Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

( Rui Dong Li ),( Zhong Liang Deng ),( Ning Hu ),( Xi Liang ),( Bo Liu ),( Jin Yong Luo ),( Liang Chen ),( Liang Jun Yin ),( Xiao Ji Luo ),( Wei Shui ),( Tong Chuan He ),( Wei Huang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2012 BMB Reports Vol.45 No.9

We have found that the previously uncharacterized bone morphogenetic protein-9 (BMP9) is one of the most osteogenic factors. However, it is unclear if BMP9 cross-talks with TGFβ1 during osteogenic differentiation. Using the recombinant BMP9 adenovirus, we find that low concentration of rhTGFβ1 synergistically induces alkaline phosphatase activity in BMP9-transduced C3H10T1/2 cells and produces more pronounced matrix mineralization. However, higher concentrations of TGFβ1 inhibit BMP9-induced osteogenic activity. Real-time PCR and Western blotting indicate that BMP9 in combination with low dose of TGFβ1 potentiates the expression of later osteogenic markers osteopontin, osteocalcin and collagen type 1 (COL1a2), while higher concentrations of TGFβ1 decrease the expression of osteopontin and osteocalcin but not COL1a2. Cell cycle analysis reveals that TGFβ1 inhibits C3H10T1/2 proliferation in BMP9-induced osteogenesis and restricts the cells in G0/G1 phase. Our findings strongly suggest that TGFβ1 may exert a biphasic effect on BMP9-induced osteogenic differentiation of mesenchymal stem cells. [BMB Reports 2012; 45(9): 509-514]

Erratum to: Biphasic effects of TGFβ1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

( Rui-dong Li ),( Zhong-liang Deng ),( Ning Hu ),( Xi Liang ),( Bo Liu ),( Jinyong Luo ),( Liang Chen ),( Liangjun Yin ),( Xiaoji Luo ),( Wei Shui ),( Tong-chuan He ),( Wei Huang ) 생화학분자생물학회(구 한국생화학분자생물학회) 2021 BMB Reports Vol.54 No.5

A Putative Histone Deacetylase Modulates the Biosynthesis of Pestalotiollide B and Conidiation in Pestalotiopsis microspora

( Xue Liang Niu ),( Xiao Ran Hao ),( Zhang Yong Hong ),( Long Fei Chen ),( Xi Yu ),( Xu Dong Zhu ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.5

Fungi of the genus Pestalotiopsis have drawn attention for their capability to produce an array of bioactive secondary metabolites that have potential for drug development. Here, we report the determination of a polyketide derivative compound, pestalotiollide B, in the culture of the saprophytic fungus Pestalotiopsis microspora NK17. Structural information acquired by analyses with a set of spectroscopic and chromatographic techniques suggests that pestalotiollide B has the same skeleton as the penicillide derivatives, dibenzodioxocinones, which are inhibitors of cholesterol ester transfer protein (CETP), and as purpactins A and C’, inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Strain NK17 can make a fairly high yield of pestalotiollide B (i.e., up to 7.22 mg/l) in a constitutive manner in liquid culture. Moreover, we found that a putative histone deacetylase gene, designated as hid1, played a role in the biosynthesis of pestalotiollide B. In the hid1 null mutant, the yield of pestalotiollide B increased approximately 2-fold to 15.90 mg/l. In contrast, deletion of gene hid1 led to a dramatic decrease of conidia production of the fungus. These results suggest that hid1 is a modulator, concerting secondary metabolism and development such as conidiation in P. microspora. Our work may help with the investigation into the biosynthesis of pestalotiollide B and the development for new CETP and ACAT inhibitors.

Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer

Li-jun Liang,Chen-xi Hu,Yi-xuan Wen,Xiao-wei Geng,Ting Chen,Guo-qing Gu,Lei Wang,You-you Xia,Yong Liu,Jia-yan Fei,Jie Dong,Feng-hua Zhao,Yiliyar Ahongjiang,Kai-yuan Hui,Xiao-dong Jiang 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed. Results For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

Chemosensitizing effect and mechanism of imperatorin on the anti-tumor activity of doxorubicin in tumor cells and transplantation tumor model

Xin-li Liang,Miao-miao Ji,Zheng-gen Liao,Guo-wei Zhao,Xi-lan Tang,Wei Dong 대한약리학회 2022 The Korean Journal of Physiology & Pharmacology Vol.26 No.3

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/ DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

Association of Functional Polymorphisms of the XRCC4 Gene with the Risk of Breast Cancer: A Meta-analysis

Zhou, Li-Ping,Luan, Hong,Dong, Xi-Hua,Jin, Guo-Jiang,Ma, Dong-Liang,Shang, Hong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Objective: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks (DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of the XRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusive results. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and the risk of breast cancer. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searched for all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons of the total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases and controls. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. Results: Five studies were included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showed that mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increased risk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer. However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms of XRCC4 gene did not appear to have an influence on breast cancer susceptibility. Conclusion: Results from the current meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 gene might increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protective factors.

Association Between XRCC5, 6 and 7 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

Zhou, Li-Ping,Luan, Hong,Dong, Xi-Hua,Jin, Guo-Jiang,Man, Dong-Liang,Shang, Hong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Objective: Non-homologous end joining (NHEJ) is a pathway for repairing DNA double-strand breaks. Recent publications indicated that XRCC5, XRCC6 and XRCC7 genes may participate in the pathogenesis of breast cancer. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate associations between XRCC5, XRCC6 and XRCC7 genetic polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between genetic polymorphisms in XRCC5, XRCC6 and XRCC7 genes and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers. The meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated based on the extracted data. Results: According to the inclusion criteria, we final included seven studies with a total of 2,864 breast cancer cases and 3,060 healthy controls. Meta-analysis results showed that rs3835 (G>A) and rs828907 (G>T) in XRCC5 gene, and rs132793 (G>A) in XRCC6 gene might increase the risk of breast cancer, while rs132788 G>T and rs6002421 (A>G) might be protective factors. However, there was no relationship between XRCC7 genetic polymorphisms and the risk of breast cancer. Conclusion: This meta-analysis suggests that the rs3835 G>A and rs828907 G>T in XRCC5 gene, rs6002421 (A>G), rs132788 (G>T) and rs132793 (G>A) in XRCC6 gene might be risk factors for breast cancer, while the rs132788 (G>T) and rs6002421 (A>G) in XRCC6 gene might be protective.

Application of Intraoperative Ultrasonography for Guiding Microneurosurgical Resection of Small Subcortical Lesions

Jia Wang,Yun You Duan,Xi Liu,Yu Wang,Guo Dong Gao,Huai Zhou Qin,Liang Wang 대한영상의학회 2011 Korean Journal of Radiology Vol.12 No.5

Objective: We wanted to evaluate the clinical value of intraoperative ultrasonography for real-time guidance when performing microneurosurgical resection of small subcortical lesions. Materials and Methods: Fifty-two patients with small subcortical lesions were involved in this study. The pathological diagnoses were cavernous hemangioma in 25 cases, cerebral glioma in eight cases, abscess in eight cases, small inflammatory lesion in five cases, brain parasite infection in four cases and the presence of an intracranial foreign body in two cases. An ultrasonic probe was sterilized and lightly placed on the surface of the brain during the operation. The location, extent, characteristics and adjacent tissue of the lesion were observed by high frequency ultrasonography during the operation. Results: All the lesions were located in the cortex and their mean size was 1.3 ± 0.2 cm. Intraoperative ultrasonography accurately located all the small subcortical lesions, and so the neurosurgeon could provide appropriate treatment. Different lesion pathologies presented with different ultrasonic appearances. Cavernous hemangioma exhibited irregular shapes with distinct margins and it was mildly hyperechoic or hyperechoic. The majority of the cerebral gliomas displayed irregular shapes with indistinct margins, and they often showed cystic and solid mixed echoes. Postoperative imaging identified that the lesions had completely disappeared, and the original symptoms of all the patients were significantly alleviated. Conclusion: Intraoperative ultrasonography can help accurately locate small subcortical lesions and it is helpful for selecting the proper approach and guiding thorough resection of these lesions. Objective: We wanted to evaluate the clinical value of intraoperative ultrasonography for real-time guidance when performing microneurosurgical resection of small subcortical lesions. Materials and Methods: Fifty-two patients with small subcortical lesions were involved in this study. The pathological diagnoses were cavernous hemangioma in 25 cases, cerebral glioma in eight cases, abscess in eight cases, small inflammatory lesion in five cases, brain parasite infection in four cases and the presence of an intracranial foreign body in two cases. An ultrasonic probe was sterilized and lightly placed on the surface of the brain during the operation. The location, extent, characteristics and adjacent tissue of the lesion were observed by high frequency ultrasonography during the operation. Results: All the lesions were located in the cortex and their mean size was 1.3 ± 0.2 cm. Intraoperative ultrasonography accurately located all the small subcortical lesions, and so the neurosurgeon could provide appropriate treatment. Different lesion pathologies presented with different ultrasonic appearances. Cavernous hemangioma exhibited irregular shapes with distinct margins and it was mildly hyperechoic or hyperechoic. The majority of the cerebral gliomas displayed irregular shapes with indistinct margins, and they often showed cystic and solid mixed echoes. Postoperative imaging identified that the lesions had completely disappeared, and the original symptoms of all the patients were significantly alleviated. Conclusion: Intraoperative ultrasonography can help accurately locate small subcortical lesions and it is helpful for selecting the proper approach and guiding thorough resection of these lesions.

Lack of Association Between LIG4 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

Zhou, Li-Ping,Luan, Hong,Dong, Xi-Hua,Jin, Guo-Jiang,Man, Dong-Liang,Shang, Hong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs). Results: According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans. Conclusion: This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.

Genetic Variants of CYP2D6 Gene and Cancer Risk: A HuGE Systematic Review and Meta-analysis

Zhou, Li-Ping,Luan, Hong,Dong, Xi-Hua,Jin, Guo-Jiang,Man, Dong-Liang,Shang, Hong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors.