Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence.

BACKGROUND: Application of mesenchymal stem cell-derived exosomes (MSC-EXO) has emerged as a novel therapeutic strategy for myocardial infarction (MI). Our previous study showed that pretreatment with hemin, a potent heme oxygenase-1 (HO-1) inducer, enhanced the cardioprotective effects of MSCs in a mouse model of MI. This study aimed to investigate the therapeutic effects of EXO derived from hemin-pretreated MSCs (Hemin-MSC-EXO) in MI and explore the potential mechanisms. METHODS: MSC-EXO and Hemin-MSC-EXO were collected and characterized. MSC-EXO and Hemin-MSC-EXO were intramuscularly injected into the peri-infarct region in a mouse model of MI. Heart function of mice was assessed by echocardiography. The mitochondrial morphology of neonatal mice cardiomyocytes (NMCMs) under serum deprivation and hypoxic (SD/H) conditions was examined by Mitotracker staining. The cellular senescence of NMCMs was determined by senescence-associated-ß-galactosidase assay. A loss-of-function approach was adopted to determine the role of Hemin-MSC-exosomal-miR-183-5p in the regulation of cardiomyocyte senescence RESULTS: EXO were successfully isolated from the supernatant of MSCs and Hemin-pretreated MSCs. Compared with MSC-EXO, injection of Hemin-MSC-EXO significantly improved cardiac function and reduced fibrosis. Both MSC-EXO and Hemin-MSC-EXO ameliorated cardiomyocyte senescence and mitochondrial fission in vitro and in vivo, and the latter exhibited better protective effects. MicroRNA sequencing revealed a higher level of miR-183-5p in Hemin-MSC-EXO than in MSC-EXO. MiR-183-5p knockdown partially abrogated the protective effects of Hemin-MSC-EXO in attenuating mitochondrial fission and cellular senescence of cardiomyocytes induced by SD/H. High mobility group box-1 (HMGB1) abundance was lower in Hemin-MSC-EXO-treated than MSC-EXO-treated mouse hearts, and HMGB1 was identified as one of the potential target genes of miR-183-5p. Mechanistically, Hemin-MSC-EXO inhibited SD/H-induced cardiomyocyte senescence partially by delivering miR-183-5p into recipient cardiomyocytes via regulation of the HMGB1/ERK pathway. Furthermore, knockdown of miR-183-5p reduced the Hemin-MSC-EXO-mediated cardioprotective effects in a mouse model of MI. CONCLUSION: Our results reveal that Hemin-MSC-EXO are superior to MSC-EXO in treating MI. Exosomal miR-183-5p mediates, at least partially, the cardioprotective effects of Hemin-MSC-EXO by inhibiting cardiomyocyte senescence via regulation of the HMGB1/ERK pathway. This study highlights that MSC-EXO have high translational value in repairing cardiac dysfunction following infarction.

Structure and Formation Mechanism of Antimicrobial Peptides Temporin B- and L-Induced Tubular Membrane Protrusion.

Temporins are a family of antimicrobial peptides (AMPs) isolated from frog skin, which are very short, weakly charged, and highly hydrophobic. They execute bactericidal activities in different ways from many other AMPs. This work investigated morphological changes of planar bilayer membranes composed of mixed zwitterionic and anionic phospholipids induced by temporin B and L (TB and TL) using all-atom and coarse-grained molecular dynamics simulations. We found that TB and TL fold to α-helices at the membrane surface and penetrate shallowly into the bilayer. These short AMPs have low propensity to induce membrane pore formation but possess high ability to extract lipids out. At relatively high peptide concentrations, the strong hydrophobicity of TB and TL promotes them to aggregate into clusters on the membrane surface. These aggregates attract a large amount of lipids out of the membrane to release compression induced by other dispersed peptides binding to the membrane. The extruded lipids mix evenly with the peptides in the cluster and form tubule-like protrusions. Certain water molecules follow the movement of lipids, which not only fill the cavities of the protrusion but also assist in maintaining the tubular structures. In contrast, the peptide-free leaflet remains intact. The present results unravel distinctive antimicrobial mechanisms of temporins disturbing membranes.

Aneurysms in Takayasu's arteritis: a retrospective study of Chinese patients.

OBJECTIVES: Aneurysm formation can cause life-threatening complications in Takayasu's arteritis (TAK). The objective of this study was to evaluate the demographic, clinical and angiographic features, and outcomes of aneurysm secondary to TAK in Chinese patients. METHODS: The medical charts of patients diagnosed with TAK in Changhai Hospital between 2001 and 2017 were retrospectively reviewed. RESULTS: Aneurysms were identified in 66 (16.6%) of 397 patients with TAK. The mean age at onset was 30.4±11.5 years, with a male:female ratio of 1:2.7. Patients with aneurysm had a higher proportion of male (p<0.01), higher incidences of bruit, chest tightness and aortic regurgitation (all p<0.001), and a lower incidence of visual disturbances (p<0.01) as compared with patients without aneurysm. The prevalence of elevated ESR and CRP and ITAS2010 score were higher in patients with than without aneurysm (all p<0.01). Angiographic classification showed that type V (30.3%) was the most frequent pattern in patients with aneurysm though Type I was dominant in patients without aneurysm. Multiple aneurysms were found in 30.3% of patients and the most common site of aneurysms was abdominal aorta (22.1%). Glucocorticoids were prescribed in 86.4% of patients with aneurysm, and surgical procedures were performed in 80.3%. Five of 52 patients died during the median 3-year follow-up period. CONCLUSIONS: These findings could provide useful information on the demographical, clinical and angiographic features of TAK patients with aneurysm. Aneurysm formation in TAK may be associated with male gender and active vascular inflammation.

Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries.

Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.

Apelin ameliorates sepsis-induced myocardial dysfunction via inhibition of NLRP3-mediated pyroptosis of cardiomyocytes.

Sepsis-induced myocardial dysfunction (SMD) is the major cause of death in sepsis. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis contributes to the occurrence and development of SMD. Although Apelin confers direct protection against SMD, the potential mechanisms remain unclear. This study aimed to determine whether Apelin protects against SMD via regulation of NLRP3-mediated pyroptosis of cardiomyocytes. Experimental SMD was induced in wild-type (WT) control mice and Apelin knockout (Apelin-/-) mice by cecal ligation and puncture (CLP). Neonatal mouse cardiomyocytes (NMCs) were treated with lipopolysaccharide (LPS) to simulate the physiological environment of SMD in vitro. The expression of Apelin was greatly decreased in the plasma from septic patients and septic mouse heart. Knockout of Apelin aggravated SMD, evidenced by decreased cardiac function, and increased cardiac fibrosis and NLRP3 inflammasome and pyroptosis levels in CLP-treated Apelin-/- mice compared with WT mice. Overexpression of Apelin activated the AMPK pathway and thereby inhibited NLRP3 inflammasome-mediated pyroptosis of NMCs induced by LPS in vitro These protective effects were partially abrogated by AMPK inhibitor. In conclusion, Apelin attenuated SMD by inhibiting NLRP3-mediated pyroptosis via activation of the AMPK pathway. Apelin may serve as a promising therapeutic target for SMD.

Potential Effects of Orally Ingesting Polyethylene Terephthalate Microplastics on the Mouse Heart.

Polyethylene terephthalate microplastics (PET MPs) are widespread in natural environment, and can enter organisms and accumulate in the body, but its toxicity has not been well studied. Therefore, in order to investigate the toxic effects of PET microplastics on mammals, this study investigated the toxic effects of PET MPs on ICR mice and H9C2 cells by different treatment groups. The results indicated the cardiac tissue of mice in the PET-H (50 µg/mL) group showed significant capillary congestion, myocardial fiber breakage, and even significant fibrosis compared to the PET-C (control) group (P < 0.01). Results of the TUNEL assay demonstrated significant apoptosis in myocardial tissue in the PET-H and PET-M (5 µg/mL) groups (P < 0.01). Meanwhile, Western blotting showed increased expression of the apoptosis-related protein Bax and decreased expression of PARP, caspase-3, and Bcl-2 proteins in both myocardial tissues and H9C2 cells. In addition, flow cytometry confirmed that PET MPs decreased the mitochondrial membrane potential and apoptosis in H9C2 cells; however, this trend was reversed by N-acetylcysteamine application. Moreover, PET MP treatment induced the accumulation of reactive oxygen species (ROS) in H9C2 cells, while the MDA level in the myocardial tissue was elevated, and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were decreased (P < 0.01), indicating a change in the redox environment. In conclusion, PET MPs promoted cardiomyocyte apoptosis by inducing oxidative stress and activating mitochondria-mediated apoptotic processes, ultimately leading to myocardial fibrosis. This study provides ideas for the prevention of PET MP toxicity and promotes thinking about enhancing plastic pollution control.

Catalpol alleviates heat stroke-induced liver injury in mice by downregulating the JAK/STAT signaling pathway.

BACKGROUND: Heat stroke (HS) generated liver injury is a lethal emergency that occurs when the body is exposed to temperatures up to 40 °C for a few hours. PURPOSE: This study aimed to evaluate the therapeutic prospects of Catalpol (CA) from the blood-cooling herb Rehamanniae Radix on liver injury by HS. STUDY DESIGN AND METHODS: A murine HS model (41 ± 0.5 °C, 60 ± 5 % relative humidity) and two cell lines (lipopolysaccharide + 42 °C) were used to assess the protective effects of CA on physiological, pathological, and biochemical features in silico, in vivo, and in vitro. RESULTS: CA treatment significantly improved survival rates in vivo and cell viability in vitro over those of the untreated group. Additionally, CA treatment reduced core body temperature, enhanced survival time, and mitigated liver tissue damage. Furthermore, CA treatment also reduced the activities of AST and ALT enzymes in the serum samples of HS mice. Molecular docking analysis of the 28 overlapping targets between HS and CA revealed that CA has strong binding affinities for the top 15 targets. These targets are primarily involved in nine major signaling pathways, with the JAK-STAT pathway being highly associated with the other eight pathways. Our findings also indicate that CA treatment significantly downregulated the expression of proinflammatory cytokines both in vivo and in vitro while upregulating the expression of anti-inflammatory cytokines. Moreover, CA treatment reduced the levels of JAK2, phospho-STAT5, and phospho-STAT3 both in vivo and in vitro, which is consistent with its inhibition of the apoptotic markers p53, Bcl2, and Bax. CONCLUSIONS: Heat stroke-induced liver injury was inhibited by CA through the downregulation of JAK/STAT signaling.

Engineering a transposon-associated TnpB-ωRNA system for efficient gene editing and phenotypic correction of a tyrosinaemia mouse model.

Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (408 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB from Deinococcus radiodurans (ISDra2 TnpB) in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA (ωRNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-ωRNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and corrected the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.

Investigation on preventive inerting approach of coal spontaneous combustion in gob considering adsorption effect.

Coal spontaneous combustion in the gob poses a significant threat to coal mining operations. Designing optimal process parameters for nitrogen injection to prevent and control fires efficiently is crucial. To achieve this, a multi-field coupling equation was established, considering the adsorption of coal to gas. The model's accuracy was verified on-site, and the effects of nitrogen injection at different locations and flow rates were simulated. The optimal injection parameters were determined by analyzing temperature and inerting time. The results showed that the coal spontaneous combustion hazardous zone in the gob tested on-site was consistent with the simulation from the perspective of physisorption. Nitrogen injection had three stages: gas expansion, rapid oxygen dilution, and complete inerting. The nitrogen injection effect presented a nonlinear change in injection location and flow rate. The optimal nitrogen injection location for the Tingnan Coal Mine in Shaanxi was determined to be 90 m behind the working face on the inlet side, with an optimal flow rate of 800 m3/min. This study focused on gas adsorption and offered valuable insights for creating high-efficiency fire-fighting techniques that involve inserting in the gob.

Region-Object Relation-Aware Dense Captioning via Transformer.

Dense captioning provides detailed captions of complex visual scenes. While a number of successes have been achieved in recent years, there are still two broad limitations: 1) most existing methods adopt an encoder-decoder framework, where the contextual information is sequentially encoded using long short-term memory (LSTM). However, the forget gate mechanism of LSTM makes it vulnerable when dealing with a long sequence and 2) the vast majority of prior arts consider regions of interests (RoIs) equally important, thus failing to focus on more informative regions. The consequence is that the generated captions cannot highlight important contents of the image, which does not seem natural. To overcome these limitations, in this article, we propose a novel end-to-end transformer-based dense image captioning architecture, termed the transformer-based dense captioner (TDC). TDC learns the mapping between images and their dense captions via a transformer, prioritizing more informative regions. To this end, we present a novel unit, named region-object correlation score unit (ROCSU), to measure the importance of each region, where the relationships between detected objects and the region, alongside the confidence scores of detected objects within the region, are taken into account. Extensive experimental results and ablation studies on the standard dense-captioning datasets demonstrate the superiority of the proposed method to the state-of-the-art methods.

Duodenal-jejunal bypass increases intraduodenal bile acids and upregulates duodenal SIRT1 expression in high-fat diet and streptozotocin-induced diabetic rats.

BACKGROUND: The mechanisms underlying diabetes remission after duodenal-jejunal bypass (DJB) remain elusive. In DJB surgery, the duodenum is excluded. However, the duodenum has emerged as an important regulator of glucose homeostasis, and elevated duodenal SIRT1 leads to improved hepatic insulin sensitivity. After DJB, bile acids (BAs) in the duodenum are not mixed and diluted by the ingested food. And activation of BA receptors promotes SIRT1 expression in many tissues. We hypothesized that BA-mediated upregulation of SIRT1 may contribute to diabetic control after DJB. AIM: To investigate the surgical effects of DJB on duodenal SIRT1 expression and uncover the potential crosslinks between BAs and SIRT1. METHODS: Twenty diabetic rats were randomly allocated to the sham (n = 10) and DJB (n = 10) groups. Body weight, food intake, fasting blood glucose (FBG), serum and intraduodenal total BA (TBA) levels were measured accordingly. Oral glucose tolerance test (OGTT) and intraperitoneal pyruvate tolerance test (ipPTT) were performed to evaluate the effects of surgeries on systemic glucose disposal and hepatic gluconeogenesis. The key genes of BA signaling pathway in the duodenal mucosa, including farnesoid X receptor (FXR), small heterodimer partner (SHP), and Takeda G-protein-coupled receptor 5 (TGR5) were evaluated by real-time quantitative polymerase chain reaction 8 wk postoperatively. The duodenal SIRT1, AMPK, and phosphorylated AMPK (p-AMPK) levels were evaluated by western blotting. Rat small intestine epithelial IEC-6 cells were treated with GW4064 and INT-777 to verify the effects of BAs on SIRT1 expression in enterocytes. RESULTS: The DJB group exhibited body weight and food intake comparable to those of the sham group at all postoperative time points. The FBG level and area under the curve for the OGTT and ipPTT were significantly lower in the DJB group. The DJB group exhibited higher fasting and postprandial serum TBA levels than the sham group at both 2 and 8 wk postoperatively. At 8 wk after surgery, the DJB group showed higher intraluminal TBA concentration, upregulated mRNA expression of FXR and SHP, and elevated protein expression of SIRT1 and p-AMPK in the descending and horizontal segments of the duodenum. Activation of FXR and TGR5 receptors by GW4064 and INT-777 increased the mRNA and protein expression of SIRT1 and promoted the phosphorylation of AMPK in IEC-6 cells. CONCLUSION: DJB elevates intraduodenal BA levels and activates the duodenal BA signaling pathway, which may upregulate duodenal SIRT1 and further contribute to improved glucose homeostasis after DJB.

Apelin-13 Pretreatment Promotes the Cardioprotective Effect of Mesenchymal Stem Cells against Myocardial Infarction by Improving Their Survival.

Although mesenchymal stem cell- (MSC-) based therapy has shown promising results for myocardial infarction (MI), low cell survival heavily limits its beneficial effects. Apelin plays an essential regulatory role in cell proliferation. This study was aimed at determining whether Apelin-13 pretreatment could improve the survival of MSCs in the ischemic heart and enhance their cardioprotective efficacy against MI. MSCs were pretreated with or without Apelin-13 for 24 hours and then exposed to serum deprivation and hypoxia (SD/H) for 48 hours. The mitochondrial morphology of MSCs was assessed by MitoTracker staining. The apoptosis of MSCs was determined by TUNEL staining. The level of mitochondrial reactive oxygen species (ROS) of MSCs was detected by Mito-Sox staining. MSCs and Apelin-13-pretreated MSCs were transplanted into the peri-infarct region in a mouse MI model. Apelin-13 pretreatment protected MSCs against SD/H-induced mitochondrial fragmentation and apoptosis. Apelin-13 pretreatment reduced ROS generation induced by SD/H in MSCs. Furthermore, Apelin-13 pretreatment enhanced the angiogenesis of MSCs under SD/H conditions. Mechanistically, Apelin-13 pretreatment inhibited SD/H-induced MSC apoptosis by downregulating mitochondrial fission via activation of the ERK pathway, and these effects were partially abrogated by ERK inhibitor U0126. Apelin-13 pretreatment promoted the survival of MSCs in the ischemic heart. Moreover, transplantation with Apelin-13-pretreated MSCs improved heart function and increased angiogenesis accompanied by decreased fibrosis compared with MSC transplantation at 28 days following MI. These findings reveal that pretreatment with Apelin-13 improves MSCs survival and enhances their therapeutic efficacy for MI. Our study provides a novel approach to improve MSC-based therapy for cardiovascular disease.

Curcumin promotes cholesterol efflux from adipocytes related to PPARgamma-LXRalpha-ABCA1 passway.

Curcumin affects the functions of adipocytes. But it is not known whether curcumin has some effect on the cholesterol efflux process of adipocytes. Rabbit subcutaneous adipocytes were incubated with 5, 10 and 20 µg/ml curcumin for 24 h. The cholesterol efflux onto apoAI was assessed, and the peroxisome proliferators-activated receptor (PPAR) γ, liver X receptor (LXR) α and ATP-binding cassette transporter A1 (ABCA1) mRNA expression in adipocytes were quantified by reverse-transcription polymerase chain reaction (RT-PCR). Curcumin increased the cholesterol efflux from adipocytes in dose-dependent manner. The increased expression of PPARγ, LXRα and ABCA1 caused by curcumin were parallel. When the adipocytes were pre-treated by GW9662, the increased expression of PPARγ induced by curcumin was partially prevented, subsequent to the down-regulation of LXRα and ABCA1. Curcumin can affect the cholesterol efflux from adipocytes by regulating the PPARγ-LXR-ABCA1 passway.

A simple method for measuring electron drift velocity in gases using grid ionization chamber.

A simple method for measuring the electron drift velocity in gases with a given electric field using a grid ionization chamber is proposed and demonstrated. By collimating incident α particles that are perpendicular to the electric field, the drift velocity can be derived easily using the electron drift distance from primary ionization to a grid divided by the time interval between the cathode and anode signal starting times. These experimental settings can avoid additional signal processing of signals and reduce the effect of electron diffusion. Using this method, the measurement of electron drift velocities in 90% Ar + 10% CO2 is presented. Measured results agree well with the simulated values and with existing experimental results.

Effect of niacin on adipocyte leptin in hypercholesterolemic rabbits.

BACKGROUND: Leptin may play an important role in the development of atherosclerosis. Several transcription genes [including peroxisome proliferator-activated receptor gamma (PPARgamma) and CD36] involved in lipid and glucose metabolism and inflammatory processes may correlate to leptin expression. The aim of this study was to investigate the effect of niacin on serum leptin levels in hypercholesterolemic rabbits and the expression of leptin, PPARgamma, and CD36 in adipocytes from hypercholesterolemic rabbits. METHODS: Eighteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (a) high-cholesterol group (n=6), which is maintained on high-cholesterol diet for 6 weeks, and (b) niacin group (n=6), which receives the same cholesterol diet plus niacin (200 mg/kg/day) for 6 weeks. The control group (n=6) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for RNA analysis. The direct effect of niacin on leptin release was assayed in hypercholesterolemic rabbit adipocytes. Leptin levels in serum and adipocyte culture supernatant were measured via enzyme-linked immunosorbent assay. RT-PCR was used to evaluate leptin, PPARgamma, and CD36 mRNA expression in adipose and adipocytes. RESULTS: Compared with the control group, rabbits fed with high-cholesterol diets showed higher levels of serum total cholesterol, low-density lipoprotein cholesterol, and leptin, all of which were significantly reduced by niacin treatment. After 6 weeks of treatment with niacin, the leptin level was significantly decreased by 21.8% (6.87+/-1.58 vs. 8.79+/-1.45, P<.05) and leptin mRNA expression of adipose was significantly lower in rabbits treated with niacin than in those fed with high-cholesterol diet continuously (0.58+/-0.11 vs. 0.73+/-0.15, P<.05). Niacin dose-dependently inhibited leptin secretion and increased CD36 and PPARgamma expression in cultured adipocytes. The reduction of leptin mRNA expression of hypercholesterolemic rabbits by niacin was negatively correlated with the up-regulation of PPARgamma and CD36 mRNA expression by niacin (r=-.69 and r=-.63, respectively, P<.01). CONCLUSION: Niacin can reduce serum level and adipose mRNA expression of leptin and up-regulate PPARgamma and CD36 mRNA expression in hypercholesterolemic rabbits.

Effect of tumor necrosis factor alpha on cholesterol efflux in adipocytes.

BACKGROUND: The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has multiple effects on adipocyte, including cell differentiation, lipolysis and the production of adipokines. It is not known whether TNF-alpha has effect on cholesterol efflux in adipocyte. METHODS: Rabbit subcutaneous adipocytes were incubated with 5, 10, 20 ng/ml TNF-alpha for 24 h. The cholesterol efflux onto apoAI was assessed, and the related peroxisome proliferators-activated receptor (PPAR) gamma, liver X receptor (LXR) alpha and ATP binding cassette transporter A1 (ABCA1) mRNA expression in adipocytes were quantified by reverse transcription polymerase chain reaction. RESULTS: Treatment of adipocytes with 5 or 10 ng/ml TNF-alpha for 24 h increased cholesterol efflux, and the effect of 10 ng/ml TNF-alpha was significant higher than the control group. In contrast, 20 ng/ml TNF-alpha decreased cholesterol efflux compared with 10 ng/ml TNF-alpha. The expression of ABCA1 was increased by 5 ng/ml or 10 ng/ml TNF-alpha compared with control group, and was inhibited by 20 ng/ml TNF-alpha. The PPARgamma and LXRalpha mRNA were also significantly induced by 10 ng/ml TNF-alpha and down regulated by higher TNF-alpha concentration. After pre-treated by GW9662, the expression of PPARgamma induced by TNF-alpha was partially prevented, subsequent to the down-regulation of LXRalpha and ABCA1. CONCLUSIONS: TNF-alpha affects cholesterol efflux and ABCA1 expression of adipocytes, and the pathway of PPARgamma-LXRalpha-ABCA1 is probably involved.

Long-term results of CT-guided percutaneous radiofrequency ablation of inoperable patients with stage Ia non-small cell lung cancer: A retrospective cohort study.

BACKGROUND: This study was performed to retrospectively evaluate the 10-year overall survival (OS), progression-free survival (PFS), and local control rates of patients with inoperable stage Ia non-small cell lung cancer (NSCLC) who underwent computed tomography (CT)-guided radiofrequency ablation (RFA) in a single center. MATERIALS AND METHODS: Fifty patients with inoperable NSCLC underwent RFA between 2004 and 2016. Thoracic surgeons evaluated the patients and performed RFA under CT guidance. Follow-up CT and positron emission tomography/CT scans were obtained. Local control rates and recurrence patterns were analyzed. RESULTS: Seventy-three lesions in 50 patients (M:F = 22:28; median age: 73 years; range: 52-82 years) were treated with CT-guided RFA. The mean lesion size was 2.2 cm (range: 1-3 cm). No procedure-related deaths occurred. Low-grade fever was the most common post-ablation complication, with an incidence rate of 36%. The 1-, 2-, 3-, 5-, and 10-year OS rates of patients with Ia NSCLC were 96.0%, 86.5%, 67.1%, 36.3%, and 1%, respectively, and the 1-, 2-, 3-, and 5-year PFS rates were 94.0%, 77.5%, 43.5%, and 10.8%, respectively. The most common pattern of recurrence was local, and 15 patients with recurrence were treated with repeat RFA. Tumor size <2.0 cm was associated with a significantly improved 3-year survival rate of 78.9%. CONCLUSION: CT-guided RFA is feasible and well tolerated by inoperable patients with inoperable stage Ia NSCLC.

Landscape pattern change and its response to anthropogenic disturbance in the Qinling Mountains during 1980 to 2015.

Understanding landscape pattern change and its response to anthropogenic disturbance is of great significance for ecosystem conservation and management. Based on high-precision land use data from 1980 to 2015, we studied the spatial and temporal changes of landscape patterns in the Qinling Mountains and its response to anthropogenic disturbance by using the landscape pattern vulnerability index and human disturbance degree constructed by the landscape pattern index and the surface coverage classification system. The results showed that the degree of landscape fragmentation gradually increased in the Qinling Mountains. The landscape shape became more complex, the degree of landscape aggregation and connectivity decreased, and the spatial distribution of the landscape pattern index showed distinct features of topographic differentiation from 1980 to 2015. The fragility of the landscape pattern in the Qinling Mountains was on a downward trend as a whole. The spatial pattern of the low-vulnerable region had changed significantly, which mainly expanded from Xi'an and Hanzhong to the surrounding areas. The degree of anthropogenic disturbance in the landscape pattern of Qinling Mountains gradually increased. The spatial distribution was "high in the east, low in the west, high in the north-slope, low in the south-slope, high on the periphery, low in the middle". The fragility of landscape pattern, patch density and Shannon diversity index increased with the increases of anthropogenic disturbance, while the aggregation index and maximum patch index decreased. In the past 35 years, the impacts of anthropogenic disturbance, which gradually weakened the vulnerability of landscape pattern, also increased Shannon diversity index and the largest patch index gradually, while it had not significantly changed the patch density and the aggregation index.

Downregulation of lncRNA MALAT1 contributes to renal functional improvement after duodenal-jejunal bypass in a diabetic rat model.

Ameliorated renal function has been reported after bariatric surgery, but the mechanisms underlying this phenomenon are not well-studied. To investigate whether the long non-coding RNA (lncRNA) MALAT1 mediates the amelioration of diabetic nephropathy after duodenal-jejunal bypass (DJB) surgery, rats were assigned randomly into four groups: diabetic (DM) group, DM with DJB surgery group, DM with sham surgery group, and healthy control group. Food intake, body weight, oral glucose tolerance test (OGTT), urine albumin excretion rate (UAER), and glomerular filtration rate (GFR) were measured and histological examination of renal sections was performed. For in vitro study, HK-2 cells were cultured under various glucose concentrations following MALAT1 siRNA transfection. Expression levels of MALAT1, SAA3, IL-6, and TNF-α in rat renal tissues or HK-2 cell lines were evaluated by qRT-PCR and/or ELISA. Results showed DJB surgery improved the renal function of diabetic rats, as indicated by ameliorated UAER and GFR and attenuated glomerular hypertrophy. Expression of MALAT1 and its downstream target SAA3 was significantly downregulated in renal tissues after DJB, which in turn decreased the expression of the pro-inflammatory cytokines IL-6 and TNF-α. Knockdown of MALAT1 in HK-2 cell lines further confirmed that expression levels of SAA3, IL-6, and TNF-α were regulated by MALAT1 under both low- and high-glucose conditions. Our findings suggest that MALAT1 is implicated in the improvement of renal function after DJB through regulation of its downstream targets SAA3, IL-6, and TNF-α.

Low-pressure pneumoperitoneum with abdominal wall lift in laparoscopic total mesorectal excision for rectal cancer: Initial experience.

AIM: To evaluate the safety and feasibility of a new technology combining low-pressure pneumoperitoneum (LPP) and abdominal wall lift (AWL) in laparoscopic total mesorectal excision (TME) for rectal cancer. METHODS: From November 2015 to July 2017, 26 patients underwent laparoscopic TME for rectal cancer using LPP (6-8 mmHg) with subcutaneous AWL in Qilu Hospital of Shandong University, Jinan, China. Clinical data regarding patients' demographics, intraoperative monitoring indices, operation-related indices and pathological outcomes were prospectively collected. RESULTS: Laparoscopic TME was performed in 26 cases (14 anterior resection and 12 abdominoperineal resection) successfully, without conversion to open or laparoscopic surgery with standard-pressure pneumoperitoneum. Intraoperative monitoring showed stable heart rate, blood pressure and paw airway pressure. The mean operative time was 194.29 ± 41.27 min (range: 125-270 min) and 200.41 ± 20.56 min (range: 170-230 min) for anterior resection and abdominoperineal resection, respectively. The mean number of lymph nodes harvested was 16.71 ± 5.06 (range: 7-27). There was no positive circumferential or distal resection margin. No local recurrence was observed during a median follow-up period of 11.96 ± 5.55 mo (range: 5-23 mo). CONCLUSION: LPP combined with AWL is safe and feasible for laparoscopic TME. The technique can provide satisfactory exposure of the operative field and stable operative monitoring indices.