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Abstract Aim To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). Methods The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. Results Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493–0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482–0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. Conclusions Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

ObjectiveThis study analysed blood donation deferral trends, reasons and demographic/lifestyle characteristics among students in Huzhou City. The aim was to understand the health status of students and reduce the deferral rate.MethodsData on blood donation deferral among students in Huzhou City from 2018 to 2022 were collected and analysed. Deferral trends and main reasons were investigated. Using demographic and lifestyle data from 2,619 cases in 2022, a risk prediction model for deferral was constructed.ResultsThe deferral rate among students in Huzhou City from 2018 to 2022 was 12.60% (p = 0.000, 95%CI: 12.14–13.06%), showing a significant increasing trend. Temporary deferral was the main reason, with alanine aminotransferase (ALT), blood pressure (BP) and haemoglobin (Hb) as the main deferral factors. ALT had a deferral rate of 5.23% (4.92–5.53%), BP 3.30% (3.06–3.55%), and Hb 2.92% (2.68–3.15%). Demographic and lifestyle characteristics in 2022 showed no significant differences between education level, household registration and deferral rate (p > 0.05). However, age, sex, blood donation history, sleep quality, diet and mental state had variable effects on ALT, BP, and Hb deferrals (p

The aim of this study was to explore the associations of moderate-to-vigorous-intensity physical activity (MVPA) time and sedentary (SED) time with a history of cardiovascular disease (CVD) and multifactorial (i.e., blood pressure (BP), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin A1c (HbA1c)) control status among type 2 diabetes mellitus (T2DM) patients in China. A cross-sectional analysis of 9152 people with type 2 diabetes from the Multifactorial Intervention on Type 2 Diabetes (MIDiab) study was performed. Patients were grouped according to their self-reported MVPA time (low, < 150 min·week−1; moderate, 150 to < 450 min·week−1; high, ≥ 450 min·week−1) and SED time (low, < 4 h·d–1; moderate, 4 to < 8 h·d–1; high, ≥ 8 h·d–1). Participants who self-reported a history of CVD were identified as having a CVD risk. Odds ratios (ORs) and 95% confidence intervals (CIs) of CVD risk and multifactorial control status associated with MVPA time and SED time were estimated using mixed-effect logistic regression models, adjusting for China’s geographical region characteristics. The participants had a mean ± standard deviation (SD) age of (60.87 ± 8.44) years, 44.5% were women, and 25.1% had CVD. After adjustment for potential confounding factors, an inverse association between high MVPA time and CVD risk that was independent of SED time was found, whereas this association was not observed in the moderate-MVPA group. A higher MVPA time was more likely to have a positive effect on the control of BMI. Compared with the reference group (i.e., those with MVPA time ≥ 450 min·week−1 and SED time

Background: Although various effective compounds for the second- and third-line treatment of advanced or recurrent cervical cancer improved the overall survival, the optimal regimen remains controversial. Previous studies revealed that apatinib had extensive anti-tumor activities. However, almost all studies on apatinib in recurrent cervical cancer are non-randomized controlled trials with small sample sizes, different first-line treatments, and uncontrolled statistical analysis, which may result in a lack of effective metrics to evaluate the efficacy and safety of apatinib. Here, this meta-analysis aims to evaluate the efficacy and safety of apatinib in patients with advanced or recurrent cervical cancer.Methods: PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for relevant studies. Outcomes including overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted for further analysis.Results: Seven studies involving 243 patients were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 22.9% and 68.6%, respectively. With regard to survival analysis, the pooled PFS and OS were 5.19 months and 10.63 months, respectively. The most common treatment-related adverse events of apatinib were hand–foot syndrome (all grade: 39.6%, ≥grade III: 7.5%), hypertension (all grade: 34.5%, ≥grade III: 9.2%), and fatigue (all grade: 28.0%, ≥grade III: 5.1%).Conclusions: In summary, this meta-analysis demonstrated that apatinib has promising efficacy and safety for patients with advanced or recurrent cervical cancer.Systematic Review Registration:https://inplasy.com/inplasy-2022-7-0049/, identifier INPLASY202270049

In order to solve the problem that it is difficult to prepare highly amorphous Ni-B alloy coating, the control variable method was used to explore the influence law of bath composition on the amorphous process of Ni-B alloy coating, and the electrodeposition method was used to prepare high-B amorphous Ni-B composite coating. X-ray diffraction (XRD) was used to characterize the phase structure of the sedimentary layer, and field emission scanning electron microscopy (FESEM) and energy spectrum analysis (EDS) were used to investigate the microscopic morphology and element distribution composition of the sedimentary layer. The results show that the sedimentary layer can be changed from crystalline state to amorphous state by controlling the composition of solution. The resulting sediments are highly amorphous. This system can be electrodeposited to obtain amorphous Ni-B alloy sediments with a complete, close and meticulous surface, and almost no metal crystal diffraction peak. The content of B in the sediments can be increased to 10.21%(mass fraction).

Abstract Background Angular pregnancy is characterized as implant medial to the uterotubal junction in lateral angular of uterine. It was a rare obstetric complication with severe complications like uterine rupture and retained placenta. Case presentation We report a case of 2 incomplete aborted angular pregnancy that was diagnosed and treated with hysteroscopy. In this case, both of patient were performed operative hysteroscopy for incomplete abortion, and with the assistance of hysteroscopy, the angular pregnancy was detected. Conclusions Hysteroscopy can more intuitively display the conditions inside the uterine cavity, reduce the intraoperative and postoperative complications, and shorten the hospitalization time of patients. During hysteroscopy, angular pregnancy can be visualized in the upper lateral side of the uterine cavity. Based on the investigation results of clinical cases, this is the first case report of hysteroscopy in the treatment of incomplete aborted angular pregnancy.

Background and aim: Pro-inflammatory macrophages aggravated progress of pulmonary fibrosis (PF) both in patients and animal models. Fuzheng Huayu (FZHY) formula, a Chinese herbal product, is effective in treating pulmonary fibrosis in our previous study. But its action mechanism against PF relating to macrophage activation was unclear. This study was designed to evaluate the anti-fibrotic and anti-inflammatory roles of FZHY in pulmonary fibrosis and to elucidate the potential mechanisms.Methods: Network pharmacology was employed to identify the interrelationships among compounds of FZHY, potential targets and putative pathways on anti-pulmonary fibrosis. According to the data of bioinformatics analysis, the key pharmacological target for FZHY against PF was screened. The network pharmacological prediction was validated by a series of experimental assays, including CCK8, western blot and immunofluorescence staining. Then molecular mechanism of FZHY on relating to the predictive target were studied in bleomycin induced pulmonary fibrosis in mice with methylprednisolone as a positive control, and in lipopolysaccharide (LPS) stimulated cultured macrophages in culture, respectively.Results: The network pharmacology analysis reveal that a total of 12 FZHY–PF crossover proteins were filtered into a protein-protein interaction network complex and designated as the potential targets of FZHY against pulmonary fibrosis, while TNF-α signal pathway ranked at the top. FZHY and methylprednisolone could attenuate the lung fibrosis and decrease pulmonary TNF-α expression in bleomycin induced fibrotic mice, without difference between two treatments. While TNF-α was mainly originated from macrophages identified by double fluorescent staining of TNF-α and F4/80. LPS stimulated cultured macrophage polarization and activation demonstrated by the enhance contents of TNF-α and iNOS but decreased level of Arg-1. FZHY could alleviate the LPS stimulated macrophage polarization and activation demonstrated by decreasing TNF-α and iNOS and increasing Arg-1. In particular, FZHY could significantly reduce the production of p65 and the nuclear translocation of phosphorylated p65.Conclusion: Fuzheng Huayu formula has a good effect against pulmonary fibrosis induced by bleomycin in mice, whose action mechanism was associated with down-regulation of NF-κB/TNF-α signaling pathway in pro-inflammatory macrophages. These findings provided an important strategy for developing new agents against lung fibrosis and accelerated FZHY product application on patients with lung fibrosis.

In order to solve the problem that the Ni-P alloy coating with an amorphous structure having excellent corrosion resistance cannot be obtained in the conventional electrodeposition process, Ni-P alloy coatings were prepared on the basis of a high-speed electroplating bath, and the law of influence of waveform parameters on the amorphization process of Ni-P alloy coatings was studied by using Fei’s square wave electrodeposition method. The micromorphologies of Ni-P alloy coatings were characterized by scanning electron microscopy (SEM) under different conditions. The P content of the coatings was analyzed by energy spectrum analysis (EDS). Structural changes of phase of the coatings were investigated by X-ray diffraction (XRD). The optimized pulse process parameters are: the average current density is 15 A/dm2, the inverse pulse coefficient is 0.3, the duty ratio is 0.6, and the frequency is 1 Hz. The results show that by adjusting Fei’s square wave pulse parameters, the fully amorphous Ni-P alloy coating can be electrodeposited, which has the features of high P content up to 17.93% (mass fraction), negligible nickel crystal diffraction peaks, and the smooth surface with a bright appearance as well.

Adiposity is caused by an imbalance between energy intake and consumption. Promotion of the browning of white fat increases energy expenditure and could combat adiposity. Thyroid-stimulating hormone (TSH) has been confirmed to positively correlate with adiposity. However, the putative connection between TSH and white adipose browning has never been explored. In this study, we sought to assess the effect of TSH on white adipose tissue browning and energy metabolism. Subclinical hypothyroidism mice, thyroid-specific Tshr-knockout mice injected with TSH, adipocyte-specific and global Tshr-knockout micewere subjected to morphological, physiological, genetic or protein expression analyses and metabolic cages to determine the role of TSH on the browning of white adipose tissue and metabolism. 3T3-L1 and primary SVF cells were used to verify the effects and mechanism of TSH on the browning of white adipocytes. We show that increased circulation TSH level decreases energy expenditure, promotes adiposity, impairs glucose and lipid metabolism. Knockout of Tshr decreases adiposity, increases energy expenditureand markedly promotes the development of beige adipocytesin both epididymal and inguinal subcutaneous white fat via a mechanism that likely involves AMPK/PRDM16/PGC1α. Our results reveal an important role of TSH in regulating energy balance and adiposity by inhibiting the browning of white fat.

In recent studies, phase junctions constructed as photocatalysts have been found to possess great prospects for organic degradation with visible light. In this study, we designed an elaborate rhombohedral corundum/cubic In2O3 phase junction (named MIO) combined with polymeric carbon nitride (PCN) via an in situ calcination method. The performance of the MIO/PCN composites was measured by photodegradation of Rhodamine B under LED light (λ = 420 nm) irradiation. The excellent performance of MIO/PCN could be attributed to the intimate interface contact between MIO and PCN, which provides a reliable charge transmission channel, thereby improving the separation efficiency of charge carriers. Photocatalytic degradation experiments with different quenchers were also executed. The results suggest that the superoxide anion radicals (O2−) and hydroxyl radicals (·OH) played the main roles in the reaction, as opposed to the other scavengers. Moreover, the stability of the MIO/PCN composites was particularly good in the four cycling photocatalytic reactions. This work illustrates that MOF-modified materials have great potential for solving environmental pollution without creating secondary pollution.

Photocatalytic water splitting is one of the promising approaches to solving environmental problems and energy crises. However, the sluggish 4e− transfer kinetics in water oxidation half-reaction restricts the 2e− reduction efficiency in photocatalytic water splitting. Herein, cobalt vanadate-decorated polymeric carbon nitride (named CoVO/PCN) was constructed to mediate the carrier kinetic process in a photocatalytic water oxidation reaction (WOR). The photocatalysts were well-characterized by various physicochemical techniques such as XRD, FT-IR, TEM, and XPS. Under UV and visible light irradiation, the O2 evolution rate of optimized 3 wt% CoVO/PCN reached 467 and 200 μmol h−1 g−1, which were about 6.5 and 5.9 times higher than that of PCN, respectively. Electrochemical tests and PL results reveal that the recombination of photogenerated carriers on PCN is effectively suppressed and the kinetics of WOR is significantly enhanced after CoVO introduction. This work highlights key features of the tuning carrier kinetics of PCN using charge-conducting materials, which should be the basis for the further development of photocatalytic O2 reactions.

The amorphous Ni-P/Al2O3 composite coatings with high P content were deposited using the bi-directional pulse electrodeposition. The micrographic morphology and chemical composition of the coatings were examined using the scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS) analysis. Also, the phase structure of the coating was characterized using the X-ray diffraction (XRD). By analyzing the electrochemical test results of the coatings, the corrosion resistances of different types of deposits were evaluated. The results show that compared to the direct current (DC) plating, the P content in the Ni-P alloy coatings increases to 12.06%(mass fraction) by bi-directional pulse electrodeposition, which facilitates the formation of the amorphous Ni-P alloy coatings. The PC plating can produce a finer and denser Ni-P/Al2O3 composite coatings with more compact crystallization than that deposited by DC. The Ni-P alloy coatings deposited by the pulse electrodeposition has a better corrosion resistance, and adding composite particles of Al2O3 can further contribute to improving the corrosion resistance of the amorphous Ni-P alloy coatings.

Nickel/diamond composite coatings were prepared on the basis of a new high speed electroplating bath. The influence of additives, plating parameters and diamond concentration on internal stress was investigated in order to find the solution to decrease the stress introduced by high current density; the micro morphology of the coatings were observed by SEM. The bath and depositing parameters were optimized that thick nickel/diamond composite coatings with low internal stress can be high speed electroplated with a high cathode current density of 30A/dm2. The results show that when plated with bath composition and parameters as follows: sodium dodecyl sulfate 0.5g/L, ammonium acetate 3g/L, sodium citrate 1.5g/L, diamond particles 30g/L; pH value 3-4, temperature 50℃, the composite coatings prepared in high speed have the lowest internal stress.

Objective. Spondyloepiphyseal dysplasia tarda (SEDT) is a rare hereditary bone disease characterized by spinal and epiphyseal anomalies. We identified the disease by gene sequencing in a Chinese pedigree with SEDT. Methods. We extracted genomic DNA from five members of a four-generation Chinese SEDT kindred with three affected males and then analyzed the genetic mutation by PCR and DNA sequencing. Results. DNA sequencing showed that the genetic missense mutation occurred one bp upstream of exon 6 in the SEDL gene in two families, and a heterozygous mutation was found in a female carrier. In addition, no mutation was found in the other members of the family. Conclusion. SEDT in this family was caused by a G/C missense mutation in exon 6 of the SEDL gene, previously not shown to be associated with X-linked SEDT.

We report the complete mitochondrial genome sequence of Poecilia formosa. The genome is found to be 16636 bp in length and has a base composition of A (29.59%), G (14.61%), C (28.26%), and T (27.54%). Similar to other Poecilia species, it contains a typically conserved structure including 13 protein-coding genes, 2 rRNA genes, 1 control region (D-loop), and 22tRNA genes. The proportion of coding sequences with a total length of 11,533 bp is 69.33%, which encodes 3837 amino acids. All protein-coding genes started with Met, ND1, CO1, ATP8, ATP6, CO3, ND4L, ND5, ND6 and CytB ended by TAA as a stop codon, ND2 and ND3 ended by TAG as a stop codon, CO3 and ND4 ended by a single T. The lengths of 12S ribosomal RNA is 948 bp, ranging from 70 bp to 1018 bp, and the lengths of 16S ribosomal RNA is 1674 bp, ranging from 1090 bp to 2764 bp. The length of control region is 879 bp, ranging from 15757 bp to 16636 bp, respectively. The complete mitochondrial genome sequence provided here would be useful for further understanding the evolution of ratite and conservation genetics of Poecilia formosa.

In this study, the complete mitochondrial genome of Dermogenys pusilla was firstly determined. The complete genome is 16,529 bp in length. It contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, a putative control region, and 1 origin of replication on the light-strand. The gene organization, nucleotide composition, and codon usage are similar to other Hemiramphidae. The overall nucleotide composition was 30.73% A, 28.18% T, 26.48% C, and 14.61% G, respectively. All protein-coding genes started with Met, ND1, ND2, CO1, ATP8, ATP6, CO3, ND3, ND4L, ND5 and ND6 ended by TAA as a stop codon, ND4 ended by AGA as a stop codon, CO2 and Cytb use an incomplete stop codon T. The lengths of 12S ribosomal RNA and 16S ribosomal RNA are 941 bp and 1670 bp, respectively. The length of control region is 862 bp, ranging from 15,668 bp to 16,529 bp. The complete mitochondrial genome sequence provided here would help us understand the evolution of ratite and conservation genetics of D. pusilla in the future.

Here, we report the complete mitochondrial genome sequence of Gephyrocharax atracaudatus. The genome is found to be 17,049 bp in length and has a base composition of A (29.95%), G (15.29%), C (26.13%) and T (28.63%). Similar to other Gephyrocharax species, it contains a typically conserved structure including 13 protein-coding genes, 2 rRNA genes, 1 control region (D-loop) and 22tRNA genes. The proportion of coding sequences with a total length of 11,420 bp is 66.98%, which encodes 3800 amino acids. All protein-coding genes started with Met, ND1, ND2, ND3, ND4L, ND5 and CytB ended by TAA as a stop codon, CO1 ended by AGG as a stop codon, CO2, ATP6, ND4 ended by a single T, ATP8, ND5 ended by TAG as a stop codon and CO3 ended by TA as a stop codon. The lengths of 12S ribosomal RNA and 16S ribosomal RNA are 950 bp and 1682 bp, respectively. The length of control region is 1396 bp, ranging from 15,653 bp to 17,049 bp. The complete mitochondrial genome sequence provided here would be useful for further understanding the evolution of ratite and conservation genetics of Gephyrocharax atracaudatus.

Here, we report the complete mitochondrial genome sequence of Hepsetus odoe. The genome is found to be 16,802 bp in length and has a base composition of A (28.67%), G (15.86%), C (31.10%), and T (24.37%). Similar to other Hepsetus species, it contains a typically conserved structure including 13 protein-coding genes, two rRNA genes, one control region (D-loop), and 22 tRNA genes. The proportion of coding sequences with a total length of 11,435 bp is 68.06%, which encodes 3816 amino acids. All protein-coding genes started with Met, ND1, CO2, ATP8, ATP6, CO3, ND4L, ND5, ND6 and CytB ended by TAA as a stop codon, ND2, ND3 ended by TAG as a stop codon, CO1, ND4 ended by a single AGG. The lengths of 12S ribosomal RNA and 16S ribosomal RNA are 955 bp and 1684 bp, respectively. The length of control region is 1142 bp, ranging from 15,660 bp to 16,802 bp. The complete mitochondrial genome sequence provided here would be helpful in understanding the evolution of ratite and conservation genetics of Hepsetus odoe in future.

In the present study, the complete mitochondrial DNA sequence of was determined for the first time. The mitochondrial genome of Lebiasina astrigata is a circular molecule of 16,899 bp in size and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 control regions. The base composition is 30.02% for A, 15.34% for G, 27.24% for C, and 27.40% for T. All protein-coding genes started with Met, ND1,ND2, CO2, ATP8, ATP6, CO3, ND4L, ND5, and ND6 ended by TAA as a stop codon, CO1 ended by AGG as a stop codon, ND4 ended by AGA as a stop codon,CO3, Cytb ended by TAG. The lengths of 12S ribosomal RNA and 16S ribosomal RNA are 951 bp and 1695 bp, respectively. The length of control region is 1221 bp, ranging from 15,678 bp to 16899 bp. The complete mitochondrial genome sequence provided here would be useful for further understanding the evolution of ratite and conservation genetics of Lebiasina astrigata.

Activated hepatic stellate cells (aHSCs) play a key role in liver fibrosis. During the regression of fibrosis, aHSCs are transformed into inactivated cells (iHSCs), which are quiescent lipid-containing cells and express higher levels of lipid-related genes, such as peroxisome proliferators-activated receptors gamma (PPARγ). Here, we investigated the role of MicroRNA29a (Mir29a) in the resolution of liver fibrosis. Mir29a and lipid-related genes were up-regulated after the recovery of CCl4-induced liver fibrosis in mice. PPARγ agonist rosiglitazone (RSG) promoted de-differentiation of aHSCs to iHSCs and up-regulated MIR29a expression in a human HSC cell line LX-2. MIR29a mimics in vitro promoted the expression of lipid-related genes, while decreased the expression of fibrosis-related genes. MIR29a inhibitor showed the reverse effects. ATPase H+ transporting V1 subunit C1 (Atp6v1c1) was increased in liver fibrosis, while down-regulated after the recovery in mice, and negatively regulated by MIR29a in LX-2 cells. Knockdown of ATP6V1C1 by siRNA decreased alpha-smooth muscle actin (α-SMA) and increased lipid-related genes expression. Simultaneous addition of MIR29a mimics and ATP6V1C1 siRNA further increased RSG promoted expression of lipid-related proteins in vitro. Collectively, MIR29a plays an important role during the trans-differentiation of aHSCs in the resolution of liver fibrosis, in part, through regulation of ATP6V1C1.

This study was aimed to measure the dietary effects of probiotic Bacillus subtilis strain fmbj (BS fmbj) on antioxidant capacity and oxidative stability of chicken breast meat during storage. Treatment groups were fed the basal diet with BS fmbj at 0 g/kg (CON), 0.2 g/kg (BS-1), 0.3 g/kg (BS-2), or 0.4 g/kg (BS-3) doses without antibiotics. During 8 days of storage at 4°C, BS-2 group showed a significant improvement (P < 0.05) on meat quality (pH, Drip loss, Cooking loss, Shear force, color L*, a*, b*), free radical scavenging activity (DPPH, ABTS+, H2O2), tissues antioxidant enzyme capacity (SOD, CAT, GSH-Px, GSH, T-SH), mitochondria antioxidant enzyme capacity (MnSOD, GPx, GSH), mRNA expression of antioxidant genes (Nrf2, HO-1, SOD, CAT, GSH-Px) and mitochondrial function genes (avUCP, NRF1, NRF2, TFAM, PGC-1α), oxidative damage index (MDA, ROS, PC, 8-OHdG), and MMP level in chicken breast meat as compared to the CON group. These results indicate that dietary BS fmbj in broiler diets can protect breast meat against the storage-induced oxidative stress by improving their free radical scavenging capacity and antioxidant activity during 8 days of storage at 4°C.

To observe effect of E2F decoy DNA on proliferation and apoptosis of androgen-independent prostate cancer cell line PC-3M the binding specificity of the E2F decoy DNA to the PC-3M nuclear protein was detected by electrophoretic mobility shift assay (EMSA). E2F decoy DNA, ARE decoy DNA and Control decoy DNA were respectively transfected into PC-3M cells with lipofectamine.Their influence on cell proliferative activity was detected by MTT assay.The cell apoptotic rate was determined by flow cytometric(FCM) analysis and chromosome DNA ladder was detected by DNA gel electrophoresis.The change of mRNA expression of C-myc and CyclinD1 were detected by RT-PCR.The change of mRNA expression of C-myc and CyclinD1 were detected by Western-blot. EMSA demonstrated specific binding of the E2F decoy to E2F transcription factor.The PC-3M cell growth was inhibited after transfection. The apoptotic rate was 26.35% and DNA ladder could be observed after transfection.The expression of C-myc and CyclinD1 were inhibited. All these results indicated that E2F decoy DNA induced apoptosis of androgen-independent prostate cancer cell lines PC-3M and inhibited cell proliferation via inhibiting expression of C-myc and CyclinD1.

Thyroid-stimulating hormone (TSH) has been shown to play an important role in the regulation of triglyceride (TG) metabolism in adipose tissue. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme controlling the hydrolysis of TG. Thus far, it is unclear whether TSH has a direct effect on the expression of ATGL. Because TSH function is mediated through the TSH receptor (TSHR), TSHR knockout mice (Tshr-/- mice) (supplemented with thyroxine) were used in this study to determine the effects of TSHR deletion on ATGL expression. These effects were verified in 3T3-L1 adipocytes and potential underlying mechanisms were explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was significantly increased compared with that in Tshr+/+ mice. ATGL expression was observed to increase with the differentiation process of 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1 adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by H89, which is a protein kinase A (PKA) inhibitor. These results indicate that TSH has an inhibitory effect on ATGL expression in mature adipocytes. The associated mechanism is related to PKA activation.

Our previous study found that thyroid-stimulating hormone promoted sterol regulatory element-binding protein-2 (SREBP-2) expression and suppressed AMP-activated protein kinase (AMPK) activity in the liver, but it was unclear whether there was a direct link between TSH, AMPK and SREBP-2. Here, we demonstrate that the 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR)-induced activation of AMPK directly inhibited the expression of SREBP-2 and its target genes HMGCR and HMGCS, which are key enzymes in cholesterol biosynthesis, and suppressed the TSH-stimulated up-regulation of SREBP-2 in HepG2 cells; similar results were obtained in TSH receptor knockout mice. Furthermore, AMPK, an evolutionally conserved serine/threonine kinase, phosphorylated threonine residues in the precursor and nuclear forms of SREBP-2, and TSH interacted with AMPK to influence SREBP-2 phosphorylation. These findings may represent a molecular mechanism by which AMPK ameliorates the hepatic steatosis and hypercholesterolemia associated with high TSH levels in patients with subclinical hypothyroidism (SCH).

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic triglyceride accumulation, ranging from steatosis to steatohepatitis and cirrhosis. NAFLD is a risk factor for cardiovascular diseases and is associated with metabolic syndrome. Antihyperlipidemic drugs are recommended as part of the treatment for NAFLD patients. Although fibrates activate peroxisome proliferator-activated receptor α (PPARα), leading to the reduction of serum triglyceride levels, the effects of these drugs on NAFLD remain controversial. Clinical studies have reported that PPARα activation does not improve hepatic steatosis. In the present study, we focused on exploring the effect and mechanism of PPARα activation on hepatic triglyceride accumulation and hepatic steatosis. Male C57BL/6J mice, Pparα-null mice and HepG2 cells were treated with fenofibrate, one of the most commonly used fibrate drugs. Both low and high doses of fenofibrate were administered. Hepatic steatosis was detected through oil red O staining and electron microscopy. Notably, in fenofibrate-treated mice, the serum triglyceride levels were reduced and the hepatic triglyceride content was increased in a dose-dependent manner. Oil red O staining of liver sections demonstrated that fenofibrate-fed mice accumulated abundant neutral lipids. Fenofibrate also increased the intracellular triglyceride content in HepG2 cells. The expression of sterol regulatory element-binding protein 1c (SREBP-1c) and the key genes associated with lipogenesis were increased in fenofibrate-treated mouse livers and HepG2 cells in a dose-dependent manner. However, the effect was strongly impaired in Pparα-null mice treated with fenofibrate. Fenofibrate treatment induced mature SREBP-1c expression via the direct binding of PPARα to the DR1 motif of the SREBP-1c gene. Taken together, these findings indicate the molecular mechanism by which PPARα activation increases liver triglyceride accumulation and suggest an adverse effect of fibrates on the pathogenesis of hepatic steatosis.

We demonstrated that angiotensin II type 2 (AT2) receptor-interacting protein (ATIP) 1 ameliorates inflammation-mediated vascular remodeling independent of the AT2 receptor, leading us to explore the possibility of whether ATIP1 could exert anti-inflammatory effects and play a role in other pathophysiological conditions. We examined the possible anti-inflammatory effects of ATIP1 in adipose tissue associated with amelioration of insulin resistance. In mice fed a high-cholesterol diet, adipose tissue macrophage (ATM) infiltration and M1-to-M2 ratio were decreased in ATIP1 transgenic mice (ATIP1-Tg) compared with wild-type mice (WT), with decreased expression of inflammatory cytokines such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in white adipose tissue (WAT), but an increase in interleukin-10, an anti-inflammatory cytokine. Moreover, 2-[(3)H]deoxy-d-glucose (2-[(3)H]DG) uptake was significantly increased in ATIP1-Tg compared with WT. Next, we examined the roles of ATIP1 in BM-derived hematopoietic cells, employing chimeric mice produced by BM transplantation into irradiated type 2 diabetic mice with obesity, KKAy, as recipients. ATM infiltration and M1-to-M2 ratio were decreased in ATIP1 chimera (ATIP1-tg as BM donor), with improvement of insulin-mediated 2-[(3)H]DG uptake and amelioration of inflammation in WAT. Moreover, serum adiponectin concentration in ATIP1 chimera was significantly higher than that in WT chimera (WT as BM donor) and KKAy chimera (KKAy as BM donor). These results indicate that ATIP1 could exert anti-inflammatory effects in adipose tissue via macrophage polarization associated with improvement of insulin resistance, and ATIP1 in hematopoietic cells may contribute to these beneficial effects on adipose tissue functions in type 2 diabetes.

ObjectivesThe role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue.MethodsT2DM mice, KK-Ay, were subjected to intraperitoneal injection of C21 and/or a PPARγ antagonist, GW9662 in drinking water for 2 weeks. Insulin resistance was evaluated by oral glucose tolerance test, insulin tolerance test, and uptake of 2-[(3)H] deoxy-D-glucose in white adipose tissue. Morphological changes of adipose tissues as well as adipocyte differentiation and inflammatory response were examined.ResultsTreatment with C21 ameliorated insulin resistance in KK-Ay mice without influencing blood pressure, at least partially through effects on the PPARγ pathway. C21 treatment increased serum adiponectin concentration and decreased TNF-α concentration; however, these effects were attenuated by PPARγ blockade by co-treatment with GW9662. Moreover, we observed that administration of C21 enhanced adipocyte differentiation and PPARγ DNA-binding activity, with a decrease in inflammation in white adipose tissue, whereas these effects of C21 were attenuated by co-treatment with GW9662. We also observed that administration of C21 restored β cell damage in diabetic pancreatic tissue.ConclusionThe present study demonstrated that direct AT(2) receptor stimulation by C21 accompanied with PPARγ activation ameliorated insulin resistance in T2DM mice, at least partially due to improvement of adipocyte dysfunction and protection of pancreatic β cells.

The title compound, C12H15ClN2O, is a piperazine derivative with the potential for use as a starting material for pharmaceutial and agrochemical applications. The structure is stabilized by C—H...O hydrogen bonds, C—H...π interactions and π–π stacking interactions [centroid–centroid distance = is 4.760 (2) Å].

Background: Microangiogenesis and lymphangiogenesis are essential for tumor growth in the tumor microenvironment, contributing to tumor invasion and metastasis. Limited literature exists on these processes in esophageal squamous cell carcinoma (ESCC). Therefore, the purpose of this study is to explore the impacts of microangiogenesis and lymphangiogenesis on the occurrence, progression, and prognosis assessment of ESCC. Methods: Surgical specimens and paraffin-embedded human tissues were procured from ESCC patients, encompassing 100 ESCC tissues and 100 cancer-adjacent normal (CAN) tissues. CD34 and D2-40 were utilized as markers for microvessel endothelial cells and lymphatic vessel endothelial cells, respectively. Microvascular density (MVD) and lymphatic vessel density (LVD) were evaluated through immunohistochemical quantification. Results: We found that tumor tissues in ESCC patients had significantly higher MVD and LVD than cancer-adjacent normal (CAN) tissues. High MVD and LVD were associated with lymph node metastasis and advanced tumor clinical stages. Additionally, both high MVD and high LVD were strongly linked to poorer prognosis among cancer patients. Furthermore, a positive correlation was found between high MVD and high LVD (p < 0.05). The presence of these markers individually indicated a worse prognosis, with their combined assessment showcasing enhanced prognostic value. Conclusions: Overall, the increased MVD and LVD indicates higher invasion and metastasis of ESCC, closely correlating with unfavorablefor poor prognosis of ESCC patients. [ABSTRACT FROM AUTHOR]