Analgesic efficacy of postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane block for laparoscopic colorectal cancer surgery: a randomized, prospective, controlled study.

BACKGROUND: We assessed whether a postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane (TAP) block could reduce 24 h rescue tramadol requirement compared with placebo in patients undergoing elective laparoscopic colorectal cancer surgery. METHODS: Patients scheduled to undergo elective laparoscopic surgery following the diagnosis of colorectal cancer were included in this study and randomized into Group and Group Control. The patients received a postoperative bilateral, ultrasound-guided, posterior TAP block in either 20 mL of 0.5% ropivacaine (Group TAP) per side or an equivalent volume of normal saline (Group Control). The primary outcome was the cumulative consumption of rescue tramadol within 24 h after the surgery. Secondary endpoints included (1) resting and movement numerical rating scale (NRS) pain scores at 2, 4, 6, 12, 24, 48, and 72 h; (2) incidences of related side effects; (3) time to the first request for rescue tramadol; (4) patient satisfaction regarding postoperative analgesia; (5) time to restoration of intestinal function; (6) time to mobilization; and (7) the length of hospital stay. RESULTS: In total, 92 patients were randomized, and 82 patients completed the analysis. The total rescue tramadol requirement (median [interquartile range]) within the first 24 h was lower in Group TAP (0 [0, 87.5] mg) than in Group Control (100 [100, 200] mg), P < 0.001. The posterior TAP block reduced resting and movement NRS pain scores at 2, 4, 6, 12, and 24 h after surgery (all P < 0.001) but showed similar scores at 48 h or 72 h. A higher level of satisfaction with postoperative analgesia was observed in Group TAP on day 1 (P = 0.002), which was similar on days 2 (P = 0.702) and 3 (P = 0.551), compared with the Group Control. A few incidences of opioid-related side effects (P < 0.001) and a lower percentage of patients requiring rescue tramadol analgesia within 24 h (P < 0.001) were observed in Group TAP. The time to the first request for rescue analgesia was prolonged, and the time to mobilization and flatus was reduced with a shorter hospital stay in Group TAP as compared with Group Control. CONCLUSIONS: A postoperative bilateral, ultrasound-guided, posterior TAP block resulted in better pain management and a faster recovery in patients undergoing laparoscopic colorectal cancer surgery, without adverse effects. TRIAL REGISTRATION: The study was registered at http://www.chictr.org.cn ( ChiCTR-IPR-17012650 ; Sep 12, 2017).

Simulation-based training following a theoretical lecture enhances the performance of medical students in the interpretation and short-term retention of 20 cross-sectional transesophageal echocardiographic views: a prospective, randomized, controlled trial.

BACKGROUND: Both simulation-based training and video-based training serve as educational adjuncts for learning TEE among medical students. In the present study, we hypothesized that simulation-based training would better enhance the performance of medical students in the interpretation of 20 cross-sectional views compared to video-based training. METHODS: A total of 120 4th-year undergraduate medical students were enrolled in the present study. The study began with a pre-test of all the participants, followed by a 90-min theoretical lecture and a post-test. Subsequently, the participants were randomly divided into the video-based group (Group V) and simulation-based group (Group S). Next, Group V received 60 min of TEE video learning, while Group S received 60 min of TEE simulator training. After the respective training, both the groups undertook the retention-test 1 and retention-test 2, 1 week and 1 month later, respectively. The performance for each test was evaluated by five views, which were selected randomly and, respectively, from a set of 20 cross-sectional views. The primary outcome was the performance of the retention-test 1. Secondary outcomes included: (1) comparison the performances of the pre-test, post-test, and retention-test 2 between two groups; (2) comparison the performances of pre-test and post-test in the same group; (3) comparison the performances of retention-test 1, and retention-test 2 in the same group. RESULTS: Better performances were observed in Group S in both retention-test 1 (Group V: 63.2 [52.6, 77.6] vs. Group S: 89.5 [68.4, 100.0], P < 0.001) and retention-test 2 (Group V: 58.0 [48.0, 72.0] vs. Group S: 74.0 [64.0, 80.0], P < 0.001) compared to Group V. No statistically significant differences were observed in the performances of pre-test (Group V: 8.3 [4.2, 12.5] vs. Group S: 8.3 [4.2, 12.5], P = 0.825) or post-test (Group V: 46.2 [38.5, 57.7] vs. Group S: 44.2 [38.5, 56.7], P = 0.694) between the two groups. The improvement had been observed in the post-test, compared with pre-test in the same group, respectively (Group V in post-test: 46.2 [38.5, 57.7] vs. Group V in pre-test: 8.3 [4.2, 12.5], P < 0.001; Group S in post-test: 44.2 [38.5, 56.7] vs. Group S in pre-test: 8.3 [4.2, 12.5], P < 0.001). However, the performance in retention-test 2 was significantly reduced, compared with retention-test 1 in the same group, respectively (Group V in retention-test 2: 58.0 [48.0, 72.0] vs. Group V in retention-test 1: 63.2 [52.6, 77.6] P = 0.005; Group S in retention-test 2: 74.0 [64.0, 80.0] vs. Group S in retention-test 1: 89.5 [68.4, 100.0], P < 0.001). CONCLUSIONS: Following a 90-min theoretical lecture, simulation-based training better enhanced the performance of medical students in the interpretation and short-term retention of 20 cross-sectional views compared to video-based training. TRIAL REGISTRATION: http://www.chictr.org.cn ( ChiCTR2000033519 , 3/June/2020).

Development of a Low-Cost Portable Electronic Nose for Cigarette Brands Identification.

In China, the government and the cigarette industry yearly lose millions in sales and tax revenue because of imitation cigarettes. Usually, visual observation is not enough to identify counterfeiting. An auxiliary analytical method is needed for cigarette brands identification. To this end, we developed a portable, low-cost electronic nose (e-nose) system for brand recognition of cigarettes. A gas sampling device was designed to reduce the influence caused by humidity fluctuation and the volatile organic compounds (VOCs) in the environment. To ensure the uniformity of airflow distribution, the structure of the sensing chamber was optimized by computational fluid dynamics (CFD) simulations. The e-nose system is compact, portable, and lightweight with only 15 cm in side length and the cost of the whole device is less than $100. Results from the machine learning algorithm showed that there were significant differences between 5 kinds of cigarettes we tested. Random Forest (RF) has the best performance with accuracy of 91.67% and K Nearest Neighbor (KNN) has the accuracy of 86.98%, which indicated that the e-nose was able to discriminate samples. We believe this portable, cheap, reliable e-nose system could be used as an auxiliary screen technique for counterfeit cigarettes.

Favourable effects of grape seed extract on intestinal epithelial differentiation and barrier function in IL10-deficient mice.

The impairment in the rate of cell proliferation and differentiation leads to a negative consequence on the renewal of the intestinal epithelium, which is the aetiological factor of a number of digestive diseases. Grape seed extract (GSE), a rich source of proanthocyanidins, is known for its beneficial health effects. The present study evaluated the beneficial effects of GSE on colonic cell differentiation and barrier function in IL10-deficient mice. Female mice aged 6 weeks were randomised into two groups and given drinking-water containing 0 or 0.1 % GSE (w/v) for 12 weeks. GSE supplementation decreased serum TNF-α level and intestinal permeability, and increased the colonic goblet cell density that was associated with increased mRNA expression of mucin (Muc)-2. Immunohistochemical analyses showed lower accumulation of ß-catenin in the crypts of colon tissues of the GSE-supplemented mice, which was associated with a decreased mRNA expression of two downstream effectors of Wingless and Int (Wnt)/catenin signalling, myelocytomatosis oncogene protein (Myc) and cyclin D1 (Ccnd1). Consistently, GSE supplementation decreased the number of colonic proliferating cell nuclear antigen-positive cells, a well-known cell proliferation marker, and a weakened extracellular signal-regulated kinases 1 and 2 (ERK1/2) signalling. In summary, these data indicate that supplementation of 0.1 % GSE for 12 weeks improved gut barrier function and colonic cell differentiation in the IL10-deficient mice probably via inhibiting Wnt/ß-catenin pathway.

Carboxylesterase-mediated insecticide resistance: Quantitative increase induces broader metabolic resistance than qualitative change.

Carboxylesterases are mainly involved in the mediation of metabolic resistance of many insects to organophosphate (OP) insecticides. Carboxylesterases underwent two divergent evolutionary events: (1) quantitative mechanism characterized by the overproduction of carboxylesterase protein; and (2) qualitative mechanism caused by changes in enzymatic properties because of mutation from glycine/alanine to aspartate at the 151 site (G/A151D) or from tryptophan to leucine at the 271 site (W271L), following the numbering of Drosophila melanogaster AChE. Qualitative mechanism has been observed in few species. However, whether this carboxylesterase mutation mechanism is prevalent in insects remains unclear. In this study, wild-type, G/A151D and W271L mutant carboxylesterases from Culex pipiens and Aphis gossypii were subjected to germline transformation and then transferred to D. melanogaster. These germlines were ubiquitously expressed as induced by tub-Gal4. In carboxylesterase activity assay, the introduced mutant carboxylesterase did not enhance the overall carboxylesterase activity of flies. This result indicated that G/A151D or W271L mutation disrupted the original activities of the enzyme. Less than 1.5-fold OP resistance was only observed in flies expressing A. gossypii mutant carboxylesterases compared with those expressing A. gossypii wild-type carboxylesterase. However, transgenic flies universally showed low resistance to OP insecticides compared with non-transgenic flies. The flies expressing A. gossypii W271L mutant esterase exhibited 1.5-fold resistance to deltamethrin, a pyrethroid insecticide compared with non-transgenic flies. The present transgenic Drosophila system potentially showed that a quantitative increase in carboxylesterases induced broader resistance of insects to insecticides than a qualitative change.

PKCδ/midkine pathway drives hypoxia-induced proliferation and differentiation of human lung epithelial cells.

Epithelial cells are key players in the pathobiology of numerous hypoxia-induced lung diseases. The mechanisms mediating such hypoxic responses of epithelial cells are not well characterized. Earlier studies reported that hypoxia stimulates protein kinase C (PKC)δ activation in renal cancer cells and an increase in expression of a heparin-binding growth factor, midkine (MK), in lung alveolar epithelial cells. We reasoned that hypoxia might regulate MK levels via a PKCδ-dependent pathway and hypothesized that PKCδ-driven MK expression is required for hypoxia-induced lung epithelial cell proliferation and differentiation. Replication of human lung epithelial cells (A549) was significantly increased by chronic hypoxia (1% O2) and was dependent on expression of PKCδ. Hypoxia-induced proliferation of epithelial cells was accompanied by translocation of PKCδ from Golgi into the nuclei. Marked attenuation in MK protein levels by rottlerin, a pharmacological antagonist of PKC, and by small interfering RNA-targeting PKCδ, revealed that PKCδ is required for MK expression in both normoxic and hypoxic lung epithelial cells. Sequestering MK secreted into the culture media with a neutralizing antibody reduced hypoxia-induced proliferation demonstrating that an increase in MK release from cells is linked with epithelial cell division under hypoxia. In addition, recombinant MK accelerated transition of hypoxic epithelial cells to cells of mesenchymal phenotype characterized by elongated morphology and increased expression of mesenchymal markers, α-smooth muscle actin, and vimentin. We conclude that PKCδ/MK axis mediates hypoxic proliferation and differentiation of lung epithelial cells. Manipulation of PKCδ and MK activity in epithelial cells might be beneficial for the treatment of hypoxia-mediated lung diseases.

Host inflammatory response inhibits Escherichia coli O157:H7 adhesion to gut epithelium through augmentation of mucin expression.

Escherichia coli O157:H7, a major Shiga toxin-producing pathogen, has a low infectious dose and causes serious illness in humans. The gastrointestinal tract of cattle is the primary reservoir of E. coli O157:H7, and thus, it is critical to eliminate or reduce E. coli O157:H7 gut colonization. Given that E. coli O157:H7 produces effectors that attenuate inflammatory signaling, we hypothesized that the host inflammatory response acts to perturb E. coli O157:H7 intestinal colonization. Tumor necrosis factor alpha (TNF-α) treatment of HT-29 cells resulted in increased expression of inflammatory cytokine interleukin 1ß (IL-1ß), IL-8, and TNF-α genes and increased IL-8 protein and resulted in decreased adhesion of E. coli O157:H7. Similarly, E. coli O157:H7 adhesion to cattle colonic explants was reduced by TNF-α treatment. Irrespective of the presence of E. coli O157:H7, TNF-α enhanced activation of p65, the key mediator of NF-κB inflammatory signaling, whereas E. coli O157:H7 infection suppressed this pathway by inhibiting p65 activation in HT-29 cells. To further explore the mechanisms linking the inflammatory response to attenuated E. coli O157:H7 adhesion, mucin 2 (MUC2) expression was analyzed, considering that the intestinal mucus layer is the first defense against enteric pathogens and MUC2 is the major secretory mucin in the intestine. MUC2 expression in HT-29 cells was increased by TNF-α treatment and by E. coli O157:H7 infection. However, reducing mucin expression by blocking mitogen-activated protein kinase (MAPK) extracellular signal-regulated protein kinases 1/2 (ERK1/2) and/or phosphatidylinositol 3-kinase (PI3K)/Akt signaling increased E. coli O157:H7 adherence to HT-29 cells. These data suggest that the inflammatory cytokine response acts to protect host epithelial cells against E. coli O157:H7 colonization, at least in part, by promoting mucin production.

Anoxic stress and rapid cold hardening enhance cold tolerance of the migratory locust.

Anoxia and rapid cold hardening (RCH) can increase the cold tolerance of many animals. However, mechanisms underlying these two kinds of stresses remain unclear. In this study, we aimed to explore the relationship of acclimation to cold stress with acclimation to anoxic stress in the migratory locust, Locusta migratoria. RCH at 0°C for 3h promoted the survival of cold stress-exposed locusts. Anoxic hypercapnia (CO2 anoxic treatment) for 40 min exerted an effect similar to that of RCH. Anoxic hypercapnia within 1h can all promote the cold hardiness of locusts. We investigated the transcript levels of six heat shock protein (Hsp) genes, namely, Hsp20.5, Hsp20.6, Hsp20.7, Hsp40, Hsp70, and Hsp90. Four genes, namely, Hsp90, Hsp40, Hsp20.5, and Hsp20.7, showed differential responses to RCH and anoxic hypercapnia treatments. Under cold stress, locusts exposed to the two regimens showed different responses for Hsp90, Hsp20.5, and Hsp20.7. However, the varied responses disappeared after recovery from cold stress. Compared with the control group, the transcript levels of six Hsp genes were generally downregulated in locusts subjected to anoxic hypercapnia or/and RCH. These results indicate that anoxic stress and RCH have different mechanisms of regulating the transcription of Hsp family members even if the two treatments exerted similar effects on cold tolerance of the migratory locust. However, Hsps may not play a major role in the promotion of cold hardiness by the two treatments.

A modified method for isolating sinoatrial node myocytes from adult mice.

Sinoatrial node (SAN) is the pacemaker of the heart in charge of initiating spontaneous electronical activity and controlling heart rate. Myocytes from SAN can generate spontaneous rhythmic action potentials, which propagate through the myocardium, thereby triggering cardiac myocyte contraction. Acutely, the method for isolating sinoatrial node myocytes (SAMs) is critical in studying the protein expression and function of myocytes in SAN. Currently, the SAMs were isolated by transferring SAN tissue directly into the digestion solution, but it is difficult to judge the degree of digestion, and the system was unstable. Here, we present a modified protocol for the isolation of SAMs in mice, based on the collagenase II and protease perfusion of the heart using a Langendorff apparatus and subsequent dissociation of SAMs. The appearance and droplet flow rate of the heart could be significantly changed during enzymatic digestion via perfusion, which allowed us to easily judge the degree of digestion and avoid incomplete or excessive digestion. The SAMs with stable yield and viability achieved from our optimized approach would facilitate the follow-up experiments.

The correlation between physical inactivity and students' health based on data mining and related influencing factors.

The sedentary behavior among college students has become one of the most important factors affecting the development of physical and mental health. Chronic lack of physical activity may lead to health problems such as decreased physical fitness, and increased psychological disorders. In the post-epidemic era, it is necessary for college students to have a strong immune system, and a strong body cannot be achieved without regular leisure physical activity. Therefore, it is necessary to explore the relationship between relevant health factors and physical activity. This paper presents an optimized COM-B model. And the experimental results show that the optimized model is well applied in describing the current situation of physical activity participation among college students, analyzing the distribution characteristics of socio-demographic variables related to physical activity, and exploring the correlation between physical activity and the subhealth status of college students.

Proximity-Induced Interfacial Room-Temperature Ferromagnetism in Semiconducting Fe3GeTe2.

The discoveries of two-dimensional ferromagnetism and magnetic semiconductors highly enrich the magnetic material family for constructing spin-based electronic devices, but with an acknowledged challenge that the Curie temperature (Tc) is usually far below room temperature. Many efforts such as voltage control and magnetic ion doping are currently underway to enhance the functional temperature, in which the involvement of additional electrodes or extra magnetic ions limits their application in practical devices. Here we demonstrate that the magnetic proximity, a robust effect but with elusive mechanisms, can induce room-temperature ferromagnetism at the interface between sputtered Pt and semiconducting Fe3GeTe2, both of which do not show ferromagnetism at 300 K. The independent electrical and magnetization measurements, structure analysis, and control samples with Ta highlighting the role of Pt confirm that the ferromagnetism with the Tc of above 400 K arises from the Fe3GeTe2/Pt interfaces, rather than Fe aggregation or other artificial effects. Moreover, contrary to conventional ferromagnet/Pt structures, the spin current generated by the Pt layer is enhanced more than two times at the Fe3GeTe2/Pt interfaces, indicating the potential applications of the unique proximity effect in building highly efficient spintronic devices. These results may pave a new avenue to create room-temperature functional spin devices based on low-Tc materials and provide clear evidence of magnetic proximity effects by using nonferromagnetic materials.

Maximum inferior vena cava diameter predicts post-induction hypotension in hypertensive patients undergoing non-cardiac surgery under general anesthesia: A prospective cohort study.

Background: Inferior vena cava (IVC) ultrasonography is a reliable variable that predicts post-induction hypotension (PIH) in patients undergoing surgery under general anesthesia. However, in patients with hypertension, the predictive performance of ultrasound IVC measurements needs further exploration. Methods: This is a prospective cohort study. Adult patients with existing hypertension scheduled to undergo non-cardiac surgery under general anesthesia were eligible. An abdominal ultrasound examination was conducted immediately prior to anesthesia induction (0.03 mg kg-1 midazolam, 0.3 mg kg-1 etomidate, 0.4 µg kg-1 sufentanil, and 0.6 mg kg-1 rocuronium). IVC collapsibility index (IVC-CI) was calculated as (dIVCmax-dIVCmin)/dIVCmax, where dIVCmax and dIVCmin represent the maximum and minimum IVC diameters at the end of expiration and inspiration, respectively. PIH was defined as a reduction of mean arterial pressure (MAP) by >30% of the baseline or to <60 mmHg within 10 min after endotracheal intubation. The diagnostic performance of IVC-CI, dIVCmax, and dIVCmin in predicting PIH was also examined in a group of normotensive patients receiving non-cardiac surgery under the same anesthesia protocol. Results: A total of 51 hypertensive patients (61 ± 13 years of age, 31 women) and 52 normotensive patients (42 ± 13 years of age, 35 women) were included in the final analysis. PIH occurred in 33 (64.7%) hypertensive patients and 19 (36.5%) normotensive patients. In normotensive patients, the area under the receiver operating curve (AUC) in predicting PIH was 0.896 (95% confidence interval [CI]: 0.804-0.987) for IVC-CI, 0.770 (95% CI: 0.633-0.908) for dIVCmax, and 0.868 (95% CI: 0.773-0.963) for dIVCmin. In hypertensive patients, the AUC in predicting PIH was 0.523 (95% CI: 0.354-0.691) for IVC-CI, 0.752 (95% CI: 0.621-0.883) for dIVCmax, and 0.715 (95% CI: 0.571-0.858) for dIVCmin. At the optimal cutoff (1.24 cm), dIVCmax had 54.5% (18/33) sensitivity and 94.4% (17/18) specificity. Conclusion: In hypertensive patients, IVC-CI is unsuitable for predicting PIH, and dIVCmax is an alternative measure with promising performance. Clinical trial registration: [http://www.chictr.org.cn/], identifier [ChiCTR2000034853].

Practical and Efficient: A Pocket-Sized Device Enabling Detection of Formaldehyde Adulteration in Vegetables.

Formaldehyde, as a carcinogenic substance, is often intentionally used to adulterate vegetables to increase their shelf life, and the adhesive tape used to attach labels can also leave formaldehyde on the surface of vegetables. However, as the "gold" standard, gas chromatography (GC) and high-performance liquid chromatography (HPLC) are expensive for individual tests and confined to the laboratory owing to their size and a suitable detector (low-cost, portable, fast detection speed) to check formaldehyde contamination in vegetables not being available. Here, we tested formaldehyde contamination in vegetables using a low-cost and hand-held detector combined with a screen-printed electrode (SPE) amperometric sensor and an open-sourced potentiostat. The analyzer can detect a concentration of 100 µmol/L formaldehyde and achieve a good linear range between 100 and 1000 µmol/L. Furthermore, the detector successfully identified formaldehyde contamination in 53 samples of six different kinds of vegetables even after residual formaldehyde on the surface was evaporated. Most importantly, under the practicability-oriented idea, a cost-effective strategy was implemented for this detector design rather than using other pricey methods (e.g., photolithography, electron-beam evaporation, chemical deposition), which enormously reduces the cost (under ∼USD 0.5 per test) and meets all of the requirements of ASSURED device. We believe this cheap, portable detector could help law-enforcing authorities, healthcare workers, and customers to screen formaldehyde contamination easily. Also, the cost-saving strategy is appropriate for low-income areas, where there is a lack of laboratories, funds, and trained experts.

Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart.

Maternal obesity in pregnancy predisposes offspring to insulin resistance and associated cardiovascular disease. Here, we used a well-established sheep model to investigate the effects of maternal obesity on cardiac functions. Multiparous ewes were assigned to a control (CON) diet [100% of National Research Council (NRC) recommendations] or an obesogenic (OB) diet (150% of NRC recommendations) from 60 d before conception to necropsy on d 135 of pregnancy. Fetal blood glucose and insulin were increased (P<0.01, n=8) in OB (35.09+/-2.03 mg/dl and 3.40+/-1.43 microU/ml, respectively) vs. CON ewes (23.80+/-1.38 mg/dl and 0.769+/-0.256 microU/ml). Phosphorylation of AMP-activated protein kinase (AMPK), a cardioprotective signaling pathway, was reduced (P<0.05), while the stress signaling pathway, p38 MAPK, was up-regulated (P<0.05) in OB maternal and fetal hearts. Phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) at Ser-307 were increased (P<0.05) in OB fetal heart associated with lower downstream PI3K-Akt activity (P<0.05), indicating impaired cardiac insulin signaling. Although OB fetal hearts exhibited a normal contractile function vs. CON fetal hearts during basal perfusion, they developed an impaired heart-rate-left-ventricular-developed pressure product in response to high workload stress. Taken together, fetuses of OB mothers demonstrate alterations in cardiac PI3K-Akt, AMPK, and JNK-IRS-1 signaling pathways that would predispose them to insulin resistance and cardiac dysfunction.

Promoting early neovascularization of SIS-repaired abdominal wall by controlled release of bioactive VEGF.

Insufficient early neovascularization post-operation is thought to be the main reason of surgical recurrence of porcine small intestinal submucosa (SIS)-repaired abdominal wall defects. The controlled release of exogenous angiogenic growth factors (GFs) from biocompatible carriers is a possible way to solve this problem. In the present study, dextran nanoparticles (DNPs) loaded with vascular endothelial growth factor 165 (VEGF165) were pre-formulated by dual-aqueous phase separation method and then electrospun into the poly(lactic-co-glycolic acid) (PLGA) polymer fibers. The aim of this material is to release VEGF in a sustained manner with the degradation of PLGA and maintain its bioactivity concurrently. The prepared VEGF/DNPs-PLGA membrane was sandwiched by dual-layer SIS to construct a SIS-DNPs/VEGF-PLGA-SIS (SVDPS) composite scaffold. The in vitro study showed that the VEGF/DNPs-PLGA obtained higher VEGF encapsulation efficiency as well as better release property and bioactivity than the emulsion electrospun VEGF-PLGA and PLGA fibrous membranes by ELISA and HUVEC proliferation. The in vivo study showed that the SVDPS composite scaffold promoted significantly higher early therapeutic neovascularization within 2 weeks post-surgery than SIS-VEGF-PLGA-SIS (SVPS) and SIS-PLGA-SIS (SPS) by immunohistochemical and immunoblotting examination.

Metformin Improves Ileal Epithelial Barrier Function in Interleukin-10 Deficient Mice.

BACKGROUND AND AIMS: The impairment of intestinal epithelial barrier is the main etiologic factor of inflammatory bowel disease. The proper intestinal epithelial proliferation and differentiation is crucial for maintaining intestinal integrity. Metformin is a common anti-diabetic drug. The objective is to evaluate the protective effects of metformin on ileal epithelial barrier integrity using interleukin-10 deficient (IL10KO) mice. METHODS: Wild-type and IL10KO mice were fed with/without metformin for 6 weeks and then ileum was collected for analyses. The mediatory role of AMP-activated protein kinase (AMPK) was further examined by gain and loss of function study in vitro. RESULTS: Compared to wild-type mice, IL10KO mice had increased proliferation, reduced goblet cell and Paneth cell lineage differentiation in the ileum tissue, which was accompanied with increased crypt expansion. Metformin supplementation mitigated intestinal cell proliferation, restored villus/crypt ratio, increased goblet cell and Paneth cell differentiation and improved barrier function. In addition, metformin supplementation in IL10KO mice suppressed macrophage pro-inflammatory activity as indicated by reduced M1 macrophage abundance and decreased pro-inflammatory cytokine IL-1ß, TNF-α and IFN-γ expressions. As a target of metformin, AMPK phosphorylation was enhanced in mice treated with metformin, regardless of mouse genotypes. In correlation, the mRNA level of differentiation regulator including bmp4, bmpr2 and math1 were also increased in IL10KO mice supplemented with metformin, which likely explains the enhanced epithelial differentiation in IL10KO mice with metformin. Consistently, in Caco-2 cells, metformin promoted claudin-3 and E-cadherin assembly and mitigated TNF-α-induced fragmentation of tight junction proteins. Gain and loss of function assay also demonstrated AMPK was correlated with epithelial differentiation and proliferation. CONCLUSIONS: Metformin supplementation promotes secretory cell lineage differentiation, suppresses inflammation and improves epithelial barrier function in IL10KO mice likely through activation of AMPK, showing its beneficial effects on gut epithelial.

Butyrate suppresses murine mast cell proliferation and cytokine production through inhibiting histone deacetylase.

Beyond their nutritional impact to colonic epithelial cells, the intestinal microbiota metabolite butyrate has pleotropic effects to host cells and is known for its beneficial effects on intestinal homeostasis and metabolism. However, it remains unclear how it modulates mast cell function. Here, we demonstrate that butyrate profoundly inhibited proliferation of mouse mastocytoma P815 cells through inducing cell cycle arrest and apoptosis, as well as decreasing c-Kit activation. In addition, butyrate increased early- and late-stage apoptotic P815 cells. In murine bone marrow-derived mast cells (BMMC), butyrate-suppressed FcεRI-dependent tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) release without affecting ß-Hexosaminidase, but that was associated with decreased mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinases activation. Butyrate treatment substantially enhanced histone 3 acetylation in both P815 and BMMC and decreased FcεRI-dependent mRNA expression of tnf-α and il-6 in BMMC, mimicking the effect of Trichostatin A, a known histone deacetylase inhibitor. Chromatin immunoprecipitation revealed that butyrate enhanced acetylation of the tnf-α and il-6 promoter regions but blocked RNA polymerase II binding to the promoters of tnf-α and il-6 genes, indicating suppressed transcription initiation. These phenotypes mimicked those of Trichostatin A treatment. In conclusion, butyrate inhibits cell proliferation and increases cell apoptosis in mastocytoma P815 cells and suppresses FcεRI-dependent cytokine production in murine primary BMMC, which are likely mediated by HDAC inhibition.

Genetic Variants in the STMN1 Transcriptional Regulatory Region Affect Promoter Activity and Fear Behavior in English Springer Spaniels.

Stathmin 1 (STMN1) is a neuronal growth-associated protein that is involved in microtubule dynamics and plays an important role in synaptic outgrowth and plasticity. Given that STMN1 affects fear behavior, we hypothesized that genetic variations in the STMN1 transcriptional regulatory region affect gene transcription activity and control fear behavior. In this study, two single nucleotide polymorphisms (SNPs), g. -327 A>G and g. -125 C>T, were identified in 317 English Springer Spaniels. A bioinformatics analysis revealed that both were loci located in the canine STMN1 putative promoter region and affected transcription factor binding. A statistical analysis revealed that the TT genotype at g.-125 C>T produced a significantly greater fear level than that of the CC genotype (P < 0.05). Furthermore, the H4H4 (GTGT) haplotype combination was significantly associated with canine fear behavior (P < 0.01). Using serially truncated constructs of the STMN1 promoters and the luciferase reporter, we found that a 395 bp (-312 nt to +83 nt) fragment constituted the core promoter region. The luciferase assay also revealed that the H4 (GT) haplotype promoter had higher activity than that of other haplotypes. Overall, our results suggest that the two SNPs in the canine STMN1 promoter region could affect canine fear behavior by altering STMN1 transcriptional activity.

Mast cell deficiency exacerbates inflammatory bowel symptoms in interleukin-10-deficient mice.

AIM: To test the role of mast cells in gut inflammation and colitis using interleukin (IL)-10-deficient mice as an experimental model. METHODS: Mast cell-deficient (Kit (W-sh/W-sh) ) mice were crossbred with IL-10-deficient mice to obtain double knockout (DKO) mice. The growth, mucosal damage and colitis status of DKO mice were compared with their IL-10-deficient littermates. RESULTS: DKO mice exhibited exacerbated colitis compared with their IL-10-deficient littermates, as shown by increased pathological score, higher myeloperoxidase content, enhanced Th1 type pro-inflammatory cytokines and inflammatory signaling, elevated oxidative stress, as well as pronounced goblet cell loss. In addition, deficiency in mast cells resulted in enhanced mucosal damage, increased gut permeability, and impaired epithelial tight junctions. Mast cell deficiency was also linked to systemic inflammation, as demonstrated by higher serum levels of tumor necrosis factor α and interferon γ in DKO mice than that in IL-10-deficient mice. CONCLUSION: Mast cell deficiency in IL-10-deficient mice resulted in systematic and gut inflammation, impaired gut barrier function, and severer Th1-mediated colitis when compared to mice with only IL-10-deficiency. Inflammation and impaired gut epithelial barrier function likely form a vicious cycle to worsen colitis in the DKO mice.

Association of renal biochemical parameters with left ventricular diastolic dysfunction in a community-based elderly population in China: a cross-sectional study.

BACKGROUND: Relationship of left ventricular diastolic dysfunction (LVDD) with parameters that could provide more information than hemodynamic renal indexes has not been clarified. We aimed to explore the association of comprehensive renal parameters with LVDD in a community-based elderly population. METHODS: 1,166 community residents (aged ≥ 65 years, 694 females) participating in the Shanghai Heart Health Study with complete data of renal parameters were investigated. Echocardiography was used to evaluate diastolic function with conventional and tissue Doppler imaging techniques. Serum urea, creatinine, urea-to-creatinine ratio, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were analyzed on their associations with LVDD. RESULTS: The prevalence of LVDD increased in proportion to increasing serum urea, urea-to-creatinine ratio and UACR. These three renal parameters were found negatively correlated to peak early (E) to late (A) diastolic velocities ratio (E/A), and positively to left atrial volume index; UACR also positively correlated with E to peak early (E') diastolic mitral annular velocity ratio (E/E'). Serum urea, urea-to-creatinine ratio and UACR correlated with LVDD in logistic univariate regression analysis, and urea-to-creatinine ratio remained independently correlated to LVDD [Odds ratio (OR) 2.82, 95% confidence interval (CI) 1.34-5.95] after adjustment. Serum urea (OR 1.18, 95%CI 1.03-1.34), creatinine (OR 6.53, 95%CI 1.70- -25.02), eGFR (OR 0.22, 95%CI 0.07-0.65) and UACR (OR 2.15, 95%CI 1.42-3.24) were revealed independent correlates of advanced (moderate and severe) LVDD. CONCLUSIONS: Biochemical parameters of renal function were closely linked with LVDD. This finding described new cardio-renal relationship in the elderly population.