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Effects of myeloid specific deficiency of FBXW7 on lung metastasis of murine melanoma
ZHANG Wei,LAI Lihua,WANG Qingqing
J Zhejiang Univ (Med Sci), 2017, 46(2): 111-117.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.01
Abstract( 33 )   HTML( 47 )     PDF(4299KB)( 28 )

Objective: To investigate the effects of myeloid-specific deficiency of FBXW7 on lung metastasis of murine B16F10 melanoma and its mechanisms. Methods: Mice carrying the floxed allele of FBXW7 and lysozyme M-Cre were used for generation of mice with myeloid cell-specific deletion of FBXW7. Mouse genotypes were examined by genomic DNA PCR. B16F10 cells in PBS were injected into the tail vein of Lysm-FBXW7f/f and Lysm+FBXW7f/f mice. After 14 d, the mice were sacrificed, and the lungs were removed and weighed. B16F10 tumor colonies in the lungs were counted. The myeloid cells were analyzed by flow cytometry. Results: Myeloid-specific deficiency of FBXW7 mice were generated successfully, as FBXW7 expressions in peritoneal macrophages and bone marrow-derived macrophages (BMDMs) of Lysm+FBXW7f/f mice were knockdown. Flow cytometry results showed the deletion of FBXW7 in myeloid lineages did not affect the development of myeloid immune cell subsets. Metastasis was reduced in Lysm+FBXW7f/f mice compared with control mice. The number of tumor colonies was 165±42, 122±12 respectively. The proportion of metastasis-associated macrophages (MAM) in the lungs of Lysm+FBXW7f/f mice was reduced [(23.15±7.59)% vs (13.13±2.26)%], while the proportion of resident macrophages was increased [(5.426±0.42)% vs (10.42±1.90)%]. The proportion of myeloid-derived suppressor cells in the lung showed no difference between Lysm-FBXW7f/f and Lysm+FBXW7f/f mice. Conclusion: Myeloid-specific deficiency of FBXW7 can inhibit lung metastasis of B16F10 melanoma in mice, and the mechanism may be associated with regulation of MAM in the metastatic tumor lesions.

Bacterial outer membrane vesicles as nano carriers to study immunological activities
CHEN Qi,WU Min,Bai Hongzhen,Guo Zeling,ZHOU Jun,WANG Qingqing,TANG Guping
J Zhejiang Univ (Med Sci), 2017, 46(2): 118-126.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.02
Abstract( 49 )   HTML( 19 )     PDF(6802KB)( 59 )

Objective: To prepare a nano-carrier based on combining bacterial outer membrane vesicles (OMV) with three block polymer pluronic F127 (PEO100-PPO65-PEO100) (OMV-F127) and to investigate its immunological activity. Methods: Attenuated salmonella (sal) was cultivated. OMV were separated by centrifugal ultrafiltration or ultrasonication, and OMV-F127 was prepared by mechanical extrudation method. The protein contents and compositions were tested with BCA and SDS-PAGE; the morphology of OMV, F127 and OMV-F127 were observed with FM and TEM; the particle sizes and their zeta potential were determined with DLS. Mouse macrophage RAW246.7 cells were treated with OMV-F127 (50 μg/mL, 100 μg/mL) in vitro, and the concentrations of IL-12, TNF-α and IFN-γ in culture supernatant were measured with ELISA kits. Results: The contents of protein in separated OMV by centrifugal ultrafiltration and ultrasonication were 2.8 mg/mL and 2.7 mg/mL, respectively. SDS-PAGE showed the marker protein OmpF/C in OMV. Under the FM and TEM, ball-like structure of F127 and OMV-F127 was observed. Size analysis revealed that the diameters of OMV, F127 and OMV-F127 were 72±2 nm, 90±3 nm and 92±2 nm, respectively. ELISA tests revealed that OMV-F127 significantly stimulated the secretion of IL-12, TNF-α and IFN-γ in RAW246.7 cells. Conclusion: A nano-carrier based on bacterial outer membrane vesicles has been prepared, which can stimulate the secretion of cytokines and may have immunomodulatory effects.

Preparation, characterization and cytology study of Pluronic-PEI micelles
WANG Hebin,LI Yang,LIU Xingang,ZHOU Jun,WANG Qingqing,TANG Guping
J Zhejiang Univ (Med Sci), 2017, 46(2): 127-133.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.03
Abstract( 44 )   HTML( 42 )     PDF(14514KB)( 18 )

Objective: To prepare and characterize Pluronic-PEI micelles as a drug/gene delivery system. Methods: We used the low-molecular-weight PEI as a cross-linking agent to prepare the Pluronic-PEI micelles. The particle size, zeta potential and critical micelle concentration (CMC) were measured by dynamic light scattering (DLS) and pyrene fluorescence probe. The cytotoxicity, transfection efficiency and the impact on the intracellular ATP and P-gp levels of Pluronic-PEI micelles were investigated at the cellular level. Results: Pluronic-PEI micelles were successfully prepared with a suitable particle size (120-180 nm), zeta potential (+6-+9 mv), and a good ability to carry the drug/gene. An in-vitro study showed that Pluronic-PEI had low cytotoxicity, and the P123-PEI600 possessed high gene transfection efficiency and could downregulate the intracellular ATP and P-gp levels. Conclusion: Pluronic-PEI is a good drug/gene delivery system, and P123-PEI600 is an ideal vector, which may be used in the combination therapy for reversing multidrug resistance.

Synthesis of BODIPY photosensitizers and their photodynamic effect on cancer cells
LIU Xingang,WU Min,LI Suying,Li Zhongbao,HU Qinglian,ZHOU Jun,TANG Guping
J Zhejiang Univ (Med Sci), 2017, 46(2): 135-143.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.04
Abstract( 35 )   HTML( 15 )     PDF(9867KB)( 28 )

Objective: To design and synthesize photosensitizers with different substituents and to identify its physicochemical characteritics and photodynamic effect on cancer cells. Methods: Two kinds of BODIPY photosensitizers BPOI and BPCI were synthesized through condensation reaction between aldehyde and reactive hydrogen of pyrrole, followed with electrophilic substitution reaction. Physicochemical properties were characterized by 1H NMR, FT-IR and UV-visible absorption spectra and fluorescence emission spectra. The ability to produce reactive oxygen species was detected by BPDF and DCFH-DA. Photodynamic therapy effect on rat glioma C6 cells in vitro was determined by MTT method. Results: Two kinds of BODIPY photosensitizers BPOI and BPCI were successfully synthesized with different substituents, which were confirmed by 1H NMR, FT-IR. Both materials had low toxicity and could be readily taken up by tumor cells. The ability of synthesized photosensitizers to produce reactive oxygen species was strongly influenced by solvent polarity when the substituent was electron-donating group, while no effect was found when the substituent was electron-withdrawing group. Conclusion: Photosensitizer BPOI with electron-donating substituent produces reactive oxygen species with a slow rate in a highly polar environment, while greatly enhanced this effect in a low polarity environment, which is expected to be used for environmental-selective photodynamic therapy in tumor cells.

Preparation, characterization and antitumor of cyclodextrin inclusion of an anti-cancer drug regorafenib
LIU Kai-hang,SUN Mengying,TANG Guping,HU Xiurong
J Zhejiang Univ (Med Sci), 2017, 46(2): 144-152.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.05
Abstract( 27 )   HTML( 5 )     PDF(5282KB)( 24 )

Objective: In order to improve the drug’s solubility, dissolution and bioavailability, RG-β-CD, RG-γ-CD and RG-Hp-β-CD were prepared by co-crystallization between Regorafenib (RG) and β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and Hydroxypropyl-β-cyclodextrin (Hp-β-CD). Methods: Three inclusion complexes were prepared by recrystallization and solvent evaporation methods and characterized by fourier transform infrared spectroscopy (FT-IR), thermal analysis (TG), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), 1H nuclear magnetic resonance (1H-NMR), nuclear overhauser effect spectroscopy (NOESY). In vivo experiments, tumor suppression assay were made with SW620 colon cancer cell. Results: The ability of solubility and dissolution were improved after inclusion with three kinds of cyclodextrins. The regorafenib-β-cyclodextrin inclusionis proved to have the best stability. The less enhanced was regorafenib-γ-cycl-odextrin inclusion. The best dissolution of regorafenib-β-cyclodextrin inclusion complex was to bring as the tumor suppression assay, the result shows that regorafenib inclusion with β-cyclodextrin is better than regorafenib itself. Conclusion: The bioavailability of regorafenib by inclusion with cyclodextrin can enhance due to the solubility enhancement of RG, which can provide an effective method for improving solubility and dissolution of insoluble drug in clinical medication.

Characterization and stability of S (-) pantoprazole sodium hydrates
CHEN Bei,ZHANG Libo,LI Hong,TANG Guping,HU Xiurong
J Zhejiang Univ (Med Sci), 2017, 46(2): 153-159.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.06
Abstract( 26 )   HTML( 6 )     PDF(2706KB)( 31 )

Objective: To study the characteristics and stability of new S(-) pantoprazole sodium hydrates. Methods: The X-ray single crystal diffractometer (SXRD), X-ray powder diffractometer (PXRD), thermogravimetric analysis (TG) and infrared spectrometry (IR) were used to characterize S(-) pantoprazole sodium hydrates. The stability of the hydrates was evaluated by high temperature test,affecting factors test and accelerated test. Results: The crystalline water in S(-) pantoprazole sodium hydrates were very easy to lose and obtain, but crystal structure was not changed significantly. The transition from S(-) pantoprazole sodium trihydrate to S(-) pantoprazole sodium hemipentahydrate occurred at approximately 40 ℃ and reversible transitions from hemipentahydrate to trihydrate occurred at high humidity. Two hydrates had no significant difference in accelerated test. Conclusion: The crystal structure of the two hydrates are almost the same, hemipentahydrate is more stable than trihydrates at high temperature or at exposure to light(at 4500 ± 500 lx).

Synthesis, characterization and antitumor activity of 5-fluorouracil-nicotinamide cocrystal
WU Min,LIU Xingang,XUE Yu,CHEN Qi,HU Xiurong,ZHOU Jun,TANG Guping
J Zhejiang Univ (Med Sci), 2017, 46(2): 160-166.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.07
Abstract( 26 )   HTML( 2 )     PDF(7214KB)( 28 )

Objective: To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. Methods: The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. Results: According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL, respectively. Conclusion: 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.

Advances in nanoparticle-targeting tumor associated macrophages for cancer imaging and therapy
GUO Fengliang,TANG Guping,HU Qinglian
J Zhejiang Univ (Med Sci), 2017, 46(2): 167-172.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.08
Abstract( 50 )   HTML( 12 )     PDF(2632KB)( 50 )

Tumor tissues are composed of tumor cells and complicate microenvironment. Tumor associated macrophages (TAMs) as an important component in tumor microenvironment, play fundamental roles in tumor progression, metastasis and microenvironment regulation. Recently, studies have found that nanotechnology, as an emerging platform, provides unique potential for cancer imaging and therapy. With the nanotechnology, TAMs imaging presents direct evidence for cancer development, progression, and the effectiveness of cancer treatments; it also can regulate the immunosuppression of tumor microenvironment and improve therapeutic efficiency through TAMs targeted killing or phenotypic transformation. In this article, we illustrate the function of TAMs and review the latest development in nano-carriers and their applications in tumor associated macrophage targeting cancer imaging and therapy.

Expression and clinical significance of DNAJB11 in epithelial ovarian cancer
YAO Guorong,FU Yunfeng,LI Yanli,ZHOU Caiyun,LV Weiguo
J Zhejiang Univ (Med Sci), 2017, 46(2): 173-178.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.09
Abstract( 23 )   HTML( 4 )     PDF(3251KB)( 20 )

Objective: To study the expression of DNAJB11 protein in epithelial ovarian cancer tissues and its clinical significance. Methods: Immunohistochemistry was used to examine DNAJB11 expressions in 105 tissue specimens of ovarian epithelial carcinoma, 23 normal ovarian tissues, 17 tissues of benign tumor, and 13 tissues of of borderline tumor. The correlations between protein expression and clinicopathological factors were analyzed by Chi square test.The correlations between protein expression and survival were analyzed by Kaplan-Meier and Cox regression. Results: Positive expression of DNAJB11 protein was observed in 0.0% in normal ovary and benign tumor, 7.69% in borderline tumor, and 78.10% in epithelial ovarian cancer, respectively. Positive expression of DNAJB11 protein was significantly higher than the rest of the ovarian tissues and normal ovarian tissues (P<0.001).Higher expression of DNAJB11 was more prevalent in tissues from patients with advanced FIGO stages, high serum CA125, poor histological differentiation, and serous cancer. Kaplan-Meier curves revealed that higher expression of DNAJB11 was significantly associated with poor disease-free survival and overall survival.Multivariate survival analysis revealed that strong positive expression of DNAJB11 was an independent prognostic factor for disease-free survival and overall survival. Conclusion: DNAJB11 may play a role in tumorigenesis and progression of epithelial ovarian cancer.Strong positive expression of DNAJB11 was an independent prognostic factor in epithelial ovarian cancer.

Nicotinamide regulates blood glucose level and affects mitochondrial superoxide level in gestational diabetic rats
WANG Li,WANG Yu,WU Haiying
J Zhejiang Univ (Med Sci), 2017, 46(2): 179-185.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.10
Abstract( 19 )   HTML( 2 )     PDF(1980KB)( 12 )

Objective: To investigate the effects of nicotinamide (NAM) on blood glucose level and anti-oxidative enzyme activity in gestational diabetic (GDM) rats. Methods: GDM model was induced by injection of STZ (35 mg/kg) in pregnant female Sprague-Dawley rats. Nicotinamide was given to GDM rats by gavage at 50, 100 or 200 mg/kg q.d from gestational d 6 to d 20. The rats were divided into normal control group, GDM group (0 mg/kg), low-dose NAM group (50 mg/kg), middle-dose NAM group (100 mg/kg) and high-dose NAM group (200 mg/kg) with 8 animals in each group. When rats were sacrificed at d 21, the blood glucose level was measured; skeletal muscle and fetal brain samples were collected. The expression and activity of anti-oxidative enzymes, including superoxide dismutase (SOD1, SOD2), catalase (CAT) and sirtuin-3 (SIRT3) were measured by RT-PCR and Western blot. Results: Nicotinamide significantly lowered the blood glucose in GDM rats and decreased mitochondrial superoxide level in the fetal cortical neurons. SOD2 was induced in skeletal muscle by nicotinamide in GDM rats (P<0.05), while no significant change was observed in the expression of CAT (P>0.05). Nicotinamide increased SIRT3 expression (P<0.05) and decreased deacetylation of SOD2 in skeletal muscle of GDM rats (P<0.05). Conclusion: Nicotinamide can lower the blood glucose level in GDM rats, and decrease mitochondrial superoxide level, which is associated with promoting SIRT3 activity to deacetylate SOD2 and elevate SOD2 activity in GDM rats.

Establishment of mouse endometrial injury model by curettage or coagulation
WANG Yanpeng,HUANG Qiongxiao,XU Sheng,SHU Jing
J Zhejiang Univ (Med Sci), 2017, 46(2): 186-191.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.11
Abstract( 25 )   HTML( 1 )     PDF(4754KB)( 15 )

Objective: To establish mouse endometrial injury model by curettage or coagulation. Methods: Female ICR mice were randomly allocated into 2 groups: in curettage group, a blunt 20G needle was inserted in one uterine horn with 0.05 megapascals negative pressure; in coagulation group, one uterine horn was coagulated using a monopolar electric needle with 0.5 watts power. In both groups the contra-lateral uterine horn was used as control. The morphological changes and thickness of endometrium were evaluated 1 week after operation. The endometrial samples were taken on d4 of pregnancy, and the expressions of endometrial receptivity-related cytokines were examined. The number of implanted embryos on each side of uterus was calculated on d10 of pregnancy. Results: There was no difference in operation time between 2 groups. In both groups, the endometrial glands and stroma were significantly reduced, and the endometrial thickness was also significantly decreased on injury side compared to contra-lateral horn. However, local injury was more severe in coagulation group, uterine obliteration and hydrops were developed in 2 mice of coagulation group, and none in curettage group. The expressions of leukemia inhibitory factor (LIF) and oncostatin M (OSM) were significantly reduced on injured side in both groups compared to opposite side; however, the expression of LIF and OSM in curettage group was higher than that in coagulation group. The numbers of implanted embryos were decreased in both groups on injured side compared to opposite side, and fetal death was only observed in coagulation group. Conclusion: Both curettage and coagulation can make injury on mouse endometrium, impair endometrial receptivity and reduce fertility. Curettage can cause moderate injury, and coagulation may lead to more severe injury.

Effect of diammonium glycyrrhizinate and phospholipids complex oninflammatory gene expression induced by palmitic acid
LIU Yinlan,LUO Yan,YANG Wenjun,SHI Junping,ZHUANG ZhenJie
J Zhejiang Univ (Med Sci), 2017, 46(2): 192-197.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.12
Abstract( 21 )   HTML( 1 )     PDF(1674KB)( 19 )

Objective: To investigate the effect of glycyrrhizinate and phospholipids (DGPL) complex on inflammatory gene expression in cell inflammation model induced by palmitic acid (PA). Methods: Huh7 cells were divided into control, PA and PA+DGPL groups. For control group, cells were treated with BSA; for PA group, cells were incubated with 0.2 mmol/L saturated fatty acid PA, PA+DGPL group was given 20 μmol/L or 100 μmol/L DGPL in addition to 0.2 μmol/L PA. After 24 h, the expression of inflammation-related genes COX-2 and iNOS and endoplasmic reticulum (ER) stress-related gene GRP78 was determined by RT PCR. Oil red staining was conducted to observe the effect of DGLP on steatosis. Results: Compared with control group, the expression of COX-2, iNOS and GRP78 in PA group was enhanced to 6.07±0.73(P<0.05), 3.18±0.91 (P<0.01) and 3.21±1.00(P<0.05), respectively. Compared to control group, the expression of COX-2,iNOS and GRP78 in 100 μmol/L DGPL group was reduced to 2.40±0.76, 1.60±0.49 and 1.17 ±0.42 (P<0.05); and 20 μmol DGPL had similar inhibition effect on COX-2 and iNOS elevation induced by PA (P<0.01, P<0.05 respectively). In addition, DGLP enhances the steatosis of Huh7 cells as demonstrated by oil red staining. Conclusion: PA can induce the up-regulated expression of inflammation associated genes COX-2, iNOS and ER stress-associated gene GRP78 in Huh7 cells. DGPL is able to protect Huh7 cells from PA induced inflammatory gene expression and the beneficial effect may be partially due to its unsaturated phospholipid component, which may improve ER stress and enhance steatosis.

Midpalatal cortex osteotomy assisted rapid maxillary expansion for correction of maxillary transverse deficiency in young adults
WENG Luxi,SONG Xiaojia,LI Juan,LIU Pengruofeng,LIN Jun
J Zhejiang Univ (Med Sci), 2017, 46(2): 198-205.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.13
Abstract( 23 )   HTML( 3 )     PDF(6858KB)( 41 )

Objective: To evaluate the application of midpalatal cortex osteotomy assisted rapid maxillary expansion for correction of maxillary transverse deficiency in young adults. Methods: Fourteen young adult patients with maxillary transverse deficiency were treated with midpalatal cortex osteotomy assisted rapid maxillary expansion. Lateral cephalogram and cone beam CT (CBCT) were taken before and 3 months after treatment. The width of basal bone, arch of maxilla and the torque of anchorage teeth were compared before and after treatment. Results: The width of dental arch of maxilla was increased from 40.54±5.26 mm before treatment to 46.83±5.83 mm after treatment (P<0.05) and the width of basal bone was increased from 64.86±4.16 mm to 67.60±4.66 mm (P<0.05) at the plane of the maxillary first molars. Accordingly, the width of dental arch of maxilla was increased from 31.92±2.55 mm to 38.65±3.14 mm (P<0.05) and the width of basal bone was increased from 43.33±3.70 mm to 45.78±4.57 mm (P<0.05) at the plane of first premolar. And the torque of maxillary anchorage teeth were increased (P<0.05). Conclusion: Midpalatal cortex osteotomy assisted rapid maxillary expansion is an effective micro-invasive method in expansion of basal bone and arch of maxilla for young adult patients with maxillary transverse deficiency.

Report of two cases of primary mediastinal tuberculosis
LUO Jiayou,HUA Feng,WANG Bin,CUI Enhai
J Zhejiang Univ (Med Sci), 2017, 46(2): 206-210.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.14
Abstract( 21 )   HTML( 5 )     PDF(5876KB)( 28 )

Two cases of primary mediastinal lymphonode tuberculosis involved right bronchus were summarized in the report. Major clinical symptoms included cough and bloody sputum. Chest enhanced CT scan showed mediastinal lymph node enlargement with ring-shaped enhancement. Bronchoscopy suggested neoplasm in right bronchus. Diagnosis of tuberculosis was confirmed by histopathology in samples from lymph node puncture and brochoscopic biopsy. The clinical symptoms and medical imaging of patients were improved after transbrochoscopic interventional therapy and systemic chemotherapy.

Advances in application of adoptive T-cell therapy for cancer patients
ZOU Jixia,ZHANG Chengyan,WANG Pingli
J Zhejiang Univ (Med Sci), 2017, 46(2): 211-217.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.15
Abstract( 28 )   HTML( 10 )     PDF(493KB)( 47 )

Adoptive T-cell therapy is the administration of tumor cytotoxic T-cells derived from either patient himself or donors, which were induced or genetically engineered and expanded in vitro, and then injected into patients. Several strategies for adoptive T-cell therapy have been developed since last 30 years. From lymphokine-activated killer cells, tumor-infiltrating lymphocytes, cytokine-induced killer cells, to gene-modified T-cells and tumor associated antigen (TAA)-specific cytotoxic T-cells, the adoptive T-cell therapy has been moving forward to more precise tumor targeting and more effective in elimination of cancer cells. This article reviewed the advances of therapeutic approaches of adoptive T-cell therapy for cancer patients.

Progress on mechanisms for pathogensto evade NOD-like receptor and Toll-like receptor signaling pathways
HE Yujie,PAN Jianping
J Zhejiang Univ (Med Sci), 2017, 46(2): 218-224.   https://doi.org/10.3785/j.issn.1008-9292.2017.04.16
Abstract( 32 )   HTML( 11 )     PDF(481KB)( 37 )

The innate immune system provides a first line of defense against invading pathogens, in which the pattern recognition receptors (PRR) recognize pathogen-associated molecular patterns (PAMP) and initiate the downstream signaling pathways to eliminate the encountered pathogens. There are two main classes of such signaling pathways: NOD-like receptor (NLR) signaling pathway and Toll-like receptor (TLR) signaling pathway. The microbial pathogens under selective pressure have evolved numerous mechanisms to avoid and/or manipulate the NLR and TLR signal transduction for survival and replication. To evade the NLR signaling pathway, pathogens interfere and/or inhibit inflammasome activation in innate immune cells by producing virulence factors or reducing PAMPs expression. The mechanisms for pathogens to evade TLR signaling pathway include: inhibition of mitogen activated protein kinases (MAPKs) cascade reaction, inhibition of NF-КB activation, and interference of down-stream signal transduction by producing Toll/interleukin-1 receptor (TIR)-containing proteins which bind directly with TLRs or adaptor proteins in the signaling pathway.

16 articles