Type 3 muscarinic acetylcholine receptor stimulation is a determinant of endothelial barrier function and adherens junctions integrity: role of protein-tyrosine phosphatase 1B

( Zhou Yang Jiao ),( Jing Wu ),( Chao Liu ),( Bing Wen ),( Wen Zeng Zhao ),( Xin Ling Du ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.10

The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and β-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and β-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase C (PKCa). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation.

Expression of the Pokemon Proto-oncogene in Nasopharyngeal Carcinoma Cell Lines and Tissues

Jiao, Wei,Liu, Fei,Tang, Feng-Zhu,Lan, Jiao,Xiao, Rui-Ping,Chen, Xing-Zhou,Ye, Hui-Lan,Cai, Yong-Lin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

To study the differentiated expression of the proto-oncogene Pokemon in nasopharyngeal carcinoma (NPC) cell lines and tissues, mRNA and protein expression levels of CNE1, CNE2, CNE3 and C666-1 were detected separately by reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and Western-blotting. The immortalized nasopharyngeal epithelial cell line NP69 was used as a control. The Pokemon protein expression level in biopsy specimens from chronic rhinitis patients and undifferentiated non keratinizing NPC patients was determined by Western-blotting and arranged from high to low: C666-1>CNE1>CNE2> CNE3>NP69. The Pokemon mRNA expression level was also arranged from high to low: CNE1>CNE2>NP69>C666-1>CNE3. Pokemon expression of NP69 and C666-1 obviously varied from mRNA to protein. The Pokemon protein level of NPC biopsy specimens was obviously higher than in chronic rhinitis. The data suggest that high Pokemon protein expression is closely associated with undifferentiated non-keratinizing NPC and may provide useful information for NPC molecular target therapy.

Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway

Zhou Meng-jiao,Yang Jia-jie,Ma Ting-yao,Feng Ge-xuan,Wang Xue-lian,Wang Li-Yong,Ge Yu-ze,Gao Ran,Hong-liang Liu,Shan Lin,Kong Lu,Chen Xiao-hong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the “MYC_TARGETS_V2” gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the “MYC_TARGETS_V2” gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.

Optimization of Nutrients for Dinactin Production by a Marine Streptomyces sp. from the High Latitude Arctic

Jiao Zhou,Hao He,Xiaolong Wang,Jian Lu,Xiangshan Zhou,Menghao Cai,YuanXingZhang 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.4

Streptomyces sp. R-527F, which produces the macrotetrolide antibiotic dinactin, was isolated from the sediments of the Arctic Ocean. In this work, optimization of the nutrients required for dinactin production including medium development and precursor stimulation, were investigated. Optimization of the medium and replacement of polar sea water were achieved using a one factor at a time experiment in conjunction with statistical analysis using methods covering Plackett–Burman design, the steepest descent method and central composite design. Dinactin production in the optimized medium was 160.8 mg/L, which was 47 fold higher than the control. Supplementation of the fermentation with exogenous acetate (1.5 mmol/L), succinate (6 mmol/L), malonate (24 mmol/L) and citrate (6 mmol/L) further enhanced dinactin biosynthesis by 42.7, 122.3, 66.7, and 62.1%, respectively. The precursors, in particular succinate, facilitated sugar use and also increased pH levels. Furthermore, a six-pulse feeding of total 6 mmol/L succinate in a 5 L bioreactor fermentation yielded a maximal production of 279.0 mg/L dinactin, 124.1% higher than that without precursor stimulation. This nutritional regulation process is easy to scale up and holds the potential for adaptation to industrial use. Keywords: arctic actinomycete, fermentation, dinactin

A new species of gall midge (Diptera: Cecidomyiidae) damaging flower buds of goji berry Lycium barbarum (Solanaceae)

Ke-Long Jiao,Xiao-Yi Zhou,Hai-Li Qiao,Hao Wang,Jun Chen,Bai-Ming Liu,Wen-Jun Bu,Peter Kolesik 한국응용곤충학회 2020 Journal of Asia-Pacific Entomology Vol.23 No.4

Larvae of a previously undescribed gall midge species have been feeding within malformed flower buds of goji berry Lycium barbarum L. (Solanaceae) in China, preventing fruit development and causing damage to the fruit industry. The new species is named Gephyraulus lycantha Jiao & Kolesik, its morphology is described, the COI mitochondrial gene segment is sequenced, and the biology is outlined. In order to taxonomically accommodate the new gall midge, the scope of the genus Gephyraulus is broadened and now encompasses also species that lack dorso-apical sensoria on the female cercus.

Expression and Immunogenicity of SARSCoV-2 Virus-Like Particles based on Recombinant Truncated HEV-3 ORF2 Capsid Protein

( Yong-fei Zhou ),( Jiao-jiao Nie ),( Chao Shi ),( Ke Ning ),( Yu-feng Cao ),( Yanbo Xie ),( Hongyu Xiang ),( Qiuhong Xie ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.10

COVID-19 is an emerging disease that poses a severe threat to global public health. As such, there is an urgent demand for vaccines against SARS-CoV-2, the virus that causes COVID-19. Here, we describe a virus-like nanoparticle candidate vaccine against SARS-CoV-2 produced by an E. coli expression system. The fusion protein of a truncated ORF2-encoded protein of aa 439~608 (p170) from hepatitis E virus CCJD-517 and the receptor-binding domain of the spike protein from SARSCoV-2 were expressed, purified and characterized. The antigenicity and immunogenicity of p170-RBD were evaluated in vitro and in Kunming mice. Our investigation revealed that p170-RBD selfassembled into approximately 24 nm virus-like particles, which could bind to serum from vaccinated people (p < 0.001) and receptors on cells. Immunization with p170-RBD induced the titer of IgG antibody vaccine increased from 14 days post-immunization and was significantly enhanced after a booster immunization at 28 dpi, ultimately reaching a peak level on 42 dpi with a titer of 4.97 log10. Pseudovirus neutralization tests showed that the candidate vaccine induced a strong neutralizing antibody response in mice. In this research, we demonstrated that p170-RBD possesses strong antigenicity and immunogenicity and could be a potential candidate for use in future SARS-CoV-2 vaccine development.

The mitochondrial unfolded protein response (UPRmt) protects against osteoarthritis

Zhou Zhibin,Lu Jiajia,Yang Mei,Cai Jiao,Fu Qiang,Ma Jun,Zhu Lei 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

The mitochondrial unfolded protein response (UPRmt) is a mitochondrial-to-nuclear signaling pathway that is activated to maintain mitochondrial function when there is an accumulation of misfolded proteins within mitochondria. Mitochondrial function is essential for chondrocyte homeostasis, and mitochondrial dysfunction is a characteristic of osteoarthritis (OA). However, the role of the UPRmt in OA remains unclear. In the present study, the level of the UPRmt was examined in primary mouse chondrocytes subjected to different stresses and in the articular cartilage of OA model mice and OA patients. The relationship between UPRmt activation and OA progression was studied. The UPRmt was induced in primary mouse chondrocytes subjected to diverse stresses and in the cartilage of OA mice. Enhancement of the UPRmt with nicotinamide riboside (NR) significantly improved mitochondrial function, reduced chondrocyte death, attenuated OA pain, and ameliorated OA progression, and the protective effects decreased significantly in chondrocyte-specific Atf5 knockout (ATF5f/fCol2a1-CreERT2) mice. UPRmt induction was also identified in the articular cartilage of OA patients and was associated with reduced chondrocyte death, less severe hip pain, and lower levels of inflammation in synovial fluid. These findings identify the induction of the UPRmt in primary mouse chondrocytes exposed to pathological stresses and in the articular cartilage of OA model mice and OA patients. Enhancement of the UPRmt ameliorates OA progression, suggesting that the UPRmt exerts a protective effect against OA and may be a potential diagnostic and therapeutic strategy for OA.

Microwave Ablation Treatment of Liver Cancer with a 2,450-MHz Cooled-shaft Antenna: Pilot Study on Safety and Efficacy

Jiao, De-Chao,Zhou, Qi,Han, Xin-Wei,Wang, Ya-Feng,Wu, Gang,Ren, Jian-Zhuang,Wang, Yan-Li,Ding, Peng-Xu,Ma, Ji,Fu, Ming-Ti Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.2

To evaluate efficacy of microwave ablation in a primary clinical study, sixty patients (44 men, 16 women; mean age 53 years) with 96, 1-8 cm (mean $3.20{\pm}0.17$ cm) liver cancers were treated with 2,450-MHz internally cooled-shaft antenna. Complete ablation (CA) and local tumor progression (LTP) rates as well as complications were determined. CA rates in small (< 3.0 cm), intermediate (3.1-5.0 cm) and large (5.1-8.0 cm) liver cancers were 96.4% (54/56), 92.3% (24/26) and 78.6% (11/14), respectively. During a mean follow-up period of $17.17{\pm}6.52$ months, LTP occurred in five (5.21%) treated cases. There was no significant difference in the CA and LTP rates between the HCC and liver metastasis patient subgroups (P<0.05). Microwave ablation provides a reliable, efficient, and safe technique to perform hepatic tumor ablation.

The Effects of Puerarin on CYP2D6 and CYP1A2 Activities In Vivo

Jiao Zheng,Bin Chen,Bing Jiang,Ling Zeng,Zhi-Rong Tang,Lan Fan,Hong-Hao Zhou 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.2

Ge-gen (Radix Puerariae) is used in traditional oriental medicine for various medicinal purposes. The drug is the root of a wild leguminous creeper, Pueraria lobata (Willd) Ohwi. It possesses a high content of avonoid derivatives, the most abundant of which is puerarin. Our goal was to find the effect of puerarin on cytochrome P450 enzymes in vivo. The study was conducted in 18 male volunteers of different genotypes (CYP2D6 *1/*1, *1/*10, *10/*10). Plasma was obtained at 6 h after oral administration and urine was collected from 0 to 8 h after probe drug administration. The logarithm value of metabolic rate decrease from -0.0055 ± 0.1887 to -0.1754 ± 0.2411 implied puerarin inhibited activity of CYP2D6. There was no significant relationship between the inhibition with the CYP2D6 genotypes. The paraxanthin/caffeine ratio in the plasma sample at 6th hour was increased by 30 ± 47% (p = 0.003), implied puerarin induced the activity of CYP1A2. While puerarin used together with the substrates of both enzymes, drug interaction worth the attention and at sometimes precautions are needed.

Clinical Features of Multiple Primary Malignancies: a Retrospective Analysis of 72 Chinese Patients

Jiao, Feng,Yao, Li-Juan,Zhou, Jin,Hu, Hai,Wang, Li-Wei Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

There is a scarcity of reports addressing patients with multiple primary malignancies (MPM), especially for Chinese cses. The aim of this study was to present a detailed analysis of Chinese patients presenting with at least two primary malignancies. Particularly, the clinical characteristics and survival between synchronous and metachronous MPM were compared. Out of 6,545 cases, 72 patients (1.1%) including 39 males (54.2%) and 33 females (45.8%) were diagnosed as MPM, giving a male: female sex ratio of 1.2:1. Of these, there were 16 (22.2%) cases of synchronous MPM (7 males, 9 females), 55(76.4%) metachronous (31 males, 24 females), and 1 "mixed form". For first tumor diagnosis time, synchronous MPM patients generally presented later than the metachronous cases. The top three sites for malignancies with metachronous MPM were colorectum, head and neck, and lung, while for synchronous they were lung, colorectum and breast. Among MPM patients, the median survival time was 15.7 years and the 5-year survival was 56%, and there was statistical difference in MPM categories (P < 0.05). The median survival time was 17.3 years and 3.8 years for metachronous and synchronous MPM patients, respectively. In comparison with synchronous MPM patients, those metachronous had a longer survival. This studies increase understanding of the clinical features of Chinese MPM patients and suggest that those presenting with metachronous cancers have a higher incidence and a better prognosis.