Follistatin N terminus differentially regulates muscle size and fat in vivo

Hui Zheng,Chunping Qiao,Ruhang Tang,Jianbin Li,Karen Bulaklak,Zhenhua Huang,Chunxia Zhao,Yi Dai,Juan Li,Xiao Xiao 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV). Overexpression of wild-type FST in normal mice greatly increased muscle mass while decreasing fat accumulation, whereas overexpression of an N terminus mutant or N terminusdeleted FST had no effect on muscle mass but moderately decreased fat mass. In contrast, FST-I-I containing the complete N terminus and double domain I without domain II and III had no effect on fat but increased skeletal muscle mass. The effects of different constructs on differentiated C2C12 myotubes were consistent with the in vivo finding. We hypothesized that ND was critical for myostatin blockade, mediating the increase in muscle mass, and was less pivotal for activin binding, which accounts for the decrease in the fat tissue. An in vitro TGF-beta1-responsive reporter assay revealed that FST-I-I and N terminus-mutated or -deleted FST showed differential responses to blockade of activin and myostatin. Our study provided direct in vivo evidence for a role of the ND of FST, shedding light on future potential molecular designs for FST-based gene therapy.

Different Catabolism Pathways Triggered by Various Methylxanthines in Caffeine-Tolerant Bacterium Pseudomonas putida CT25 Isolated from Tea Garden Soil

( Yi-xiao Ma ),( Xiao-han Wu ),( Hui-shi Wu ),( Zhan-bo Dong ),( Jian-hui Ye ),( Xin-qiang Zheng ),( Yue-rong Liang ),( Jian-liang Lu ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.7

The degradation efficiency and catabolism pathways of the different methylxanthines (MXs) in isolated caffeine-tolerant strain Pseudomonas putida CT25 were comprehensively studied. The results showed that the degradation efficiency of various MXs varied with the number and position of the methyl groups on the molecule (i.e., xanthine > 7-methylxanthine ≈ theobromine > caffeine > theophylline > 1-methylxanthine). Multiple MX catabolism pathways coexisted in strain CT25, and a different pathway would be triggered by various MXs. Demethylation dominated in the degradation of N-7-methylated MXs (such as 7- methylxanthine, theobromine, and caffeine), where C-8 oxidation was the major pathway in the catabolism of 1-methylxanthine, whereas demethylation and C-8 oxidation are likely both involved in the degradation of theophylline. Enzymes responsible for MX degradation were located inside the cell. Both cell culture and cell-free enzyme assays revealed that N-1 demethylation might be a rate-limiting step for the catabolism of the MXs. Surprisingly, accumulation of uric acid was observed in a cell-free reaction system, which might be attributed to the lack of activity of uricase, a cytochrome c-coupled membrane integral enzyme.

Decitabine in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes, Which Combined with Complex Karyotype Respectively

Gao, Su,Li, Zheng,Fu, Jian-Hong,Hu, Xiao-Hui,Xu, Yang,Jin, Zheng-Ming,Tang, Xiao-Wen,Han, Yue,Chen, Su-Ning,Sun, Ai-Ning,Wu, De-Pei,Qiu, Hui-Ying Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. Materials and Methods: From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone ($20mg/m^2$ daily for 5 days) or combination AAG chemotherapy (Acla 20mg qod*4d, Ara-C $10mg/m^2$ q12h*7d, G-CSF $300{\mu}g$ qd, the dose of G-CSF adjusted to the amount in blood routinely). Results: In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ${\geq}$two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological toxicity was observed in 27 cases (75%). Grade III to IV infections were clinically documented in 7 (20%). Grades I to II non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Conclusions: Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.

Icariside II Promotes the Differentiation of Adipose Tissue-Derived Stem Cells to Schwann Cells to Preserve Erectile Function after Cavernous Nerve Injury

Zheng, Tao,Zhang, Tian-biao,Wang, Chao-liang,Zhang, Wei-xing,Jia, Dong-hui,Yang, Fan,Sun, Yang-yang,Ding, Xiao-ju,Wang, Rui Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.6

Icariside II (ICA II) is used in erectile dysfunction treatment. Adipose tissue-derived stem cells (ADSCs) are efficient at improving erectile function. This study aimed to explore the action mechanism of ADSCs in improving erectile function. ADSCs were isolated from the adipose tissues of rats. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. The expressions of mRNA and protein were determined separately through qRT-PCR and western blot. The endogenous expressions of related genes were regulated using recombinant plasmids and cell transfection. A Dual-Luciferase Reporter Assay was performed to determine the interaction between miR-34a and STAT3. Rat models with bilateral cavernous nerve injuries (BCNIs) were used to assess erectile function through the detection of mean arterial pressure (MAP) and intracavernosal pressure (ICP). ICA II promoted ADSCs' proliferation and differentiation to Schwann cells (SCs) through the inhibition of miR-34a. Suppressed miR-34a promoted the differentiation of ADSCs to SCs by upregulating STAT3. ICA II promoted the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway. The combination of ICA II and ADSCs preserved the erectile function of the BCNI model rats. ADSCs treated with ICA II markedly preserved the erectile function of the BCNI model rats, which was reversed through miR-34a overexpression. ICA II promotes the differentiation of ADSCs to SCs through the miR34a/STAT3 pathway, contributing to erectile function preservation after the occurrence of a cavernous nerve injury.

Wavelet PWM Technique for Single-Phase Three-Level Inverters

Zheng, Chun-Fang,Zhang, Bo,Qiu, Dong-Yuan,Zhang, Xiao-Hui,Xiao, Le-Ming The Korean Institute of Power Electronics 2015 JOURNAL OF POWER ELECTRONICS Vol.15 No.6

The wavelet PWM (WPWM) technique has been applied in two-level inverters successfully, but directly applying the WPWM technique to three-level inverters is impossible. This paper proposes a WPWM technique suitable for a single-phase three-level inverter. The work analyzes the control strategy with the WPWM and obtains the design of its parameters. Compared with the SPWM technique for a single-phase three-level inverter under the same conditions, the WPWM can obtain high magnitudes of the output fundamental frequency component, low total harmonic distortion, and simpler digital implementation. The feasibility experiment is given to verify of the proposed WPWM technique.

An Improved Wavelet PWM Technique with Output Voltage Amplitude Control for Single-phase Inverters

Zheng, Chun-Fang,Zhang, Bo,Qiu, Dong-Yuan,Zhang, Xiao-Hui,Li, Rui The Korean Institute of Power Electronics 2016 JOURNAL OF POWER ELECTRONICS Vol.16 No.4

Unlike existing pulse-width modulation (PWM) techniques, such as sinusoidal PWM and random PWM, the wavelet PWM (WPWM) technique based on a Harr wavelet function can achieve a high fundamental component for the output voltage, low total harmonic distortion, and simple digital implementation. However, the original WPWM method lacks output voltage control. Thus, the practical application of the WPWM technique is limited. This study proposes an improved WPWM technique that can regulate output voltage amplitude with the addition of a parameter. The relationship between the additional parameter and the output voltage amplitude is analyzed in detail. Experimental results verify that the improved WPWM exhibits output voltage control in addition to all the merits of the WPWM technique.

Cold hardiness characteristic of the overwintering pupae of fall webworm Hyphantria cunea (Drury) (Lepidoptera: Arctiidae) in the northeast of China

Xiao-Rui Xu,Ming-Ming Zhu,Liang-Liang Li,Guang-Cai Zhang,Ye Zheng,Ting Li,Shou-Hui Sun 한국응용곤충학회 2015 Journal of Asia-Pacific Entomology Vol.18 No.1

The fallwebworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), is an invasive and important pest in China. Understanding the physiological–biochemical characteristics of the overwintering pupae is essential for its cold tolerance and potential distribution in the northeast of China. Results indicated that the supercooling point (SCP) of H. cunea overwintering pupae varied significantly among Jilin city (43°N, 126°E), Jilin Province, Shenyang (41.8°N, 123.4°E), Liaoning Province and Yingkou (40.39°N, 122.13°E), Liaoning Province. The average SCP in Jilin was the lowest (−23.49 ± 0.46 °C) in those of three areas. The water content in overwintering pupae had a significant positive correlation with the SCP (R = 0.848,P = 0.03). Contents of alanine (ALA) (26.00%), lysine (LYS) (30.51%) and arginine (ARG) (22.88%) in the overwintering pupae's hemolymph were higher than others. During the overwintering, the fat content in pupae's bodies decreased gradually. Analysis of variance (ANOVA) indicated that the content of trehalose in the body of H. cunea was remarkably different (P= 0.007) month by month, with the maximum in March (2.88 mg·mL−1) and the minimum (0.40 mg·mL−1) in November. Pearson's correlation test indicated that SCP had a significant negative correlation with the SOD enzyme activity (R = −0.850; P = 0.008). Thermal hysteresis activity (THA) of hemolymph was 0.68°C and 0.7–0.8°C for H. cunea pupae and larva, respectively, using differential scanning calorimetry, which suggests that the H. cunea can improve their cold tolerance through producing antifreeze proteins. These results could help us to predict the distribution of the H. cunea in the northeast of China.

Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88’s effects on the gut microbiota

Hui-wen Xiao,Yuan Li,Dan Luo,Jia-li Dong,Li-xin Zhou,Shu-yi Zhao,Qi-sheng Zheng,Hai-chao Wang,Ming Cui,Sai-jun Fan 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings.

Gene Expression Profiles of HeLa Cells Impacted by Hepatitis C Virus Non-structural Protein NS4B

Zheng, Yi,Ye, Lin-Bai,Liu, Jing,Jing, Wei,Timani, Khalid A.,Yang, Xiao-Jun,Yang, Fan,Wang, Wei,Gao, Bo,Wu, Zhen-Hui Korean Society for Biochemistry and Molecular Biol 2005 Journal of biochemistry and molecular biology Vol.38 No.2

By a cDNA array representing 2308 signal transduction related genes, we studied the expression profiles of HeLa cells stably transfected by Hepatitis C virus nonstructural protein 4B (HCV-NS4B). The alterations of the expression of four genes were confirmed by real-time quantitative RT-PCR; and the aldo-keto reductase family 1, member C1 (AKR1C1) enzyme activity was detected in HCV-NS4B transiently transfected HeLa cells and Huh-7, a human hepatoma cell line. Of the 2,308 genes we examined, 34 were up-regulated and 56 were down-regulated. These 90 genes involved oncogenes, tumor suppressors, cell receptors, complements, adhesions, transcription and translation, cytoskeletion and cellular stress. The expression profiling suggested that multiple regulatory pathways were affected by HCV-NS4B directly or indirectly. And since these genes are related to carcinogenesis, host defense system and cell homeostatic mechanism, we can conclude that HCV-NS4B could play some important roles in the pathogenesis mechanism of HCV.

Value of contrast-enhanced ultrasonography in microwave ablation treatment of symptomatic focal uterine adenomyosis

Xiao-Long Li,Jia-Xin Li,Song-Yuan Yu,Pei-Li Fan,Yun-Jie Jin,Er-Jiao Xu,Sai-Nan Guan,Er-Ya Deng,Qiu-Yan Li,Zheng-Biao Ji,Jiu-Ling Qi,Hui-Xiong Xu,China Alliance of Multi-Center Clinical Study for Ultra 대한초음파의학회 2024 ULTRASONOGRAPHY Vol.43 No.1

Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis.Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up.Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered.Conclusion: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes. Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCE- MRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. Conclusion: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pre- treatment CEUS indicates satisfactory treatment outcomes.