Exosomes promote pre-metastatic niche formation in ovarian cancer.

Ovarian cancer is one of the most common gynecological malignancies. Upon initial diagnosis, the majority of patients present with widespread metastatic growth within the peritoneal cavity. This metastatic growth occurs in stages, with the formation of a pre-metastatic niche occurring prior to macroscopic tumor cell invasion. Exosomes released by the primary ovarian tumor are small extracellular vesicles which prepare the distant tumor microenvironment for accelerated metastatic invasion. They regulate intercellular communication between tumor cells and normal stroma, cancer-associated fibroblasts, and local immune cells within the tumor microenvironment. In this review, we highlight the emerging roles of ovarian cancer exosomes as coordinators of pre-metastatic niche formation, biomarkers amenable to liquid biopsy, and targets of chemotherapy

STROBE-GnRHa pretreatment in frozen-embryo transfer cycles improves clinical outcomes for patients with persistent thin endometrium: A case-control study.

The well-prepared endometrium with appropriate thickness plays a critical role in successful embryo implantation. The thin endometrium is the main factor of frozen-embryo transfer (FET), resulting in the failure of implantation undergoing FET. Hormone treatment is suggested to improve endometrium thickness; however, among the larger numbers of cases, it cannot reach the sufficient thickness, which leads to a high cancelation rate of embryo transfer as well as waste high-quality embryos. Thus, it increases the burden to patients in both economic and psychological perspectives. We performed a retrospective observational study, which was composed with 2 cohorts, either with the conventional hormone replacement therapy (HRT) protocol or HRT with gonadotrophin-releasing hormone agonist (GnRHa) pretreatment to prepare the endometrium before FET. The measurements of endometrium thickness, hormone level, transfer cycle cancelation rate, pregnancy rate, and implantation rate were retrieved from the medical records during the routine clinic visits until 1 month after embryo transfer. The comparisons between 2 cohorts were performed by t-test or Mann-Whitney U test depending on the different attributions of data. In total, 49 cycles were under HRT with GnRHa pretreatment and 84 cycles were under the conventional HRT protocol. HRT with GnRHa pretreatment group improved the endometrial thickness (8.13 ± 1.79 vs 7.51 ± 1.45, P = .031), decreased the transfer cancelation rate (P = .003), and increased clinical pregnancy rate and implantation rate significantly (both P = .001). Additionally, luteinizing hormone level in pretreatment group was consistently lower than conventional HRT group (P < .05). Our study revealed HRT with GnRHa pretreatment efficiently improved the endometrial thickness, therefore, decreased the FET cycle cancelation. It also elevated the embryo implantation rate and clinical pregnancy rate by improving endometrial receptivity

Effects of metastasis-associated in colon cancer 1 inhibition by small hairpin RNA on ovarian carcinoma OVCAR-3 cells

<p>Abstract</p> <p>Background</p> <p>Metastasis-associated in colon cancer 1 (MACC1) is demonstrated to be up-regulated in several types of cancer, and can serve as biomarker for cancer invasion and metastasis. To investigate the relations between MACC1 and biological processes of ovarian cancer, MACC1 specific small hairpin RNA (shRNA) expression plasmids were used to investigate the effects of MACC1 inhibition on ovarian carcinoma OVCAR-3 cells.</p> <p>Methods</p> <p>Expressions of MACC1 were detected in different ovarian tissues by immunohistochemistry. MACC1 specific shRNA expression plasmids were constructed and transfected into OVCAR-3 cells. Then, expressions of MACC1 were examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Cell proliferation was observed by MTT and monoplast colony formation assay. Flow cytometry and TUNEL assay were used to measure cell apoptosis. Cell migration was assessed by wound healing and transwell migration assay. Matrigel invasion and xenograft model assay were performed to analyze the potential of cell invasion. Activities of Met, MEK1/2, ERK1/2, Akt, cyclinD1, caspase3 and MMP2 protein were measured by Western blot.</p> <p>Results</p> <p>Overexpressions of MACC1 were detected in ovarian cancer tissues. Expression of MACC1 in OVCAR-3 cells was significantly down-regulated by MACC1 specific small hairpin RNA. In OVCAR-3 cells, down-regulation of MACC1 resulted in significant inhibition of cell proliferation, migration and invasion, meanwhile obvious enhancement of apoptosis. As a consequence of MACC1 knockdown, expressions of Met, p-MEK1/2, p-ERK1/2, cyclinD1 and MMP2 protein decreased, level of cleaved capase3 was increased.</p> <p>Conclusions</p> <p>RNA interference (RNAi) against MACC1 could serve as a promising intervention strategy for gene therapy of ovarian carcinoma, and the antitumor effects of MACC1 knockdown might involve in the inhibition of HGF/Met and MEK/ERK pathways.</p

LncRNA HOTAIR Regulates CCND1 and CCND2 Expression by Sponging miR-206 in Ovarian Cancer

Background/Aims: The long noncoding RNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been demonstrated to be a vital modulator in the proliferation and metastasis of ovarian cancer cells, but its potential molecular mechanism remains to be elucidated. In the current study, we aimed to uncover the biological role of lncRNA HOTAIR and its underlying regulatory mechanism in the progression and metastasis of ovarian cancer. Methods: HOTAIR expression was detected by quantitative RT-PCR (qRT-PCR) and northern blotting. The SKOV3 ovarian cancer cell line was chosen for the subsequent assays. In addition, the molecular mRNA and protein expression levels were examined by qRT-PCR and western blotting. The competitive endogenous RNA (ceRNA) mechanism was validated by bioinformatics analysis and a dual luciferase reporter gene assay. Results: HOTAIR expression was significantly higher in ovarian carcinoma tissues and cell lines than in the control counterparts. Both CCND1 and CCND2 were downstream targets of miR-206. The inhibition of HOTAIR elevated the expression of miR-206 and inhibited the expression of CCND1 and CCND2. Moreover, CCND1 and CCND2 were highly expressed in ovarian cancer tissues, and their expression was positively correlated with HOTAIR expression. Finally, the functional assays indicated that the anticancer effects of miR-206 could be rescued by the simultaneous overexpression of either CCND1 or CCND2 in ovarian cancer. Conclusion: HOTAIR enhanced CCND1 and CCND2 expression by negatively modulating miR-206 expression and stimulating the proliferation, cell cycle progression, migration and invasion of ovarian cancer cells

Differences in brain gray matter volume in patients with Crohn’s disease with and without abdominal pain

Increasing evidence indicates that abnormal pain processing is present in the central nervous system of patients with Crohn’s disease (CD). The purposes of this study were to assess changes in gray matter (GM) volumes in CD patients in remission and to correlate structural changes in the brain with abdominal pain. We used a 3.0 T magnetic resonance scanner to examine the GM structures in 21 CD patients with abdominal pain, 26 CD patients without abdominal pain, and 30 healthy control subjects (HCs). Voxel-based morphometric analyses were used to assess the brain GM volumes. Patients with abdominal pain exhibited higher CD activity index and lower inflammatory bowel disease questionnaire scores than those of the patients without abdominal pain. Compare to HCs and to patients without abdominal pain, patients with abdominal pain exhibited lower GM volumes in the insula and anterior cingulate cortex (ACC); whereas compare to HCs and to patients with abdominal pain, the patients without abdominal pain exhibited higher GM volumes in the hippocampal and parahippocampal cortex. The GM volumes in the insula and ACC were significantly negatively correlated with daily pain scores. These results suggest that differences exist in the brain GM volume between CD patients in remission with and without abdominal pain. The negative correlation between the GM volumes in the insula and ACC and the presence and severity of abdominal pain in CD suggests these structures are closely related to visceral pain processing

Difference in regional neural fluctuations and functional connectivity in Crohn’s disease: a resting-state functional MRI study

Patients with Crohn’s disease (CD) are shown to have abnormal changes in brain structures. This study aimed to further investigate whether these patients have abnormal brain activities and network connectivity. Sixty patients with CD and 40 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) were used to assess differences in spontaneous regional brain activity and functional connectivity. Compared to the HCs, patients with CD showed significantly higher ALFF values in hippocampus and parahippocampus (HIPP/paraHIPP), anterior cingulate cortex, insula, superior frontal cortex and precuneus. The ALFF values were significantly lower in secondary somatosensory cortex (S2), precentral gyrus, and medial prefrontal cortex. Functional connectivities between left HIPP and left inferior temporal cortex, and right middle cingulate cortex, HIPP, and fusiform area were significantly lower. The functional connectivities between right HIPP and right inferior orbitofrontal cortex and left HIPP were also significantly lower. Patients with CD showed higher or lower spontaneous activity in multiple brain regions. Altered activities in these brain regions may collectively reflect abnormal function and regulation of visceral pain and sensation, external environmental monitoring, and cognitive processing in these patients. Lower functional connectivity of the hippocampus-limbic system was observed in these patients. These findings may provide more information to elucidate the neurobiological mechanisms of the disease

Mean Platelet Volume and Platelet Distribution Width as Markers in the Diagnosis of Acute Gangrenous Appendicitis

Introduction. Acute gangrenous appendicitis (AGA) is a common medical condition; however, the grade of appendicitis usually cannot be established preoperatively. We have attempted to identify some indicators, such as the mean platelet volume (MPV) and the platelet distribution width (PDW), to diagnose AGA. Aims. To evaluate whether or not the MPV and PDW are suitable markers to diagnose AGA. Methods. A retrospective study of 160 patients with AGA and 160 healthy patients was undertaken. Disease diagnosis was confirmed based on the pathologic examination of surgical specimens. Patient white blood cell (WBC) count, neutrophil ratio (NR), platelet (PLT) count, MPV, PDW, and hematocrit (HCT) were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of these indices in AGA. Results. There were no significant differences between the AGA and control groups in age and gender. Compared to the control group, the WBC count, NR, and PDW were significantly higher ( &lt; 0.001, resp.) and the MPV and HCT were significantly lower ( &lt; 0.001, resp.) in the AGA group. The diagnostic specificities of the WBC count, NR, PLT count, MPV, PDW, and HCT were 86.3%, 92.5%, 58.1%, 81.7%, 83.9%, and 66.3%, respectively. Therefore, the NR had the highest diagnostic specificity for the diagnosis of AGA. Conclusions. This is the first study to assess the MPV and PDW in patients with AGA. Our present study showed that the MPV is reduced and the PDW is increased in patients with AGA; the sensitivity of PDW was superior to the MPV. A decreased MPV value and an increased PDW could serve as two markers to diagnose AGA. The NR had the highest specificity for the diagnosis of AGA

The progression rate of spinocerebellar ataxia type 3 varies with disease stage

Background: In polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions. Methods: Data were derived from the longest longitudinal study, with 642 examinations by International Cooperative Ataxia Rating Scale (ICARS) from 82 SCA3 participants. Using different time scales of disease duration, we performed multiple different linear, quadratic and piece-wise linear growth models to fit the relationship between ICARS scores and duration. Models comparison was employed to determine the best-fitting model according to goodness-of-fit tests, and the analysis of variance among nested models. Results: An acceleration was detected after 13 years of duration: ICARS scores progressed 2.445 (SE: 0.185) points/year before and 3.547 (SE: 0.312) points/year after this deadline. Piece-wise growth model fitted better to studied data than other two types of models. The length of expanded CAG repeat (CAGexp) in ATXN3 gene significantly influenced progression. Age at onset of gait ataxia (AOga), a proxy for aging process, was not an independent modifier but affected the correlation between CAGexp and progression. Additionally, gender had no significant effect on progression rate of ICARS. The piece-wise growth models were determined as the predictive models, and ICARS predictions from related models were available. Conclusions: We first confirmed that ICARS progressed as a nonlinear pattern and varied according to different stages in SCA3. In addition to ATXN3 CAGexp, AOga or aging process regulated the progression by interacting with CAGexp

Different brain responses to electro-acupuncture and moxibustion treatment in patients with Crohn's disease

This study aimed to investigate changes in resting state brain activity in remissive Crohn's Disease (CD) patients after electro-acupuncture or moxibustion treatment. Fifty-two CD patients and 36 healthy subjects were enrolled, and 36 patients were equally and randomly assigned to receive either electro-acupuncture or moxibustion treatment for twelve weeks. We used resting state functional magnetic resonance imaging to assess Regional Homogeneity (ReHo) levels, and Crohn's Disease Activity Index (CDAI) and Inflammatory Bowel Disease Questionnaire (IBDQ) scores to evaluate disease severity and quality of life. The results show that (i) The ReHo levels in CD patients were significantly increased in cortical but decreased in subcortical areas, and the coupling between them was declined. (ii) Both treatments decreased CDAI, increased IBDQ scores, and normalized the ReHo values of the cortical and subcortical regions. (iii) ReHo changes in multiple cortical regions were significantly correlated with CDAI score decreases. ReHo changes in several subcortical regions in the electro-acupuncture group, and those of several cortical regions in the moxibustion group, were correlated with reduced CDAI. These findings suggest that both treatments improved cortex-subcortical coupling in remissive CD patients, but electro-acupuncture regulated homeostatic afferent processing network, while moxibustion mainly regulated the default mode network of the brain

Effects of Moxibustion Stimulation on the Intensity of Infrared Radiation of Tianshu (ST25) Acupoints in Rats with Ulcerative Colitis

ST25 is a key acupoint used in the treatment of ulcerative colitis by moxibustion stimulation, but the biophysical mechanism underlying its effects is still unknown. The aim of the present study was to explore the biophysical properties of ST25 acupoint stimulated by moxibustion in a rat model of ulcerative colitis. The infrared radiation intensity of fourteen wavelengths of ST25 showed significant differences between the normal and model control groups. The intensity of infrared radiation of forty wavelengths showed significant differences compared with the corresponding control points in normal rats. The intensity of infrared radiation of twenty-eight wavelengths showed significant differences compared with the corresponding control points in model rats. The intensity of infrared radiation of nine wavelengths in the herb-partition moxibustion group, eighteen wavelengths in the ginger-partition moxibustion group, seventeen wavelengths in the garlic-partition moxibustion group, and fourteen wavelengths in the warming moxibustion group of the left ST25 showed significant differences compared with that of the model control group. For the right-hand-side ST25, these values were 33, 33, 2, and 8 wavelengths, respectively. This indicated that one possible biophysical mechanism of moxibustion on ST25 in ulcerative colitis model rats might involve changes in the intensity of infrared radiation of ST25 at different wavelengths