Ontogenetic changes in root and shoot respiration, fresh mass and surface area of Fagus crenata.

BACKGROUND AND AIMS: To date, studies on terrestrial plant ecology and evolution have focused primarily on the trade-off patterns in the allocation of metabolic production to roots and shoots in individual plants and the scaling of whole-plant respiration. However, few empirical studies have investigated the root : shoot ratio by considering scaling whole-plant respiration at various sizes throughout ontogeny. METHODS: Here, using a whole-plant chamber system, we measured the respiration rates, fresh mass and surface area of entire roots and shoots from 377 Fagus crenata individuals, from germinating seeds to mature trees, collected from five different Japanese provenances. Non-linear regression analysis was performed for scaling of root and shoot respiration, fresh mass and surface area with body size. KEY RESULTS: Whole-plant respiration increased rapidly in germinating seeds. In the seedling to mature tree size range, the scaling of whole-plant respiration to whole-plant fresh mass was expressed as a linear trend on the log-log coordinates (exponent slightly greater than 0.75). In the same body size range, root and shoot respiration vs. whole-plant fresh mass were modelled by upward-convex (exponent decreased from 2.35 to 0.638) and downward-convex trends (exponent increased from -0.918 to 0.864), respectively. The root fraction in whole-plant respiration, fresh mass and surface area shifted continuously throughout ontogeny, increasing in smaller seedlings during early growth stages and decreasing in larger trees. CONCLUSIONS: Our results suggest a gradual shift in allocation priorities of metabolic energy from roots in seedlings to shoots in mature trees, providing insights into how roots contribute to shoot and whole-plant growth during ontogeny. The models of root : shoot ratio in relation to whole-plant physiology could be applied in tree growth modelling, and in linking the different levels of ecological phenomena, from individuals to ecosystems.

Consistent scaling of whole-shoot respiration between Moso bamboo (Phyllostachys pubescens) and trees.

Both Moso bamboo (Phyllostachys pubescens) and tree forests have a large biomass; they are considered to play an important role in ecosystem carbon budgets. The scaling relationship between individual whole-shoot (i.e., aboveground parts) respiration and whole-shoot mass provides a clue for comparing the carbon budgets of Moso bamboo and tree forests. However, nobody has empirically demonstrated whether there is a difference between these forest types in the whole-shoot scaling relationship. We developed whole-shoot chambers and measured the shoot respiration of 58 individual mature bamboo shoots from the smallest to the largest in a Moso bamboo forest, and then compared them with that of 254 tree shoots previously measured. For 30 bamboo shoots, we measured the respiration rate of leaves, branches, and culms. We found that the scaling exponent of whole-shoot respiration of bamboo fitted by a simple power function on a log-log scale was 0.843 (95 % CI 0.797-0.885), which was consistent with that of trees, 0.826 (95 % CI 0.799-0.851), but higher than 3/4, the value typifying the Kleiber's rule. The respiration rates of leaves, branches, and culms at the whole-shoot level were proportional to their mass, revealing a constant mean mass-specific respiration of 1.19, 0.224, and 0.0978 µmol CO2 kg- 1 s- 1, respectively. These constant values suggest common traits of organs among physiologically integrated ramets within a genet. Additionally, the larger the shoots, the smaller the allocation of organ mass to the metabolically active leaves, and the larger the allocation to the metabolically inactive culms. Therefore, these shifts in shoot-mass partitioning to leaves and culms caused a negative metabolic scaling of Moso bamboo shoots. The observed convergent metabolic scaling of Moso bamboo and trees may facilitate comparisons of the ecosystem carbon budgets of Moso bamboo and tree forests.

The Responses of Pulmonary and Systemic Circulation and Airway to Allergic Mediators in Anesthetized Rats.

Lung allergic diseases sometimes accompany pulmonary vaso- and broncho-constriction. Rats are currently used for the experimental study of lung allergies. However, their hemodynamic mechanisms are not fully understood. Therefore the effects of allergic mediators were determined systematically in vivo in rats in terms of pulmonary vascular resistance (PVR), airway pressure (AWP) and total peripheral resistance (TPR). We directly measured pulmonary arterial pressure, left atrial pressure, systemic arterial pressure, central venous pressure and aortic blood flow to determine PVR and TPR, as well as AWP, following injections of platelet-activating factor (PAF), histamine, serotonin, leukotriene (LT) C4, and prostaglandin (PG) D2 in anesthetized open-chest artificially ventilated Sprague-Dawley (SD) rats. PVR was dose-dependently increased by consecutive administration of PAF, LTC4, and PGD2, with the maximal responsiveness being PAF>LTC4>PGD2. However, neither histamine nor serotonin changed PVR. TPR was decreased by all agents except LTC4 which actually increased it. PAF and serotonin, but not the other agents, increased AWP. In conclusion, allergic mediators exert non-uniform actions on pulmonary and systemic circulation and airways in anesthetized SD rats: PAF, LTC4 and PGD2, but not histamine or serotonin, caused substantial pulmonary vasoconstriction; LTC4 yielded systemic vasoconstriction, while the others caused systemic vasodilatation; only two mediators, PAF and serotonin, induce airway constriction.

Pulmonary vascular and airway responses to systemic vasoconstrictors in anesthetized BALB/c mice.

There is no systematic study in which the effects of vasoactive substances were investigated on pulmonary vascular resistance (PVR) in in vivo mouse by directly measuring cardiac output and the inflow and outflow pressures in the pulmonary circulation. We determined the responses of PVR, total peripheral resistance (TPR), and airway pressure (AWP) to angiotensin II, endothelin-1, vasopressin, phenylephrine, and thromboxane A2 analog U46619 in anesthetized BALB/c mice. Pulmonary arterial pressure, left atrial pressure (LAP), and aortic blood flow were measured. TPR increased dose-dependently in response to consecutive administration of all vasoconstrictors except vasopressin which reduced TPR at the highest dose of 100 nmol/kg. At high doses of vasoconstrictors, pulmonary arterial pressure and AWP increased due to increased LAP, as demonstrated by the separate LAP elevation experiments. When LAP transiently increased at high doses, PVR did not increase but decreased. Nonetheless, enodothelin-1, angiotensin II, and U46619 increased PVR. Vasopressin at 100 nmol/kg increased AWP without LAP elevation. In conclusion, the high doses of the vasoconstrictors studied here exert indirectly a transient pulmonary vasodilatory and AWP increasing actions due to pulmonary congestion evoked by strong systemic vasoconstriction. Nevertheless, enodothelin-1, angiotensin II, and U46619 cause pulmonary vasoconstriction, and vasopressin constricts airway in anesthetized BALB/c mice.

Effects of perioperative blood transfusion on the prognosis in hereditary and sporadic colon cancer.

We investigated the effects of perioperative blood transfusion in the prognosis of hereditary and sporadic colon cancer. There are 1075 colon cancer patients, including 936 sporadic colon cancer and 139 with hereditary colon cancer undergoing surgery at our hospital. All patients underwent 10 years of follow-up. In the sporadic group, mortality, local recurrence rate and distant metastases rate of transfused patients were significantly higher than non-transfused patients. The 10-year survival rates were significantly lower in patients receiving blood transfusions compared to non-transfused patients. In the hereditary group, mortality was higher in transfused patients compared to non-transfused patients.

Systemic vasoconstriction modulates the responses of pulmonary vasculature and airway to vasoconstrictors in anesthetized rats.

PURPOSE: The physiological responses of the pulmonary vasculature and airway to various vasoconstrictors were studied using isolated perfused lungs and pulmonary arteries, but these responses were not systematically studied in in vivo rats. We determined these responses and modulating effects of systemic circulation in anesthetized rats. METHODS: We measured directly pulmonary arterial pressure (PAP), left atrial pressure (LAP), aortic blood flow, and airway pressure (AWP) to determine pulmonary vascular resistance (PVR), following injections of angiotensin II (ANG II), endothelin-1 (ET-1), vasopressin, phenylephrine and thromboxane A2 mimetic U46619 in anesthetized SD rats. RESULTS: ANG II, phenylephrine and vasopressin at high doses caused strong systemic vasoconstriction and left heart overload, resulting in a transient increase in LAP and pulmonary congestion, which consequently decreased PVR. Nonetheless, prior to LAP elevation, PVR was slightly but significantly increased by ANG II and phenylephrine. In contrast, ET-1 and U46619 substantially increased PVR in the absence of LAP elevation, while vasopressin did not increase PVR. In separate experiments, PAP and AWP increased when LAP was forcedly elevated. AWP was increased by U46619 through bronchoconstriction and by the other agents through increased LAP-induced pulmonary congestion. CONCLUSION: Airway constriction is induced by U46619, and pulmonary vasoconstriction is induced strongly by U46619 and ET-1, and weakly by ANG II and phenylephrine, but not by vasopressin in anesthetized rats. ANG II, vasopressin and phenylephrine exert indirectly a transient pulmonary vasodilatory action due to pulmonary congestion evoked by strong systemic vasoconstriction, which may account for weak pulmonary pressor responses to these agents.

Mapping microarchitectural degeneration in the dilated ascending aorta with ex vivo diffusion tensor imaging.

Aims: Thoracic aortic aneurysms (TAAs) carry a risk of catastrophic dissection. Current strategies to evaluate this risk entail measuring aortic diameter but do not image medial degeneration, the cause of TAAs. We sought to determine if the advanced magnetic resonance imaging (MRI) acquisition strategy, diffusion tensor imaging (DTI), could delineate medial degeneration in the ascending thoracic aorta. Methods and results: Porcine ascending aortas were subjected to enzyme microinjection, which yielded local aortic medial degeneration. These lesions were detected by DTI, using a 9.4 T MRI scanner, based on tensor disorientation, disrupted diffusion tracts, and altered DTI metrics. High-resolution spatial analysis revealed that fractional anisotropy positively correlated, and mean and radial diffusivity inversely correlated, with smooth muscle cell (SMC) and elastin content (P < 0.001 for all). Ten operatively harvested human ascending aorta samples (mean subject age 61.6 ± 13.3 years, diameter range 29-64 mm) showed medial pathology that was more diffuse and more complex. Nonetheless, DTI metrics within an aorta spatially correlated with SMC, elastin, and, especially, glycosaminoglycan (GAG) content. Moreover, there were inter-individual differences in slice-averaged DTI metrics. Glycosaminoglycan accumulation and elastin degradation were captured by reduced fractional anisotropy (R2 = 0.47, P = 0.043; R2 = 0.76, P = 0.002), with GAG accumulation also captured by increased mean diffusivity (R2 = 0.46, P = 0.045) and increased radial diffusivity (R2 = 0.60, P = 0.015). Conclusion: Ex vivo high-field DTI can detect ascending aorta medial degeneration and can differentiate TAAs in accordance with their histopathology, especially elastin and GAG changes. This non-destructive window into aortic medial microstructure raises prospects for probing the risks of TAAs beyond lumen dimensions.

Alpha-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats.

Anaphylactic shock is sometimes life-threatening, and it is accompanied by hepatic venoconstriction in animals, which, in part, accounts for anaphylactic hypotension. Roles of norepinephrine and α-adrenoceptor in anaphylaxis-induced hypotension and portal hypertension were investigated in anesthetized ovalbumin-sensitized Sprague-Dawley rats. The sensitized rats were randomly allocated to the following pretreatment groups (n = 6/group): 1) control (nonpretreatment), 2) α1-adrenoceptor antagonist prazosin, 3) nonselective α-adrenoceptor antagonist phentolamine, 4) 6-hydroxydopamine-induced chemical sympathectomy, and 5) surgical hepatic sympathectomy. Anaphylactic shock was induced by an intravenous injection of the antigen. The systemic arterial pressure (SAP), central venous pressure (CVP), portal venous pressure (PVP), and portal venous blood flow (PBF) were measured, and splanchnic [Rspl: (SAP-PVP)/PBF] and portal venous [Rpv: (PVP-CVP)/PBF] resistances were determined. Separately, we measured efferent hepatic sympathetic nerve activity during anaphylaxis. In the control group, SAP markedly decreased, followed by a gradual recovery toward baseline. PVP and Rpv increased 3.2- and 23.3-fold, respectively, after antigen. Rspl decreased immediately, but only transiently, after antigen, and then increased 1.5-fold later than 10 min. The α-adrenoceptor antagonist pretreatment or chemical sympathectomy inhibited the late increase in Rspl and the SAP recovery. Pretreatment with α-adrenoceptor antagonists, or either chemical or surgical hepatic sympathectomy, did not affect the antigen-induced increase in Rpv. Hepatic sympathetic nerve activity did not significantly change after antigen. In conclusion, α-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal hypertension, in anesthetized rats. Hepatic sympathetic nerves are not involved in anaphylactic portal hypertension.

Circulating macrophages as the mechanistic link between mosaic loss of Y-chromosome and cardiac disease.

BACKGROUND: Genetics evidences have long linked mosaic loss of Y-chromosome (mLOY) in peripheral leukocytes with a wide range of male age-associated diseases. However, a lack of cellular and molecular mechanistic explanations for this link has limited further investigation into the relationship between mLOY and male age-related disease. Excitingly, Sano et al. have provided the first piece of evidence directly linking mLOY to cardiac fibrosis through mLOY enriched profibrotic transforming growth factor ß1 (TGF-ß1) regulons in hematopoietic macrophages along with suppressed interleukin-1ß (IL-1ß) proinflammatory regulons. The results of this novel finding can be extrapolated to other disease related to mLOY, such as cancer, cardiac disease, and age-related macular degeneration. RESULTS: Sano et al. used a CRISPR-Cas9 gRNAs gene editing induced Y-chromosome ablation mouse model to assess results of a UK biobank prospective analysis implicating the Y-chromosome in male age-related disease. Using this in vivo model, Sano et al. showed that hematopoietic mLOY accelerated cardiac fibrosis and heart failure in male mice through profibrotic pathways. This process was linked to monocyte-macrophage differentiation during hematopoietic development. Mice confirmed to have mLOY in leukocytes, by loss of Y-chromosome genes Kdm5d, Uty, Eif2s3y, and Ddx3y, at similar percentages to the human population were shown to have accelerated rates of interstitial and perivascular fibrosis and abnormal echocardiograms. These mice also recovered poorly from the transverse aortic constriction (TAC) model of heart failure and developed left ventricular dysfunction at higher rates. This was attributed to aberrant proliferation of cardiac MEF-SK4 + fibroblasts promoted by mLOY macrophages enriched in profibrotic regulons and lacking in proinflammatory regulons. These pro-fibrotic macrophages localized to heart and eventually resulted in cardiac fibrosis via enhanced TGF-ß1 and suppressed IL-1ß signaling. Furthermore, treatment of mLOY mice with TGFß1 neutralizing antibody was able to improve their cardiac function. This study by Sano et al. was able to provide a causative link between the known association between mLOY and male cardiac disease morbidity and mortality for the first time, and thereby provide a new target for improving human health. CONCLUSIONS: Using a CRISPR-Cas9 induced Y-chromosome ablation mouse model, Sano et al. has proven mosaic loss of Y-chromosome in peripheral myeloid cells to have a causative effect on male mobility and mortality due to male age-related cardiac disease. They traced the mechanism of this effect to hyper-expression of the profibrotic TGF-ß1 and reduced pro-inflammatory IL-1ß signaling, attenuation of which could provide another potential strategy in improving outcomes against age-related diseases in men.

[Corrigendum] miR­593 inhibits proliferation and invasion and promotes apoptosis in non­small cell lung cancer cells by targeting SLUG­associated signaling pathways.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that Fig. 5D on p. 5180 appeared to contain a pair of data panels with overlapping data comparing between the H1299/NC and H1299/Mimic experiments, such that these data panels may have been derived from the same original source. The authors have consulted their original data, and realized that one of the images was inadvertently selected inappropriately for the figure. Nevertheless, they were able to present all the original data to the Editorial Office, and the repeated experiments revealed the same trends in terms of significant differences in cell migration and invasion. The corrected version of Fig. 5, showing all the correct data for Fig. 5D, is shown on the next page. Note that the errors in Fig. 5 did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 20: 5172­5182, 2019; DOI: 10.3892/mmr.2019.10776].

Effects of Kalimeris indica (L.) Sch Bip on colitis-associated colorectal cancer.

Kalimeris indica (L.) Sch Bip (K. indica) is a plant of the genus Kalimeris in Asteraceae, and its whole herb can be used as medicine for the treatment of intestinal inflammatory diseases. But the mechanism is not clear. Therefore, this study was designed to explore the mechanism of K. indica (KI) in colitis-associated colorectal cancer. The expression levels of miR-31-5p and proinflammatory factors were detected using THP-1 and Caco2 cells in vitro. KI could rescue the upregulation of miR-31-5p induced by IL-6 and TNF-α in Caco2 and THP-1 cells. In LPS-stimulated PMA-differentiated THP-1 cells, KI restored miR-31-5p expression by downregulating the expression of IL-6 and TNF-α. C57BL/6 mice were used to construct CAC model through the induction of azoxymethane/dextran sulfate sodium. The successfully established CAC mice were treated with water extract of KI through intragastric administration for 5 weeks. The result showed that KI could significantly reduce the atypical hyperplasia in colon tissue, and inhibit the expression of proinflammatory factors such as IL-6, TNF, IL-11, IL-7, etc. At the same time, KI could restore the level of miR-31-5p in mice, and therefore the downstream LATS2 to inhibit the development of CAC. These above results indicate that KI is a potentially effective herb medicine to prevent CAC.

Modified Laparoscopic Sugarbaker Repair of Parastomal Hernia With a Totally Extraperitoneal Technique.

Purpose: Many patients develop a parastomal hernia within the first 2 years of stoma formation, and even surgical repair is associated with high recurrence rates. An intraperitoneal approach is typically used for the laparoscopic repair of parastomal hernia; it is unknown whether a totally extraperitoneal technique (TEP) is feasible. Here we describe a laparoscopic TEP approach using a modified Sugarbaker method for the repair of parastomal hernia. Methods: Seven patients underwent parastomal hernia repair. The retrograde puncture technique was used to create the extrapneumoperitoneum, and the peritoneum was separated with a laparoscopic TEP approach; the mesh was placed using a modified Sugarbaker technique. Results: All patients had an oncologic etiology for stoma creation. The mean (±SD) size of the hernia defect was 3.1 ± 2.7 cm and the mesh size was 303.4 ± 96.8 cm2. The mean operative time was 195.5 ± 20.7 min and average length of hospital stay after surgery was 4.8 ± 2.1 days. One patient had intraoperative subcutaneous emphysema. The average follow-up time was 8.5 ± 2.7 months; mild pain occurred in 2 patients, 3 experienced seroma formation (with no special treatment required), and 1 had early intestinal obstruction (which was treated with conservative care). There was no hernia recurrence, wound complications, or infections of the surgical site or mesh during follow-up. Conclusion: A laparoscopic TEP technique is technically challenging but feasible. Modified laparoscopic Sugarbaker repair of a parastomal hernia with the TEP technique is safe and effective, although the recurrence rate and late complications require confirmation in more cases with long-term follow-up.

Corrigendum: Long Non-Coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling.

[This corrects the article DOI: 10.3389/fonc.2020.00291.].

Endoscopic Totally Extraperitoneal Repair of Parastomal Hernia: A Case Report.

A parastomal hernia is a type of incisional hernia that occurs in abdominal integuments in the proximity of a stoma. It is a frequent late complication following colostomy. Surgical repair is currently the only treatment option for parastomal hernia. Here we present the case of a 74-year-old patient with parastomal hernia and a history of open surgery treated with a totally extraperitoneal (TEP) endoscopic approach. There was no recurrence of the hernia at the 3-month follow-up. We discuss the feasibility and possible operative approaches for endoscopic repair of parastomal hernia with the TEP technique.

Metabolomics of Fuzi-Gancao in CCl4 induced acute liver injury and its regulatory effect on bile acid profile in rats.

BACKGROUND: Fuzi (Radix aconiti lateralis)-Gancao (Radix glycyrrhizae) is one of the most classical drug pairs of traditional Chinese medicine. In clinical practice, decoctions containing Fuzi-Gancao (F-G) are often used in the treatment of liver diseases such as hepatitis and liver failure. AIM: To investigate the metabolomics of F-G in CCl4 induced acute liver injury in rats and its regulatory effect on the bile acid profile. METHODS: The pharmacodynamic effect of F-G on CCl4 induced acute liver injury in rats was evaluated, and an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver. RESULTS: Twenty-four differential metabolites were identified in serum samples. The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. Subsequently, a UPLC-MS/MS method for simultaneous determination of 11 bile acids, including cholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, and glycinic acid, was established to analyze the regulatory mechanism of F-G in serum. F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group. CONCLUSION: F-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine, and reducing the accumulation of free bile acids in the liver. F-G could also regulate the compensatory degree of taurine, decreasing the content of taurine-conjugated bile acids to protect hepatocytes.

Structure-activity relationship of a novel pentapeptide with cancer cell growth-inhibitory activity.

We previously reported that yamamarin, a pentapeptide with an amidated C-terminus (DILRG-NH(2)) isolated from larvae of the silkmoth, and its palmitoylated analog (C16-DILRG-NH(2)) suppressed proliferation of rat hepatoma (liver cancer) cells. In this study, we investigated the structure-activity relationship of yamamarin by in vitro assay and spectroscopic methods (CD and NMR) for various analogs. The in vitro assay results demonstrated that the chemical structure of the C-terminal part (-RG-NH(2)) of yamamarin is essential for its activity. The CD and NMR results indicated that yamamarin and its analog adopt predominantly a random coil conformation. Moreover, a comparison of NMR spectra of DILRG-NH(2) and C16-DILRG-NH(2) revealed that the N-terminal palmitoyl group of C16-DILRG-NH(2) did not affect the conformation of the C-terminal part, which is essential for activity. Together, these results should assist in the design of more sophisticated anticancer drugs.

Long Non-coding RNA MIR570MG Causes Regorafenib Resistance in Colon Cancer by Repressing miR-145/SMAD3 Signaling.

An increasing number of studies have shown that long non-coding RNA (lncRNA) dysregulation plays a fundamental role in the development of various cancers, including colon cancer. Nonetheless, the mechanisms of lncRNA in regorafenib-resistance remain unclear. Our research revealed the lncRNA MIR570MG increased in regorafenib-resistant colon cancer cells compared to the regorafenib-sensitive cells. Furthermore, MIR570MG sponged miR-145, which declined in regorafenib-resistant colon cancer cell lines. More importantly, overexpression of miR-145 hampered cell proliferation and retrieved colon cancer regorafenib-sensitivity, contrary to the function of MIR570MG. Dual-luciferase reporter assay confirmed that miR-145 bound to 3'-UTR of SMAD3, a transcriptional modulator activated by TGFß, resulting in blockage of TGFß /SMAD3-mediated cell growth and cycle progression. Besides, ectopic expression of miR-145 inhibitor in the parental cells endowed resistance to regorafenib. Inversely, knockdown of MIR570MG impoverished resistance against regorafenib. Additionally, overexpression of MIR570MG conquered the suppression of tumor growth by miR-146 and rehabilitated the resistance to regorafenib in HCT116R human colon cancer mouse models. In summary, our findings suggested that MIR570MG promoted regorafenib resistance via releasing SMAD3 from miR-145, leading to activation of SMAD3-mediated signaling pathways.

Adiponectin/SIRT1 Axis Induces White Adipose Browning After Vertical Sleeve Gastrectomy of Obese Rats with Type 2 Diabetes.

PURPOSE: White adipose tissue (WAT) browning plays a crucial role in energy metabolism. However, it remains unclear whether WAT browning is involved in the adipose reduction following sleeve gastrectomy (SG). Adiponectin is upregulated after Roux-en-Y gastric bypass surgery. The role of adiponectin in SG was further investigated in the current study. MATERIALS AND METHODS: Diabetic Sprague Dawley rats were randomly divided into control, sham + libitum, sham + food restriction, and sleeve groups. Browning markers, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor (PPAR) γ, and PPARγ coactivator-1 alpha (PGC-1α), were examined 4 weeks after the operation. RESULTS: UCP1, PPARγ, and PGC-1α expression were significantly higher in the sleeve group compared to the other study groups. The adipose tissue of the sleeve group exhibited tissue weight loss and additional morphological browning features. In addition, adiponectin expression in the sleeve group was significantly increased. Adiponectin upregulated the expression of the browning genes and sirtuin 1 (SIRT1) in 3T3-L1 adipocytes. SIRT1 could increase the WAT browning levels, revealing that adiponectin induced the browning process via the upregulation of SIRT1. Furthermore, SIRT1 represented a positive regulatory feedback loop for adiponectin. SIRT1 activated adenosine monophosphate-activated protein kinase (AMPK), which can mediate WAT browning. Inhibition of the AMPK signaling pathway by dorsomorphin decreased UCP1, PPARγ, and PGC-1α expression. However, additional studies are needed to understand the relationship between adiponectin and glucose homeostasis. CONCLUSIONS: Sleeve gastrectomy increased adiponectin levels, which in turn upregulated SIRT1. Thus, SIRT1 may function as an endocrine signal to mediate WAT browning.

miR­593 inhibits proliferation and invasion and promotes apoptosis in non­small cell lung cancer cells by targeting SLUG­associated signaling pathways.

Increasing evidence suggests that microRNAs (miRNAs or miRs) serve a critical role in tumor development. However, the role of miRNAs in non­small cell lung cancer (NSCLC) progression remains largely unknown. The present study observed that miR­593 was significantly impaired in patients with NSCLC and was a novel regulator of NSCLC progression. Patients whose tumors had high expression levels of miR­593 had longer overall survival than patients whose tumors had low levels of miR­593 expression (P=0.0219). miR­593 expression levels were inversely correlated with zinc finger protein SNAI2 (SLUG) messenger RNA (mRNA) levels in 87 clinical tissue specimens of NSCLC (P<0.001). A luciferase assay demonstrated that miR­593 interacted with the binding sites present in the SLUG 3'­untranslated region and reduced the expression of SLUG. Introduction of a miR­593 mimic suppressed cell proliferation by inactivating the SLUG/protein kinase B (Akt)/cyclin D1/CDK4 or CDK6 signaling pathway, while it induced apoptosis by activating the SLUG/Akt/Bcl­2/BAX signaling pathway. Furthermore, introduction of a miR­593 mimic recovered the expression of E­cadherin at the protein and mRNA level, and inhibited cell migration and invasion. In conclusion, these results indicated that miR­593 may act as a tumor suppressor in NSCLC to decelerate cancer aggressiveness by inhibiting SLUG expression.

Status of the Field of Bariatric Surgery: a National Survey of China in 2018.

BACKGROUND: Due to the slow development of bariatric surgery in mainland China, we aimed to provide fact-based status reports and recommendations for the development of bariatric surgery in mainland China by investigating the basic context, social environment, and perioperative treatment options of surgeons who perform bariatric surgery. STUDY DESIGN: A questionnaire was prepared based on a literature review, consultations with experts and current issues. The three-part questionnaire was sent to medical professionals in the field of bariatric surgery. The results were gathered, and analysis was performed after collecting the data. RESULTS: In total, 98.5% of respondents were employed at public grade 3 class A hospitals, 70.8% were chief physicians and professors, 53.2% were trained at other institutions before their first bariatric surgery, 65.0% were previously engaged in gastrointestinal surgery, 76.9% were currently engaged in multiple fields of general surgery, 39.5% believed that low self-acceptance was the primary obstacle, 39.0% regarded news media networks as the most valued publicity platform, 48.0% accepted patients less than 16 years old, and 46.0% accepted patients greater than 65 years old. Additionally, 84.6% of respondents addressed comorbidities, 73.4% developed exercise guidance for patients, 81.6% believed that the total hospitalization cost was greater than 50,000 (CNY), 41.5% chose oral purgative for bowel preparation, 40.0% allowed patients to resume oral intake of liquids on the first day after surgery, and 70.7% routinely placed an abdominal drainage tube. CONCLUSION: Bariatric surgery has great potential in mainland China, but many inconsistencies exist. This field is still in its infancy, and much work is needed.