in patient with situs inversus totalis.

Situs inversus totalis (SIT) is a rare anatomical condition, where all the viscera appear in its reverse position. Although minimally invasive surgery has evolved to achieve totally laparoscopic gastrectomy for gastric cancer patients with SIT, it is difficult to perform lymphadenectomy in such a transposed anatomical condition. Recently, we performed a single-port laparoscopic total gastrectomy (SPTG) for gastric cancer in a patient with SIT. No postoperative complications or dietary problems were observed. Based on this experience, we are to design a safe strategy to perform D2 lymphadenectomy during SPTG in patients with SIT.