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Fulvic acid (FA) can affect the dispersion of graphene oxide (GO) in aquatic environments, however, the possible mechanisms remain unclear. Dynamic light scattering techniques combined with a multiple regression model were applied to explore the influence of FA sub-fractions (FA

Ambient fine particulate matter (PM2.5) pollution has been implicated in the development of hypertensive disorders of pregnancy. However, evidence on the effects of PM2.5-derived chemical constituents on gestational blood pressure (BP) is limited, and the potential mechanisms underlying the association remain unclear. In this study, we repeated three consecutive 72-h personal air sampling and BP measurements in 215 pregnant women for 590 visits during pregnancy. Individual PM2.5 exposure level was assessed by gravimetric method and 28 PM2.5 chemical constituents were analyzed by ED-XRF method. Plasma biomarkers of endothelial function and inflammation were measured using multiplexed immunoassays. Robust multiple linear regression models were used to estimate the associations among personal PM2.5 exposure and chemical constituents, BP changes (compared with pre-pregnancy BP) and plasma biomarkers. Mediation analyses were performed to evaluate underlying potential pathways. Result showed that exposure to PM2.5 was significantly associated with increases in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in the early second trimester. Meanwhile, elevated concentration of lead (Pb) constituent in PM2.5 was significant associated with increases in DBP and MAP after adjusting for PM2.5 total mass. PM2.5 and Pb constituent also presented positive associations with plasma biomarkers of endothelial function (ET-1, E-selectin, ICAM-1) and inflammation (IL-1β, IL-6, TNFα) significantly. After multiple adjustment, elevated ET-1 and IL-6 were significantly correlated with increased gestational BP, and respectively mediated 1.24%-25.06% and 7.01%-10.69% of the increased BP due to PM2.5 and Pb constituent exposure. In conclusion, our results suggested that personal exposure to PM2.5 and Pb constituent were significantly associated with increased BP during pregnancy, and the early second trimester might be the sensitive window of PM2.5 exposure. The endothelial dysfunction and elevated inflammation partially mediated the effect of PM2.5 and Pb constituent on BP during pregnancy.

Ambient fine particulate matter (PM

Biopsies from 318 cases with squamous cell carcinoma of the uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 with normal cervical epithelium were collected from different geographic regions with different cervical cancer mortalities. The DNA.DNA dot-blot and Southern blot hybridization results show that there is a close relationship between HPV-16 and the uterine cervical squamous cell carcinoma in China. One very interesting observation is that the finding of HPV-16-homologous DNA differs significantly among five geographic regions, and corresponds with the mortalities from cervical cancer of these five regions. HPV-11 was found mainly in benign lesions. The rate of detection of HPV-16 in Chinese women increased from 8.3% in normal cervical epithelium to 20% in chronic cervicitis, 28% in cervical condyloma, 50% in CIN and 60.4% in cervical cancer. It is suggested that HPV-16 infection may be an etiological factor in the development of human cervical carcinoma. From the results of Southern blot hybridization, it appeared that HPV-16 DNA had been integrated into the genome of the host cell in cervical cancer. Whereas the HPV-16 DNA sequence was only present as an episome in normal cervical epithelium and cervical benign lesions. The rate of occurrence of E6-E7 genes is the highest (88.9%) compared with that of other subgenomic fragments of HPV-16 in specimens of human cervical cancer in China. This implies that E6 and E7 may be the oncogenic genes of HPV-16 and play an important role in the carcinogenesis of human cervical epithelial cells. The amplification and rearrangement of the c-myc protooncogene are closely associated with the occurrence of cervical cancer. The results presented here revealed that the activated c-myc oncogene may cooperate with HPV-16 in the carcinogenic processes.

In order to elucidate the role of HPV-16 in the development of genital cancer, NIH3T3 cells were transfected by HPV-16 whole genome and its two early genes, E6-E7. Besides ordinary calcium phosphate/DNA coprecipitation technique, a newly designed recombinant retrovirus containing the HPV-16 genome or subgenomes was used to infect cells for transfer of the target genes. The transforming activities have been demonstrated to be most efficient when a bioengineering technique of this kind is used. HPV-16 DNA was proved to have transforming potential for NIH3T3 cells, and the DNA of HPV-16 was proved to undergo multisite integration into transformed cells and nude mice tumour cells. The E6-E7 open reading frames are sufficient for transforming NIH3T3 cells independently in vitro, which implies that E6-E7 open reading frames are transforming genes or even viral oncogenes of HPV-16. The RNA transcribed by the E6-E7 of HPV-16 was expressed in transformed cells and in tumour cells of nude mice. The use of a recombinant retrovirus for gene transfer in this study is much more efficient than that of calcium phosphate/DNA coprecipitation. The lack of a tissue-culture system suitable for HPV replication in vitro makes HPV gene recombination into a specially engineered retrovirus for viral-mediated gene transfer of particular significance for the possible application of viral carcinogenesis, both in vitro and in vivo, for basic and clinical research.

There are more supports for the view that human papillomavirus (HPV) infection might be an etiological factor in the development of cervical cancer when the association of persistent condylomata is considered. Biopsies from 318 cases with squamous cell carcinoma of uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 normal cervical epithelium were collected from 5 geographic regions of China with different cervical cancer mortalities. All specimens were prepared for Dot blot, Southern blot and in situ DNA-DNA hybridizations by using HPV-11, 16, 18 DNA labelled with 32P and 3H as probes to detect viral homologous sequences in samples. Among them, 32 cases with cervical cancer, 27 with condyloma and 10 normal cervical epitheliums were randomly chosen for comparative EM observation. The results showed that: 1), 192 out of 318 (60.4%) cases of cervical cancer were positive for HPV-16 DNA probe (Table I)

Human papillomavirus(HPV) type 16 is the most prevalent viral type and its E6 and E7 early genes might play a key role in the carcinogenesis of cervical cancer in Chinese women. In order to elucidate the role of HPV-16 in the development of genital cancer, the present study was designed to transfect NIH3T3 cells with HPV-16 whole early genes and its E6, E7 genes separately. Besides the ordinary calcium phosphate/DNA coprecipitation technique, a newly designed recombinant retrovirus containing HPV-16 genes were used to infect cells for transfer the aim genes as shown in Fig.1.1). The cells transformed by recombinant retrovirus containing whole early gene and its E6-E7 respectively appeared more refractive, round shaped with rapid growth and loss of contact inhibition. Hundreds of cell colonies presented in cells transformed by the recombinant retrovirus after selected culture for one week, compared with the routine method, only a few colonies till 3 weeks. By using such a genomic engineering technique,the transforming activities have been shown to be most efficient. 2). The tumorigenicity of transformed cells: Transformed cells HZIP16-3T3 and HZIP16K-3T3, as well as negative controlled cells, NIH3T3 and pZIP-3T3 which was infected by recombinant retrovirus containing no HPV-16 gene, were transplanted into nude mice respectively. Tumours were formed in all mice within 15 days after inoculation of transformed cells (Fig.2). Whereas, no tumour was found in all controlled animals as long as 50 days. 3).

To determine the pathogenesis of herpes cervicitis and the relationship between herpes simplex virus type 2 (HSV-2) and the carcinogenesis of human uterine cervix, the ultrastructural changes of 15 cases of long-term organ cultures of human uterine cervix infected with HSV-2 were studied. In order to demonstrate the morphogenesis of the virus and the interactions between virus and host cells, EM autoradiography was performed. After viral inoculation, the course of viral DNA replication, and the processes of maturation of virus were examined. Pathological alterations of infected nuclei-including two kinds of granular matrix aggregations, proliferative changes in nuclei and nuclear envelope, multi-lobular nucleated giant cell formation, intranuclear microtubules, and some evidence of replication of HSV-2 in cytoplasm-were observed. Because of the similarity of the pathologic alterations and the course and duration of infection in the clinic cases and our experimental subjects, this system appears to be a good model to investigate the pathogenesis of herpes cervicitis and the relationship between human cervical cancer and HSV-2, other viruses, or other co-carcinogens.