Toll-like receptor 2 deficiency ameliorates obesity-induced cardiomyopathy via inhibiting NF-κB signaling pathway.

Growing evidence demonstrates that chronic low-grade inflammation, which is induced by high-fat diet (HFD) or saturated fatty acid, plays an important role in the obesity-induced cardiomyopathy (OIC) process. Moreover, obesity is associated with the activation of different inflammatory pathways, including nuclear factor-κB (NF-κB), Toll-like-receptor-2 (TLR2) and Toll-like-receptor-4 (TLR4). In this study, we established an HFD-induced cardiac injury mouse model and palmitate (PA)-induced myocardial cell model to evaluate the role of TLR2 in OIC. Our data show that TLR2 blockade using TLR2 knockout (KO) mice or a TLR2-specific inhibitor, C29, markedly ameliorated HFD- or PA-induced inflammation, myocardial fibrosis, and hypertrophy both in vivo and in vitro. Moreover, the PA-induced myocardial cell injury was mediated via inducing the formation of TLR2-MyD88 complex in a TLR4-independent manner in cardiomyocytes. Our data prove the critical role of cardiac TLR2 in the pathogenesis of HFD- and saturated fatty acid-induced myocarditis, fibrosis, myocardial hypertrophy, and cardiac dysfunction. Inhibition of TLR2 pathway may be a therapeutic strategy of OIC.

Compound c17 alleviates inflammatory cardiomyopathy in streptozotocin-induced diabetic mice by targeting MyD88.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus and is associated with increased morbidity and mortality due to cardiac dysfunction. Chronic inflammation plays a significant role in the development of DCM, making it a promising target for novel pharmacological strategies. Our previous study has synthesized a novel compound, c17, which exhibited strong anti-inflammatory activity by specifically targeting to myeloid differentiation primary response 88 (MyD88). In this study, we evaluated the therapeutic effect of c17 in DCM. METHODS: The small molecular selective MyD88 inhibitor, c17, was used to evaluate the effect of MyD88 on DCM in both high concentration of glucose- and palmitic acid-stimulated macrophages and streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) mice. RESULTS: The treatment of c17 in T1DM mice resulted in improved heart function and reduced cardiac hypertrophy, inflammation and fibrogenesis. RNA sequencing analysis of the heart tissues revealed that c17 effectively suppressed the inflammatory response by regulating the MyD88-dependent pathway. Co-immunoprecipitation experiments further confirmed that c17 disrupted the interaction between MyD88 and Toll-like receptor 4 (TLR4), consequently inhibiting downstream NF-κB activation. In vitro studies demonstrated that c17 exhibited similar anti-inflammatory activity by targeting MyD88 in macrophages, which are the primary regulators of cardiac inflammation. Furthermore, conditioned medium derived from c17-treated macrophages showed reduced capacity to induce hypertrophy, pro-fibrotic reactions, and secondary inflammation in cardiomyocytes. CONCLUSIONS: In conclusion, the small-molecule MyD88 inhibitor, c17, effectively combated the inflammatory DCM, therefore could be a potential candidate for the treatment of this disease.

Propofol suppresses hormones levels more obviously than sevoflurane in pediatric patients with craniopharyngioma: A prospective randomized controlled clinical trial.

OBJECTIVE: General anesthesia can disturb the hormone levels in surgical patients. Hormone deficiency is one of the major symptoms of craniopharyngioma (CP) in pediatric patients. The aim of this prospective randomized controlled clinical study is to evaluate whether propofol and sevoflurane influence the perioperative hormone levels in these patients and to determine which anesthesia technique causes less impact on hormone levels. MATERIALS: Sixty-four ASA I and II pediatric patients with CP undergoing elective neurosurgery were randomly divided into the sevoflurane group (S group, n = 32) and the propofol group (P group, n = 32). Anesthesia was maintained with sevoflurane and propofol until the end of the operation. Demographic information, operation information and hemodynamic variables were recorded. The levels of hormones were evaluated preoperatively as the baseline (T0), 1h after the beginning of the operation (T1), immediately at the end of the operation (T2) and 72 h postoperatively (T3). RESULTS: There were no significant differences in the two groups in terms of patients' demographics and intraoperative information, such as operation duration, blood loss and transfusion volumes, and fluid infusion volume (P>0.05). In both groups, compared to those at T0, the levels of TSH, FT3, TT3 and ACTH at T1, T2 and T3 were significantly lower. The levels of FSH, PRL and GH at T3 were also significantly lower (P<0.05). The FT3 and TT3 levels of both groups at T2 and T3 were significantly lower than those at T1, but the ACTH level was significantly increased (P<0.05). Compared to the levels at T2, the TSH, FT3, FT4 and ACTH levels of the two groups at T3 were significantly reduced (P<0.05). The baseline hormone levels of both groups were similar (P>0.05). At T1, the FT3, TT3, FT4, TT4 and ACTH levels in the P group were significantly lower than those in the S group (P<0.05). At T2, the TT3 and ACTH levels of the P group were significantly lower than those of the S group (P<0.05) At T3, the TT4 level in the P group was significantly lower than that of the S group (P<0.05). CONCLUSION: Propofol and sevoflurane could reduce the levels of hormones intraoperatively and postoperatively in pediatric patients with craniopharyngioma. However, propofol reduced hormone levels more intensively, mainly intraoperatively. Postoperatively, propofol and sevoflurane had similar inhibition effects on the shift in hormone levels. Therefore, in pediatric patients with craniopharyngioma undergoing neurosurgery, sevoflurane might be the preferred anesthetic because it causes less interruption of hormone levels. However, because of their similar postoperative effects, which long-term effects of sevoflurane or propofol could produce optimal clinical situations? Thus more extensive clinical studies are needed. TRIAL REGISTRATION: Clinical trial registration. This trail was registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn, Jun Xiong) on 28/12/2021, registration number was ChiCTR2100054885.

Dexmedetomidine premedication increases preoperative sedation and inhibits stress induced by tracheal intubation in adult: a prospective randomized double-blind clinical study.

OBJECTIVE: The aim of this prospective randomized double-blind study is to evaluate whether oral dexmedetomidine (DEX) premedication could increase sedation in order to reduce preoperative anxiety and inhibit stress response during general anesthesia tracheal intubation. MATERIALS: A total of 100 ASA I and II adult patients undergoing elective neurosurgery were randomly divided into the control group (C group, n = 50) and the oral DEX premedication (DEX group, n = 50). Patients were administrated 4 µg/kg dexmedetomidine orally pre-anesthesia 120 min. Hemodynamic variables were monitored and recorded from premedication to 10 min after tracheal intubation. The primary outcome, the sedation level of all participants, was evaluated by Richmond Agitation Sedation Scale (RASS), and Numerical Rating Scale was to measure their intensity of thirst and satisfaction of patients' family members. During general anesthesia induction, the total dosage of induction anesthetics and complications relative to anesthesia induction were recorded. After tracheal intubation, blood sample was drain from radial atrial line to measure levels of adrenocorticotropic hormone (ACTH) and cortisol. RESULTS: RASS scores at 60 min after premedication and on arrival in the operating room were significantly reduced in the DEX group (P < 0.001). Oral DEX premedication not only increased the intensity of thirst but also the satisfaction of their family members (P < 0.001). The cortisol level after tracheal intubation was deduced by oral DEX premedication (P < 0.05). Oral DEX premedication reduced heart rate (HR) and mean arterial pressure (MAP) on arrival in the operating room, and HR when tracheal intubation (P < 0.05). During the whole process of anesthesia induction, although the lowest MAP in two groups were not significantly different, the lowest HR was significantly lower in the DEX group (P < 0.05). Oral DEX premedication might reduce HR from premedication to 10 min after tracheal intubation. However MAP was reduced just from premedication to on arrival in the operating room. Total induction dosages of propofol, midazolam, sulfentanil and rocuronium were similar in two groups (P > 0.05), as well as the complications relative to anesthesia induction and cases of rescue dopamine therapy were similar (P > 0.05). CONCLUSION: Oral DEX 4 µg/kg premedication was an efficient intervention to increase preoperative sedation and reduce stress reaction induced by general anesthesia tracheal intubation, but also it was with the stable hemodynamic during the process of general anesthesia tracheal intubation, and improved the satisfaction of patients' family members. In this study, the sparing-anesthetic effect of 4 µg/kg DEX oral premedication was not significant, and this would be needed to study in future. TRIAL REGISTRATION: This trail was registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn , Jie Gao) on 15/04/2021, registration number was ChiCTR2100045458.

The Right Internal Jugular at the Cricoid Cartilage Level May Represent the Optimal Central Vein Puncture Site in Pediatric Patients.

Objective: Internal jugular vein puncture or cannulation is far more difficult in children compared with adults. Anthropometric measures of the internal jugular vein acquired by two-dimensional ultrasound are useful in the practice of puncture and catheterization. The aim of this study is to measure anthropometric parameters of bilateral internal jugular veins in children and to determine the best puncture site based on these parameters. Materials: A total of 107 pediatric patients undergoing elective operation were included. Ultrasound-visible evaluation of bilateral internal jugular veins was used to obtain the depth from skin, maximum antero-posterior diameter, and cross-sectional area at the levels of the superior border of thyroid cartilage and cricoid cartilage. Statistical analysis was performed using these anthropometric data and demographic variables of all studied pediatric patients, such as age, height, and weight. Results: A very weak correlation was noted between the depth, maximal antero-posterior diameter, and cross-sectional area of both internal jugular veins and the age, height, weight, and body surface index of all included children. All Pearson's R correlation coefficients were <0.45. The largest diameter and cross-sectional area were in the right internal jugular vein at the cricoid cartilage level (p < 0.01) followed by the left internal jugular vein at this level (p < 0.01). In addition, the internal jugular vein at the cricoid cartilage level was more superficial than that of the superior border of the thyroid cartilage (p < 0.01). Conclusion: The right internal jugular vein at the cricoid cartilage level is the best site for puncture. The most appropriate alternative site is the left internal jugular vein on the same level. Better correlation was not observed between the anthropometric parameters of the internal jugular vein and children's biological characteristics. This finding should be confirmed in a larger-scale demographical study in the future.

Construction of a PCN/Fe2O3/CdS double Z-type heterojunction photocatalyst and its application in the oxidative coupling reaction of benzylamine.

In this work, a PCN/Fe2O3/CdS ternary heterojuction photocatalyst was constructed by introducing an appropriate amount of ferric oxide (Fe2O3) and cadmium sulfide (CdS) onto porous carbon nitride (PCN), denoted as PCN/Fe2O3/CdS. In the presence of PCN/Fe2O3/CdS, the turnover frequency value and selectivity of the oxidative coupling reaction of benzylamine were 6740 µmol g-1 h-1 and 99.4%, respectively. The excellent catalytic performance of the PCN/Fe2O3/CdS photocatalyst is attributed to fully exposed active sites due to the porous structure of PCN, improved light utilization efficiency by introduction of Fe2O3 and CdS, and increased mobility of e--h+ pairs by construction of a ternary heterostructure, and was proved by the analysis of its structural and optical properties. According to the substrate scope study and Hammett diagram analysis, the rate determining step of the benzylamine self-coupling reaction photocatalyzed by PCN/Fe2O3/CdS was the condensation of imine and benzylamine into N-benzylidenebenzylamine. The results of the free radical quenching experiment and electron spin resonance tests showed that h+ played a major role in the photoreaction process, followed by ˙O2- and ˙OH. After four photocatalytic reaction cycles, the catalytic performance of the PCN/Fe2O3/CdS heterojunction composite material remained good. Finally, combined with the free radical trapping experiment and energy band structure analysis, a possible double Z-type reaction mechanism was proposed.

A nano-sized Cu-MOF with high peroxidase-like activity and its potential application in colorimetric detection of H2O2 and glucose.

Peroxidase widely exists in nature and can be applied for the diagnosis and detection of H2O2, glucose, ascorbic acid and other aspects. However, the natural peroxidase has low stability and its catalytic efficiency is easily affected by external conditions. In this work, a copper-based metal-organic framework (Cu-MOF) was prepared by hydrothermal method, and characterized by means of XRD, SEM, FT-IR and EDS. The synthesized Cu-MOF material showed high peroxidase-like activity and could be utilized to catalyze the oxidation of o-phenylenediamine (OPDA) and 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. The steady-state kinetics experiments of the oxidation of OPDA and TMB catalyzed by Cu-MOF were performed, and the kinetic parameters were obtained by linear least-squares fitting to Lineweaver-Burk plot. The results indicated that the affinity of Cu-MOF towards TMB and OPDA was close to that of the natural horseradish peroxidase (HRP). The as-prepared Cu-MOF can be applied for colorimetric detection of H2O2 and glucose with wide linear ranges of 5 to 300 µM and 50 to 500 µM for H2O2 and glucose, respectively. Furthermore, the specificity of detection of glucose was compared with other sugar species interference such as sucrose, lactose and maltose. In addition, the detection of ascorbic acid and sodium thiosulfate was also performed upon the inhibition of TMB oxidation. Based on the high catalytic activity, affinity and wide linear range, the as-prepared Cu-MOF may be used for artificial enzyme mimics in the fields of catalysis, biosensors, medicines and food industry.

The influence of home-based exercise on gestational diabetes: a meta-analysis of randomized controlled trials.

Introduction: The impact of home-based exercise for gestational diabetes remains controversial. We conduct a systematic review and meta-analysis to explore the influence of home-based exercise on glycemic control for gestational diabetes.Methods: We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through April 2018 for randomized controlled trials (RCTs) assessing the effect of home-based exercise on glycemic control for gestational diabetes.Results: Five RCTs involving 266 patients are included in the meta-analysis. Overall, compared with control group for gestational diabetes, home-based exercise shows no important impact on fasting glucose (std. MD =0.18; 95% CI = -0.11-0.46; p = .22), HbA1c (std. MD = -0.05; 95% CI = -0.32-0.22; p = .70), insulin requirement (risk ratios (RR) = 1.63; 95% CI =0.51-5.17; p = .41), insulin sensitivity index (std. MD = -0.18; 95% CI = -1.02-0.66; p = .67), gestational age at delivery (std. MD =0.01; 95% CI = -0.26-0.28; p = .95), preterm birth (RR =1.01; 95% CI =0.34-2.99; p = .99), birth weight (std. MD =0.06; 95% CI = -0.45-0.58; p = .81) and head circumference (std. MD =0.11; 95% CI = -0.16-0.38; p = .44).Conclusions: Home-based exercise demonstrates no substantial benefits to fasting glucose, HbA1c, insulin requirement, insulin sensitivity index, gestational age at delivery, preterm birth, birth weight and head circumference for gestational diabetes women.

Synthesis of copper graphene materials functionalized by amino acids and their catalytic applications.

Graphene oxide and its derivative have attracted extensive interests in many fields, including catalytic chemistry, organic synthesis, and electrochemistry, recently. We explored whether the use of graphene after chemical modification with amino acids to immobilize copper nanoparticles could achieve a more excellent catalytic activity for N-arylation reactions. A facile and novel method to prepare copper supported on amino-acid-grafted graphene hybrid materials (A-G-Cu) was first reported. The as-prepared hybrid materials were characterized by a variety of techniques, including Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy, atomic force microscopy, transmission electron microscopy, and inductively coupled plasma-atomic emission spectrometry. The results showed that the morphology, distribution, and loading of copper nanoparticles could be well-adjusted by controlling the type of amino acids grafted on graphene. Moreover, most A-G-Cu hybrid materials could catalyze N-arylation of imidazole with iodobenzene with yields more than 90%, while the copper supported on graphene (G-Cu) displayed a yield of just 65.8%. The high activity of A-G-Cu can be ascribed to the good synergistic effects of copper nanoparticles (Cu NPs) and amino-acid-grafted graphene.

Organophilic worm-like ruthenium nanoparticles catalysts by the modification of CTAB on montmorillonite supports.

A supported Ru catalyst was prepared by using cetyltrimethylammonium bromide (CTAB) intercalated montmorillonite as the supporting matrix. The as-prepared Ru catalyst was subsequently characterized by XRD, XPS, N(2) sorption, TEM, and dispersibility measurement. The results showed that the Ru nanoparticles were in the modified montmorillonite interlayers, and the morphology of Ru nanoparticle was worm-like. Moreover, this supported Ru catalyst could be well dispersed in organic solvents such as toluene. The catalyst exhibited high activity and selectivity in the hydrogenation of quinoline even without stirring.

Modification of montmorillonite surfaces using a novel class of cationic gemini surfactants.

A novel class of cationic gemini surfactants were prepared and used as modifiers for sodium montmorillonite (MMT-Na). The modified montmorillonites were characterized by X-ray diffraction (XRD), thermal analysis (TG), Fourier transform infrared spectroscopy (FTIR), dispersibility measurement, and scanning electron microscopy (SEM). The results show that the surfactants have been intercalated into the montmorillonite layers successfully. XRD measurements indicate that the gemini surfactant is more effective at expanding the interlayer space of the MMT than the corresponding single chain surfactant. Moreover, the high efficiency can be obtained by lengthening the hydrophobic chains of gemini surfactants. Thermal analysis shows that there are four different molecular environments for gemini surfactants in the modified montmorillonite. The dispersibility measurement and SEM results indicate that the modified montmorillonite are more hydrophobic and prone to agglomerate in water than MMT-Na. These modified materials have the potential for removal of environment pollutants such as pesticides, phenol, etc. or being used as antimicrobial materials.