MicroRNA-21 promotes proliferation, migration, and invasion of cervical cancer through targeting TIMP3.

BACKGROUND: The expression of microRNA-21 (miR-21) is up-regulated in various cancers, including cervical cancer. However, the function of miR-21 through tissue inhibitor of metalloproteinase 3 (TIMP3) on the proliferation, migration, and invasion in cervical cancer is still unclear. METHODS: A total of 60 paired fresh cervical cancer tissues, the corresponding adjacent non-neoplastic tissues and serum samples were collected from cervical cancer patients, while 60 matched normal tissues and serum samples were collected from the control group. MiR-21 expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). TIMP3 expression was evaluated by Western blot and qRT-PCR. Cell proliferation was determined by MTT assay. Migratory and invasive activities were assessed by cell migration and invasion assays, respectively. Luciferase reporter assay was employed to validate the direct targeting of TIMP3 by miR-21. RESULTS: MiR-21 was up-regulated in cervical cancer tissues and serum samples, in contrast, TIMP3 was down-regulated in cervical cancer tissues. MiR-21 promoted the proliferation, viability and the migratory and invasive activities of cervical cancer cells through targeting TIMP3. Overexpression of TIMP3 attenuated the positive effects of miR-21. CONCLUSIONS: These findings provide a novel insight into the molecular functions of miR-21 in cervical cancer, which may be used as a diagnostic and prognostic biomarker for the treatment of cervical cancer in the future.

The fabrication of N-doped carbon dots by methionine and their utility in sensing Cu2+ in real water.

Copper ions (Cu2+) are ubiquitous in the ecosystem and cause serious environmental pollution, posing a threat to human health. Therefore, sensitive detection of Cu2+ is urgently needed. Herein, we employed a solvothermal method to prepare blue-emitting carbon dots (Met-CDs) using formamide (FA) and methionine (Met) as precursors, with a high quantum yield (QY) of 38%. Based on the good optical stability of Met-CDs and selective quenching by Cu2+, a sensitive probe using Met-CDs for the detection of Cu2+ in water was successfully designed. Within the linear range of 0.15-2 µM, the limit of detection (LOD) was determined to be as low as 47.7 nM, enabling the quantitative detection of Cu2+. Moreover, the recovery data of the spiked analysis of lake/river water samples were also satisfactory and verified the feasibility of the probe by the analysis of Cu2+ in natural conditions.

Hericium coralloides Ameliorates Alzheimer's Disease Pathologies and Cognitive Disorders by Activating Nrf2 Signaling and Regulating Gut Microbiota.

Alzheimer's disease (AD) is prone to onset and progression under oxidative stress conditions. Hericium coralloides (HC) is an edible medicinal fungus that contains various nutrients and possesses antioxidant properties. In the present study, the nutritional composition and neuroprotective effects of HC on APP/PS1 mice were examined. Behavioral experiments showed that HC improved cognitive dysfunction in APP/PS1 mice. Immunohistochemical and Western blotting results showed that HC reduced the levels of p-tau and amyloid-ß deposition in the brain. By altering the composition of the gut microbiota, HC promoted the growth of short-chain fatty acid-producing bacteria and suppressed the growth of Helicobacter. Metabolomic results showed that HC decreased D-glutamic acid and oxidized glutathione levels. In addition, HC reduced the levels of reactive oxygen species, enhanced the secretion of superoxide dismutase, catalase, and glutathione peroxidase, inhibited the production of malondialdehyde and 4-hydroxynonenal, and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Collectively, HC demonstrated antioxidant activity by activating Nrf2 signaling and regulating gut microbiota, further exerting neuroprotective effects. This study confirms that HC has the potential to be a clinically effective AD therapeutic agent and offers a theoretical justification for both the development and use of this fungus.

Lysine (K)-specific demethylase 5C regulates the incidence of severe preeclampsia by adjusting the expression of bone morphogenetic protein-7.

This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (n = 60), a late-onset sPE group (LOsPE) (n = 60), and a control group (normal pregnancy; n = 60). The messenger RNA (mRNA) and protein expression levels of bone morphogenetic protein receptor II (BMPRII), BMP-7, and KDM5C were detected in placenta samples from the two sPE groups, and their sites were evaluated using immunohistochemistry (IHC). The sPE groups showed an increased KDM5C mRNA expression, and the EOsPE group showed a decreased BMP-7 and BMPRII mRNA expression compared with the LOsPE group. However, contradictory results were discovered in terms of protein expression. Immunostaining of KDM5C, BMP-7, and BMPRII was observed in villous trophoblast and extravillous trophoblast cells. Compared with the control group, the staining intensity of KDM5C in the placental tissue trophoblast cell nucleus and vascular endothelial cells of the sPE groups was weaker, while that of BMP-7 and BMPRII was stronger, and the staining intensity was more subjective in the LOsPE group. Consistent findings were obtained by IHC and Western blot analysis. KDM5C nuclear-cytoplasmic translocation may regulate sPE through BMP-7 and its receptors. The KDM5C-BMP-7 signaling pathway may also lead to less invasion and increased apoptosis of the trophoblast cells, which is involved in the pathogenesis of sPE.

Detection of mitochondrial coupling factor 6 in placental tissues from preeclamptic pregnancies and its influence on biological behavior of trophoblast cells.

Increased levels of mitochondrial coupling factor 6 (CF6) are present in the peripheral blood of patients with preeclamptic pregnancies, and are particularly evident in cases of early-onset or severe preeclampsia. The present study examined the location and expression levels of CF6 in the placental tissue and its effect on the biological behavior of trophoblast cells. Placental tissue microarrays, including placental villous cytotrophoblast and extravillous cytotrophoblast microarrays, were used to detect the location and relative expression levels of CF6 in the placenta using immunohistochemistry. It was found that CF6 was expressed in both the normal and preeclamptic placenta, but its levels were higher in the preeclamptic tissues. In addition, the effects of the hypoxic environment on the biological behaviors of trophoblast cells were investigated in the JAR and JEG-3 cell lines. Following induction of hypoxia, the expression levels of CF6 were increased. Moreover, exogenous addition of human recombinant CF6 attenuated cell invasion, but exerted no effect on cell proliferation. At the molecular level, the expression levels of MMP-2 were decreased and were accompanied with a reduction in cell invasion following addition of exogenous CF6. In conclusion, the increased expression levels of CF6 and its effects in reducing the invasive abilities of trophoblast cells may be involved in the pathogenesis of severe preeclampsia.

MicroRNA-150 promotes cell proliferation, migration, and invasion of cervical cancer through targeting PDCD4.

Recent studies have showed that microRNA-150 (miR-150) is up-regulated in various cancers including cervical cancer. However, the specific mechanism of miR-150 in the regulation of cell proliferation, migration and invasion is still unclear. In this study, a total of 150 cervical cancer samples, including 50 cervical cancer tissues, 50 corresponding adjacent non-neoplastic tissues, and 50 serum samples were collected from cervical cancer patients. 50 matched normal tissues and 50 serum samples were collected from the control group. MiR-150 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Programmed cell death protein 4 (PDCD4) was evaluated by qRT-PCR and western blot. Cell migration and invasion were assessed by transwell assays. Proliferative abilities were determined by MTT assays. Luciferase reporter assay was employed to validate the direct target of PDCD4 by miR-150. We found that miR-150 was increased in cervical cancer specimens. In contrast, PDCD4 was decreased in cervical cancer tissues. MiR-150 promoted cell migration, invasion and proliferation through targeting PDCD4. These results collectively indicated that miR-150 might be used as a potential therapeutic biomarker in cervical cancer.

MiR-1266 promotes cell proliferation, migration and invasion in cervical cancer by targeting DAB2IP.

Cervical cancer (CC) is one of the most prevalent cancers in women in the world. However, the pathogenesis is still very unclear, and the current screening methods are too expensive. Emerging evidence shows that miR-1266 has great influence on tumor cell migration and invasion. In order to clarify the role of miR-1266 in CC, we collected serum from CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL) and normal control (NC), collected tissues from CC and control group (CG), and followed up 50 CC patients. We used HeLa and SiHa cells to clarify the roles of miR-1266 on cell proliferation, migration and invasion. The CC mouse model was conducted to prove the role of miR-1266 on tumorigenesis. qRT-PCR was used to measure the expressions of miR-1266 and DAB2IP mRNA. Western blot was used to determine the expression of DAB2IP protein. Cell counting kit-8 proliferation assay (CCK-8), Colony formation assay, Wound-healing assay and Transwell invasion assay were used to determine the cell survival, proliferative, migrative and invasive abilities. Our study found that miR-1266 had a rising trend in serum from NC to LSIL to HSIL to CC, and increased in CC tissues. High expression serum miR-1266 had lower overall survival rates than patients with miR-1266 low expression. MiR-1266 promoted cell viability, proliferation, migration and invasion by targeting DAB2IP. And miR-1266 could promote tumorigenesis in vivo. In conclusion, miR-1266 could be used as a new biomarker for diagnosis, prediction and treatment of CC in the future.

Wnt/ß-catenin signaling pathway in severe preeclampsia.

This study aims to elucidate the mechanisms of Wnt/ß-catenin signaling pathway in the development of preeclampsia (PE). The mRNA levels of Wnt1, ß-catenin, c-myc and cyclinD1 were determined by real-time PCR in the placentas. Moreover, the expression levels of Wnt1, ß-catenin, Dickkopf-1 (DKK1) and glycogen synthase kinase 3ß (GSK-3ß) proteins were detected by Western blot. Immunohistochemistry was used in placental tissue microarray to localize the expression of Wnt1, ß-catenin, DKK1 proteins in the placentas of two groups. Compared with the control placentas, the mRNA levels of Wnt1, ß-catenin, c-myc and cyclinD1 were decreased in the severe preeclamptic placentas. The Western blot results showed that the expression levels of Wnt1, ß-catenin, and GSK-3ß proteins were significantly elevated in the control group, while the expression level of DKK1 was significantly decreased. In addition, the staining intensity of Wnt1, ß-catenin were weaker in the placentas of the severe PE group while the staining intensity of DKK1 was significantly stronger in the placentas of the severe PE group. Wnt/ß-catenin signaling pathway may play a significant role in the pathogenesis of PE by regulating the invasion and proliferation of trophoblast.

Increased circulating Th22 cells correlated with Th17 cells in patients with severe preeclampsia.

OBJECTIVE: We aimed to investigate Th22 cells and their association with Th17 and Treg cells in the etiology of severe preeclampsia (sPE). METHODS: Thirty sPE patients and 30 healthy pregnant women were recruited in this study. The percentages of Th17, Th22, and regulatory T cells (Tregs) in the peripheral blood were measured by flow cytometry. ELISA was used to measure the plasma concentrations of interleukin (IL)-17, IL-22, and IL-10. RESULTS: The percentages of Th17 and Th22 cells and the plasma concentrations of IL-17 and IL-22 were significantly increased in sPE patients along with a decreased percentage of Treg cells and a decreased plasma IL-10 concentration. There was a positive correlation between the levels of Th22 cells and Th17 cells in sPE patients. Moreover, a positive correlation was found between plasma IL-22 concentration and the percentage of Th22 cells in sPE patients. CONCLUSIONS: Increased circulating Th22 cells, which were correlated with Th17 cells, were observed in patients with sPE. The immune imbalance between T helper (Th) cells may contribute to the pathogenesis of sPE.