Decreased CD56+CD16-CD94+uNK cells in the mid-luteal phase in women with recurrent implantation failure are associated with IL-15 deficiency.

PROBLEM: Whether the abnormal development of uterine natural killer (uNK) cells contributes to women with recurrent implantation failure (RIF) remains unclear. METHOD OF STUDY: We characterized the development of uNK cells and peripheral blood NK cells (pbNK) in the mid-luteal phase in women with RIF (n = 31) and controls (n = 14) by flow cytometry. Endometrial IL-15 mRNA expression was studied by quantitative reverse transcription-PCR. The GSE58144 dataset was used to validate the correlation results. RESULTS: We found decreased proportions of stage 4 CD56+CD16-CD94+ uNK cells (median: 9.56% vs. 17.78%, P .014) and increased proportions of stage 6 CD56+CD16+CD57+ uNK cells (median: 1.54% vs. 0.74%, P = .020) in the mid-luteal endometrium of women with RIF compared to fertile women. We also found that there was no quantitative correlation between uNK cells and the corresponding pbNK cell subpopulations (P > .05). In addition, IL-15 mRNA levels in the mid-luteal endometrium were positively correlated with the proportion of CD56+ uNK cells (r = .392, P = .008), especially with stage 4 uNK cell populations (r = .408, P = .005). CONCLUSIONS: We showed that the proportion of stage 4 uNK cells decreased in the RIF group compared to controls, and the decrease in stage 4 uNK cells correlated positively with low IL-15 mRNA expression. We suggest that the reduced stage 4 uNK cells in women with RIF are associated with IL-15 deficiency.

Knockdown of Porf-2 restores visual function after optic nerve crush injury.

Retinal ganglion cells (RGCs), the sole output neurons in the eyes, are vulnerable to diverse insults in many pathological conditions, which can lead to permanent vision dysfunction. However, the molecular and cellular mechanisms that contribute to protecting RGCs and their axons from injuries are not completely known. Here, we identify that Porf-2, a member of the Rho GTPase activating protein gene group, is upregulated in RGCs after optic nerve crush. Knockdown of Porf-2 protects RGCs from apoptosis and promotes long-distance optic nerve regeneration after crush injury in both young and aged mice in vivo. In vitro, we find that inhibition of Porf-2 induces axon growth and growth cone formation in retinal explants. Inhibition of Porf-2 provides long-term and post-injury protection to RGCs and eventually promotes the recovery of visual function after crush injury in mice. These findings reveal a neuroprotective impact of the inhibition of Porf-2 on RGC survival and axon regeneration after optic nerve injury, providing a potential therapeutic strategy for vision restoration in patients with traumatic optic neuropathy.

Comparing the pregnancy outcomes of Re­ICSI and ICSI embryos in fresh ET and FET cycles.

Early rescue intracytoplasmic sperm injection (Re-ICSI) can prevent total fertilization failure (TFF) during conventional in vitro fertilization (IVF). However, the implantation rate of Re-ICSI embryos is lower than that of direct ICSI during fresh embryo transfer (ET). The aim of the present study was to investigate the effect of frozen ET (FET) after Re-ICSI. In the present retrospective study, primary infertility patients that underwent the first Re-ICSI and ICSI treatment, were studied. The clinical pregnancy rate, implantation rate, ectopic pregnancy, abortion rate and live birth rate were analyzed between the Re-ICSI and ICSI groups in fresh ET and FET cycles. The average age of patients between Re-ICSI and ICSI groups in fresh ET and FET cycles was (29.0±3.2 vs. 29.1±3.1, and 29.1±3.3 vs. 28.9±3.0), respectively (P>0.05). Compared with ICSI embryos, the clinical pregnancy, implantation and live birth rates of Re-ICSI embryos were lower in fresh ET cycles. By contrast, there were no significant differences in the pregnancy, implantation and live birth rates between the Re-ICSI and ICSI embryos during the FET cycles. Re-ICSI coupled with FET may overcome the impaired outcomes in fresh ET.

Pregnancy outcome and follow-up of offspring of donor oocytes recipient from PCOS patients.

BACKGROUND: The use of donated oocytes (DO) for in vitro fertilization(IVF) treatment in patients with infertility is generally recognized, and females with polycystic ovarian syndrome (PCOS) can participate in oocyte donation programs as donor patients. However, the pregnancy outcomes and offspring follow-up in patients with PCOS as the recipients are unclear. This study was to compare the pregnancy outcomes and follow-up of offspring in PCOS and non-PCOS receptor. METHODS: This was a retrospective cohort study of 62 patients undergoing the oocyte reception program were separated into 2 groups: Group I, PCOS oocyte recipients (n = 30); Group II, non-PCOS recipients (n = 32). Medical records were reviewed, and rates of fertilization, cleavage, high-quality embryos and blastocysts were compared between PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, multiple pregnancies, and offspring outcomes were calculated using the first single vitrified-warmed blastocyst transfer (SVBT) analysis between the groups. RESULTS: The average recipient age and body mass index (BMI) of PCOS and non-PCOS patients was (36.3 ± 2.6 vs. 36.2 ± 2.8, and 23.4 ± 3.9 vs. 23.7 ± 4.0), respectively (P > 0.05). The fertilization, cleavage, high-quality embryos and blastocyst rates were not significantly different between the PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, and multiple pregnancies were not significantly different in SVBT between the PCOS and non-PCOS groups. The incidence of complications, such as pre-eclampsia or gestational diabetes, between PCOS and non-PCOS groups was similar (11.8% vs.11.1%, 5.9% vs.5.5%; P > 0.05). Preterm births were also similar (11.8% vs.16.7%, P > 0.05). Donor oocytes are more likely to be delivered via cesarean Sect. (80.0% vs. 86.7%: P > 0.05). The mean gestational age, birth weight, and height were comparable between the 2 groups during full-term delivery. CONCLUSION: There was no difference in the pregnancy outcomes and follow-up of the offspring between the PCOS and non-PCOS groups.

Case report: Analysis of novel compound heterozygous TPP1 variants in a Chinese patient with neuronal ceroid lipofuscinosis type 2.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive neurodegenerative disease caused by variants in the TPP1 gene that lead to the deficiency of the lysosomal enzyme tripeptidyl peptidase I (TPP1) activity. Herein, we report a rare case of CLN2 caused by two novel variants of TPP1. The patient presented with seizures at onset, followed by progressive cognitive impairment, motor decline, and vision loss. Novel compound heterozygous variants, c.544_545del and c.230-3C>G, in TPP1 were identified by whole-exome sequencing. The variant assessment showed that the c.544_545del is a frameshift variant mediating mRNA decay and that c.230-3C>G is a splice variant generating aberrantly spliced TPP1 mRNA, as confirmed by a Splicing Reporter Minigene assay. In conclusion, clinical history, variant assessment, and molecular analyses demonstrate that the novel compound heterozygous variants are responsible for CLN2 disease in this patient. This study expands the mutation spectrum of TPP1.

Genetic analysis of recurrent parthenogenesis: A case report and literature review.

The present study reported a case of bilateral salpingectomy for an ectopic pregnancy with recurrent parthenogenesis over two in vitro fertilization (IVF) cycles. The first IVF cycle resulted in short-time fertilization. Two cleaved embryos were present after removing the cumulus cells. In the second cycle, intracytoplasmic sperm injection (ICSI) was performed directly and two 6-cell embryos were discovered again prior to the injection. Embryo biopsy, genome amplification, copy number variation (CNV) and single nucleotide polymorphism (SNP) analysis were performed on the two 6-cell embryos of the second cycle. The results of the CNV analysis indicated a genotype of 39,XX,+1,+1,+1,+1,+6q,+6q,+6q,-7p(x1),-10(x1),-13(x0),-15(x0),-17(x1),-18(x1),-19(x1),-20(x1) and the SNP analysis reported that only those chromosomes with one copy had a signal pattern similar to that obtained for an uniparental disomy. Although repeated spontaneous parthenogenesis was observed, the other metaphase II oocytes were fertilized normally after ICSI and the patient became pregnant. A literature review indicated that parthenogenesis may occur in individuals from various populations, and the patients always have a history of either recurrent miscarriages or bilateral tubal obstruction with or without ovarian/fallopian tube surgery. In certain cases, 1 pronucleus (PN) appears and cleaves later and in others, four-to six-cell embryos appear directly.

Structural Characterization and In Vitro Antioxidant Activity of Metallothionein from Oratosquilla oratoria.

We report here the purification of a novel metal-binding protein from Oratosquilla oratoria (O. oratoria MT-1) by gel and ion-exchange chromatography. SDS-PAGE and MALDI-TOF analyses demonstrated that isolated O. oratoria MT-1 was of high purity with a molecular weight of 12.4 kDa. The fluorescence response to SBD-F derivatives revealed that O. oratoria MT-1 contained a large number of sulfhydryl groups, which is a general property of metallothioneins. Zn and Cu metal stoichiometries for O. oratoria MT-1 were 3.97:1 and 0.55:1, respectively. The proportion of cysteine (Cys) residues in the amino acid composition was 32.69%, and aromatic amino acids were absent. The peptide sequence coverage with Macrobrachium rosenbergii calmodulin (accession AOA3S8FSK5) was 60%. Infrared spectroscopy of O. oratoria MT-1 revealed two obvious peaks at absorption frequencies for the amide I band and the amide II band. CD spectra revealed that the secondary structure was mainly composed of random coil (57.6%) and ß-sheet (39.9%). An evaluation of in vitro antioxidant activity revealed that isolated O. oratoria MT-1 has strong reducing activities, exhibiting scavenging rates for DPPH and OH of 77.8% and 75.8%, respectively (IC50 values 0.57 mg/mL and 1.1 mg/mL). O. oratoria MT-1 may be used as a functional additive in cosmetics, health foods, and medical products, as well as a reference material for quantitative analysis of metallothionein in such products.

Frozen blastocysts: Assessing the importance of day 5/day 6 blastocysts or blastocyst quality.

The aim of the present study was to analyze the high-quality blastocyst (HB) rate in all embryo frozen cycles and investigate the pregnancy outcomes for day 5/day 6 (D5/D6) blastocysts with respect to the blastocyst quality in programmed single vitrified-warmed blastocyst transfer (SVBT). We performed a retrospective study comparing D5/D6 HBs in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for all blastocyst frozen cycles. Patients were <35 years at the oocyte collection in their first fresh cycle without fresh transfer. A total of 1,560 IVF/ICSI cycles and 5,328 blastocysts were analyzed. The IVF HB rate was higher than that of ICSI (52.7% vs. 42.6%; P<0.05). The D5 HB rate was much higher than the D6 HB rate (61.6% vs. 29.4%; P<0.05). There were 22.4% (349/1,560) cycles that only had D6 blastocysts, of which IVF cycles were lower than ICSI (19.8% vs. 28.5%; P<0.05). The clinical pregnancy rate and implantation rate in the D5 group were significantly higher than these rates in the D6 group (57.4% vs. 46.2%, 58.9% vs. 47.3%; P<0.05). However, the clinical pregnancy rate and implantation rate of the D5 HBs were not significantly different from those of the D6 HBs (60% vs. 54.5%, 62% vs. 56.3%; P>0.05). In conclusion, the fertilization method (IVF/ICSI) directly influences the HB rate and blastocyst development rates. When we controlled for patient age, transfer frequency, and endometrium on day 5, it was not the development stage (D5/D6), rather the transfer blastocyst quality that played an important role in pregnancy outcomes.

Altered Retinal Dopamine Levels in a Melatonin-proficient Mouse Model of Form-deprivation Myopia.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.

Glutamine as a Potential Noninvasive Biomarker for Human Embryo Selection.

To determine whether glutamine consumption is associated with embryo quality and aneuploidy, a retrospective study was conducted in an in vitro fertilization center. Spent embryo culture media from patients undergoing assisted reproduction treatment and preimplantation genetic testing (PGT) were obtained on day 3 of in vitro culture. Embryo quality was assessed for cell number and fragmentation rate. PGT for aneuploidy was performed using whole genome amplification and DNA sequencing. Glutamine levels in spent embryo culture media were analyzed by gas chromatography-mass spectrometry. The results demonstrated that glutamine was a primary contributor to the classification of the good-quality and poor-quality embryos based on the orthogonal partial least-squares discriminant analysis model. Glutamine consumption in the poor-quality embryos was significantly higher than that in the good-quality embryos (P < 0.05). A significant increase in glutamine consumption was observed from aneuploid embryos compared with that from euploid embryos (P < 0.01). The Pearson correlation coefficients between embryo quality and glutamine consumption, and between aneuploidy and glutamine consumption, were 0.430 and 0.757, respectively. The area under the ROC curve was 0.938 (95% CI: 0.902-0.975) for identifying aneuploidy. Animal experiments demonstrate that increased glutamine consumption may be a compensatory mechanism to mitigate oxidative stress. Our data suggest that glutamine consumption is associated with embryo quality and aneuploidy. Glutamine may serve as a molecular indicator for embryo assessment and aneuploidy testing.

Lower growth arrest-specific 5 level in endometrium is related to endometriosis via promoting cell proliferation and angiogenesis.

Long noncoding RNAs are a group of more than 200 nt, nonprotein coding RNAs, some of which are dysregulated in many pathophysiological processes including endometriosis. This study aims to clarify the roles of dysregulated growth arrest-specific 5 (GAS5) in patients with endometriosis, and unveil the underlying mechanisms. We obtained endometrium samples from 37 patients with endometriosis and 23 controls without endometriosis. Primary endometrial stromal cells (ESCs) and endothelial cells were separated from the endometrium. Levels of GAS5 were quantified using quantitative real-time polymerase chain reaction, and levels of p27, cleaved caspase-3, cleaved poly (ADP-Ribose) polymerase 1, vascular endothelial growth factor A, tissue inhibitor of metalloproteinases 3 (TIMP3), and trypsin-modified soy protein 10 were assessed by immunoblotting. Cell viability was examined using MTT assays, and the cell cycle and apoptosis were analyzed by flow cytometry. Endothelial cell tube formation capacity was assayed in vitro. GAS5 and p27 levels were found lower in the endometrium samples from patients with endometriosis. Primary ESCs from patients with endometriosis had increased viability, reduced apoptosis, and a relatively uncontrolled cell cycle. Gain- and loss-of-function studies confirmed that GAS5 regulated p27 expression in ESCs. Furthermore, GAS5 level was relatively low in primary endothelial cells from patients with endometriosis and GAS5 acted as an angiogenesis inhibitor by regulating the miR-181c-TIMP3 axis. Thus, lower GAS5 level in endometrium might be related to endometriosis by regulating cell proliferation, apoptosis, cell cycle, and angiogenesis.

Does the additional use of clomiphene citrate or letrozole for in vitro fertilization deserve more attention?

BACKGROUND: Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations. RESULTS: Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P < 0.001) and from 1.1 to 0.0% (P = 0.090). Other, there was no statistical difference with respect to the T-retrieved ova (total retrieved ova), high quality embryos, cultured blastocyst and blastocyst number in high responders. For normal responders and poor ovary responders, T-Gn, Gn days, T-retrieved ova, high quality embryos, cultured blastocyst and blastocysts number in oral medications group all apparently decreased. Clinical pregnancy rate per fresh cycle of poor responders with prior oral medications was significantly decreased (25.7% vs. 50.8%, P = 0.005), and no significant differences in high responders and normal responders were expressed (52.5% vs. 44.2%, P = 0.310; 51.9% vs. 42.4%, P = 0.163) between two groups of participants. The numbers of cumulative pregnancy rates were lower in the conventional group compared to the add group for high (75.90% versus 81.03%, P = 0.279), normal (62.69% versus 71.36%, P = 0.016) and poor (39.74% versus 68.21%, P < 0.001) responders. CONCLUSIONS: The addition of CC/LE to the ovulation induction during IVF has certain efficacy in terms of low cost, low OHSS incidence. CC/LE deserves more recommendations as a responsible strategy in high responders due to advantageous pregnancy outcomes. For normal responders, the strategy needs to be considered with more comprehensive factors.

Genomic Profiling of Chinese Cervical Cancer Patients Reveals Prevalence of DNA Damage Repair Gene Alterations and Related Hypoxia Feature.

BACKGROUND: Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. In China, it is the most common cancer in the female genital tract. However, the genomic profiles of Chinese cervical cancer patients remain unclear. MATERIALS AND METHODS: A total of 129 cervical cancer patients were enrolled in this study (113 squamous, 12 adenocarcinoma, 2 adenosquamous, and 2 neuroendocrine carcinoma). To classify the clinical features and molecular characteristics of cervical cancer, the genomic alterations of 618 selected genes were analyzed in the samples of these patients, utilizing target next-generation sequencing (NGS) technology. Furthermore, the findings from the Chinese cohort were then compared with the data of Western patients downloaded from The Cancer Genome Atlas (TCGA) database, in terms of gene expression files, mutation data, and clinical information. RESULTS: All studied patients had valid somatic gene alterations, and the most frequently altered genes were PIK3C, TP53, FBXW7, ARID1A, ERBB2, and PTEN. Comparison of genomic profiling showed significantly different prevalence of genes, including TP53, KMT2C, and RET, between the Chinese and the TCGA cohorts. Moreover, 57 patients (44.19%) with 83 actionable alterations were identified in our cohort, especially in PI3K and DNA damage repair (DDR) pathways. After an in-depth analysis of cervical cancer data from the TCGA cohort, DDR alteration was found to be associated with extremely higher tumor mutation burden (TMB) (median mutation count: 149.5 vs 66, p <0.0001), and advanced stages (p <0.05). Additionally, DDR alteration, regardless of its function, was positively correlated with hypoxia feature and score. Moreover, patients with a high hypoxia score were positively correlated with a high abundance of mast cell resting, but lower abundance of CD8+ T cells and activated mast cell. Finally, CDHR5 was identified as the hub gene to be involved in the DDR-hypoxia network, which was negatively correlated with both the DDR alteration and hypoxia score. CONCLUSIONS: Overall, a unique genomic profiling of Chinese patients with cervical cancer was uncovered. Besides, the prevalent actionable variants, especially in PI3K and DDR pathways, would help promote the clinical management. Moreover, DDR alteration exerted the significant influence on the tumor microenvironment in cervical cancer, which could guide the clinical decisions for the treatment. CDHR5 was the first identified hub gene to be negatively correlated with DDR or hypoxia in cervical cancer, which had potential effects on the treatment of immune checkpoint inhibitors (ICIs).

Oridonin induces apoptosis in HGC-27 cells by activating the JNK signaling pathway.

Gastric cancer (GC) is a very common type of cancer. Although current treatment modalities include surgical resection and chemotherapy, many patients are either not eligible for radical resection or have a poor response to chemotherapy. Due to the complex features of the disease, there is a need for complementary therapy. In the present study, the effects of oridonin on cell proliferation, invasion and apoptosis were assessed in the HGC-27 cell line using the Cell Counting Kit-8 assay, real-time cell analysis, and an Annexin V-FITC/propidium iodide (PI) detection kit, respectively. The effect of oridonin on apoptosis, through the JNK pathway, was also investigated using western blotting. The present study demonstrated that oridonin can suppress cell viability and inhibit cell proliferation by inducing G2/M arrest. Oridonin also induced caspase-dependent apoptosis in cells by activating the phosphorylated-JNK/C-JUN pathway. These results demonstrate the potential of oridonin as a potential therapeutic compound for the treatment of GC.

Optic nerve crush modulates refractive development of the C57BL/6 mouse by changing multiple ocular dimensions.

Higher visual centers could modulate visually-guided ocular growth, in addition to local mechanisms intrinsic to the eye. There is evidence that such central modulations could be species (even subspecies)-dependent. While the mouse has recently become an important experimental animal in myopia studies, it remains unclear whether and how visual centers modulate refractive development in mice, an issue that was examined in the present study. We found that optic nerve crush (ONC), performed at P18, could modify normal refractive development in the C57BL/6 mouse raised in normal visual environment. Unexpectedly, sham surgery caused a steeper cornea, leading to a modest myopic refractive shift, but did not induce significant changes in ocular axis length. ONC caused corneal flattening and re-calibrated the refractive set-point in a bidirectional manner, causing significant myopic (<-3 D, 54.5%) or hyperopic (>+3 D, 18.2%) shifts in refractive error in most (totally 72.7%) animals, both due to changes in ocular axial length. ONC did not change the density of dopaminergic amacrine cells, but increased retinal levels of dopamine and DOPAC. We conclude that higher visual centers are likely to play a role in fine-tuning of ocular growth, thus modifying refractive development in the C57BL/6 mouse. The changes in refractive error induced by ONC are accounted for by alternations in multiple ocular dimensions, including corneal curvature and axial length.

Changes and correlations of anti-Müllerian hormone and stem-cell factors in different ovarian reserve patients during GnRH-antagonist protocol and the effects on controlled ovarian hyperstimulation outcomes.

PURPOSE: To explore the changes and correlations of anti-Müllerian hormone (AMH) and stem-cell factors (SCF) in different ovarian reserve patients during controlled ovarian hyperstimulation (COH) and the effects on COH outcomes. METHODS: Serum at six different timepoints during GnRH-antagonist protocol and follicular fluid (FF) on oocyte retrieval day of 52 patients with polycystic ovary syndrome (PCOS), 61 patients with normal ovarian reserve (NOR) and 42 patients with diminished ovarian reserve (DOR) were collected. AMH and SCF were assessed using enzyme-linked immunosorbent assay. RESULTS: During COH, AMH in the PCOS group was the highest, but SCF did the opposite, and serum AMH gradually decreased, while SCF inversely increased. In the PCOS group, SCF on the first and fourth days of gonadotropin (Gn) administration was negative with Gn dosage (r = - 0.362, P < 0.05; r = - 0.344, P < 0.05). In the NOR group, the basal AMH was also negative with Gn dosage (r = - 0.297, P < 0.05) and positive with COH outcomes (number of retrieved oocytes, MII oocytes, and 2PN fertilization) as well as serum SCF after Gn administration. In the DOR group, both AMH and SCF were significantly associated with COH outcomes. Serum AMH in the DOR group after Gn administration and FF AMH showed a negative correlation with SCF. CONCLUSIONS: Serum AMH decreased, while SCF increased during COH. AMH and SCF are effective for Gn time and dosage adjustment and predicting COH outcomes for NOR and DOR patients. In addition, serum AMH in DOR patients after Gn administration and FF AMH has a negative effect on SCF.

Prognostic Significance of FKBP14 in Gastric Cancer.

INTRODUCTION: Although our understanding on gastric cancer biology is better than a decade ago, its practical effect on screening and diagnosis remains limited. Moreover, there are no markers that can be accurately used in the clinic to diagnose early-stage gastric cancer or monitor the patient's response to therapy. Herein, we investigate whether FKBP14 is involved in the progression of gastric cancer. METHODS: The AGS cell line was chosen for over-expression analysis, whereas the SGC-7901 cell line was selected for knock-down analysis. AGS cells were transfected with an FKBP14 overexpression plasmid (AGS-PLV.O-FLAG). The expression pattern of FKBP14 in both cell lines was determined by Western blot and RT-PCR. Cell proliferation was assessed using Cell Counting Kit-8, whereas apoptosis was performed using flow cytometry. The expression of FKBP14 in 70 Chinese patients with gastric cancer was also investigated using tissue microarrays and compared with gastric cancer patients from The Cancer Genome Atlas. RESULTS: FKBP14 was highly expressed in SGC7901 and had a relatively low expression in AGS cells. Upregulation of FKBP14 in AGS cells promoted migration and invasion and inhibits apoptosis. Knock-down of FKBP14 resulted in a suppression in migration and invasion and promoted apoptosis in the SGC-7901 cell line. Effectively, gastric cancer patients had a higher expression of FKBP14, with a lower survival rate (P = 0.028). Patients with a high expression of FKBP14 were significantly correlated with lymph node metastasis (P =0.016), and an advanced histologic grade (P =0.021). CONCLUSION: FKBP14 is often up-regulated in gastric cancer. Patients with a high expression of FKBP14 are usually associated with worse overall survival. FKBP14 is an oncogene in gastric cancer, and is a potential biomarker for GC diagnosis, invasion, and prognosis.

A small compound spindlactone A sensitizes human endometrial cancer cells to TRAIL-induced apoptosis via the inhibition of NAD(P)H dehydrogenase quinone 1.

Introduction: Spindlactone A (SPL-A) is a novel small molecule inhibitor of TACC3 that selectively inhibits the nucleation of centrosome microtubules and induces mitotic arrest in ovarian cancer cells. SPL-A is derived from dicoumarol which inhibits the activity of NAD(P)H dehydrogenase quinone oxidoreductase 1 (NQO1). This study aimed to investigate the mechanism by which SPL-A enhances TRAIL-induced apoptosis in endometrial carcinoma cells. Materials and methods: Endometrial carcinoma cells were treated with SPL-A and/or TRAIL, and the apoptosis and protein expression in the treated cells were examined. Results: Combined treatment with SPL-A and TRAIL significantly induced apoptosis in various human endometrial carcinoma cells, but not in normal human endometrial stromal cells and endometrial epithelial cells. Notably, both NQO1 inhibitor ES936 and NQO1 siRNA enhanced TRAIL-induced apoptosis of endometrial carcinoma cells. Furthermore, SPL-A downregulated the expression of c-FLIP, Bcl-2, Bcl-xl, and Mcl-1, while increasing p53 expression. Conclusion: In particular, luciferase assay showed that SPL-A inhibited Bcl-2 promoter activity, and p53 inhibitor PFT-α could reverse the effect of SPL-A on Bcl-2 expression. Moreover, Bcl-2 overexpression inhibited the apoptosis induced by SPL-A and TRAIL. Taken together, our results suggest that SPL-A sensitizes endometrial cancer cells to TRAIL-induced apoptosis via the regulation of apoptosis-related proteins and the inhibition of NQO1 activity.

Characteristics of women with mixed mass formation after evacuation following uterine artery chemoembolization for cesarean scar pregnancy.

PURPOSE: To explore the efficacy of treatment for early cesarean scar pregnancy (CSP) and to evaluate the characteristics of women with subsequent mixed mass formation. METHODS: Women with CSP, who received UACE followed by evacuation, were retrospectively analyzed. Clinical/sonographic characteristics in patients with or without mixed mass formation were compared. RESULTS: From a total of 395 cases, 105 cases had a pregnancy residual with mixed mass formation. Blood loss and subsequent salvage intervention were significantly lower in patients without mixed mass, although all women retained their uteri. It required 50 days for the mass to resolve, 40 days for ß-hCG concentrations to drop back to normal, and 61 days for menses to be restored; all of which were significantly longer than the same indices in women without a mixed mass. Clinical/sonographic characteristics predicting residual mass formation were maximal diameter of gestational sac (OR = 1.05, P = 0.001, with a sensitivity and specificity of 68.6 and 80.3%, respectively), presence of a fetal heart beat (OR = 2.63, P = 0.002, with a sensitivity and specificity of 62.9 and 67.2%, respectively), remnant myometrial thickness (OR = 108.91, P = 0.001 when thickness was less than 1 mm, with a sensitivity and specificity of 42.9% and 96.6%), location of gestational sac (OR = 59.20, P = 0.01 for complete type, with a sensitivity and specificity of 99.0 and 36.9%), and Doppler signal grading (OR = 8.08, P = 0.013 for Grade III, with a sensitivity and specificity of 83.8 and 51.0%). CONCLUSIONS: UACE followed by evacuation was effective for CSP and subsequent mixed mass formation could be predicted by some clinical/sonographic characteristics.