Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Diagnosis of endometrial pathologies: transvaginal sonography versus hysteroscopy

Background: Abnormal uterine bleeding (AUB) constitutes 69% of all gynecological complaints in the peri- and postmenopausal age groups. The aim of present study was to compare the accuracy of transvaginal sonography and hysteroscopy in diagnosing intracavitary pathologies in women with abnormal uterine bleeding.Methods: A total of 303 premenopausal women with abnormal uterine bleeding who admitted to the gynecology outpatient clinic of the Istanbul Kanuni Sultan Suleyman Research and Training Hospital, Istanbul, Turkey, between April 2010 and July 2015, and received hysteroscopy, were evaluated retrospectively. The collected data were assembled from the computerised database. All patients underwent pelvic examination, transvaginal ultrasonography, office hysteroscopy and hystopathologic evaluation. Patients with normal appearing uterine cavities on hysteroscopy additionally underwent full curettage. The pathology reports were considered to be the definitive diagnoses of patients. Transvaginal ultrasonography and office hysteroscopy findings were compared with the pathological reports and the sensitivity, specificity, positive and negative predictive values, accuracy values and likelihood ratios of office hysteroscopy and transvaginal ultrasonography were calculated for the detection of endometrial abnormalities.Results: Endometrial polyps were the most commonly identified pathology with a rate of 77.56%. The sensitivity, specificity, positive and negative predictive values of transvaginal sonography for diagnosing endometrial pathologies were 77%, 32%, 75% and 32%, respectively. The same values for hysteroscopy were 93%, 44%, 88% and 48% respectively. Transvaginal sonography had a sensitivity of 20% with a specificity of 4% for submucous myomas. The sensitivity, specificity, positive and negative predictive values of hysteroscopy for submucous myomas when compared to histopathology were 100% for all.Conclusions: The diagnostic accuracy of office hysteroscopy for focal lesions such as polyps or submucous myomas is higher than the accuracy of transvaginal ultrasonography. Due to its high diagnostic accuracy, lower complication rate and the ability to obtain direct biopsy specimens while providing simultaneous treatment, we believe that hysteroscopy will retain its place as the gold standard procedure for the investigation of endometrial pathologies

Determination of Microbiological Quality of Stuffed Mussels Sold in Aydinand Izmir

Mytilus galloprovincialis is called ‘‘black mussel’’ in Turkey and is mostly consumed as stuffed mussels and fried mussels. Mussels pump large quantities of water through their bodies, so they accumulate the toxic substances and microorganisms present in ambient water. In recent years, stuffed mussel sale increased in various foods consumption places (restaurants, supermarkets, etc.) in Turkey. The aim of this study was invastigated the microbiological quality of thirty stuffed mussels samples (270 stuffed mussels in total) collected from street sellers according to Turkish Food Codex (TFC) in Aydın and in İzmir provience. The microbiological analysis of stuffed mussel samples showed that the total viable counts were ranging between <2 and 6.44 log cfu/g. The numbers of Bacillus cereus, Staphylococcus aureus, and coliform were ranging between <2.00 and 4.36 log cfu/g, <2.00 and 4.55 log cfu/g, and <10 cfu/g, respectively. L. monocytogenes was determined in none samples. However L. ivanovii was identified in 4 samples, Vibrio spp. in 7 samples. Also, two samples were showed positive for the both pathogens. So, the result of this investigation indicated that stuffed mussels might constitute a potential health hazard, especially when kept at high ambient temperatures, depending on contamination level and lack of sanitary practices, and therefore, handling practices should require more attention and improvemen

Excess Dietary Sugar Alters Colonocyte Metabolism and Impairs the Proliferative Response to Damage

Background & Aims The colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries contains increasing amounts of sugar, such as sucrose. ISCs and TA cells are sensitive to dietary metabolites, but whether excess sugar affects their function directly is unknown. Methods Here, we used a combination of 3-dimensional colonoids and a mouse model of colon damage/repair (dextran sodium sulfate colitis) to show the direct effect of sugar on the transcriptional, metabolic, and regenerative functions of crypt ISCs and TA cells. Results We show that high-sugar conditions directly limit murine and human colonoid development, which is associated with a reduction in the expression of proliferative genes, adenosine triphosphate levels, and the accumulation of pyruvate. Treatment of colonoids with dichloroacetate, which forces pyruvate into the tricarboxylic acid cycle, restored their growth. In concert, dextran sodium sulfate treatment of mice fed a high-sugar diet led to massive irreparable damage that was independent of the colonic microbiota and its metabolites. Analyses on crypt cells from high-sucrose–fed mice showed a reduction in the expression of ISC genes, impeded proliferative potential, and increased glycolytic potential without a commensurate increase in aerobic respiration. Conclusions Taken together, our results indicate that short-term, excess dietary sucrose can directly modulate intestinal crypt cell metabolism and inhibit ISC/TA cell regenerative proliferation. This knowledge may inform diets that better support the treatment of acute intestinal injury

A Roadmap for the Human Gut Cell Atlas

The number of studies investigating the human gastrointestinal tract using various single-cell profiling methods has increased substantially in the past few years. Although this increase provides a unique opportunity for the generation of the first comprehensive Human Gut Cell Atlas (HGCA), there remains a range of major challenges ahead. Above all, the ultimate success will largely depend on a structured and coordinated approach that aligns global efforts undertaken by a large number of research groups. In this Roadmap, we discuss a comprehensive forward-thinking direction for the generation of the HGCA on behalf of the Gut Biological Network of the Human Cell Atlas. Based on the consensus opinion of experts from across the globe, we outline the main requirements for the first complete HGCA by summarizing existing data sets and highlighting anatomical regions and/or tissues with limited coverage. We provide recommendations for future studies and discuss key methodologies and the importance of integrating the healthy gut atlas with related diseases and gut organoids. Importantly, we critically overview the computational tools available and provide recommendations to overcome key challenges

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = –0.45 to –0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = –0.14 to –0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = –0.88 to –0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = –0.13 to –0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = –0.21 to –0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EU-GEI)

Dietary suppression of MHC-II expression in intestinal stem cells enhances intestinal tumorigenesis

Little is known about how interactions between diet, immune recognition, and intestinal stem cells (ISCs) impact the early steps of intestinal tumorigenesis. Here, we show that a high fat diet (HFD) reduces the expression of the major histocompatibility complex II (MHC-II) genes in ISCs. This decline in ISC MHC-II expression in a HFD correlates with an altered intestinal microbiome composition and is recapitulated in antibiotic treated and germ-free mice on a control diet. Mechanistically, pattern recognition receptor and IFNg signaling regulate MHC-II expression in ISCs. Although MHC-II expression on ISCs is dispensable for stem cell function in organoid cultures in vitro, upon loss of the tumor suppressor gene Apc in a HFD, MHC-II- ISCs harbor greater in vivo tumor-initiating capacity than their MHC-II+ counterparts, thus implicating a role for epithelial MHC-II in suppressing tumorigenesis. Finally, ISC-specific genetic ablation of MHC-II in engineered Apc-mediated intestinal tumor models increases tumor burden in a cell autonomous manner. These findings highlight how a HFD alters the immune recognition properties of ISCs through the regulation of MHC-II expression in a manner that could contribute to intestinal tumorigenesis

Response of seeds and pollen of Onobrychis viciifolia and Onobrychis oxyodonta var. armena to NaCl stress

Sainfoin (Onobrychis viciifolia Scop.) is an important forage legume crop with 52 species adapted to dry and poor soils in Turkey, but little is known about the effects of salinity on germination and seedling growth in arid and semiarid regions suffering from salinity problem. The seeds and pollen of two species of sainfoin O. viciifolia and O. oxyodonta var. armena (Syn: O. armena) were exposed to 0, 5, 10, 20 and 30 dS m-1 of NaCl under in vivo and in vitro conditions and evaluated for germination under salt stress by comparing germination percentage, mean germination time, root and shoot length, fresh and dry seedling weight and dry matter. Increased salinity levels generally resulted in decrease in all traits except time to germination, dry seedling weight and dry matter, which increased at high salinity levels. O. viciifolia seeds germinated and grew more rapidly compared to O. armena seeds under NaCl stress. No decrease in germination and seedling growth up to 10 dS m-1 was recorded. On the other hand, there was a clear difference for germination and seedling growth between in vivo and in vitro conditions. Lower values were obtained from in vitro experiments; suggesting that mineral salts, sucrose and agar may have resulted in higher osmotic potential inhibiting germination and seedling growth of species compared in vivo conditions. Decrease in pollen germination with increasing salinities was very sharp, indicating that pollen germination had higher sensitive to salinity. But, pollen grains of O. armena germinated rapidly compared to O. viciifolia. The results emphasize that in vivo experiments could be used for screening of NaCl tolerance in sainfoin cultivars without expensive chemicals and sophisticated equipments, but pollen germination is more appropriate for its wild relatives

Immunometabolism at the crossroads of obesity and cancer-a Keystone Symposia report.

peer reviewedImmunometabolism considers the relationship between metabolism and immunity. Typically, researchers focus on either the metabolic pathways within immune cells that affect their function or the impact of immune cells on systemic metabolism. A more holistic approach that considers both these viewpoints is needed. On September 5-8, 2022, experts in the field of immunometabolism met for the Keystone symposium "Immunometabolism at the Crossroads of Obesity and Cancer" to present recent research across the field of immunometabolism, with the setting of obesity and cancer as an ideal example of the complex interplay between metabolism, immunity, and cancer. Speakers highlighted new insights on the metabolic links between tumor cells and immune cells, with a focus on leveraging unique metabolic vulnerabilities of different cell types in the tumor microenvironment as therapeutic targets and demonstrated the effects of diet, the microbiome, and obesity on immune system function and cancer pathogenesis and therapy. Finally, speakers presented new technologies to interrogate the immune system and uncover novel metabolic pathways important for immunity