Replication-Dependent Unhooking of DNA Interstrand Cross-Links by the NEIL3 Glycosylase.

During eukaryotic DNA interstrand cross-link (ICL) repair, cross-links are resolved ("unhooked") by nucleolytic incisions surrounding the lesion. In vertebrates, ICL repair is triggered when replication forks collide with the lesion, leading to FANCI-FANCD2-dependent unhooking and formation of a double-strand break (DSB) intermediate. Using Xenopus egg extracts, we describe here a replication-coupled ICL repair pathway that does not require incisions or FANCI-FANCD2. Instead, the ICL is unhooked when one of the two N-glycosyl bonds forming the cross-link is cleaved by the DNA glycosylase NEIL3. Cleavage by NEIL3 is the primary unhooking mechanism for psoralen and abasic site ICLs. When N-glycosyl bond cleavage is prevented, unhooking occurs via FANCI-FANCD2-dependent incisions. In summary, we identify an incision-independent unhooking mechanism that avoids DSB formation and represents the preferred pathway of ICL repair in a vertebrate cell-free system.

Evaluation of the impact of repeated intravenous phage doses on mammalian host-phage interactions.

Phage therapy has shown great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.IMPORTANCEPhage therapy has demonstrated potential in addressing multidrug-resistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes.

Astrocytic expression of Yes-associated protein (YAP) regulates retinal neovascularization in a mouse model of oxygen-induced retinopathy.

Pathological neovascularization is the hallmark of many vascular oculopathies. There is still a great deal of uncertainty surrounding retinal neovascularization research. A working hypothesis that astrocytic Yes-associated protein (YAP) act as a key factor in retinal neovascularization was proposed. And our study was conducted to verified this hypothesis. In vivo, we successfully generated mice deficient in YAP in astrocytes (YAPf/f GFAP-Cre mice) and set up oxygen-induced retinopathy (OIR) model. Pathological neovascularization was evaluated by immunofluorescence staining and western blotting. In vitro, cultured retinal astrocytes were transfected with YAP siRNA. Enzyme-linked immunosorbent assay (ELISA) and western blot were used to determine the proteins in the supernatants and cells. The results showed that YAP was upregulated and activated in the OIR mice retinas. Conditional ablation of YAP aggravated pathological neovascularization, along with the upregulation of vascular endothelial growth factor A (VEGF-A) and monocyte chemoattractant protein-1 (MCP-1). Studies in vitro confirmed that the knockdown of YAP in astrocytes lead to increases in VEGF-A and MCP-1 levels, thus enhancing pro-angiogenic capability of YAP-deficit astrocytes. In conclusion, astrocytic YAP alleviates retinal pathological angiogenesis by inhibiting the over-activation of astrocytes, which suppresses excessive VEGF-A production and neuroinflammation.

Epidemiology and genotypes analysis of human papillomavirus infection in Beijing, China.

BACKGROUND: This study aimed to investigate the epidemiology of high-risk human papillomavirus (HPV) in the female population in Beijing, China, and identify the relationship between HPV genotypes and host factors. METHODS: HPV testing was performed on women aged 15-89 (mean age 38.0 ± 10.9 years) from Beijing in 2020. High-risk HPV genotyping real-time polymerase chain reaction was used to determine HPV genotypes. The overall prevalence, age-specific prevalence, genotype distribution, and the correlation between HPV genotypes and cervical cytology were analyzed. RESULTS: Among the 25,344 study participants, the single and double infection rates were 18.8% (4,777/25,344) and 4.2% (1,072/25,344), respectively. A total of 6,119 HPV-positive individuals were found to have 91.6% negative results for intraepithelial lesion or malignancy (NILM), 5.8% atypical squamous cells of undetermined significance (ASC-US), 0.9% low-grade squamous intraepithelial lesion (LSIL), and 1.7% high-grade squamous intraepithelial lesion (HSIL). In single HPV infections, the HPV16 genotype was highly associated with cervical cytology severity (χ2 trend = 172.487, P < 0.001). Additionally, HPV infection rates increased gradually with age, and statistical differences were observed across age groups (χ2 = 180.575; P < 0.001). High-risk HPV genotypes were highly prevalent in women below 25 years of age and those aged 55-59 years. Cluster analysis revealed that the 13 HPV genotypes could be roughly divided into two groups in a single infection; however, patterns of infection consistent with biological characteristics were not observed. CONCLUSION: High-risk HPV was found in 24.1% of outpatients, with HPV52, HPV58, HPV16, HPV39, and HPV51 being the most common high-risk genotypes. Single high-risk HPV infection was predominant. HPV16, HPV39, HPV51, and HPV52 were associated with cervical lesion progression. HPV16 infection was especially worrying since it aggravates cervical lesions. Because the infection rates of the 13 HPV genotypes differed by age, the peak HPV infection rate should not guide vaccination, screening, and prevention programs. Instead, these initiatives should be tailored based on the regional HPV distribution characteristics. Moreover, it was determined that Beijing's populace needed to receive treatment for HPV39 infection.

Time trends and regional variation in utilization of antidiabetic medicines in China, 2015-2022.

AIM: To assess the use of non-insulin antidiabetic medicines in China. MATERIALS AND METHODS: We analysed the national procurement data for 29 non-insulin antidiabetic medicines from nine subgroups in China from 2015 to 2022. We estimated the number of defined daily doses (DDDs) procured per year in seven regions of China for nine subgroups and adjusted the data by the number of patients with diabetes. For each subgroup, the regional ratio was calculated by comparing the procurement per patient in each region with the procurement nationwide. The regional disparity was the difference between the highest and lowest regional ratios. We compared the medication patterns across regions. RESULTS: Nationally, between 2015 and 2022, the number of DDDs per patient increased from 14.45 to 47.37. The two most commonly used categories were sulphonylurea and biguanides, which increased from 7.04 to 15.39 (119%) and 3.28 to 11.11 (239%) DDDs per patient, respectively. The procurement of new drugs (dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists) increased quickly and had >5000% relative changes. Particularly for sodium-glucose cotransporter type 2 inhibitors, it increased from 0.08 to 5.03 DDDs (6662%). The southwest region had the highest relative change (319%), while the southern region had the lowest (118%). Biguanide and thiazolidinediones had the lowest (1.19) and highest level (2.21) of regional disparity in 2022, respectively. CONCLUSION: The procurement of non-insulin antidiabetic medicines in China has increased a lot from 2015 to 2022. In terms of DDDs per patient, sulphonylurea ranked first, followed by metformin. The procurement of new drugs increased greatly. A large regional disparity existed in medicine usage and patterns.

Deficient deposition of new myelin impairs adult optic nerve function in a murine model of diabetes.

Visual impairment in diabetes is a growing public health concern. Apart from the well-defined diabetic retinopathy, disturbed optic nerve function, which is dependent on the myelin sheath, has recently been recognized as an early feature of visual impairment in diabetes. However, the underlying cellular mechanisms remain unclear. Using a streptozotocin-induced diabetic mouse model, we observed a myelin deficiency along with a disturbed composition of oligodendroglial lineage cells in diabetic optic nerve. We found that new myelin deposition, a continuous process that lasts throughout adulthood, was diminished during pathogenesis. Genetically dampening newly generated myelin by conditionally deleting olig2 in oligodendrocyte precursor cells within this short time window extensively delayed the signal transmission of the adult optic nerve. In addition, clemastine, an antimuscarinic compound that enhances myelination, significantly restored oligodendroglia, and promoted the functional recovery of the optic nerve in diabetic mice. Together, our results point to the role of new myelin deposition in optic neuropathy under diabetic insult and provide a promising therapeutic target for restoring visual function.

LcERF2 modulates cell wall metabolism by directly targeting a UDP-glucose-4-epimerase gene to regulate pedicel development and fruit abscission of litchi.

Elucidating the biochemical and molecular basis of premature abscission in fruit crops should help develop strategies to enhance fruit set and yield. Here, we report that LcERF2 contributes to differential abscission rates and responses to ethylene in Litchi chinensis (litchi). Reduced LcERF2 expression in litchi was observed to reduce fruit abscission, concurrent with enhanced pedicel growth and increased levels of hexoses, particularly galactose, as well as pectin abundance in the cell wall. Ecoptic expression of LcERF2 in Arabidopsis thaliana caused enhanced petal abscission, together with retarded plant growth and reduced pedicel galactose and pectin contents. Transcriptome analysis indicated that LcERF2 modulates the expression of genes involved in cell wall modification. Yeast one-hybrid, dual-luciferase reporter and electrophoretic mobility shift assays all demonstrated that a UDP-glucose-4-epimerase gene (LcUGE) was the direct downstream target of LcERF2. This result was further supported by a significant reduction in the expression of the A. thaliana homolog AtUGE2-4 in response to LcERF2 overexpression. Significantly reduced pedicel diameter and enhanced litchi fruit abscission were observed in response to LcUGE silencing. We conclude that LcERF2 mediates fruit abscission by orchestrating cell wall metabolism, and thus pedicel growth, in part by repressing the expression of LcUGE.

Procurement of medicines to treat cancer, 2015-2020, China.

Objective: To assess the procurement of medicines to treat cancer in China. Methods: We conducted a descriptive analysis of the national procurement data for 20 anti-cancer medicines in China from 2015 to 2020. We estimated the number of defined daily doses procured per year in three areas of China for essential medicines and medicines for targeted therapies. We adjusted the data by the number of cancer patients in each region for each year. Findings: Between 2015 and 2020, the number of defined daily doses per patient decreased from 40.87 to 35.86 (-12.27%) for essential medicines, while the number increased from 0.85 to 12.52 (1381.15%) for target medicines. The procurement of three out of 10 essential medicines decreased, whereas procurement of all 10 targeted medicines increased. In 2020, the eastern area procured the most essential medicines (44.98 doses per patient) and targeted medicines (16.55 doses per patient), but had the smallest relative change in procurement of both essential medicines (-22.76%) and targeted medicines (978.16%). The central area had the largest increase in procurement of both essential medicines (9.64%; from 25.25 to 27.68 doses per patient) and targeted medicines (4587.81%; from 0.23 to 10.64 doses per patient). Conclusion: Procurement of anti-cancer medicines varied across regions. Specific policies are needed at the national level to eliminate inequalities in access to these medicines. Two issues that need attention are the lower access to many essential anti-cancer medicines in some provinces and the increase in use of targeted medicines.

Rapid, Simultaneous, and Automatic Determination of Lead and Cadmium in Cereals with a New High Performance Composite Hollow Cathode Lamp Coupled to Graphite Furnace Atomic Absorption Spectrometry.

A simple, rapid, sensitive, accurate, and automatic graphite furnace atomic absorption spectrometry (GFAAS) method for detecting Cd and Pb in cereals is presented. This method enables the simultaneous determination of Cd and Pb in cereals with a pre-treatment method of diluted acid extraction and a high-performance lead-cadmium composite hollow-cathode lamp (LCC-HCL), and it realizes automatic determination from sample weighing to result output through an automatic diluted acid extraction system. Under the optimization, Pb and Cd in cereals were simultaneously and automatically detected in up to 240 measurements in 8 h. The LOD and LOQ of this method were 0.012 and 0.040 mg·kg-1 for Pb, and 0.0014 and 0.0047 mg·kg-1 for Cd, respectively. The results of the four certified reference materials were satisfied; there was no significant difference compared with the ICP-MS method according to a t-test, and the RSDs were less than 5% for Cd and Pb. The recoveries of naturally contaminated samples compared with the ICP-MS method were favorable, with 80-110% in eight laboratories. The developed method is rapid, low-cost, and highly automated and may be a good choice for grain quality discrimination and rapid analysis of Cd and Pb in different institutions.

Plant Dehydrins: Expression, Regulatory Networks, and Protective Roles in Plants Challenged by Abiotic Stress.

Dehydrins, also known as Group II late embryogenesis abundant (LEA) proteins, are classic intrinsically disordered proteins, which have high hydrophilicity. A wide range of hostile environmental conditions including low temperature, drought, and high salinity stimulate dehydrin expression. Numerous studies have furnished evidence for the protective role played by dehydrins in plants exposed to abiotic stress. Furthermore, dehydrins play important roles in seed maturation and plant stress tolerance. Hence, dehydrins might also protect plasma membranes and proteins and stabilize DNA conformations. In the present review, we discuss the regulatory networks of dehydrin gene expression including the abscisic acid (ABA), mitogen-activated protein (MAP) kinase cascade, and Ca2+ signaling pathways. Crosstalk among these molecules and pathways may form a complex, diverse regulatory network, which may be implicated in regulating the same dehydrin.

Evaluation of Varicella-zoster virus-specific cell-mediated immunity by interferon-γ Enzyme-Linked Immunosorbent Assay in adults ≥50 years of age administered a herpes zoster vaccine.

Varicella-zoster virus (VZV)-specific cell-mediated immunity (CMI) is critical for preventing and controlling the onset of herpes zoster (HZ). To assess VZV CMI, an interferon-γ (IFN-γ) enzyme-linked immunosorbent assay (ELISA) was validated by examining the influence of VZV-specific antigen content, incubation time, and interval from whole blood collection on the assay. In phase II clinical trial, VZV-specific CMI in adults ≥50 years of age administered an HZ vaccine were evaluated by IFN-γ ELISA, as determined by measuring IFN-γ production in the whole blood in response to stimulation with ultraviolet light-inactivated VZV. The VZV-specific IFN-γ levels varied among individuals from prevaccination (baseline) to 6 weeks postvaccination. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The HZ vaccine elicited a significant increase in the VZV-specific CMI response as measured by ELISA; the geometric mean fold-rises from baseline to 6 weeks postvaccination were 3.50, 4.22, and 5.24 in the 4.3, 4.7, and 4.9 log plaque-forming unit vaccine groups, respectively, which was significantly higher than in the placebo group (P < 0.05). These results indicate that vaccination enhances the VZV-specific CMI responses in subjects; IFN-γ ELISA is an effective method for evaluating the CMI response and may be useful for identifying individuals at a high risk of HZ infection.

A group of SUVH methyl-DNA binding proteins regulate expression of the DNA demethylase ROS1 in Arabidopsis.

DNA methylation is typically regarded as a repressive epigenetic marker for gene expression. Genome-wide DNA methylation patterns in plants are dynamically regulated by the opposing activities of DNA methylation and demethylation reactions. In Arabidopsis, a DNA methylation monitoring sequence (MEMS) in the promoter of the DNA demethylase gene ROS1 functions as a methylstat that senses these opposing activities and regulates genome DNA methylation levels by adjusting ROS1 expression. How DNA methylation in the MEMS region promotes ROS1 expression is not known. Here, we show that several Su(var)3-9 homologs (SUVHs) can sense DNA methylation levels at the MEMS region and function redundantly to promote ROS1 expression. The SUVHs bind to the MEMS region, and the extent of binding is correlated with the methylation level of the MEMS. Mutations in the SUVHs lead to decreased ROS1 expression, causing DNA hypermethylation at more than 1,000 genomic regions. Thus, the SUVHs function to mediate the activation of gene transcription by DNA methylation.

Biosynthesis of quebrachitol, a transportable photosynthate, in Litchi chinensis.

Although methylated cyclitols constitute a major proportion of the carbohydrates in many plant species, their physiological roles and biosynthetic pathway are largely unknown. Quebrachitol (2-O-methyl-chiro-inositol) is one of the major methylated cyclitols in some plant species. In litchi, quebrachitol represents approximately 50% of soluble sugars in mature leaves and 40% of the total sugars in phloem exudate. In the present study, we identified bornesitol as a transient methylated intermediate of quebrachitol and measured the concentrations of methyl-inositols in different tissues and in tissues subjected to different treatments. 14CO2 feeding and phloem exudate experiments demonstrated that quebrachitol is one of the transportable photosynthates. In contrast to other plant species, the biosynthesis of quebrachitol in litchi is not associated with osmotic stress. High quebrachitol concentrations in tissues of the woody plant litchi might represent a unique carbon metabolic strategy that maintains osmolality under reduced-sucrose conditions. The presence of bornesitol but not ononitol in the leaves indicates a different biosynthetic pathway with pinitol. The biosynthesis of quebrachitol involves the methylation of myo-inositol and the subsequent epimerization of bornesitol. An inositol methyltransferase gene (LcIMT1) responsible for bornesitol biosynthesis was isolated and characterized for the first time, and the biosynthesis pathways of methyl-inositols are discussed.

Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages.

Although M2-like tumor-associated macrophages (TAMs) have been considered as a vital therapeutic target in cancer therapy due to their role in promoting tumor progression and metastasis, very few compounds have been identified to inhibit M2-like polarization of TAMs. Here, we showed that Imatinib significantly prevented macrophage M2-like polarization induced by IL-13 or IL-4 in vitro, as illustrated by reduced expression of cell surface marker CD206 and M2-like genes, including Arg1, Mgl2, Mrc1, CDH1, and CCL2. Further, the migration of lung cancer cells promoted by the conditioned medium from M2-like macrophages could be restrained by Imatinib. Mechanistically, Imatinib inhibited STAT6 phosphorylation and nuclear translocation, resulting in the macrophage M2-like polarization arrest. Furthermore, Imatinib reduced the number of metastasis of Lewis lung cancer without affecting tumor growth. Both in tumor and lung tissues, the percentage of M2-like macrophages decreased after the administration of Imatinib for one week. Taken together, these data suggest that Imatinib is able to inhibit macrophage M2-like polarization, which plays a vital role in Imatinib suppressed metastasis of Lewis lung cancer.

Macrophage Polarization: Anti-Cancer Strategies to Target Tumor-Associated Macrophage in Breast Cancer.

Tumor-associated macrophages (TAMs) are the most abundant inflammatory cells and orchestrate different stages of breast cancer development. TAMs participate in the tumor angiogenesis, matrix remodeling, invasion, immunosuppression, metastasis, and chemoresistance in breast cancer. Several clinical studies indicate the association between the high influx of TAMs in tumor with poor prognosis in hepatocellular, ovarian, cervical, and breast cancer. Previously developed hypotheses have proposed that TAMs participate in antitumor responses of the body, while recently many clinical and experimental studies have revealed that TAMs in tumor microenvironment predominantly resemble with M2-like polarized macrophages and produce a high amount of anti-inflammatory factors which are directly responsible for the development of tumor. Various studies have shown that TAMs in tumor either enhance or antagonize the anti-tumor efficacy of cytotoxic agents, antibodies-targeting cancer cells, and therapeutic agents depending on the nature of treatment. Thereby, multiple roles of TAMs suggests that it is very important to develop novel therapeutic strategies to target TAMs in breast tumor. In this review, we have discussed the functional role of TAMs in breast cancer and summarized available recent advances potential therapeutic strategies that effectively target to TAMs cells. J. Cell. Biochem. 118: 2484-2501, 2017. © 2017 Wiley Periodicals, Inc.

Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis lung cancer by targeting the STAT6 signaling pathway.

M2-like polarized tumor-associated macrophages (TAMs) play a pivotal role in promoting cancer cell growth, invasion, metastasis and angiogenesis. The identification of M2-like TAMs during tumor progression is an attractive approach for cancer therapy. In this study, we investigated the relevance of macrophage polarization and the antitumor effect of gefitinib in Lewis Lung cancer (LLC) in vitro and in vivo. Gefitinib at a concentration below 2.5 µmol/L did not cause significant growth inhibition on LLC and RAW 264.7 cell lines and bone marrow-derived macrophage (BMDMs). However, a small concentration of gefitinib (0.62 µmol/L) significantly inhibited IL-13-induced M2-like polarization of macrophages, evidenced by the decreased expression of the M2 surface markers CD206 and CD163, down-regulation of specific M2-marker genes (Mrc1, Ym1, Fizz1, Arg1, IL-10 and CCL2) as well as inhibition of M2-like macrophage-mediated invasion and migration of LLC cells. In RAW 264.7 cells, gefitinib inhibits IL-13-induced phosphorylation of STAT6, which was a crucial signaling pathway in macrophage M2-like polarization. In LLC mice metastasis model, oral administration of gefitinib (75 mg·kg-1·d-1, for 21 d) significantly reduced the number of lung metastasis nodules, down-regulated the expression of M2 marker genes and the percentages CD206+ and CD68+ macrophages in tumor tissues. These results demonstrated that gefitinib effectively inhibits M2-like polarization both in vitro and in vivo, revealing a novel potential mechanism for the chemopreventative effect of gefitinib.

Functional characterization of a glucosyltransferase gene, LcUFGT1, involved in the formation of cyanidin glucoside in the pericarp of Litchi chinensis.

Anthocyanins generate the red color in the pericarp of Litchi chinensis. UDP-glucose: flavonoid 3-O-glycosyltransferase (UFGT, EC. 2.4.1.91) stabilizes anthocyanidin by attaching sugar moieties to the anthocyanin aglycone. In this study, the function of an UFGT gene involved in the biosynthesis of anthocyanin was verified through heterologous expression and virus-induced gene silencing assays. A strong positive correlation between UFGT activity and anthocyanin accumulation capacity was observed in the pericarp of 15 cultivars. Four putative flavonoid 3-O-glycosyltransferase-like genes, designated as LcUFGT1 to LcUFGT4, were identified in the pericarp of litchi. Among the four UFGT gene members, only LcUFGT1 can use cyanidin as its substrate. The expression of LcUFGT1 was parallel with developmental anthocyanin accumulation, and the heterologously expressed protein of LcUFGT1 displayed catalytic activities in the formation of anthocyanin. The LcUFGT1 over-expression tobacco had darker petals and pigmented filaments and calyxes resulting from higher anthocyanin accumulations compared with non-transformed tobacco. In the pericarp with LcUFGT1 suppressed by virus-induced gene silencing, pigmentation was retarded, which was well correlated with the reduced-LcUFGT1 transcriptional activity. These results suggested that the glycosylation-related gene LcUFGT1 plays a critical role in red color formation in the pericarp of litchi.

[Advances in study of macrophages in chemotherapy resistance of cancer].

As extremely important inflammatory cells in the tumor microenvironment, tumor-associated macrophages (TAMs) can secrete a variety of chemokines and cytokines, which play an important role in the occurrence of tumor growth and metastasis. Recent years, increasing studies have shown that macrophages are associated with tumor chemotherapy sensitivity. The chemical substances produced by macrophages affect the efficacy of chemotherapeutic agents. In addition, some chemotherapeutic agents have an effect on the recruitment and bioactivity of macrophages in the tumor issue, which influences the anti-tumor efficacy of chemotherapy drugs. In this review, we summarize the roles of macrophages in the chemotherapy resistance, including the regulatory mechanism and the strategy of targeting macrophages.

[Transcatheter delivery of recombinant adenovirus vector containing exogenous aquaporin gene in treatment of Sjögren's syndrome].

Sjögren's syndrome is a kind of autoimmune disease, whose main clinical symptoms are dry mouth, dry eye and chronic parotid glandular inflammation. The conservative treatments include artificial tears or saliva,oral administration of corticosteroids,and immunosuppressantsl with limited effectiveness. Along with the development of molecular biology, vast attentions are being paid to researches on gene therapy for Sjögren's syndrome, hopefully to bring gospel to patients with Sjögren's syndrome. This article reviews the recent research progresses on transcatheter delivery of recombinant adenovirus vector with aquaporin gene in experimental treatment of Sjögren's syndrome.

[Combination of lapatinib with chlorogenic acid inhibits breast cancer metastasis by suppressing macrophage M2 polarization].

OBJECTIVE: To determine the effect of the combination of lapatinib with chlorogenic acid on metastasis of breast cancer in mouse model. METHODS: The classical macrophage M2 polarization model induced by interlukin13in vitro was adopted in the study. Flow cytometric analysis was performed to detect the expression of M2 marker CD206. The transcription of M2-associated genes was measured by RT-PCR. HE staining was used to analyze the metastatic nodes of breast cancer in lungs of MMTV-PyVT mice. Immunostaining analysis was used to detect the expression of related proteins in breast cancer. RESULTS: The combination of lapatinib and chlorogenic acid inhibited the expression of CD206 induced by IL-13[(42.17%±2.59%) vs (61.15%±7.58%), P<0.05]. The combination more markedly suppressed expression of M2-associated gene Ym1 than lapatinib alone[(0.9±0.1) vs (1.8±0.0), P<0.05]. The combination of lapatinib and chlorogenic acid significantly reduced metastatic nodes in lung[P<0.05], and also significantly decreased the percentage of CD206(+) cells in breast cancer compared to controls[(6.08%±2.60%) vs(29.04%±5.86%), P<0.05]. CONCLUSION: The combination of lapatinib and chlorogenic acid can effectively inhibit macrophage M2 polarization and metastasis of breast cancer.