SIGIRR suppresses hepatitis B virus X protein-induced chronic inflammation in hepatocytes.

Although antiviral drugs can effectively inhibit hepatitis B virus (HBV) replication, the maintenance of chronic inflammation in the liver is still considered to be an important cause for the progression of HBV-related liver disease to liver fibrosis and advanced liver disease. As an endogenous inhibitory receptor of IL-1R and TLR signaling pathways, single immunoglobulin interleukin-1-related receptor (SIGIRR) has been proven to reduce inflammation in tissues to maintain system homeostasis. However, the relationship between SIGIRR expression and HBV replication and inflammatory pathway activation in hepatocytes remains unclear. In this study, hepatitis B virus X protein (HBx) upregulated MyD88 in liver cells, promoting NF-κB signaling and inflammatory factor production with LPS treatment, and the cell supernatant accelerated the activation and collagen secretion of hepatic stellate cells. However, SIGIRR overexpression suppressed HBx-mediated MyD88/NF-κB inflammatory signaling activation and inflammatory cytokine production induced by LPS in hepatocytes and HBV replication hepatocytes. Although we did not find any effect of SIGIRR on HBV replication in vitro, this study investigated the role of SIGIRR in blocking the proinflammatory function of HBx, which may provide a new idea for the treatment of chronic hepatitis B.

Two host-guest grown ether supramolecules show switchable phase transition, dielectric and second-harmonic generation effect.

The excellent properties of host-guest crown ether inclusions in phase transition, dielectric and second-order nonlinear optical properties have attracted much attention. In this paper, we successfully designed and prepared two novel host-guest crown ether supramolecules [(DFBA)(15-crown-5)]X (X = ClO4-, 1; ReO4-, 2) by reactions of 2,6-difluorobenzylamine (DFBA) with 1,4,10,13-pentaoxacyclopentadecane (15-crown-5) in HClO4, or HReO4 aqueous solution. By the introduction of difluoro-substituted benzylamine as a guest cation, the phase transition temperatures are greatly increased to 377 K for 1 and 391 K for 2. More importantly, the space group of 1 has changed from centrosymmetric (CS) P2/c to the non-centrosymmetric (NCS) Pca21 in 2 when substituting perchlorate (ClO4-) with the larger and heavier perrhenate (ReO4-), which leads to 2 showing a switchable and stable second-harmonic generation (SHG) effect. According to the principle of momentum matching between a cation and anion, the perrhenate group increases the energy barrier of the molecular thermal motion, which not only significantly increases the phase transition temperature of 2 but also causes it to be frozen and crystallized in a NCS space group at room temperature. This research demonstrates that a polar molecule can adjust the suitability of anions and cations inside the crystal by practical chemical means.

Contribution of upregulated aminoacyl-tRNA biosynthesis to metabolic dysregulation in gastric cancer.

BACKGROUND AND AIM: Metabolic reprogramming is characterized by dysregulated levels of metabolites and metabolic enzymes. Integrated metabolomic and transcriptomic data analysis can help to elucidate changes in the levels of metabolites and metabolic enzymes, screen the core metabolic pathways, and develop novel therapeutic strategies for cancer. METHODS: Here, the metabolome of gastric cancer tissues was determined using liquid chromatography-mass spectrometry. The transcriptome data from The Cancer Genome Atlas dataset were integrated with the liquid chromatography-mass spectrometry data to identify the common dysregulated gastric cancer-specific metabolic pathways. Additionally, the protein expression and clinical significance of key metabolic enzymes were examined using a gastric cancer tissue array. RESULTS: Metabolomic analysis of 16 gastric cancer tissues revealed that among the 15 dysregulated metabolomic pathways, the aminoacyl-tRNA biosynthesis pathway in the gastric tissues was markedly upregulated relative to that in the adjacent noncancerous tissues, which was consistent with the results of transcriptome analysis. Bioinformatic analysis revealed that among the key regulators in the aminoacyl-tRNA biosynthesis pathway, the expression levels of threonyl-tRNA synthetase (TARS) and phenylalanyl-tRNA synthetase (FARSB) were correlated with tumor grade and poor survival, respectively. Additionally, gastric tissue array data analysis indicated that TARS and FARSB were upregulated in gastric cancer tissues and were correlated with poor prognosis and tumor metastasis. CONCLUSIONS: This study demonstrated that the aminoacyl-tRNA biosynthesis pathway is upregulated in gastric cancer and both TARS and FARSB play key roles in the progression of gastric cancer. Additionally, a novel therapeutic strategy for gastric cancer was proposed that involves targeting the aminoacyl-tRNA biosynthesis pathway.

The role of non-coding RNA on macrophage modification in tuberculosis infection.

Tuberculosis (TB), a serious disease caused by Mycobacterium tuberculosis (Mtb), remains the world's top infectious killer. It is well-established that TB can circumvent the host's immune response for long-term survival. Macrophages serve as the major host cells for TB growth and persistence and their altered functions are critical for the response of the host defense against TB exposure (elimination, latency, reactivation, and bacillary dissemination). Noncoding RNAs are crucial posttranscriptional regulators of macrophage discrimination. Therefore, this review highlights the regulatory mechanism underlying the relationship between noncoding RNAs and macrophages in TB infection, which may facilitate the identification of potential therapeutic targets and effective diagnosis biomarkers for TB disease.

Efficacy of Fe3O4@polydopamine nanoparticle-labeled human umbilical cord Wharton's jelly-derived mesenchymal stem cells in the treatment of streptozotocin-induced diabetes in rats.

Diabetes mellitus (DM) is characterized by the irreversible destruction of insulin-secreting pancreatic ß-islet cells and requires life-long exogenous insulin therapy. Umbilical cord Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to improve islet function in animal models of diabetes. However, inadequate MSC homing to injured sites has limited their efficacy. Since efficient cell therapy heavily relies on appropriate homing to target tissues, increasing the specificity to the target organ and the extent of homing of the injected WJ-MSCs is paramount to successful clinical outcomes. Therefore, in this study, we synthesized Fe3O4@polydopamine nanoparticle (NP)-labeled MSCs and evaluated their therapeutic efficacy in a clinically relevant rat model of streptozotocin-induced diabetes using an external magnetic field. We found that NPs were successfully incorporated into WJ-MSCs and did not negatively affect stem cell properties. Magnetic targeting of WJ-MSCs contributed to long-term cell retention in pancreatic tissue and improved the islet function of diabetic rats, compared to injection of WJ-MSC alone. In addition, anti-inflammatory effects and the anti-apoptotic capacity of WJ-MSCs appeared to play a major role in the functional and structural recovery of the pancreas. Thus, therapy relying on the magnetic targeting of WJ-MSCs may serve as an effective approach for DM treatment.

Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes.

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Anti-Inflammatory Effects of Magnetically Targeted Mesenchymal Stem Cells on Laser-Induced Skin Injuries in Rats.

INTRODUCTION: Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. METHODS: MSCs were labeled with magnetic Fe3O4 nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. RESULTS: Fe3O4 NP application did not adversely affect MSC characteristics. Moreover, Fe3O4 NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. CONCLUSION: This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries.

Germline BRCA2 Truncating Mutation in Familial Esophageal Squamous Cell Carcinoma: A Case Controlled Study in China.

BACKGROUND Germline mutations of BRCA2 have been reported in various malignancies. We investigated BRCA2 germline mutations in familial clusters with esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS We screened the DNA of familial ESCC patients for BRCA2 germline mutations with whole gene sequencing. Multiple BRCA2 mutations including one novel splice variant, c.426-2A>G were identified. Other family members, sporadic ESCC patients, and controls were also assessed for the novel mutation. RESULTS The mutation c.426-2A>G was found in 2 affected ESCC sisters and 7 other family members. The splice variant mutation results in exon 5 skipping with a frame shift leading to a premature stop codon in exon 6 and truncation. Novel mutation tracking ruled out single nucleotide polymorphism (SNP) in 100 chromosomes of healthy individuals. CONCLUSIONS BRCA2 germline mutation in ESCC patients may play a role in genetic susceptibility to familial ESCC. Genetic analysis of BRCA2 in patients with familial ESCC could provide opportunities for targeted therapies.

In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for tissue regeneration and repair. However, efficient targeted delivery to specific tissues remains an open challenge. Here, we non-invasively monitored the migration of MSCs labeled with Fe3O4@polydopamine nanoparticles (Fe3O4@PDA NPs) toward laser burn injury sites in a living rat model and evaluated the effects of the labeled MSCs at the injury site. The Fe3O4@PDA NPs could be effectively incorporated into the MSCs without any negative effects on stem cell properties. Furthermore, they enhanced the migration ability of the MSCs by up-regulating the expression level of C-X-C chemokine receptor type 4 (CXCR4). They also increased the secretion of some cytokines and the expression of healing-related genes in comparison with unlabeled MSCs. Labeled MSCs were intravenously administered into injured rats, and live imaging was performed to monitor MSC migration. Fluorescent signals of the labeled MSCs appeared at burn injury lesions 1 day after injection and then gradually increased up to 7 days. After 7 days, the group injected with the labeled MSCs showed less inflammation compared with those injected with the unlabeled MSCs. Additionally, the labeled MSC group showed increased cytokines and reduced pro-inflammatory factors compared with the unlabeled MSC group. The Fe3O4@PDA NPs enhanced stromal cell-derived factor-1/CXCR4-mediated MSC migration in vivo. Thus, we demonstrated the safety, feasibility, and potential efficacy of using the Fe3O4@PDA NPs for optimizing MSC-based therapeutic strategies for burn wound healing.

Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites.

BACKGROUND: Developing new methods to deliver cells to the injured tissue is a critical factor in translating cell therapeutics research into clinical use; therefore, there is a need for improved cell homing capabilities. MATERIALS AND METHODS: In this study, we demonstrated the effects of labeling rat bone marrow-derived mesenchymal stem cells (MSCs) with fabricated polydopamine (PDA)-capped Fe3O4 (Fe3O4@PDA) superparticles employing preassembled Fe3O4 nanoparticles as the cores. RESULTS: We found that the Fe3O4@PDA composite superparticles exhibited no adverse effects on MSC characteristics. Moreover, iron oxide nanoparticles increased the number of MSCs in the S-phase, their proliferation index and migration ability, and their secretion of vascular endothelial growth factor relative to unlabeled MSCs. Interestingly, nanoparticles not only promoted the expression of C-X-C chemokine receptor 4 but also increased the expression of the migration-related proteins c-Met and C-C motif chemokine receptor 1, which has not been reported previously. Furthermore, the MSC-loaded nanoparticles exhibited improved homing and anti-inflammatory abilities in the absence of external magnetic fields in vivo. CONCLUSION: These results indicated that iron oxide nanoparticles rendered MSCs more favorable for use in injury treatment with no negative effects on MSC properties, suggesting their potential clinical efficacy.

Clinical study of video-assisted thoracoscopic surgery wedge resection in early-stage lung cancer by tumor mapping with indocyanine green.

AIM: This study aimed to assess the clinical effectiveness of video-assisted thoracoscopic surgery (VATS) in early-stage lung cancer by indocyanine green (ICG) for tumor mapping. MATERIAL AND METHODS: Thirty patients with early-stage lung cancer with peripheral nodules smaller than 2 cm scheduled for computed tomography (CT)-guided microcoil placement followed by ICG tumor mapping by VATS wedge resection were enrolled. After microcoil deployment, 100 to 150 ml of diluted ICG was injected percutaneously near the nodule. The nodule initially was localized solely by using a near-infrared ray (NIR) thoracoscope to visualize ICG fluorescence. Thoracoscopic instruments were used to determine the staple line. Wedge resection was performed after confirmation of the location of the microcoil using fluoroscopy and pathology results. RESULTS: Thirty patients underwent VATS resection. The median tumor size was 1.3 cm by CT. The median depth from the pleural surface was 1.7 cm (range: 0.5-3.8 cm). The median CT-guided intervention time was 25 min, and VATS procedural time was 50 min. ICG fluorescence was clearly identified in 30 of 30 patients (100%). The surgical margins were all negative on final pathology in all included cases. The final diagnoses were 30 primary lung cancers; none needed additional resection. CONCLUSIONS: CT-guided percutaneous ICG injection and intraoperative NIR localization of small nodules are safe and feasible. These offer surgeons the ease of localization through direct indocyanine green fluorescence imaging without the use of fluoroscopy and may be a complementary technique to preoperative microcoil placement for nonvisible, nonpalpable intrapulmonary nodules.

Synthesis of ginsenoside Re-based carbon dots applied for bioimaging and effective inhibition of cancer cells.

BACKGROUND: Fluorescent carbon-based nanomaterials have promising properties such as biosensing, cell imaging, tracing and drug delivery. However, carbon dots (CDs) with specific inherent biological functions have not been investigated. Ginsenosides are the components with multiple bioactivities found in plants of the genus Panax, which have attracted a lot of attention for their anticancer effect. MATERIALS AND METHODS: In this study, we prepared a kind of novel photoluminescent CDs from ginsenoside Re by one-step hydrothermal synthesis method. The conventional methods including transmission electron microscopy, Fourier transform infrared spectroscopy, HPLC and fluorescence spectrum were used for characterization of CDs. In vitro anticancer effect was investigated by cytotoxicity assay, flow cytometry and Western blot analysis. RESULTS: The as-prepared Re-CDs had an average diameter of 4.6±0.6 nm and excellent luminescent properties. Cellular uptake of Re-CDs was facilitated by their tiny nanosize, with evidence of their bright excitation-dependent fluorescent images. Compared with ginsenoside Re, the Re-CDs showed greater inhibition efficiency of cancer cell proliferation, with lower toxicity to the normal cells. The anticancer activity of Re-CDs was suggested to be associated with the generation of large amount of ROS and the caspase-3 related cell apoptosis. CONCLUSION: Hopefully, the dual functional Re-CDs, which could both exhibit bioimaging and anticancer effect, are expected to have great potential in future clinical applications.

Magnetic delivery of Fe3O4@polydopamine nanoparticle-loaded natural killer cells suggest a promising anticancer treatment.

Natural killer (NK)-cell-based immunotherapy has been reported to have promising prospects in the treatment of non-small cell lung cancer, one of the most common malignancies in the world. It has been proven that higher the NK cell infiltration into the tumor, the better is the curative effect. Therefore, it would be beneficial to develop a method that increases NK cell recruitment and infiltration into the tumor site. The purpose of this study was to establish an immune-cell delivery system for clear lung cancer cells based on magnetic nanoparticle (NP)-labeled NK cells that can be accumulated at the tumor site by placing a tiny external magnetic device inside animals. We developed superparamagnetic iron oxide NPs consisting of a magnetic Fe3O4 core and a shell of polydopamine (PDA) for magnetic targeting therapy. Fe3O4@PDA NPs possess favorable physiological stability and biocompatibility that facilitate their active uptake by NK cells. The biology of NK cells was not affected by the presence of NPs. In vitro and in vivo studies showed that Fe3O4@PDA NP-labeled NK cells significantly inhibited tumor growth and reduced the expression of Ki-67 and increased the apoptosis of A549 cancer cells. H&E staining showed Fe3O4@PDA NP-labeled NK cells, under a magnetic field, had higher intra-tumoral iron density and increased accumulation of CD56+ NK cells. Our results suggest that Fe3O4@PDA NPs are a promising magnetic nanomaterial that can manipulate immune cells, thereby inhibiting tumor growth.

Dysregulation of miRNA-21 and their potential as biomarkers for the diagnosis of cervical cancer.

OBJECTIVE: This study aimed to characterize the miR-21 and evaluated its clinical significance. METHODS: Total RNA was extracted from 30 pairs of fresh specimens of cervical cancer and normal tissues. The expression levels of the miR-21-3p and miR-21-5p were detected by quantitative reverse transcriptase polymerase chain reaction, with U6 as the internal reference gene. We compared the expression of miR-21-3p and miR-21-5p between study group and control groups, the association between miRNA expression level and clinicopathological factors was investigated. RESULTS: The expression of miR-21-3p and miR-21-5p in HPV positive cervical cancer samples was significantly upregulated compared to that in the paired normal samples (P < 0.05); A multivariate analysis demonstrated that the expression of miR-21 was associated with clinicopathological parameters, including depth of invasion and lymph node metastasis. CONCLUSIONS: MiR-21 upregulation is associated with aggressive progression and poor prognosis in cervical cancer, which suggests that miR-21 might be identified as an independent marker for predicting the clinical outcome of cervical cancer patients.

Synthesis and characterization of copper(ii) complexes with multidentate ligands as catalysts for the direct hydroxylation of benzene to phenol.

Four copper(ii) complexes with multidentate ligands, ([CuL1Cl2]), ([Cu(HL2)Cl2]), ([Cu2(L2)2](ClO4)2) and ([CuL3(HOCH3)ClO4]) {L1 = N,N-bis((pyridin-2-yl)methyl) prop-2-yn-1-amine, HL2 = 2-((((1-methyl-1H-imidazol-2-yl)methyl)(pyridin-2-ylmethyl)amino)methyl)phenol and HL3 = 2-((((1-methyl-1H-imidazol-2-yl)methyl)(pyridin-2-ylmethyl)amino)methyl)-2-t-butyl-phenol} are reported. The complexes were characterized by UV-vis spectroscopy, elemental analysis and electrochemical analysis. Complexes and were further characterized by X-ray single crystal diffraction analysis. The catalytic performances of these complexes were evaluated in the direct hydroxylation of benzene to phenol with hydrogen peroxide as an oxidant in aqueous acetonitrile media. Under optimized reaction conditions, complex with the most negative reduction potential exhibited the highest conversion without considering the dinuclear complex . A correlation between the catalytic efficiency and the reduction potentials of these complexes was observed, that is the more negative the reduction potential, the higher the benzene conversion. A radical mechanism for the catalysis was confirmed by the fact that addition of radical scavengers such as TEMPO into the reaction mixture could severely suppress the catalysis.

Characteristics of bacterial vaginosis infection in cervical lesions with high risk human papillomavirus infection.

UNLABELLED: High risk human papillomavirus (HPV) infection is the major cause of cervical cancer. Bacterial vaginosis (BV) is considered as the most prevalent vaginal imbalance affecting women of reproductive age. However, the relationship between HPV and BV infection is unclear. This study aimed to assess the prevalence of human papillomavirus (HPV) infection combined with bacterial vaginosis (BV) infection in Shanghai suburbs and evaluate associations between bacterial vaginosis with HPV infection, cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: From October 1, 2009 to October 31, 2013, a total number of 3502 women who visited Fengxian Hospital, Southern Medical University were enrolled in this study. All participants gave informed consent and agreed to HPV, BV, chlamydia, mycoplasma and thinprepcytologic test (TCT). In addition, all women took histopathologic examination under colposcopy. Statistical analyses were done using SPSS 17.0 for windows (IBM). In present study the overall BV-positive rate was 9.25%. The top three high risk HPV types were listed as follows (in descending order): HPV16, 52, 58. Moreover, our data showed BV infection tended to occur in the HPV positive women, HPV infection also tended to occur in the BV positive women. Most of the women who present HPV with BV infection were younger than 30 years old. We also found that CIN and cervical cancer occurred mainly in HPV/BV positive and HPV with BV positive group. BV infection and HPV infection may haveconsistency or synergies. HPV with BV infection may increase the incidence of CIN and cervical cancer.

Diagnosis of 25 genotypes of human papillomaviruses for their physical statuses in cervical precancerous/cancerous lesions: a comparison of E2/E6E7 ratio-based vs. multiple E1-L1/E6E7 ratio-based detection techniques.

BACKGROUND: Cervical lesions caused by integrated human papillomavirus (HPV) infection are highly dangerous because they can quickly develop into invasive cancers. However, clinicians are currently hampered by the lack of a quick, convenient and precise technique to detect integrated/mixed infections of various genotypes of HPVs in the cervix. This study aimed to develop a practical tool to determine the physical status of different HPVs and evaluate its clinical significance. METHODS: The target population comprised 1162 women with an HPV infection history of > six months and an abnormal cervical cytological finding. The multiple E1-L1/E6E7 ratio analysis, a novel technique, was developed based on determining the ratios of E1/E6E7, E2/E6E7, E4E5/E6E7, L2/E6E7 and L1/E6E7 within the viral genome. Any imbalanced ratios indicate integration. Its diagnostic and predictive performances were compared with those of E2/E6E7 ratio analysis. The detection accuracy of both techniques was evaluated using the gold-standard technique "detection of integrated papillomavirus sequences" (DIPS). To realize a multigenotypic detection goal, a primer and probe library was established. RESULTS: The integration rate of a particular genotype of HPV was correlated with its tumorigenic potential and women with higher lesion grades often carried lower viral loads. The E1-L1/E6E7 ratio analysis achieved 92.7% sensitivity and 99.0% specificity in detecting HPV integration, while the E2/E6E7 ratio analysis showed a much lower sensitivity (75.6%) and a similar specificity (99.3%). Interference due to episomal copies was observed in both techniques, leading to false-negative results. However, some positive results of E1-L1/E6E7 ratio analysis were missed by DIPS due to its stochastic detection nature. The E1-L1/E6E7 ratio analysis is more efficient than E2/E6E7 ratio analysis and DIPS in predicting precancerous/cancerous lesions, in which both positive predictive values (36.7%-82.3%) and negative predictive values (75.9%-100%) were highest (based on the results of three rounds of biopsies). CONCLUSIONS: The multiple E1-L1/E6E7 ratio analysis is more sensitive and predictive than E2/E6E7 ratio analysis as a triage test for detecting HPV integration. It can effectively narrow the range of candidates for colposcopic examination and cervical biopsy, thereby lowering the expense of cervical cancer prevention.

Coxsackievirus A16 infection induces neural cell and non-neural cell apoptosis in vitro.

Coxsackievirus A16 (CA16) is one of the main causative pathogens of hand, foot and mouth disease (HFMD). Viral replication typically results in host cell apoptosis. Although CA16 infection has been reported to induce apoptosis in the human rhabdomyosarcoma (RD) cell line, it remains unclear whether CA16 induces apoptosis in diverse cell types, especially neural cells which have important clinical significance. In the current study, CA16 infection was found to induce similar apoptotic responses in both neural cells and non-neural cells in vitro, including nuclear fragmentation, DNA fragmentation and phosphatidylserine translocation. CA16 generally is not known to lead to serious neurological symptoms in vivo. In order to further clarify the correlation between clinical symptoms and cell apoptosis, two CA16 strains from patients with different clinical features were investigated. The results showed that both CA16 strains with or without neurological symptoms in infected patients led to neural and muscle cell apoptosis. Furthermore, mechanistic studies showed that CA16 infection induced apoptosis through the same mechanism in both neural and non-neural cells, namely via activation of both the mitochondrial (intrinsic) pathway-related caspase 9 protein and the Fas death receptor (extrinsic) pathway-related caspase 8 protein. Understanding the mechanisms by which CA16 infection induces apoptosis in both neural and non-neural cells will facilitate a better understanding of CA16 pathogenesis.

Iron(III) complexes of multidentate pyridinyl ligands: synthesis, characterization and catalysis of the direct hydroxylation of benzene.

Three multidentate ligands, L1-L3, derived from bis(pyridin-2-ylmethyl)amine (L1) were synthesized. Reaction of these ligands with FeCl3·6H2O in methanol led to the formation of the iron complexes Fe1-Fe3 (Fe1: [FeL1Cl3]; Fe2: [FeL2Cl3]; Fe3: [FeL3Cl3]) in good yields. These complexes have been fully characterized. The structures of complexes Fe1-Fe3 have been determined using X-ray single crystal diffraction analysis. Electrochemical investigation revealed that complex Fe3 partially converts to Fe4 ([FeL3Cl2]PF6) by the replacement of one of its three chlorides with its pendant triazolyl group in solution. Fe4 was also synthesized by dechlorination using AgPF6 as the Cl(-) abstractor and its composition was further confirmed by both elemental analysis and X-ray single crystal diffraction analysis. All four complexes catalyze the direct hydroxylation of benzene to phenol with hydrogen peroxide as an oxidant in a mixed medium of water and acetonitrile. The reactivity of the complexes correlates well with their reduction potentials. The more negative the potential, the more reactive (high conversion rate) the catalysts. These complexes catalyze not only the oxidation of benzene, but also the further oxidation of the product, phenol. In the oxidation, a radical mechanism is certainly involved but an alternative pathway may also exist.

Risk factors for human papillomavirus infection in Shanghai suburbs: a population-based study with 10,000 women.

BACKGROUND: High risk human papillomavirus (HPV) infection is the major cause of cervical cancer. Several epidemiological studies have performed HPV screening in Chinese women, but no report was for Shanghai suburb women. OBJECTIVES: To understand the prevalence of HPV infection and risk factors in Shanghai suburbs. STUDY DESIGN: Between March 2011 and May 2011, 10,000 female volunteers lived in Fengxian District of Shanghai were recruited for the detection of 21 HPV types using PCR and fast flow hybridization of gene chip array. For the 508 HPV-positive patients, we performed the liquid-based ThinPrep cytology test (TCT) and histological examination for the diagnosis of local cervical lesions. The questionnaire surveyed demographic and behavioral indicators for the evaluation of risk factors of HPV infection. RESULTS: We found that the HPV-positive rate was 12.6%. The five top HPV types were as follows (in descending order): HPV52, 16, 58, 18 and 33. Moreover, HPV-positive rates were higher in women with older age, lower educational level, younger age of the first sexual intercourse, multiple sexual partners, no usage of condom for contraception, multiple deliveries, vaginal delivery, menopause, vaginal inflammation, cervical erosion and no regular cervical cytological examination. We also found that an HPV genotyping in combination with TCT and histological examination could improve early diagnosis for local cervical lesions. CONCLUSION: HPV infection was associated with age, sexual behavior and chronic inflammation of the cervix and vagina. We recommend popularizing HPV genotyping in women with high risk factors for the early diagnosis and prevention of cervical cancer.