Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis.

BACKGROUND AND PURPOSE: Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment. METHODS: A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT00731692) was undertaken. Data were available from 324 patients with magnetic resonance imaging scans up to 3 years after screening. New lesions at year 1 were identified with convolutional neural networks, and SELs obtained through a deformation-based method. Clinical disability was assessed annually by Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test, Timed 25-Foot Walk, and Paced Auditory Serial Addition Test. Linear, logistic, and mixed-effect models were used to assess the relationship between the Jacobian expansion in new lesions and SELs, disability scores, and treatment status. RESULTS: One hundred seventy patients had ≥1 new lesions at year 1 and had a higher lesion count at screening compared to patients with no new lesions (median = 27 vs. 22, p = 0.007). Among the new lesions (median = 2 per patient), 37% evolved into definite or possible SELs. Higher SEL volume and count were associated with EDSS worsening and confirmed disability progression. Treated patients had lower volume and count of definite SELs (ß = -0.04, 95% confidence interval [CI] = -0.07 to -0.01, p = 0.015; ß = -0.36, 95% CI = -0.67 to -0.06, p = 0.019, respectively). CONCLUSIONS: Incident chronic active lesions are common in PPMS, and fingolimod treatment can reduce their number.

Deep learning analysis for differential diagnosis and risk classification of gastrointestinal tumors.

OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.

Endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) in small bowel subepithelial lesions: experience in treating fifteen cases.

AIM: The study objective was to evaluate the primary feasibility of endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) to treat small bowel subepithelial lesions (SELs). METHOD: A retrospective case series study was performed. The first fifteen consecutive patients who underwent ESD (n = 10) and EFTR (n = 5) via BAE to remove small bowel SELs from November 2016 to December 2023 were included. The main outcome measures were the technique success rate, operative time and complication rate. RESULTS: This research focused on 15 cases of jejunoileal SELs, four cases of lipomyoma, three cases of ectopic pancreas, two cases of NETs, three cases of benign fibrous tumours and three cases of angioma. The overall technique success rate was 86.7%, with 100% (10/10) and 60% (3/5) for BAE-ESD and BAE-EFTR, respectively, in removing small bowel SELs. Two cases of EFTR failed, as the BAE operation was unsuitable for tumour resection and suture repair of a perforated wound. No serious bleeding or any postoperative complications occurred. The median time of endoscopic resection via BAE for SELs was 44 min (range 22-68 min). CONCLUSION: ESD and EFTR via BAE might be alternative choices for treating small SELs in the small bowel, with the advantages of clear and accurate positioning and minimal invasiveness. However, its superiority over surgery still needs to be further investigated.

Effect of food on oral pharmacokinetics of edaravone coamorphous dispersion containing bile salts as coformers - Part II.

OBJECTIVES: Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known for improving solubility and inhibiting drug crystallization in supersaturated conditions of the gastrointestinal tract (GIT). In our previous work, we prepared coamorphous dispersion (COAM) of EDR with sodium taurocholate (NaTC) using spray drying. The optimized EDR COAM exhibited superior in vitro performance compared to plain EDR. EDR is well absorbed in fasted-over-fed conditions. METHODS: The present work, we conducted a pharmacokinetic study for EDR and EDR COAM in fasted and fed conditions to check effect of food on its oral absorption. The LC-MS/MS-based method was developed and validated to determine the amount of EDR in plasma. RESULTS: The results suggested that EDR COAM did not show a significant difference in Cmax (P=0.3544) and AUC (P=0.1696) of fasted and fed states. On the other hand, plain EDR showed 2-fold and 3-fold reduced Cmax (P<0.0001) and AUC (P=0.0094) in the fed condition, respectively. The Cmax and AUC of EDR COAM were improved in fasted (AUC: 2.56-fold) and fed states (AUC: 5.74-fold) than plain EDR, suggesting better oral absorption of COAM than crystalline EDR without having the effect of food. CONCLUSIONS: The unique structural attributes of NaTC had the potential to inhibit the recrystallization of EDR in GIT, while concurrently reducing the impact of food on the oral absorption of EDR.

Relationship between paramagnetic rim lesions and slowly expanding lesions in multiple sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI) markers for chronic active lesions in MS include slowly expanding lesions (SELs) and paramagnetic rim lesions (PRLs). OBJECTIVES: To identify the relationship between SELs and PRLs in MS, and their association with disability. METHODS: 61 people with MS (pwMS) followed retrospectively with MRI including baseline susceptibility-weighted imaging, and longitudinal T1 and T2-weighted scans. SELs were computed using deformation field maps; PRLs were visually identified. Mixed-effects models assessed differences in Expanded Disability Status Scale (EDSS) score changes between the group defined by the presence of SELs and or PRLs. RESULTS: The median follow-up time was 3.2 years. At baseline, out of 1492 lesions, 616 were classified as SELs, and 80 as PRLs. 92% of patients had ⩾ 1 SEL, 56% had ⩾ 1 PRL, while both were found in 51%. SELs compared to non-SELs were more likely to also be PRLs (7% vs. 4%, p = 0.027). PRL counts positively correlated with SEL counts (ρ= 0.28, p = 0.03). SEL + PRL + patients had greater increases in EDSS over time (beta = 0.15/year, 95% confidence interval (0.04, 0.27), p = 0.009) than SEL+PRL-patients. CONCLUSION: SELs are more numerous than PRLs in pwMS. Compared with either SELs or PRLs found in isolation, their joint occurrence was associated with greater clinical progression.

Selenoprotein S: A versatile disordered protein.

Selenoprotein S (selenos) is a small, intrinsically disordered membrane protein that is associated with various cellular functions, such as inflammatory processes, cellular stress response, protein quality control, and signaling pathways. It is primarily known for its contribution to the ER-associated degradation (ERAD) pathway, which governs the extraction of misfolded proteins or misassembled protein complexes from the ER to the cytosol for degradation by the proteasome. However, selenos's other cellular roles in signaling are equally vital, including the control of transcription factors and cytokine levels. Consequently, genetic polymorphisms of selenos are associated with increased risk for diabetes, dyslipidemia, and cardiovascular diseases, while high expression levels correlate with poor prognosis in several cancers. Its inhibitory role in cytokine secretion is also exploited by viruses. Since selenos binds multiple protein complexes, however, its specific contributions to various cellular pathways and diseases have been difficult to establish. Thus, the precise cellular functions of selenos and their interconnectivity have only recently begun to emerge. This review aims to summarize recent insights into the structure, interactome, and cellular roles of selenos.

Surface Evaluation of Living Skin (SELS) parameter correlation analysis using data taken from astronauts working under extreme conditions of microgravity.

BACKGROUND: In space, due to fluid shift a 45% decrease in the skin topography parameter volume (mm3 ) was seen using the VisioScan® camera. Simultaneously, the parameters roughness, scaling and wrinkles changed dramatically as well. Thus, the present study has the objective to understand the relationship between the SELS parameters under extreme conditions and their application by addressing scientific-dermatological questions. MATERIAL AND METHODS: SELS measurements were performed on the volar forearms of six astronauts. The Pearson correlation coefficient was used to determine the association between the variables. RESULTS: A significant correlation was found between the skin topography parameter volume and the skin parameters roughness, scaling and wrinkles. A closer look at each astronaut revealed a significant correlation for all astronauts for the parameters volume and roughness and for more than 65% of the astronauts for the parameters volume and scaling and volume and wrinkles. However, no correlation could be found between the parameters skin hydration and roughness and scaling, respectively. CONCLUSION: Only the parameter skin volume leads to meaningful data under microgravity. Physiological changes observed by fluid shift are comparable to the skin condition edema on earth. Based on the obtained data, we can conclude that the formulas for the SELS parameters roughness, scaling and wrinkles for this special skin condition need to be reviewed.

Effect of single nucleotide polymorphisms in SEPS1 and SEPP1 on expression in the protein level in metabolic syndrome in subjects with cardiovascular disease.

Metabolic syndrome (MetS) results from the interaction between environmental and genetic factors. Several previous studies considered the role of selenium in developing MetS. Two selenoproteins, selenoprotein S (SelS), and the Selenoprotein P (SePP) play an important role in antioxidative defense and therefore susceptibility to MetS. The involvement of SNPs in SEPP1 and SEPS1 have not been studied in MetS subjects. This study aims to investigate the association between the risk of MetS and four polymorphisms SEPS1 (rs28665122, rs4965373), SEPP1 (rs7579, rs3877899) in an Iranian population. The sample of this case-control study consisted of 132 Iranian patients with cardiovascular disease (71 MetS and 65 non-MetS subjects) from December 2015 to March 2016. Demographic data, medical history, and para-clinical were measured, and Taqman probes were used for allelic discrimination. The level of the SelS and the SePP were measured by the ELIZA method. No significant differences were found in the genotype frequencies of SEPS1 (rs4965373, rs28665122), SEPP1 (rs7579, rs3877899) in patients with MetS and the non-MetS group. The mean of SelS in MetS subjects with SEPS1 (rs4965373) GG genotype is significantly lower than the non-MetS group (4496.99 ± 3688.5 vs. 6148.6 ± 1127.0, P = 0.009). The mean of SePP in MetS subjects with SEPP1 (rs3877899) GG genotype is significantly lower than the non-MetS group (40.73 ± 8.44 vs.83.91 ± 21.33, P = 0.002). The mean of SePP in MetS subjects with SEPP1 (rs7579) GG genotype is lower than the non-MetS group (55.52 ± 16.7 vs. 109.48 ± 29.78, P = 0.01). In summary, the results of this study does not indicate significant differences in the SEPP1 (rs7579, rs3877899) and SEPS1 (rs4965373, rs28665122) genotypes between MetS and non-MetS subjects. However, the results show that the mean of expression of SelS and SePP decreased in the subjects with SEPP1 (rs7579) GG and SEPP1 (rs3877899) GG.

Selenoprotein S protects against adipocyte death through mediation of the IRE1α-sXBP1 pathway.

As the most conserved branch of the unfolded protein response (UPR), the inositol-requiring enzyme 1a (IRE1a)/X-box binding protein 1 (XBP1) pathway plays crucial roles in cell survival and cell death by upregulating UPR-associated genes involved in protein entry into the endoplasmic reticulum (ER) and ER-associated degradation (ERAD). Selenoprotein S (SelS) is localized to the ER membrane and involved in ERAD. Although SelS plays an important role in restoring ER stress, the SelS-dependent protective mechanisms against cell death remain unclear. Here, using an inducible SelS knockdown (KD) 3T3-L1 cell model, we showed that SelS KD resulted adipocyte death, which was associated with imbalance of the Bcl-2 family members. Furthermore, SelS KD decreased spliced XBP1 (sXBP1), increased IRE1α and p-JNK, suggesting a role of SelS in the modulation of the IRE1α-sXBP1 pathway. Moreover, adipocyte death induced by SelS suppression can be inhibited by overexpression of sXBP1. Thus, it is proposed that SelS promotes cell survival through the IRE1α-XBP1 signaling pathway.

[Hypersensitivity to platinum salts and taxanes: The value of skin tests and tolerance induction procedures]. / Hypersensibilité aux sels de platine et aux taxanes : intérêt des tests cutanés et des inductions de tolérance.

AIM: The rate of hypersensitivity reactions to platinum salts (PS) and taxanes (TX) is on the increase. The aim of our study was to show the value of skin testing and efficacy of rapid drug desensitization. PATIENTS AND METHODS: This was a retrospective study conducted between January 2007 and February 2016 in patients consulting for immediate or delayed hypersensitivity to PS and TX. Skin prick tests (pT) and intradermal reaction tests (IDR) were performed according to the ENDA/EAACI recommendations. We used a 12-step desensitization protocol for rapid drug desensitization. RESULTS: Among the 99 patients included (30 men, 69 women, age 60.4) PS were suspected in 86 cases and taxanes in 13 cases. Skin tests were positive in 25 patients (7 pT, 18 IDR), 23 for platinum salts and 2 for taxanes. Rapid drug desensitization was proposed in 50 patients and performed in 33 (30 PS and 3 TX), proved effective in 29 patients, with protocol adaptation being necessary in 7 cases, and was ineffective in 4 patients. The skin tests for the latter 4 patients were positive. Seventy-five percent of patients with positive skin tests to oxaliplatin presented hypersensitivity reactions during desensitization, i.e. twice as many as patients having negative skin tests. Two percent of patient for PS and 7% for TX had cross reactivity. CONCLUSION: This French study confirms the efficacy of the 12-step protocol that allows patients to receive chemotherapy after hypersensitivity reaction. Skin test permits the detection of cross-reactions but their practice must be considered based on the patient's history.

Lithium and suicide prevention in bipolar disorder.

INTRODUCTION: Bipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations. METHODS: We conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: "lithium" AND "suicide" OR "suicidality" OR "suicide attempt". RESULTS: As confirmed by a recent meta-analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The "impulsive-aggressive" endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3α/ß (GSK3α and ß; proteins inhibited by Li) seem to be associated with more impulsiveness in BD populations. CONCLUSION: The anti-suicidal effect of Li has been very well demonstrated. By its specific action on the serotoninergic system, treatment with Li significantly reduces "impulsive-aggressive" behaviour which is a vulnerability factor common to suicide and BD. Long-term appropriately modulated treatment with Li seems to have considerable impact on the reduction of suicidal behaviours, suicidal ideation and death by suicide in the BD population.

Selenium and selenoproteins role in Parkinson's disease: Is there a link between selenoproteins and accumulated alpha-synuclein?

BACKGROUND: While Parkinson's disease (PD) etiology is not clear yet, accumulated alpha-synuclein is proposed to induce neurodegeneration. Selenium (Se) and its functional proteins play a key role in aggregation of misfolded proteins. However, their implications in neurodegenerative process are unclear. AIM: Diagnosing Se and selenoprotein P (SelP), selenoprotein S (SelS) proportions in serum of PD patients to compare with healthy controls, whether the changes in their concentration could be a biomarker for PD. METHODS: Se concentration was investigated in 30 PD patients and 30 controls using atomic absorption spectrometry. Also, alpha-Synuclein, SelP, and SelS levels were evaluated by ELISA. The parameters were compared in PD patients and controls. Also, the variations within the case group according to their age, disorder stage, and drug administration were evaluated. RESULTS: PD subjects had higher Se concentration. The mean SelP in PD patients was lower from controls, whilst SelS levels were higher. Also, the concentration of alpha-synuclein was higher in PD patients. However, age, stage (except UPDRS III), and disorder duration had no influence on the Se and selenoproteins level, whilst there was a direct association between alpha-synuclein levels and disorder stage. Also, alpha-synuclein proportions in subjects using levodopa was significantly higher. CONCLUSION: Our results suggest that serum levels of Se and SelP could be a biomarker or risk factor for PD. Although SelS interferes to reduce aggregated proteins, its pathway in PD is not clearly understood. Future studies could focus on how SelS can reduce on alpha-synuclein aggregation. Thus, other studies should be performed on this issue to induce the selenoproteins in PD.

Therapeutic Effects of Selenium on Alpha-Synuclein Accumulation in Substantia Nigra Pars Compacta in a Rat Model of Parkinson's Disease: Behavioral and Biochemical Outcomes.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder characterized by the accumulation of accumulated alpha-synuclein (α-Syn) in substantia nigra. Research has shown that selenium (Se) can protect neural cells through the actions of selenoproteins, including selenoprotein P (SelP) and selenoprotein S (SelS), which participate in endoplasmic reticulum-associated protein degradation (ERAD). In this study, we investigated the potential protective role of Se in a pre-clinical PD rat model.We aimed to evaluate the therapeutic effects of Se administration in the 6-hydroxydopamine (6-OHDA) induced unilateral rat PD model. Male Wistar rats were utilised for unilateral PD animal model which were subjected to stereotaxic surgery and injected with 20 µg 6-OHDA/5 µl 0.2% ascorbate saline. After confirming the model, the rats were intraperitoneally injected with 0.1, 0.2, and 0.3 mg/kg of sodium selenite for 7 days. We then performed behavioral tests, including apomorphine-induced rotation, hanging, and rotarod tests. Following sacrifice, we analysed the substantia nigra area of the brain and serum for protein quantification, element analysis, and gene expression analysis.Our results indicate that the administration of 0.3 mg/kg of Se improved the motor deficiency in hanging, rotarod, and apomorphine-induced rotational tests. While there was no significant improvement in the expression of α-Syn, Se increased the expression of selenoproteins. Additionally, levels of selenoproteins, Se, and α-Syn both brain and serum were re-established by the treatment, suggesting the role of Se on the α-Syn accumulation. Furthermore, Se improved PD-induced biochemical deficits by increasing the levels of SelS and SelP (p<0.005).In conclusion, our findings suggest that Se may have a protective role in PD. 0.3 mg/kg dosage of Se increased the expression of selenoproteins, reduced the accumulation of α-Syn in the brain, and improved PD-induced motor deficits. These results suggest that Se may be a potential therapeutic option for PD treatment.

Selenoprotein S Interacts with the Replication and Transcription Complex of SARS-CoV-2 by Binding nsp7.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replicates and evades detection using ER membranes and their associated protein machinery. Among these hijacked human proteins is selenoprotein S (selenos). This selenoprotein takes part in the protein quality control, signaling, and the regulation of cytokine secretion. While the role of selenos in the viral life cycle is not yet known, it has been reported to interact with SARS-CoV-2 nonstructural protein 7 (nsp7), a viral protein essential for the replication of the virus. We set to study whether selenos and nsp7 interact directly and if they can still bind when nsp7 is bound to the replication and transcription complex of the virus. Using biochemical assays, we show that selenos binds directly to nsp7. In addition, we found that selenos can bind to nsp7 when it is in a complex with the coronavirus's minimal replication and transcription complex, comprised of nsp7, nsp8, and the RNA-dependent RNA polymerase nsp12. In addition, through crosslinking experiments, we mapped the interaction sites of selenos and nsp7 in the replication complex and showed that the hydrophobic segment of selenos is essential for binding to nsp7. This arrangement leaves an extended helix and the intrinsically disordered segment of selenos-including the reactive selenocysteine-exposed and free to potentially recruit additional proteins to the replication and transcription complex.

Selenoprotein S regulates tumorigenesis of clear cell renal cell carcinoma through AKT/ GSK3ß/NF-κB signaling pathway.

Clear cell renal cell carcinoma (ccRCC) is one of the most lethal genitourinary tumors with rapid progression and metastasis. Selenoprotein S (SELS), which is broadly expressed in human tissues, has been reported to be involved in ER homeostasis and inflammation. However, the biological roles of SELS in ccRCC remain unclear. In this study, we found that SELS expression was significantly higher in ccRCC and correlated with multiple clinicopathological features. Overexpression of SELS could promote cell proliferation and inhibit apoptosis in 786-O cells, whereas silence of SELS elicited opposite effect. Further mechanistic studies revealed that SELS enhanced cell proliferation and inhibited apoptosis through activating AKT/GSK3ß/NF-κB signaling pathway. Besides, SELS could stabilize c-Myc by preventing ubiquitin-proteasome-mediated degradation. Interestingly, we found that SELS could also inhibit migration of ccRCC cell likely through repressing epithelial-mesenchymal transition (EMT). Collectively, our findings suggested that SELS promoted tumor progression, and inhibited apoptosis and migration through AKT/GSK3ß/NF-κB signaling pathway and EMT in ccRCC.

Applying selenocysteine-mediated expressed protein ligation to prepare the membrane enzyme selenoprotein S.

The intrinsically disordered membrane-bound selenoprotein s (selenos) takes part in the protein quality control pathway, vesicle trafficking, and NF-kB signaling. The reactive selenocysteine (Sec) at the penultimate position is responsible for its enzymatic activity. We report the preparation of the soluble segment as well as the full-length selenos using expressed protein ligation. This chapter discusses the practical considerations of expressed protein ligation using selenopeptides and describes our optimized procedure for the semi-synthesis of selenos.

Safety and efficacy of endoscopic resection for the treatment of duodenal subepithelial lesions.

BACKGROUND: Endoscopic management of duodenal subepithelial lesions is challenging, and there are only a few studies on this topic. This study aimed to evaluate the safety and efficacy of endoscopic resection for the treatment of duodenal subepithelial lesions. METHODS: We retrospectively analyzed the clinical data, including epidemiologic characteristics, therapeutic outcomes, complications, and follow-up results, of 49 patients with duodenal subepithelial lesions who underwent endoscopic resection at our hospital between August 2010 and September 2019. RESULTS: We performed 35 endoscopic submucosal dissection, 9 endoscopic mucosal resection, 3 endoscopic submucosal excavation, and 2 endoscopic full-thickness resection. The en bloc resection rate and R0 resection rate were 95.9% and 89.8%, respectively. Delayed perforations developed in 2 (4.1%) patients; surgical intervention was required for both. Coagulation syndrome developed in 1 (2.0%) patient; however, it was treated conservatively. Delayed bleeding or other serious complications did not occur. One patient underwent complementary surgery after endoscopic resection. One (2.3%) recurrence occurred in patients who underwent endoscopic resection at a median follow-up duration of 24 months (range, 1-88 months). CONCLUSIONS: Endoscopic resection is an effective, safe, and minimally invasive method for the histopathologic assessment and curative treatment of duodenal subepithelial lesions originating from the submucosal or muscularis propria.

Nomogram developed with selenoprotein S (SelS) genetic variation and clinical characteristics predicting risk of coronary artery disease in a Chinese population.

BACKGROUND: Selenoprotein S (SelS) is a novel selenoprotein encoded by the SelS gene on chromosome 15q26.3. SelS is associated with the development of diabetes, dyslipidemia and macrovascular complications. However, the relationship between genetic polymorphisms of SelS and coronary artery disease (CAD) remains unclear. METHODS: In the present study, we genotyped four single nucleotide polymorphisms (rs117613208, rs117512970, rs986500879, rs542989868) of SelS gene using direct sequencing method in a case-control study (576 CAD cases and 452 control subjects). Furthermore, we developed a predictive model using SelS genetic variation and clinical variables to predict risk of CAD. RESULTS: We found that rs117613208 T allele was more frequent in the CAD cases than that in the controls. Logistic regression analysis suggested after adjustment of other confounders, the difference remained significant between the two groups [odds ratio (OR) =2.107, 95% confidence interval (CI): 1.239-3.583, P<0.006]. Using SelS rs117613208 T allele, age, smoking, diabetes, hypertension, apolipoprotein A1 (apoA1), and lipoprotein A [Lp(a)] (GASDLY score), we developed a diagnostic model of CAD (AUC: 0.806, 95% CI: 0.776-0.836, P<0.001, sensitivity: 74.7%, specificity:75.5%). CONCLUSIONS: The present study suggested that genetic polymorphism of SelS was independent associated with CAD and GASDLY score may be a novel diagnostic model for CAD in a Chinese population.

Selenoprotein S regulates adipogenesis through IRE1α-XBP1 pathway.

The induction of endoplasmic reticulum (ER) stress is associated with adipogenesis, during which the inositol-requiring enzyme 1 alpha (IRE1α)-X-box-binding protein 1 (XBP1) pathway is involved. Selenoprotein S (SelS), which is an ER resident selenoprotein, is involved in ER homeostasis regulation; however, little is known about the role of SelS in regulating adipogenesis. In vivo studies showed that SelS protein levels in white adipose tissue were increased in obese subjects and high-fat diet (HFD)-fed mice. Moreover, we identified that SelS protein levels increased in the early phase of adipogenesis and then decreased in the late phase during adipogenesis. Overexpression of SelS promoted adipogenesis. Conversely, knockdown (KD) of SelS resulted in the inhibition of adipogenesis, which was related to increasing cell death, decreased mitotic clonal expansion, and cell cycle G1 arrest. In vivo studies also showed that ER stress markers (p-IRE1α/IRE1α, XBP1s, and Grp78) were significantly increased with upregulating of SelS expression in subcutaneous and visceral adipose tissues in the obese subjects and HFD-fed mice. Furthermore, in SelS KD cells, the levels of Grp78 were increased and the levels of p-IRE1α/IRE1α were unchanged , but mRNA levels of spliced XBP1 (XBP1s) produced by IRE1α-mediated splicing were decreased, suggesting a role of SelS in the modulation of IRE1α-XBP1 pathway. Moreover, inhibition of adipogenesis by SelS suppression can be rescued by overexpression of XBP1s. Thus, SelS appears to function as a novel regulator of adipogenesis through the IRE1α-XBP1 signaling pathway.