Environmental Science and Pollution Research

Physiopathology and effectiveness of therapeutic vaccines against human papillomavirus

Human papillomavirus (HPV) is a well-known sexually transmitted disorder globally. Human papillomavirus (HPV) is the 3rd most common cancer that causes cervical carcinoma, and globally it accounts for 275,000 deaths every year. The load of HPV-associated abrasions can be lessened through vaccination. At present, three forms of prophylactic vaccines, Cervarix, Gadrasil, and Gardasil 9, are commercially accessible but all these prophylactic vaccines have not the ability to manage and control developed abrasions or infections. Therefore, a considerable amount of the population is not secured from HPV infectivity. Consequently, the development of therapeutic HPV vaccines is a crucial requirement of this era, for the treatment of persisting infections, and to stop the progression of HPV-associated cancers. Therapeutic vaccines are a developing trial approach. Because of the constitutive expression of E6 and E7 early genes in cancerous and pre-cancerous tissues, and their involvement in disturbance of the cell cycle, these are best targets for this therapeutic vaccine treatment. For the synthesis and development of therapeutic vaccines, various approaches have been examined comprising cell-based vaccines, peptide/protein-based vaccines, nucleic acid-based vaccines, and live-vector vaccines all proceeding towards clinical trials. This review emphasizes the development, progress, current status, and future perspective of several vaccines for the cure of HPV-related abrasions and cancers. This review also provides an insight to assess the effectiveness, safety, efficacy, and immunogenicity of therapeutic vaccines in the cure of patients infected with HPV-associated cervical cancer.

CircRNA circ_0000554 promotes ovarian cancer invasion and proliferation by regulating miR-567

Circular RNAs (circRNAs) indicated potential modulating effects in tumor development. However, the specific role of circ_0000554 in ovarian tumor remains unknown. We found that circ_0000554 was overexpressed in ovarian tumor specimens and cells. Forced expression of circ_0000554 promoted cell growth, invasion, and epithelial to mesenchymal transition (EMT). We illustrated that miR-567 was downregulated in ovarian tumor specimens and cells. circ_0000554 was negatively correlated with miR-567 in ovarian tumor specimens. circ_0000554 sponged miR-567 expression in ovarian tumor. RIP assay showed that elevated expression of miR-567 could be enriched with circ_0000554. Luciferase reporter assay indicated that luciferase intensity was inhibited after treated with miR-567 mimic; however, the luciferase value of mut type was not decreased. Elevated expression of circ_0000554 suppressed miR-567 expression in HO8910 cell. circ_0000554 promoted ovarian tumor cell growth, invasion, and EMT via sponging miR-567. It suggested that circ_0000554 represent a potential therapy target for ovarian tumor.

PM2.5 exposure and cervical cancer survival in Liaoning Province, northeastern China

Particulate matter with a diameter of 2.5 μm or less (PM

DSCAM-AS1 promotes cervical carcinoma cell proliferation and invasion via sponging miR-338-3p

Deregulated lncRNA DSCAM-AS1 expression was found in several tumors. However, mechanism and functional role of DSCAM-AS1 in cervical carcinoma remain unknown. DSCAM-AS1 was detected in cervical carcinoma specimens and cells by RT-qPCR. CCK-8, Matrigel transwell, and flow cytometry were conducted to determine cell functions. In this research, we firstly we explored DSCAM-AS1 expression in cervical carcinoma cells and specimens. We revealed that DSCAM-AS1 was upregulated in cervical carcinoma lines (C4-1, Caski, Hela, and Siha) compared to GH329 cells. DSCAM-AS1 was upregulated in cervical carcinoma specimens compared to control no-tumor specimens. Overexpression of DSCAM-AS1 induced cervical carcinoma cell growth and cycle. Moreover, our data revealed that miR-338-3p expression was downregulated in cervical carcinoma cells and specimens. There was a negative correlation between miR-338-3p expression and DSCAM-AS1 expression in cervical carcinoma specimens. Elevated expression of miR-338-3p decreased cervical carcinoma cell growth and cycle and invasion. Furthermore, luciferase reporter analysis revealed that miR-338-3p overexpression suppressed luciferase activity of WT-DSCAM-AS1 vector but not the mut-DSCAM-AS1. Ectopic expression of DSCAM-AS1 decreased miR-338-3p expression in the Siha cell. Overexpression of DSCAM-AS1 promoted cervical carcinoma cell growth and cycle via regulating miR-338-3p. These results suggested that DSCAM-AS1 functions as one oncogene through sponging miR-338-3p in cervical carcinoma.

Research progress on the association between environmental pollutants and the resistance mechanism of PARP inhibitors in ovarian cancer

The occurrence and progression of ovarian cancer are closely related to genetics and environmental pollutants. Poly(ADP-ribose) polymerase (PARP) inhibitors have been a major breakthrough in the history of ovarian cancer treatment. PARP is an enzyme responsible for post-translational modification of proteins and repair of single-stranded DNA damage. PARP inhibitors can selectively inhibit PARP function, resulting in a synthetic lethal effect on tumor cells defective in homologous recombination repair. However, with large-scale application, drug resistance also inevitably appears. For PARP inhibitors, the diversity and complexity of drug resistance mechanisms have always been difficult problems in clinical treatment. Herein, we mainly summarized the research progress of DNA damage repair and drug resistance mechanisms related to PARP inhibitors and the impact of environmental pollutants on DNA damage repair to aid the development prospects and highlight urgent problems to be solved.

Bisphenol A induces ovarian cancer cell proliferation and metastasis through estrogen receptor-α pathways

Bisphenol A (BPA) is a widely used raw material that can be detected both in the environment and in the human body. Due to its estrogen-like effects, wide concerns have been raised about the potential role of BPA in the initiation and development of hormone-dependent cancers. Ovarian cancer is the most common reproductive system cancer and has a high mortality rate in women. Despite recent investigations into BPA's carcinogenic effects, studies on its role in ovarian cancer development remain limited. In this study, we aimed to assess the effect of BPA at various environmentally relevant concentrations on proliferation and metastasis of ovarian cancer cells. We discovered that BPA can stimulate proliferation of OVCAR-3 ovarian cancer cells after exposure for up to 5 days. Strikingly, BPA enhanced ovarian cancer cell migration, invasion, and adhesion (to vascular endothelial cells) through upregulation of matrix metalloproteinase-2 (MMP-2), MMP-9, and intercellular cell adhesion molecule-1 (IMAC-1). The stimulatory effects of BPA on cancer cell proliferation and metastasis were reversed by treatment with an ERα inhibitor, but not by treatment with an ERβ inhibitor. Together, these results suggest that BPA induces proliferation and metastasis of ovarian cancer cells through ERα signaling pathways. This study provides new insights into the carcinogenic effects of BPA with regard to ovarian cancer.

Biogenic synthesis of gold nanoparticles using Satureja rechingeri Jamzad: a potential anticancer agent against cisplatin-resistant A2780CP ovarian cancer cells

Drug resistance of cancer cells is a major issue in cancer treatment. Plant-mediated nanoparticle synthesis has been applied in recent years to overcome this problem. In this study, the biogenic synthesis of AuNPs was explored using Satureja rechingeri Jamzad aqueous leaf extract, and their anticancer effects were evaluated in cisplatin-resistant A2780CP ovarian cancer cells. The chemical composition of S. rechingeri Jamzad was analyzed using gas chromatography-mass spectrometry. The characteristics of green-synthesized AuNPs were confirmed using XRD, FTIR, UV-visible spectroscopy, TEM, SEM, EDX, DLS, and zeta potential. The cytotoxic effects of AuNPs and S. rechingeri Jamzad aqueous extract on cisplatin-resistant A2780CP ovarian cancer cells were evaluated by MTT assay and flow cytometry. Real-time PCR analyzed gene expression. The chemical composition revealed that carvacrol (89%) was the main component of the S. rechingeri Jamzad extract. The average size of the spherical biosynthesized AuNPs was 15.1 ± 3.7 nm. The AuNPs and plant extract inhibited the growth of cisplatin-resistant ovarian cancer cells in a time- and dose-dependent manner. The apoptotic cell death was confirmed by flow cytometry and DAPI staining. The proapoptotic genes were upregulated, while anti-apoptotic and metastatic genes were downregulated. According to the cell cycle analysis, cancer cells were arrested in the G0/G1 phase. Considering the anticancer activity of the synthesized AuNPs using S. rechingeri Jamzad and the low side effects of AuNPs on normal cells, these AuNPs showed strong potential for use as biological agents in drug-resistant cancer cells treatment.

Black coffee mitigates diethyl phthalate disrupted folliculogenesis, reduced gonadotropins, and ovarian lesions in female albino mice

Phthalates are multifunctional compounds with extensive applications and emerging environmental pollutants. Due to their ubiquity in the environment and unavoidable exposure to humans, concerns have been voiced about public health dangers. This study was aimed to explore the diethyl phthalate (DEP) toxicity and the potential protective effect of black coffee in female Swiss albino mice. Four-week-old mice, weighing 12 ± 1 g were segregated into five groups (n = 10), designated as G-I (without any treatment), G-II (treated with corn oil), G-III (exposed to 1.5 mg/g body wt. (B.W.) DEP), G-IV (received 2 μg/g B.W coffee), and G-V (co-administrated with 1.5 mg/g DEP and 2 μg/g B.W coffee). Before dose administration, the coffee extract was assessed for its antioxidant potential through FRAP, TPC, and GC-MS analyses. Respective phthalates/coffee doses were administrated orally, once a day for 8 weeks consecutively starting from the prepubescent stage. After 56 days, mice were acclimated for 4 days then dissected. Morphological assessments showed an irregular shape of the ovaries in DEP-treated mice as compared to the control. The average bodyweight of DEP-intoxicated mice (p ≤ 0.05) increased notably against control, while DEP plus coffee group showed a regular gain in the average weight of mice. The gonado-somatic index showed non-significant variations among all groups. Micrometric studies showed that the diameter of secondary follicles (115 µm) in the ovaries of DEP-exposed mice (p ≤ 0.001) decreased significantly as compared to control (204 µm); conversely, follicular diameter in the coffee control group (248) increased significantly. Serum FSH and LH levels were significantly increased in DEP-exposed mice with a noteworthy decrease in estrogen level while hormonal levels of all other groups were comparable to control. Histological sections of DEP-exposed mice ovaries showed anatomical disruptions contrary to other groups, which were comparable with control. Antioxidant potential was checked in ovaries homogenates; FRAP values showed a notable decrease in DEP group in comparison with the control group, in contrast to G-V, when DEP was co-administrated with coffee. This study concluded that black coffee has protective effect, against DEP-instigated reproductive toxicity in Swiss albino female mice.

Urinary phthalate metabolite and BPA concentrations in women with cervical cancer

Environmental pollutants are involved in the development and progression of numerous cancers, including cervical cancer (CC). One possible explanation for this is the ability of several pollutants to mimic natural hormones. This study aimed to evaluate the urinary concentrations of monoesters of phthalates and bisphenol A (BPA) in women with CC. A total of 45 women were included: 15 in the control group, 12 with CC diagnosis classified in early stages IA-IIB, and 18 in late stages III-IV. Urine samples were analyzed for BPA, mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and mono 2-ethylhexyl phthalate (MEHP) using high-performance liquid chromatography coupled to a tandem mass detector. The detection rate of environmental pollutants was 100%, with a median concentration in the control group and early-, and late-stage groups of 10.4, 9.2, 4.3, 38.4, and 12.9 µg L

Environmental and occupational exposure of metals and female reproductive health

Untainted environment promotes health, but the last few decades experienced steep upsurge in environmental contaminants posing detrimental physiological impact. The responsible factors mainly include the exponential growth of human population, havoc rise in industrialization, poorly planned urbanization, and slapdash environment management. Environmental degradation can increase the likelihood of human exposure to heavy metals, resulting in health consequences such as reproductive problems. As a result, research into metal-induced causes of reproductive impairment at the genetic, epigenetic, and biochemical levels must be strengthened further. These metals impact upon the female reproduction at all strata of its regulation and functions, be it development, maturation, or endocrine functions, and are linked to an increase in the causes of infertility in women. Chronic exposures to the heavy metals may lead to breast cancer, endometriosis, endometrial cancer, menstrual disorders, and spontaneous abortions, as well as pre-term deliveries, stillbirths. For example, endometriosis, endometrial cancer, and spontaneous abortions are all caused by the metalloestrogen cadmium (Cd); lead (Pb) levels over a certain threshold can cause spontaneous abortion and have a teratogenic impact; toxic amounts of mercury (Hg) have an influence on the menstrual cycle, which can lead to infertility. Impact of environmental exposure to heavy metals on female fertility is therefore a well-known fact. Thus, the underlying mechanisms must be explained and periodically updated, given the growing evidence on the influence of increasing environmental heavy metal load on female fertility. The purpose of this review is to give a concise overview of how heavy metal affects female reproductive health.

Effect of air pollution on the prevalence of breast and cervical cancer in China: a panel data regression analysis

The association between the prevalence of breast and cervical cancer in Chinese women and air pollution is obscure. The study aims to analyze the correlation between air pollution and the prevalence of breast and cervical cancer, and whether the gross domestic product (GDP) has a modifying effect on the impact of air pollution on the prevalence of breast and cervical cancer. Extracting panel data from 31 provinces and cities between 2006 and 2020, we evaluated the association between breast and cervical cancer prevalence and pollutant emissions from 2006 to 2015 with two-way fixed-effect models. We also analyzed the interaction between GDP and pollutant emissions and further check the robustness of the moderating effect results using group regression from 2016 to 2020. Cluster robust standard errors were used to correct for the heteroskedasticity and autocorrelation. The coefficients of models show that the coefficients of logarithmic soot and dust emissions are estimated to be significantly positive, and the coefficients of their square terms are significantly negative. The robust results suggest that the relationship between soot and dust emissions and breast or cervical cancer prevalence is non-linear, from 2006 to 2015. In the analysis of particulate matter (PM) data in 2016-2020, the PM-GDP interaction term was also significantly negative, indicating that GDP growth weakened the effect of PM on the prevalence of breast cancer and cervical cancer. In provinces with higher GDP, the indirect effect of PM emissions concerning breast cancer is -0.396 while in provinces with lower GDP, it is about -0.215. The corresponding coefficient concerning cervical cancer is about -0.209 in provinces with higher GDP but not significant in provinces with lower GDP. Our results suggest that there is an inverted U-shaped relationship between the prevalence of breast cancer and cervical cancer and air pollutants from 2006 to 2015. GDP growth has a significant negative moderating effect on the impact of air pollutants on the prevalence of breast cancer and cervical cancer. PM emissions have a higher effect on the prevalence of breast and cervical cancer in provinces with higher GDP and a lower impact in provinces with lower GDP.

Antiproliferative and apoptogenic effects of Cassia fistula L. n-hexane fraction against human cervical cancer (HeLa) cells

The current study was performed to evaluate the antiproliferative and apoptosis-inducing potential of n-hexane fraction from Cassia fistula L. (Caesalpinioideae) fruits. The antiproliferative property of the fraction was determined by MTT assay against cancer cell lines including HeLa, MG-63, IMR-32, and PC-3 with GI

Lead (Pb) exposure from outdoor air pollution: a potential risk factor for cervical intraepithelial neoplasia related to HPV genotypes

Abstract Human papillomavirus genotypes (HPVs) have been confirmed to be the major cause of cervical intraepithelial neoplasia (CIN) that remains to be one of the most common women cancers around the world. It seems other risk factors have synergistic effects on cervical cancer occurrence including smoking, dietary pattern, sexual behavior, ethnicity, epigenetics, and environmental hazardous materials. Our study characterized the potential cancerous role of lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. Lead concentration was quantified using an atomic absorption spectrometer in liquid-based cytology specimens of 40 CIN-HPV positive subjects, 50 HPV infected non-cancerous cases, and 43 non-HPV infected/non-cancerous women. Pb concentration was 5.5 (4.7–6.4) μg/dL, 4.7 (4.2–8.7) μg/dL, and 4.7 (4.5–5.4) μg/dL in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07, P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CIN existence. The consequences need to be further validated by including more relevant risk factors and controlling the confounders for better understating of Pb impact from outdoor air pollution on cervical cancer progression.