Synthesis, characterization, and efficacy evaluation of a PH-responsive Fe-MOF@GO composite drug delivery system for the treating colorectal cancer.

Luteolin is a potent anti-colorectal cancer chemical. However, its effectiveness is hindered by its poor solubility in water and fat, and it is easy to degrade by gastrointestinal enzymes. In this study, a nano-composite carrier, NH2-MIL-101(Fe)@GO (MG), based on aminated MIL-101(Fe) and graphene oxide (GO) was developed and evaluated. This carrier co-delivered luteolin and matrine, while marine was used to balance the pH for the nano-preparation. The loading capacities for luteolin and matrine were approximately 9.8% and 14.1%, respectively. Luteolin's release at pH = 5 was significantly higher than at pH = 7.4, indicating it had an acidic pH response release characteristic. Compared to MOF and GO alone, MG and NH2-MIL-101(Fe)@GO@Drugs (MGD) enhanced anti-cancer activity by inhibiting tumor cell migration, increasing ROS generation, and upregulating the expression of Caspase-3 and Caspase-9. In conclusion, this study contributes new ideas and methods to the treatment strategy of multi-component anti-colorectal cancer therapy. It also advances drug delivery systems and supports the development of more effective and targeted treatment approaches for colorectal cancer.

A Survey of Latest Wi-Fi Assisted Indoor Positioning on Different Principles.

As the location-based service (LBS) plays an increasingly important role in real life, the topic of positioning attracts more and more attention. Under different environments and principles, researchers have proposed a series of positioning schemes and implemented many positioning systems. With widely deployed networks and massive devices, wireless fidelity (Wi-Fi) technology is promising in the field of indoor positioning. In this paper, we survey the authoritative or latest positioning schemes for Wi-Fi-assisted indoor positioning. To this end, we describe the problem and corresponding applications, as well as an overview of the alternative methods. Then, we classify and analyze Wi-Fi-assisted indoor positioning schemes in detail, as well as review related work. Furthermore, we point out open challenges and forecast promising directions for future work.

Corrigendum to 'Endometrial membrane organoids from human embryonic stem cell combined with the 3D Matrigel for endometrium regeneration in asherman syndrome' [Bioactive Mater. 6 (2021) 3935-3946].

[This corrects the article DOI: 10.1016/j.bioactmat.2021.04.006.].

Endometrial membrane organoids from human embryonic stem cell combined with the 3D Matrigel for endometrium regeneration in asherman syndrome.

Asherman's syndrome (AS), a leading cause of uterine infertility worldwide, is characterized by scarring of the uterine surfaces lacking endometrial epithelial cells, which prevents endometrial regeneration. Current research on cell therapy for AS focuses on mesenchymal and adult stem cells from the endometrium. However, insufficient number, lack of purity, and rapid senescence of endometrial epithelial progenitor cells (EEPCs) during experimental processes restrict their use in cell therapies. In this study, we induced human embryonic stem cells-9 (H9-ESC) into EEPCs by optimizing the induction factors from the definitive endoderm. EEPCs, which act as endometrial epithelial cells, accompanied by human endometrial stromal cells provide a niche environment for the development of endometrial membrane organoids (EMOs) in an in vitro 3D culture model. To investigate the function of EMOs, we transplanted tissue-engineered constructs with EMOs into an in vivo rat AS model. The implantation of EMOs into the damaged endometrium facilitates endometrial regeneration and angiogenesis. Implanting EMOs developed from human embryonic stem cells into the endometrium might prove useful for "endometrial re-engineering" in the treatment of Asherman's syndrome.

A dual functional fluorogenic probe for visualization of intracellular pH and formaldehyde with distinct fluorescence signals.

In this study, a single fluorescent probe (DPFP) containing a 1,8-naphthalimide dye and a homoallylamino group for imaging pH and formaldehyde (FA) has been developed that exhibits significant blue fluorescence (λem at 455 nm) under acidic pH conditions (pH < 7.0) and green fluorescence (λem at 555 nm) in the presence of FA, respectively. Furthermore, probe DPFP was successfully applied to image acidic lysosomes and exogenous or endogenous FA in living HeLa cells.

Endothelin-1 promotes human germinal vesicle-stage oocyte maturation by downregulating connexin-26 expression in cumulus cells.

STUDY QUESTION: Does endothelin-1 (ET-1) promote human oocyte maturation and by what mechanism? SUMMARY ANSWER: Addition of ET-1 to the medium in which human germinal vesicle (GV)-stage immature oocytes are cultured enhances the GV breakdown (GVBD) rate; the resumption of meiosis may be initiated by ET-1 downregulating the expression of connexin-26 (Cx26) in cumulus cells via endothelin receptor type B (ETRB), leading to decreased cAMP levels in the oocyte. WHAT IS KNOWN ALREADY: The paracrine factor ET-1 is secreted by ovarian somatic cells in pre-ovulatory follicles and regulates oocyte maturation in mice. Connexins, or gap junction proteins, form intercellular membrane channels that play important roles in the resumption of meiosis. STUDY DESIGN, SIZE, DURATION: This laboratory study was conducted over a 1-year period. The effects of ET-1 on meiotic resumption were evaluated in human GV-stage cumulus-oocyte complexes (COCs; 70 oocytes/group). The transcriptome profiles of ET-1-treated or untreated cumulus cells were compared to explore the possible mechanisms by which ET-1 may regulate oocyte maturation. PARTICIPANTS/MATERIALS, SETTING, METHODS: The ET-1, ETRA and ETRB expression levels in human cumulus cells from oocytes at different stages of maturation were evaluated using real-time quantitative PCR. Human GV-stage COCs collected from patients undergoing IVF at a university-affiliated infertility centre were cultured with or without ET-1, and cumulus cells were subsequently denuded using hyaluronidase and cultured in α-MEM. A GeneChip® Human Transcriptome Array was applied to explore differences in the whole-genome transcriptome profiles of cumulus cells treated with or without ET-1. Real-time quantitative PCR and Western blotting were used respectively to examine Cx26 mRNA and protein levels in cumulus cells. Changes in cAMP levels in both oocytes and cumulus cells after ET-1 treatment were measured using an enzyme-linked immunosorbent assay. MAIN RESULTS AND THE ROLE OF CHANCE: Cumulus cells from MII-stage oocytes exhibited upregulated ET-1 expression, compared to those from GV-stage oocytes. The addition of ET-1 to the culture medium enhanced the GVBD rate of cumulus cell-enclosed human oocytes. Whole-genome transcriptome microarray analyses revealed significantly downregulated Cx26 expression in cumulus cells after ET-1 treatment, and this action was blocked by an ETRB antagonist. The involvement of Cx26 was further supported by the finding that ET-1 treatment led to decreased cAMP levels in oocytes but increased cAMP levels in cumulus cells. LARGE SCALE DATA: Microarray data are published in the GEO database (GSE97684). LIMITATIONS, REASONS FOR CAUTION: The heterogeneity of human COCs collected from patients undergoing IVF might affect the maturation results in vitro. Although we focused on the effects of ET-1 on human oocyte maturation in the present study, mammalian oocyte maturation is a complicated process involving many endocrine and paracrine factors. WIDER IMPLICATIONS OF THE FINDINGS: Our present study suggests that in vitro, human GV-stage oocyte maturation could be enhanced by adding ET-1 to the culture medium. In the present study, we explored the molecular mechanisms by which ET-1 initiates the resumption of meiosis and demonstrated that ET-1 promotes oocyte maturation by downregulating the expression of the gap junction protein Cx26 in cumulus cells. These results expand our understanding of the molecular mechanisms underlying mammalian oocyte maturation and provide a basis for better in-vitro maturation strategies. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by grants from the China Natural Science Foundation (Grant Nos. 81170567 and 81370761). The authors declare that they have no conflicts of interest associated with this manuscript.

A selective chromofluorogenic chemodosimeter for fluoride ions based on distyrylbenzenes derivatives containing dual Si-O groups.

A new chemodosimeter for fluoride ions based on F(-) triggered dual Si-O bond cleavage of distyrylbenzenes derivatives was developed for the first time. Upon the addition of F(-) ions, the chemodosimeter (7) displayed apparent color changes from colorless to faint yellow, with a dramatic red-shift in the emission wavelength (~100 nm), and higher selectivity for fluoride over other common anions. With the aid of fluorescence measurements, the limit of detection could be as low as 89.8 nm. Using a 'dipstick' approach, chemodosimeter (7) might serve as a prototype device for fluorescent detecting F(-) without the need for any additional equipment. Copyright © 2015 John Wiley & Sons, Ltd.

Mismatch repair gene MLH3 Pro844Leu and Thr942Ile polymorphisms and the susceptibility to cervical carcinoma and HPV infection: a case-control study in a Chinese population.

To investigate the association between MLH3 Pro844Leu, Thr942Ile polymorphisms and potential linkage with the risk of cervical carcinoma and potential effect on protein function, we carried out a case-control study with 400 cervical squamous cell carcinoma, 400 CIN3 and 1200 normal controls in a Chinese population. The results showed that there was an increased risk of cervical carcinoma and CIN3 associated with the genotype 844CT [OR 2.17 (1.61-2.94); P<0.001; OR 1.49 (1.08-2.07), P 0.017, respectively] and a decreased risk with the 942CT genotype [OR 0.56 (0.38-0.82); P<0.001; OR 0.37 (0.24-0.58), P<0.001, respectively]. Most 844CT genotypes were linkage CT(844)-CC(942), which increased the risk of cervical carcinoma and CIN3 [77/83, OR 2.04 (1.48-2.80), P<0.001; 55/61, OR 1.46 (1.03-2.06), P 0.035, respectively]. Most 942CT were linkage CC(844)-CT(942), which decreased the risk of cervical carcinoma [29/35, OR 0.60 (0.40-0.91); P 0.017; 18/24, OR 0.33 (0.20-0.55), P<0.001, respectively]. In some grouping, the 844CT and 942CT were further enriched; especially HR-HPV-positive subjects both in the CIN3 and the cervical carcinoma, the 844CT had greater enrichment. These results included that CT(844)-CC(942) was associated with a high risk of cervical carcinoma and CIN3, and the CC(844)-CT(942) decreased the risk. The 844CT had a higher level of enrichment in HR-HPV positive individuals, which is probably related to HR-HPV susceptibility. There was no significant difference of the MLH3 mRNA expression and these two amino acid substitutions did not impact on the protein function.

The LIG4 Ile658Val polymorphism does not affect the risk of cervical carcinoma.

The aim of this study was to investigate whether gene LIG4 genetic polymorphism affects the risk of cervical carcinoma. We studied 500 cervical carcinoma patients and 800 normal women as controls. Demographic and epidemiologic risk factors were recorded. Single nucleotide polymorphisms (SNPs) (LIG4 Ile658Val) were genotyped. Compared to LIG4 Ile658Ile (AA) genotype, LIG4 Ile658Val (AG) did not increase or decrease the risk of cervical carcinoma or cervical squamous cell carcinoma [ORs and 95% CIs being 1.07 (0.70-1.63) and 1.01 (0.65-1.55)], while no homozygous LIG4 Val658Val (GG) was found in the cervical carcinoma group. Analyzing the risk of variant LIG4 Ile658Val genotypes for cervical carcinoma of different histologic types or HPV infection status, we found striking similarities between the squamous cell carcinoma group and the HPV-positive group and the overall carcinoma. In conclusion, in the Chinese population, LIG4 Ile658Val has only a slight impact on the risk of developing cervical carcinoma.

p53 Codon 72 polymorphism is associated with occurrence of cervical carcinoma in the Chinese population.

We investigated the genotype distribution of the p53 Arg72Pro polymorphisms in 500 cervical carcinoma and 800 normal women in Chinese population. HPV infection rates in carcinoma patients and control were 89.4% and 31.0%. Women carrying the p53 Arg72Pro or p53 Pro72Pro increased the risk of cervical carcinoma (ORs and 95% CIs being 3.74 (2.65-5.30), 2.23 (1.49-3.34)). In HPV positive population, elevated risks were also associated with p53 Arg72Pro, Pro72Pro (ORs and 95% CIs being 3.83 (2.02-7.24), 2.38 (1.14-4.99)). These results suggest that a proline in position 72 of p53 increases the risk of cervical carcinoma in Chinese population.

Susceptibility of XRCC3, XPD, and XPG genetic variants to cervical carcinoma.

OBJECTIVE: DNA repair genes play a key role in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as those of XRCC3 and xeroderma pigmentosum, complementation group D and G (XPD, XPG), contribute to carcinogenesis. In this study, we investigated the correlation between cervical carcinoma risk and XRCC3, XPD, XPG genetic variants. METHODS: A case-control study of 400 cases including 200 carcinoma, 200 cervical intraepithelial neoplasia (CIN) and 200 normal women was performed. Four single nucleotide polymorphisms (SNPs) (XRCC3 Thr241Met, XPG His1104Asp, XPD Asp312Asn, and XPD Lys751Gln) were genotyped by mismatch amplification polymerase chain reaction. RESULTS: Women carrying homozygous Asp1104Asp genotypes had a significantly decreased risk of cervical or cervical squamous cell carcinoma compared to His1104Asp or His1104His genotypes. Similarly, XPD Asn312Asn (AA) reduced the risk of cervical or cervical squamous cell carcinoma. No association of XRCC3 Thr241Met or XPD Lys751Gln and cervical carcinoma was found. None of the 4 SNPs influenced the risk of CIN in our study. CONCLUSION: Our results support the hypothesis that genetic variations in DNA repair genes may contribute to an inherited genetic susceptibility to cervical carcinoma.

REV1 genetic variants associated with the risk of cervical carcinoma.

PURPOSE: To explore the REV1 genetic variants effect the risk of cervical carcinoma. METHODS: Total 543 cases, including 282 carcinoma and 261 CIN, and 480 normal controls were performed. Two single nucleotide polymorphisms (SNPs) (REV1 Phe257Ser and REV1 Asn373Ser) were genotyped by PCR-squencing, and analysis the correlation to clinical character including HPV infection. RESULTS: Compared with the REV1 Phe257Ser, women carrying Ser257Ser and Phe257Ser genotypes had a significantly decreased the risk for cervical carcinoma or cervical squamous cell carcinoma. On contrary, homozygous Ser373Ser increased the risk for carcinoma. In addition, we found that the association of Phe257Ser and Asn373Ser with the risk for cervical carcinoma was specific to squamous cell carcinomas and not relevant for adenocarcinoma. Our results suggest that women carry Phe257Ser variant genotype decrease the risk for cervical carcinoma, more in women that have high-risk sexual reproductive histories, when women who carried Asn373Ser variant genotype and had high-risk sexual and reproductive histories had a significantly elevated risk for cervical carcinoma. CONCLUSION: Our results support Phe257Ser and Ser257Ser genotypes are associated with a decreased risk for cervical carcinoma, while Asn373Ser and Ser373Ser genotypes increased the risk. In addition, the effects were more significant in the groups with high-risk sexual and reproductive histories.

Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells.

BACKGROUND: Nanog, nucleostemin (NS) and musashi1 (Msi1) are proteins that are highly expressed in undifferentiated embryonic stem (ES) cells and have been shown to be essential in maintaining the pluripotency and regulating the proliferation and asymmetric division of ES cells and several nervous system tumor cells. The roles of Nanog, NS and Msi1 in development and progression of cervical carcinoma have, until now, not been well documented. METHODS: In this study, expression of Nanog, NS and Msi1 was detected by immunohistochemistry analysis in 235 patients with various degrees of cervical epithelial lesions, including 49 with normal cervical epithelia, 31 with mild dysplasia (CIN I), 77 with moderate-severe dysplasia (CIN II-III) and 78 with squamous cervical carcinomas (SCCs). Associations with various clinical pathological prognostic variables were analyzed in 50 early-stage SCC patients. RESULTS: Nanog, NS and Msi1 expression levels were significantly higher in SCC patients compared with CIN patients, and were higher in CIN patients compared with those with normal cervical epithelia. Nanog expression levels showed significantly differences according to different tumor sizes (P < 0.05), whereas there were no differences in NS and Msi1 expression levels according to different clinical pathological parameters. CONCLUSION: Our findings indicate that Nanog, NS and Msi1 may be involved in carcinogenesis of the cervix and progression of cervical carcinoma.