A combination of all-trans retinoic acid derivative and COX-2 inhibitor has anticancer effects in human pharyngeal carcinoma cells.

Backgrounds and aims: Carcinogenesis is characterized by an unlimited growth of cells exacerbated by Cox-2 overexpression. Cox-2 inhibitors have been proven effective in preventing and treating tumors. In our previous studies, we found that 4-Amino-2-Trifluoromethylphenyl Retinate (ATPR) induces cell apoptosis and inhibits cell proliferation to exhibit anti-cancer properties. The use of ATRA as well as Cox-2 inhibitors in clinical settings can cause adverse reactions. It is unknown what the effects and mechanisms of co-administration of ATPR and Cox-2 inhibitors are. Results: A combination of ATPR and Cox-2 inhibitors, Celecoxib, inhibited pharyngeal cancer cell proliferation in vitro and induced apoptosis. The cell cycle was arrested at G0/G1 by activating P53 and CDNA1. By activating MAPK/JNK pathways, ATPR and Celecoxib led to intrinsic and extrinsic apoptosis in pharyngeal cancer cells. ATPR/Celecoxib combined treatment suppressed tumor growth in the pharyngeal cancer cell-derived xenograft mouse model by increasing the number of apoptotic cells. The expression of the RARA and PTGS2 genes was significantly increased in tumor tissue compared to non-tumor tissue in the clinical analysis of the head and neck squamous cell carcinoma dataset. An association was found between this and the level of intrinsic apoptotic signals. Furthermore, a survival analysis conducted over a period of five years indicated that higher levels of RARA expression were associated with a better clinical outcome. Conclusion: ATPR and celecoxib inhibit the proliferation of cancer cells as well as induce apoptosis. Co-administration of ATPR and Cox-2 inhibitors has the potential to be a novel treatment plan for cancer.

Study on Magnetization Roasting Kinetics of High-Iron and Low-Silicon Red Mud.

High-iron and low-silicon red mud is not only an alkaline solid waste from Bayer process alumina production, but it is also a very important secondary iron resource. Magnetization roasting is considered as an effective and typical method for the iron recovery and removal of impurities in red mud. In this work, based on the characteristics of large specific surface area and high porosity of red mud, the kinetics of magnetization roasting and phase transformation of red mud were studied. Thermodynamic analysis results show that the reduction of iron oxide in red mud is more easily promoted by CO as reducing agent at low roasting temperature. The reduction reaction is prone to overreduction, and fayalite and ferrospinel can be formed in the reaction system. The phase transformation and iron reduction mechanism during the roasting process were evaluated. Most of hematite and goethite in the red mud decomposed in the process of magnetization roasting, released CO2, and transformed into strongly magnetic magnetite. The reaction process has some characteristics controlled by homogeneous reaction. The process of magnetization roasting reduction with CO was controlled by the hybrid control dynamics model, and the apparent activation energy was 38.31 kJ·mol-1.

[Cytogenetic and Clinical Characteristics of Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the cytogenetic characteristics and prognostic risk factors for elderly patients with newly diagnosed elderly acute myeloid leukemia(AML). METHODS: Cytogenetic test results of 76 elderly patients with AML admitted to the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital) from April 2015 to December 2021 were retrospectively analyzed, and analyzed clinical characteristics of patients and risk factors influencing prognosis. RESULTS: According to cytogenetic risk stratification, 76 newly treated elderly AML patients were divided into the favorable, intermediate, and unfavorable groups with 6(7.9%), 58(76.3%), and 12(15.8%) cases, respectively. There was no significant difference in the patient's clinical characteristics and prognosis with the cytogenetics-risk classification groups. Correlation analysis showed that patients' objective response rate (ORR) was related to the age of onset and the mutation status of the CEBPA gene. Logistic regression analysis found that age ≥70 years was an independent risk factor for patients' ORR (OR=0.110, P=0.005). Remission determined the 1-year OS rate (OR=0.049, P=0.005). CONCLUSION: There is no significant difference in clinical characteristics among aged AML patients treated at initial treatment in different cytogenetic risk groups. The age of onset ≥70 years is the determinant of whether patients can obtain ORR, and the rate of ORR is closely related to the 1-year OS rate.

IL-17A promotes endothelial cell senescence by up-regulating the expression of FTO through activating JNK signal pathway.

Endothelial aging is a sign of vascular aging that predisposes patients to vascular disease. We explored the effects of IL-17A on endothelial cell aging and determined the potential underlying mechanisms. In human umbilical vein endothelial cells, IL-17A promoted senescence, evidenced as increased positive staining of senescence-associated ß-galactosidase, increased proportion of cells arrested at G0/G1 stage, and upregulated p21 and p16 expression. IL-17A increased the expression of the m6A methylase FTO. We then investigated the relationship between FTO and endothelial cell aging. After interfering with FTO expression by siRNA, we observed that FTO induced endothelial cell aging. An increase in the expression of p-Jun N-terminal kinases (JNK) increased after IL-17A treatment indicated, that the JNK signaling pathway affected FTO expression. Moreover, the addition of the JNK signaling pathway inhibitor SP600125 blocked the effect of IL-17A on FTO expression. In conclusion, our findings revealed that IL-17A can promote endothelial cell aging by activating the JNK signaling pathway and upregulating FTO expression. This discovery can help in the identification of new therapeutic targets against endothelial cell aging and related vascular complications.

Interfacial Strengthening and Self-Monitoring in Carbon Fiber-Reinforced Composites via Carbon Nanotube-Based Damage Sensors.

Carbon fiber-reinforced polymers are important constituents of aerospace materials. However, due to the inert surface of CFs, their interfacial property is relatively weak, which severely hinders their practical applications. Here, we deposited multi-walled carbon nanotubes (MWCNTs) along with a coupling agent on the surface of carbon fiber to improve the interfacial properties of the carbon fiber/resin. Via a simple dip-coating method, the MWCNTs were uniformly distributed on the CF surface with the assistance of the pre-coated coupling agent. The interfacial shear strength between the fiber and the matrix was significant enhanceed when the CF was loaded with the coupling agent and the MWCNTs. In addition, the MWCNTs were used as sensors to in-situ monitor the interfacial state in order to elucidate the interfacial strengthening mechanism. It revealed that the collaborative contribution of the coupling agent and the MWCNTs in the interphase region is the key to the high interfacial strength.

Proteomics analysis reveals the correlation of programmed ROS-autophagy loop and dysregulated G1/S checkpoint with imatinib resistance in chronic myeloid leukemia cells.

Although tyrosine kinase inhibitors (TKIs), including imatinib, have greatly improved clinical treatment of patients with chronic myeloid leukemia (CML), drug resistance remains a major obstacle. Studies on the mechanisms underlying imatinib resistance and other alternative drugs are urgently needed. Liquid chromatography tandem mass spectrometry was applied to investigate the differences in proteomics and phosphoproteomics between K562 and K562/G (imatinib resistant K562). Multiple bioinformatics analyses were performed to unveil the differential signal pathways. CCK-8 was used to detect cell proliferation. Flow cytometry was performed to analyze reactive oxygen species (ROS), cell cycle, and cell apoptosis. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were used to observe the changes of ROS and autophagy associated with imatinib resistance in CML. Our results indicated that ROS-autophagy formed one negative feedback loop and was associated with imatinib resistance. Additionally, the limited-rate enzymes of serine synthesis pathway were escalated in K562/G, which could contribute to the increased cyclin-dependent kinases and cell proliferation index. According to phosphoproteomics data, K562/G cells exhibited abnormal phosphorylation of splicing signals. These results revealed that it could be one useful strategy to correct metabolism shift and oxidative stress, or moderately regulate autophagy. Future research should focus on the discovery of potential targets in ROS-autophagy loop.

Hypoxic exosomal HIF-1α-stabilizing circZNF91 promotes chemoresistance of normoxic pancreatic cancer cells via enhancing glycolysis.

Research has indicated that hypoxia profoundly contributes to chemoresistance of pancreatic cancer (PC), while the precise mechanism has not been fully elucidated. In this study, we report a hypoxic exosomal circular RNA (circRNA)-mediated mechanism of conferred chemoresistance in PC cells. Gemcitabine (GEM) resistance was enhanced in normoxic PC cells incubated with exosomes derived from hypoxic PC cells. CircRNA microarray displayed that circZNF91 was remarkably increased in hypoxic exosomes of PC cells compared with normoxic exosomes. Overexpression of circZNF91 obviously stimulated chemoresistance in PC cells, while knockdown of circZNF91 retarded the hypoxic exosome-transmitted chemoresistance. Mechanistically, the hypoxic-induced exosomal circZNF91 transmitted into normoxic PC cells could competitively bind to miR-23b-3p, which deprives the inhibition of miR-23b-3p on expression of deacetylase Sirtuin1 (SIRT1). Consequently, the upregulated SIRT1 enhanced deacetylation-dependent stability of HIF-1α protein, leading to glycolysis and GEM chemoresistance of recipient PC cells. In addition, we revealed that the increased circZNF91 in hypoxic exosome was attributed to the transcriptional regulation by HIF-1α. Coincidently, transmission of hypoxic exosomes into subcutaneous xenografts in nude mice obviously facilitated the chemoresistance of transplanted PC tumor, which could be reversed by depletion of circZNF91 or upregulation of miR-23b-3p. Furthermore, clinical data showed that circZNF91 was significantly upregulated in PC tissues and correlated with overexpression of glycolytic enzymes and short overall survival time. Collectively, exosomal circZNF91 can function as a cargo mediating the signal transmission between hypoxic and normoxic tumor cells to promote GEM chemoresistance of PC and may potentially serve as a therapeutic target.

Th17/IL-17 induces endothelial cell senescence via activation of NF-κB/p53/Rb signaling pathway.

Cellular senescence is a key mechanism of age-related vascular endothelial dysfunction. Interleukin-17A (IL-17A) is an inflammatory cytokine produced by Th17 cells (a subgroup of helper T cells), which is a key factor in the development of atherosclerosis. However, the effect of IL-17A on the senescence of vascular endothelial cells is still unclear. In this study, we aimed to explore the role of IL-17A on endothelial cell senescence and its signaling pathways associated with senescence. The proportion of Th17 cells in the spleen and the expression levels of IL-17A, IL-6, and vascular cell adhesion molecule-1 (VCAM-1) in mice of different ages were increased with aging. In vitro experiments showed that proliferation was inhibited, senescent ß-galactosidase and senescence-associated proteins (p16, p19, p21, and p53) of mouse aortic endothelial cells (MAECs) were increased with IL-17A treatment. Blocking the NF-κB pathway with ammonium pyrrolidinedithiocarbamate (PDTC) successfully inhibited IL-17A-induced expression of senescence-associated proteins. In conclusion, our data reveal a previously unsuspected link between IL-17A and endothelial cell senescence, which was mediated by the NF-κB /p53/Rb pathway.

Role of Indole-3-Acetic Acid in NAFLD Amelioration After Sleeve Gastrectomy.

BACKGROUND: This study aimed to investigate the weight-independent mechanism of sleeve gastrectomy on the relief of nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 58 obese patients who had undergone sleeve gastrostomy (SG) were recruited. Plasma levels of indole-3-acetic acid (I3A), a metabolite from gut microbiota before and after SG were investigated. In addition, we had 78 C57BL/6J mice included in the study. High-fat diet (HFD) was used to induce obesity in mice. Sleeve gastrectomy (SG) was then performed. The liver of the mice was analyzed by HE and oil red staining to study lipid accumulation. Fluorescence-activated cell sorting (FACS) analysis was performed to study the phenotype of macrophages in the liver. The levels of I3A in serum, stool, and liver were tested by ELISA. Macrophages and hepatocytes were cultured in vitro and stimulated with I3A to study the effects on differentiation and proliferation/apoptosis. RESULTS: In human samples, I3A increased after SG and plasma I3A levels were positively correlated with liver CT values and negatively correlated with liver fat attenuation. In mice models, after surgery, the percentage of M2 macrophages significantly increased in the liver. Both oral gavage and in vitro stimulation of I3A could promote M2 differentiation and did not significantly affect the state of hepatocytes. CONCLUSIONS: This study suggested that increased I3A from the intestine after SG could reduce the M1/M2 ratio in the liver and thus promote relief of NAFLD in obese individuals. Graphical Abstract.

A reciprocal feedback of Myc and lncRNA MTSS1-AS contributes to extracellular acidity-promoted metastasis of pancreatic cancer.

Rationale: Previous studies have reported on the role of extracellular acidity in the metastasis of numerous cancers. However, the involvement of long noncoding RNA (lncRNA) in the extracellular acidity-induced cancer metastasis of pancreatic cancer (PC) remains unclear. Methods: Different expression levels of lncRNAs in PC cells under normal and acidic conditions were compared by RNA sequencing (RNA-seq). The effects of antisense lncRNA of metastasis suppressor 1 (MTSS1-AS) on acidic PC cells were assessed by gain- and loss-of-function experiments. Fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down, Western blot, luciferase reporter, and Chromatin immunoprecipitation assays were employed to determine the regulatory mechanisms of MTSS1-AS in the acidity-induced metastasis of PC cells. The expression of MTSS1-AS and associated pathways were compared in PC samples and peritumoral normal tissues. Results: RNA-seq demonstrated that MTSS1-AS was significantly downregulated in pancreatic cells cultured with the acidic medium. The overexpression of MTSS1-AS remarkably inhibited the acidity-promoted metastasis of PC cells by upregulating the expression of its sense gene metastasis suppressor 1 (MTSS1). Mechanistically, MTSS1-AS scaffolded the interaction between E3 ubiquitin-protein ligase STIP1 homology and U-box containing protein 1 (STUB1) and transcription regulator myeloid zinc finger 1 (MZF1), leading to ubiquitination-mediated degradation of MZF1. Further, MZF1 inhibited the expression of MTSS1 by binding to the MTSS1 promoter. Thus, the acidity-reduced MTSS1-AS facilitated the stability of MZF1 and its inhibitory effect on MTSS1 transcription, thereby promoting the metastasis of PC cells under acidic conditions. Moreover, MTSS1-AS was transcriptionally repressed by the binding of MYC proto-oncogene (Myc) with initiator (Inr) elements of the MTSS1-AS promoter. Meanwhile, MTSS1-AS mutually repressed the expression of Myc by impairing the MZF1-mediated transcription activation of Myc, thereby forming a negative feedback loop between MTSS1-AS and Myc in acidic PC cells. In accordance with the experimental results, MTSS1-AS and MTSS1 were downregulated in PC and correlated with poor overall survival. Conclusions: The results implicated that a reciprocal feedback loop between Myc and MTSS1-AS contributed to the extracellular acidity-promoted metastasis of PC, and indicated that MTSS1-AS was a valuable biomarker and therapeutic target for PC.

The effect of emergency surgery on acute abdomen patients with COVID-19 pneumonia: a retrospective observational study.

During the COVID-19 outbreak, some patients with COVID-19 pneumonia also suffered from acute abdomen requiring surgical treatment; however, there is no consensus for the treatment of such patients. In this study, we retrospectively reviewed 34 patients with acute abdomen who underwent emergency surgery during the COVID-19 outbreak. Among the 34 patients with acute abdomen, a total of six cases were found with COVID-19 pneumonia (clinical classification for COVID-19 pneumonia: all were the common type). On the premise of similar demographics between both groups, patients with COVID-19 pneumonia had worse indicators of liver and coagulation function. Compared with acute abdomen patients without COVID-19, patients with COVID-19 pneumonia had a longer hospital stay, but there were no significant differences in postsurgical complications (P = 0.58) or clinical outcomes (P = 0.56). In addition, an obvious resolution of lung inflammation after surgery was observed in five COVID-19 patients (83.3%). No new COVID-19 cases occurred during the patients' hospital stays. Therefore, for the common type of COVID-19 pneumonia, emergency surgery could not only improve the outcomes of COVID-19 pneumonia patients with acute abdomen, but also benefit the resolution of pulmonary inflammation.

Damage Orientation and Depth Effect on the Guided Wave Propagation Behavior in 30CrMo Steel Curved Plates.

s: In this paper, the guided wave propagation behavior in damaged 30CrMo steel curved plates was investigated experimentally and numerically. The effects of the notch orientation, depth in the curved plate, as well as its radius, on the wave propagation characteristics were mainly analyzed by the amplitude distribution curves and the directivity diagrams of A0/S0 (zero-th order of the symmetric/antisymmetric Lamb wave) modes. An ellipse-based algorithm was compiled to locate the notches in the curved plates. Results show that the normalized S0 wave amplitude in the circumferential orientation was the largest, and it increases as notch depth increases in the axial orientation. The A0 wave amplitude in axial orientation was the largest, while it decreases with the increasing of notch depth in the other orientations. The normalized A0 wave amplitude in axial orientation increases with the increasing of radius. With the increasing of radius, the other normalized A0/S0 amplitudes linearly decreased for the other paths. The ellipse-based algorithm has high notch localization accuracy, and the notch localization error increase from 0.005% to 1.47% with the notch depth decreasing from 5 mm to 1 mm in the curved plates. For the curved plates with different radius, the maximum notch localization error is 1.20%. These satisfactory results demonstrate the effectiveness of the developed algorithm in locating damages in the researched structure.

Identification of differential gene expression in endothelial cells from young and aged mice using RNA-Seq technique.

Aging is a complex phenomenon. Endothelial cell senescence is regarded as a vital characteristic of cardiovascular diseases. This study aims to identify differentially expressed genes in vascular endothelial cells (ECs) of different age groups by RNA sequencing (RNA-Seq) technique, and to explore which molecular pathways differentially expressed genes (DEGs) may enrich in. In this study, we used RNA-Seq to analyze DEGs in primary endothelial cells of young and old mice, and further analyzed them by gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Our results showed that in total identified 229 of the DEGs, 104 were upregulated and 125 were downregulated in endothelial cells of aged mice compared with young mice. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the involvement of these DEGs in the regulation of morphogenesis of a branching structure, angiogenesis, upregulation of cell proliferation, and extracellular matrix (ECM)-receptor interaction. These results provided a novel insight to understand the molecular mechanisms underlying aortic endothelial cell senescence, and some of the novel candidate genes identified in this study may be valuable in elucidating the molecular mechanisms underlying endothelial cell senescence.

Increased sFRP3 expression correlated to senescence of endothelial cells in the aging process of mice.

Aging is tightly associated with various diseases, such as cardiovascular diseases; however, there is no effective biomarker to detect and evaluate the aging process in vivo. Therefore, it is critical to identify new aging biomarkers for earlier diagnose of aging-related diseases. This study investigated the profile of cytokines in serum samples of young and aged mice with the purpose of exploring new biomarkers that have remarkable alterations in aging. A solid-phase antibody array was used to screen 200 proteins in the mouse serum, among which 32 cytokines differentially expressed between young and aged mice were screened. The major proteins were secreted frizzled-related protein 3 (sFRP3), Fractalkine, IGFBP-5, IGFBP-6, etc. We select secreted frizzled-related protein 3 (sFRP3) in follow-up study. Then, enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of sFRP3. Our results revealed that the expression levels of sFRP3 in serum samples from aged mice were significantly higher than those in samples from young mice. ELISA data were identical to those obtained by the antibody array. Our findings indicated that sFRP3 has remarkable significance in senescence. Furthermore, we detected sFRP3 level in culture supernatants of primary endothelial cells, and the variation trend of sFRP3 levels in culture supernatant was consistent with serum data. We also detected serum sFRP3 amounts in healthy young and elderly individuals. Interestingly, serum sFRP3 amounts in the elderly were significantly increased compared with those of young individuals.

In-Situ Monitoring of a Filament Wound Pressure Vessel by the MWCNT Sensor under Hydraulic Fatigue Cycling and Pressurization.

As a result of the high specific strength/stiffness to mass ratio, filament wound composite pressure vessels are extensively used to contain gas or fluid under pressure. The ability to in-situ monitor the composite pressure vessels for possible damage is important for high-pressure medium storage industries. This paper describes an in-situ monitoring method to permanently monitor composite pressure vessels for their structural integrity. The sensor is made of a multi-walled carbon nanotube (MWCNT) that can be embedded in the composite skin of the pressure vessels. The sensing ability of the sensor is firstly evaluated in various mechanical tests, and in-situ monitoring experiments of a full-scale composite pressure vessel during hydraulic fatigue cycling and pressurization are performed. The monitoring results of the MWCNT sensor are compared with the strains measured by the strain gauges. The results show that the measured signal by the developed sensor matches the mechanical behavior of the composite laminates under various load conditions. In the hydraulic fatigue test, the relationship between the resistance and the strain is built, and could be used to quantitative monitor the filament wound pressure vessel. The bursting of the pressure vessel can be detected by the sharp increase of the MWCNT sensor resistance. Embedding the MWCNT sensor into the composite pressure vessel is successfully demonstrated as a promising method for structural health monitoring.

Optimization of a Technique to Standardize the Rodent Roux-En-Y Gastric Bypass Model and Troubleshooting of Postoperative Failures.

BACKGROUND: Rodent models are required in studies on the mechanism of Roux-en-Y gastric bypass (RYGB). However, the construction of the model is hard, and there are various causes of death after surgery in rats. METHODS: RYGB models with procedures containing a series of anatomic landmark were established in rats. Optimized procedures during surgery, possible complications after surgery, and corresponding solutions were studied. RESULTS: With the introduction of perioperative nursing and optimized surgery procedures, less time-consuming surgeries were performed and higher survival rates were achieved. Trouble-shooting data based on death time points are listed and discussed for various causes of failure. CONCLUSIONS: This study provides practical suggestions for investigators to perform RYGB surgery on rats. The troubleshooting suggestions will help operators to efficiently identify problems in their procedures.

Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway.

Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor ß (TGF-ß) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-γ-treated (M1) RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in M1-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-γ and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward M1-like macrophages, at least in part, through modulating JAK2/STAT3 pathway.

MicroRNA-221 sensitizes chronic myeloid leukemia cells to imatinib by targeting STAT5.

MicroRNAs (miRNAs) are involved in various processes from the development to drug resistance of tumors, including chronic myeloid leukemia (CML). In this study, we examined the STAT5-related miRNA-expression profile in CML cell lines (K562 and imatinib-resistant K562/G) by quantitative real-time reverse-transcriptase polymerase chain reactions. MiR-221 expression was markedly decreased in K562/G cells and peripheral blood mononuclear cells from patients with treatment failure, when compared to imatinib-sensitive CML cells and patients with optimal responses respectively. We also observed the expression of STAT5 inversely correlated with miR-221 expression in K562 and KBM5 cells. Additionally, STAT5 was validated as a direct target of miR-221 in dual-luciferase reporter vector assays. MiR-221 restoration and STAT5 knockdown in K562/G cells increased the sensitivity of CML cells to imatinib by reducing the Bcl2: Bax ratio. Collectively, our data suggested that miR-221-STAT5 axis played crucial roles in controlling the sensitivity of CML cells to imatinib.

Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion.

BACKGROUND: The unique effects of gastric resection after vertical sleeve gastrectomy (VSG) on type 2 diabetes mellitus remain unclear. This work aimed to investigate the effects of VSG on gastric leptin expression and intestinal glucose absorption in high-fat diet-induced obesity. METHODS: Male C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. HFD mice were randomized into VSG and sham-operation groups, and the relevant parameters were measured at 8 weeks postoperation. RESULTS: Higher gastric leptin expression and increased intestinal glucose transport were observed in the HFD mice. Furthermore, VSG reduced gastric leptin expression and the intestinal absorption of alimentary glucose. Both exogenous leptin replenishment during the oral glucose tolerance test (OGTT) and the addition of leptin into the everted isolated jejunum loops in vitro restored the glucose transport capacity in VSG-operated mice, and this effect was abolished when the glucose transporter GLUT2 was blocked with phloretin. Moreover, phloretin almost completely suppressed glucose transport in the HFD mice. Intestinal immunohistochemistry in the obese mice showed increased GLUT2 and diminished sodium glucose co-transporter 1 (SGLT-1) in the apical membrane of enterocytes. Decreased GLUT2 and enhanced SGLT1 were observed following VSG. VSG also reduced the phosphorylation status of protein kinase C isoenzyme ß II (PKCß II) in the jejunum, which was stimulated by the combination of leptin and glucose. CONCLUSION: Our data demonstrated that the decreased secretion of gastric leptin in VSG results in a decrease in intestinal glucose absorption via modulation of GLUT2 translocation.