Helicobacter pylori-induced gastric cancer is orchestrated by MRCK beta-mediated Siah2 phosphorylation

Background Helicobacter pylori-mediated gastric carcinogenesis is initiated by a plethora of signaling events in the infected gastric epithelial cells (GECs). The E3 ubiquitin ligase seven in absentia homolog 2 (Siah2) is induced in GECs in response to H. pylori infection. Posttranslational modifications of Siah2 orchestrate its function as well as stability. The aim of this study was to evaluate Siah2 phosphorylation status under the influence of H. pylori infection and its impact in gastric cancer progression. Methods H. pylori-infected various GECs, gastric tissues from H. pylori-infected GC patients and H. felis-infected C57BL/6 mice were evaluated for Siah2 phosphorylation by western blotting or immunofluorescence microscopy. Coimmunoprecipitation assay followed by mass spectrometry were performed to identify the kinases interacting with Siah2. Phosphorylation sites of Siah2 were identified by using various plasmid constructs generated by site-directed mutagenesis. Proteasome inhibitor MG132 was used to investigate proteasome degradation events. The importance of Siah2 phosphorylation on tumorigenicity of infected cells were detected by using phosphorylation-null mutant and wild type Siah2 stably-transfected cells followed by clonogenicity assay, cell proliferation assay, anchorage-independent growth and transwell invasion assay. Results Siah2 was phosphorylated in H. pylori-infected GECs as well as in metastatic GC tissues at residues serine(6) (Ser(6)) and threonine(279) (Thr(279)). Phosphorylation of Siah2 was mediated by MRCK beta, a Ser/Thr protein kinase. MRCK beta was consistently expressed in uninfected GECs and noncancer gastric tissues but its level decreased in infected GECs as well as in metastatic tissues which had enhanced Siah2 expression. Infected murine gastric tissues showed similar results. MRCK beta could phosphorylate Siah2 but itself got ubiquitinated from this interaction leading to the proteasomal degradation of MRCK beta and use of proteasomal inhibitor MG132 could rescue MRCK beta from Siah2-mediated degradation. Ser(6) and Thr(279) phosphorylated-Siah2 was more stable and tumorigenic than its non-phosphorylated counterpart as revealed by the proliferation, invasion, migration abilities and anchorage-independent growth of stable-transfected cells. Conclusions Increased level of Ser(6) and Thr(279)-phosphorylated-Siah2 and downregulated MRCK beta were prominent histological characteristics of Helicobacter-infected gastric epithelium and metastatic human GC. MRCK beta-dependent Siah2 phosphorylation stabilized Siah2 which promoted anchorage-independent survival and proliferative potential of GECs. Phospho-null mutants of Siah2 (S6A and T279A) showed abated tumorigenicity.Peer reviewe

Retention of foreign body in the gut can be a sign of congenital obstructive anomaly: a case report

<p>Abstract</p> <p>Introduction</p> <p>Small smooth objects that enter the gut nearly always pass uneventfully through the gastrointestinal tract. Retention of foreign objects may occur due to congenital obstructive anomaly of the gut.</p> <p>Case presentation</p> <p>We report here a child who presented with features of small gut obstruction which were attributed to a foreign body impacted in the intestine. At surgery, an annular pancreas was detected and the foreign body was found to be lodged in the distended proximal duodenum.</p> <p>Conclusion</p> <p>The reported case highlights the fact that an impacted radio-opaque foreign body in a child should warn the pediatrician to the possibility of an obstructive congenital anomaly.</p

Electron-Phonon Interaction and Ultrasonic Attenuation in the Ruthenate and Cuprate superconductors

This article derives an electron-phonon interaction suitable for interpreting ultrasonic attenuation measurements in the ruthenate and cuprate superconductors. The huge anisotropy found experimentally (Lupien et al., 2001) in Sr2RuO4 in the normal state is accounted for in terms of the layered square-lattice structure of Sr2RuO4, and the dominant contribution to the attenuation in Sr2RuO4 is found to be due to electrons in the gamma band. The experimental data in the superconducting state is found to be inconsistent with vertical lines nodes in the gap in either (100) or (110) planes. Also, a general method, based on the use of symmetry, is developed to allow for the analysis of ultrasonic attenuation experiments in superconductors in which the electronic band structure is complicated or not known. Our results, both for the normal-state anisotropy, and relating to the positions of the gap nodes in the superconducting state, are different from those obtained from analyses using a more traditional model for the electron-phonon interaction in terms of an isotropic electron stress tensor. Also, a brief discussion of the ultrasonic attenuation in UPt3 is given.Comment: 12 pages. Comments have been added to the original version of this article showing how, for the ultrasonic attenuation for a hexagonal crystal (which must be isotropic with respect to rotations about the c axis) our approach reproduces the results of the traditional isotropic electron stress tensor mode

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

A rare presentation of an ectopic breast tissue in axilla

Accessory breast tissue is rare accounting to less than 1% cases seen in females. It is usually bilateral. We report a case of 24-year-old woman with a lump in the left axilla in view of its rarity and made a differential diagnosis of fibroadenoma, which following the investigations and histopathological report was confirmed as revealed fibroadenoma in the axilla. It should also be considered as a differential diagnosis for all axillary swellings

Lack of consensus for usage of beta-blockers in end-stage liver disease

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Impact of sodium glucose cotransporter-2 inhibitors on liver steatosis/fibrosis/inflammation and redox balance in non-alcoholic fatty liver disease

BACKGROUND Sodium glucose cotransporter-2 inhibitors (SGLT2-I) are the most recently approved drugs for type 2 diabetes (T2D). Recent clinical trials of these compounds reported beneficial cardiovascular (CV) and renal outcomes. A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress. Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress. AIM To investigate the effects of SGLT2-I on markers of oxidative stress, inflammation, liver steatosis, and fibrosis in patients of T2D with non-alcoholic fatty liver disease (NAFLD). METHODS We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre. We introduced the outpatients to an SGLT2-I (dapagliflozin, empagliflozin, or canagliflozin; n = 26) or a different hypoglycemic drug [other glucose-lowering drugs (OTHER), n = 26]. We evaluated circulating interleukins and serum hydroxynonenal (HNE)- or malondialdehyde (MDA)-protein adducts, fatty liver index (FLI), NAFLD fibrosis score, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST-to-platelet-ratio index (APRI), and fibrosis-4 on the day before (T0) and following treatment for six months (T1). We also performed transient elastography at T0 and T1. RESULTS Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups. Of note, following treatment for six months, a reduction of FLI and APRI, as well as of the FibroScan result, was reported in patients treated with SGLT2-I, but not in the OTHER group; furthermore, in the SGLT2-I group, we reported lower circulating levels of interleukin (IL)-1 beta, IL-6, tumor necrosis factor, vascular endothelial growth factor, and monocyte chemoattractant protein-1, and higher levels of IL-4 and IL-10. We did not observe any modification in circulating interleukins in the OTHER group. Finally, serum HNE- and MDA-protein adducts decreased significantly in SGLT2-I rather than OTHER patients and correlated with liver steatosis and fibrosis scores. CONCLUSION The present data indicate that treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status, more than optimizing glycemic control

INASL-SAASL consensus statements on NAFLD name change to MAFLD

There is an ongoing debate on the change of terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). Experts from the Indian National Association for Study of the Liver (INASL) and the South Asian Association for Study of the Liver (SAASL) involved in diagnosing, managing, and preventing NAFLD met in March 2022 to deliberate if the name change from NAFLD to MAFLD is appropriate, as proposed by a group of experts who published a consensus statement in 2020. Proponents of name change to MAFLD opined that NAFLD does not reflect current knowledge, and the term MAFLD was suggested as a more appropriate overarching term. However, this consensus group which proposed the name change to MAFLD did not represent the views and opinions of gastroenterologists and hepatologists, as well as perceptions of patients across the globe, given the fact that change of nomenclature for any disease entity is bound to have multidimensional impact on all aspects of patient care. This statement is the culmination of the participants\u27 combined efforts who presented recommendations on specific issues concerning the proposed name change. The recommendations were then circulated to all the core group members and updated based on a systematic literature search. Finally, all the members voted on them using the nominal voting technique as per the standard guidelines. The quality of evidence was adapted from the Grades of Recommendation, Assessment, Development and Evaluation syste