Exploring the Cocktail Factor Approach to Generate Salivary Gland Progenitors through Co-Culture Techniques

Zhang Yifei,Yan Shuang,Mei Zi,Zhang He,Ding Chong,Zhang Siqi,Wei Shicheng 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.5

Background: The derivation of salivary gland (SG) progenitors from pluripotent stem cells (PSCs) presents significant potential for developmental biology and regenerative medicine. However, the existing protocols for inducing SG include limited factors, making it challenging to mimic the in vivo microenvironment of embryonic SGs. Methods: We reported a cocktail factor approach to promote the differentiation of mouse embryonic stem cell (mESC)-derived oral epithelium (OE) into SG progenitors through a three-dimensional co-culture method. Upon confirming that the embryonic SG can promote the differentiation of mESC-derived OE, we performed RNA sequence analysis to identify factors involved in the differentiation of SG progenitors. Results: Our findings highlight several efficient pathways related to SG development, with frequent appearances of four factors: IFN-γ, TGF-β2, EGF, and IGF-1. The combined treatment using these cocktail factors increased the expression of key SG progenitor markers, including Sox9, Sox10, Krt5, and Krt14. However, absence of any one of these cocktail factors did not facilitate differentiation. Notably, aggregates treated with the cocktail factor formed SG epithelial-like structures and pre-bud-like structures on the surface. Conclusion: In conclusion, this study offers a novel approach to developing a differentiation protocol that closely mimics the in vivo microenvironment of embryonic SGs. This provides a foundation for generating PSC-derived organoids with near-physiological cell behaviors and structures. Background: The derivation of salivary gland (SG) progenitors from pluripotent stem cells (PSCs) presents significant potential for developmental biology and regenerative medicine. However, the existing protocols for inducing SG include limited factors, making it challenging to mimic the in vivo microenvironment of embryonic SGs. Methods: We reported a cocktail factor approach to promote the differentiation of mouse embryonic stem cell (mESC)-derived oral epithelium (OE) into SG progenitors through a three-dimensional co-culture method. Upon confirming that the embryonic SG can promote the differentiation of mESC-derived OE, we performed RNA sequence analysis to identify factors involved in the differentiation of SG progenitors. Results: Our findings highlight several efficient pathways related to SG development, with frequent appearances of four factors: IFN-γ, TGF-β2, EGF, and IGF-1. The combined treatment using these cocktail factors increased the expression of key SG progenitor markers, including Sox9, Sox10, Krt5, and Krt14. However, absence of any one of these cocktail factors did not facilitate differentiation. Notably, aggregates treated with the cocktail factor formed SG epithelial-like structures and pre-bud-like structures on the surface. Conclusion: In conclusion, this study offers a novel approach to developing a differentiation protocol that closely mimics the in vivo microenvironment of embryonic SGs. This provides a foundation for generating PSC-derived organoids with near-physiological cell behaviors and structures.

SPON2 Promotes M1-like Macrophage Recruitment and Inhibits Hepatocellular Carcinoma Metastasis by Distinct Integrin–Rho GTPase–Hippo Pathways

Zhang, Yan-Li,Li, Qing,Yang, Xiao-Mei,Fang, Fang,Li, Jun,Wang, Ya-Hui,Yang, Qin,Zhu, Lei,Nie, Hui-Zhen,Zhang, Xue-Li,Feng, Ming-Xuan,Jiang, Shu-Heng,Tian, Guang-Ang,Hu, Li-Peng,Lee, Ho-Young,Lee, Su-J American Association for Cancer Research 2018 Cancer research Vol.78 No.9

<P>Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P>Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis. SPON2-α4β1 integrin signaling activated RhoA and Rac1, increased F-actin reorganization, and promoted M1-like macrophage recruitment. F-Actin accumulation also activated the Hippo pathway by suppressing LATS1 phosphorylation, promoting YAP nuclear translocation, and initiating downstream gene expression. However, SPON2-α5β1 integrin signaling inactivated RhoA and prevented F-actin assembly, thereby inhibiting HCC cell migration; the Hippo pathway was not noticeably involved in SPON2-mediated HCC cell migration. In HCC patients, SPON2 levels correlated positively with prognosis. Overall, our findings provide evidence that SPON2 is a critical factor in mediating the immune response against tumor cell growth and migration in HCC.</P><P><B>Significance:</B> Matricellular protein SPON2 acts as an HCC suppressor and utilizes distinct signaling events to perform dual functions in HCC microenvironment.</P><P><B>Graphical Abstract:</B> http://cancerres.aacrjournals.org/content/canres/78/9/2305/F1.large.jpg. <I>Cancer Res; 78(9); 2305–17. ©2018 AACR</I>.</P><P><B>Graphical Abstract</B></P><P> [Figure]</P>

Efficacy and Safety of Endostar^® Combined with Chemotherapy in Patients with Advanced Soft Tissue Sarcomas

Zhang, Lu-Ping,Liao, Xing-Yun,Xu, Yan-Mei,Yan, Lv-Jun,Yan, Gui-Fang,Wang, Xin-Xin,Duan, Yu-Zhong,Sun, Jian-Guo Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed. Objective: To evaluate the efficacy and safety of Endostar$^{(R)}$ combined with chemotherapy in patients with advanced STS. Methods: A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar$^{(R)}$ were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed. Results: In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P=0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P=0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups. Conclusions: Endostar$^{(R)}$ combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.

Use of Clozapine for the Treatment of Schizophrenia: Findings of the 2006 Research on the China Psychotropic Prescription Studies

Tian-Mei Si,Yun-shu Zhang,Liang Shu,Ke-Qing Li,Xie-He Liu,Qi-Yi Mei,Gao-Hua Wang,Pei-Shen Bai,Li-Ping Ji,Xian-Sheng Cheng,Cui Ma,Jian-Guo Shi,Hong-Yan Zhang,Hong Ma,Xin Yu 대한정신약물학회 2012 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.10 No.2

Objective: Clozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. Methods: Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10provinces with differing levels of economic development. Results: Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36±128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. Conclusion: Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.

Efficacy and Safety of Neurokinin-1 Receptor Antagonists for Prevention of Chemotherapy-Induced Nausea and Vomiting: Systematic Review and Meta-analysis of Randomized Controlled Trials

Yuan, Dong-Mei,Li, Qian,Zhang, Qin,Xiao, Xin-Wu,Yao, Yan-Wen,Zhang, Yan,Lv, Yan-Ling,Liu, Hong-Bin,Lv, Tang-Feng,Song, Yong Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Objectives: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. Materials and Methods: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. Results: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, P<0.001), acute phase (85.1% vs 79.6%, P<0.001), and delayed phase (71.4% vs 58.2%, P<0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, P<0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, P<0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, P<0.001; occurrence of vomiting: 22.6% vs 38.9%, P<0.001; usage of rescue drugs: 23.5% vs 34.1%, P<0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. Conclusions: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.

A Rapidly New-typed Detection of Norovirus Based on F0F1-ATPase Molecular Motor Biosensor

Zhuo Zhao,Jie Zhang,Mei-Ling Xu,Zhi-Peng Liu,Hua Wang,Ming Liu,Yan-Yan Yu,Li Sun,Hui Zhang,Hai-Yan Wu 한국생물공학회 2016 Biotechnology and Bioprocess Engineering Vol.21 No.1

In order to adapt port rapid detection of food borne norovirus, presently we developed a new typed detection method based on F0F1-ATPase molecular motor biosensor. A specific probe was encompassed the conservative region of norovirus and F0F1-ATPase within chromatophore was constructed as a molecular motor biosensor through the “ε-subunit antibody-streptomycinbiotin- probe” system. Norovirus was captured based on probe-RNA specific binding. Our results demonstrated that the Limit of Quantification (LOQ) is 0.005 ng/mL for NV RNA and also demonstrated that this method possesses specificity and none cross-reaction for food borne virus. What’s more, the experiment used this method could be accomplished in 1 h. We detected 10 samples by using this method and the results were consistent with RT-PCR results. Overall, based on F0F1-ATPase molecular motors biosensor system we firstly established a new typed detection method for norovirus detection and demonstrated that this method is sensitive and specific and can be used in the rapid detection for food borne virus.

Quantitative Analysis of Enlarged Cervical Lymph Nodes with Ultrasound Elastography

Zhang, Jun-Peng,Liu, Hua-Yan,Ning, Chun-Ping,Chong, Jing,Sun, Yong-Mei Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.16

Purpsoe: To investigate the diagnostic value of quantitative analysis of a tissue diffusion and virtual touch tissue imaging quantification (VTIQ) technique with acoustic radiation force impulse (ARFI) elastography for assessing enlarged cervical lymph nodes. Materials and Methods: Fifty-six enlarged cervical lymph nodes confirmed by pathologic diagnoses were covered in the study. According to the results of pathologic diagnosis, patients were classified into benign and malignant groups. All the patients were examined by both conventional ultrasonography and elastography. AREA% and shear wave velocity (SWV) in ROI of different groups were calculated and compared using ROC curves. Cut-off points of AREA% and SWV were determined with receiver operating characteristic curves. Results: Final histopathological results revealed 21 cases of benign and 35 cases of malignant lymph nodes. The mean values of AREA% and SWV in benign and malignant groups were $45.0{\pm}17.9%$ and $2.32{\pm}0.57m/s$, and $61.3{\pm}21.29%$ and $4.36{\pm}1.25$)m/s, respectively. For the parameters of elastography, "AREA%" and SWV demonstrated significant differences between groups (p=0.002). AREA% was positively correlated with SWV with a correlation coefficient of 0.809 (P<0.001). Conclusions: Stiffness of different lymph node diseases in patients may differ. Elastography can evaluate changes sensitively and provide valuable information to doctors. The study proved that the VTIQ elastography technique can play an important role in differential diagnosis of lymph nodes.

Clinical Efficacy of Bevacizumab Concomitant with Pemetrexed in Patients with Advanced Non-small Cell Lung Cancer

Zhang, Yu-Mei,Li, Yong-Qiang,Liu, Zhi-Hui,Liao, Xiao-Li,Liang, Rong,Lin, Yan,Yuan, Chun-Ling,Liao, Si-Na,Liang, Chao-Yong,Li, Qian,Li, Le-Qun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Objective: To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: A total of 72 patients were randomly divided into a combination group (pemetrexed+bevacizumab, n=36) and a pemetrexed group (n=36) and assessed for disease control (CR+PR+SD) after 4-cycles of first-line GP chemotherapy (gemcitabine+cisplatin). Clinical efficacy, progression-free survival time (PFS), overall survival time (OS), overall response rate (ORR), disease control rate (DCR) and rate of adverse responses between two groups were observed and compared. Results: ORR and DCR were 27.8% and 83.4% in combination group, and 16.7% and 69.5% in the pemetrexed group, respectively, but there were no significant differences (P>0.05). PFS in combination group and pemetrexed group were 4.6 months and 3.9 months respectively (P=0.09), whereas OS in the combination group was 14 months, evidently higher than in the pemetrexed group (11 months, P=0.004). Adverse responses in both groups included high blood pressure, bleeding, thrombocytopenia, anemia, elevated transaminase, diarrhea, vomiting and proteinuria, but there were no significant differences (P>0.05). Conclusions: Bevacizumab concomitant with pemetrexed has better clinical efficacy and safety, giving rise to prolonged survival time in patients with advanced NSCLC.

DAZL binds to the transcripts of several Tssk genes in germ cells

Mei Zeng,Wen Qian Deng,Xin Ying Wang,Wei Min Qiu,Yan Yan Liu,Hua Qin Sun,Da Chang Tao,Si Zhong Zhang,Yong Xin Ma 한국생화학분자생물학회 2008 BMB Reports Vol.41 No.4

Effects of winter and spring housing on growth performance and blood metabolites of Pengbo semi-wool sheep in Tibet

Yan Mei Jin,Xiao Qing Zhang,Warwick B Badgery,Peng Lin,Jun Xi Wu 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.10

Objective: Sixty Pengbo semi-wool sheep ewes (approximately 1.5-years-old; 31.33±0.43 kg) were randomly assigned to two groups, either grazing (G) or dry lot feeding (D), to examine the effects of traditional daily grazing and dry lot feeding on performance and blood metabolites during the cold season in Tibetan Plateau. Methods: The ewes in the G group were grazed continuously each day and housed in one shed each evening, while the ewes in the D group were housed in another shed all day. All animals were fed 400 g/d of commercial concentrate, and grass hay was available freely throughout the experimental period. Results: Compared with the G group, the ewes in the D group had higher (p<0.05) live weight and weight gain. The D group ewes had greater (p<0.05) numbers of white blood cells and platelets, while they had lower (p<0.05) platelet-large cell ratios, cholesterol, high-density lipoprotein cholesterol and glutathione peroxidase, as compared with the G group ewes. Additionally, three serum metabolites, abscisic acid, xanthoxin and 3,4-dihydroxy-5-polypren, were upregulated (p<0.05) in the G group in comparison with the D group. Conclusion: In conclusion, a dry lot feeding regime during the winter and spring period will increase the productivity of sheep and improve blood physiological and biochemical profiles.