Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment: A prospective study.

BACKGROUND: Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques. AIM: To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE). METHODS: This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. The two groups were matched for age, body mass index, parity, and baseline characteristics of uterine fibroids. The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), as well as ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). The secondary outcome was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The participants were followed-up for 36 months and assessed at 1, 3, 6, 12, 24, and 36 months after treatment. RESULTS: The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women, resolving within a week. No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones (FSH, LH, E2, AMH) and ovarian reserve indicators (AFC, OV) at any point up to 36 months post-treatment. Additionally, there were no significant differences in conception, pregnancy, or delivery rates, with the average time to conception and gestational age at delivery being similar between the two groups. Birth weights were also comparable. Finally, there was no significant correlation between ovarian function, fertility indicators, and the type or amount of embolic agent used or the change in fibroids post-treatment. CONCLUSION: UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Portal vein computed tomography imaging characteristics and their relationship with bleeding risk in patients with liver cirrhosis undergoing interventional therapy.

BACKGROUND: This study aimed to analyze the predictive value of multi-slice spiral computed tomography (CT) perfusion imaging for upper gastrointestinal bleeding in patients with cirrhotic portal hypertension. A total of 62 patients with cirrhotic portal hypertension and 28 healthy individuals were included. The results showed that multi-slice spiral CT perfusion imaging had a significant predictive value for upper gastrointestinal bleeding in patients with cirrhotic portal hypertension. The vascular area, number of vascular cross-sections, and gastric coronary vein diameter (GCVD) showed high predictive values, with the vascular area having the best predictive value. AIM: To investigate the predictive accuracy of multi-slice spiral CT perfusion imaging for upper gastrointestinal bleeding in patients with cirrhosis and portal hypertension. METHODS: This study included 62 patients with cirrhotic portal hypertension (disease group) and 28 healthy individuals (control group). The disease group was further divided into two subgroups: Group A (n = 27, bleeding) and group B (n = 35, no bleeding). All patients underwent multi-slice spiral CT perfusion imaging at our hospital, and we compared various parameters such as liver blood flow, vein size, number of blood vessels, and blood vessel area between the two groups. We employed statistical analysis to identify factors associated with upper gastrointestinal bleeding and created a graph comparing the predictive value of different factors for bleeding. RESULTS: We found no difference in hepatic artery (HAP) levels among the three groups (all P > 0.05). The portal vein levels in groups A and B were much lower than in the control group; group A was much lower than group B (all P < 0.05). The HAP perfusion index levels in groups A and B were much higher than in the control group; group A was much higher than group B (all P < 0.05). The portal vein diameter, splenic vein diameter, and GCVD levels in groups A and B were much higher than in the control group; those in group A were much higher than those in group B (all P < 0.05). The number of blood vessels and blood vessel area in groups A and B were much higher than in the control group; those in group A were much higher than those in group B (all P < 0.05). The statistical method showed a strong link between GCVD, number of blood vessels, blood vessel area, and upper gastrointestinal bleeding (odds ratio = 1.275, 1.346, 1.397, P < 0.05). The graph showed that GCVD, number of blood vessels, and blood vessel area could predict bleeding well, with blood vessel area having the best prediction power. CONCLUSION: That multi-slice spiral CT perfusion imaging can predict upper gastrointestinal bleeding well in patients with cirrhosis and high blood pressure in the portal vein. GCVD, number of blood vessels, and blood vessel area had high prediction power. The blood vessel area had the best prediction power, with an area under the curve of 0.831.

Transcriptome analyses reveal the effects of mixed saline-alkali stress on indoleacetic acid and cytokinins in Malus hupehensis Rehd. leaves.

Saline-alkali stress is a universal abiotic stress factor limiting fruit tree cultivation worldwide. Apple (Malus×domestica Borkh.) is one of the fruits with the largest yields worldwide. Tea crabapple (Malus hupehensis Rehd. var. pingyiensis Jiang) is a type of common apple rootstock in China. Because facultative apomixis occurs in this species, it is often used in molecular research. The present study investigated the molecular mechanism of the response of indoleacetic acid (IAA) and cytokinins [zeatin, trans-zeatin riboside (tZR), isopentenyladenine (iP), and isopentenyladenosine (iPA)] to mixed saline-alkali stress (MSAS) in tea crabapple leaves. The endogenous hormone content of tea crabapple leaves under MSAS was measured, and the expression of stress response-related genes was analyzed by RNA sequencing. The results showed that the concentration of IAA was initially higher and then lower than that in the control, whereas the concentration of zeatin, tZR, iP, and iPA was higher than that in the control. A total of 1262 differentially expressed genes were identified in the three comparison groups. Further analyses suggested that IAA and cytokinin biosynthetic genes were mostly upregulated in tea crabapple leaves, indicating that auxin and cytokinin signaling pathway regulation occurred in response to MSAS. These findings suggest that IAA and cytokinins play an important role in the response of tea crabapple to MSAS. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01275-4.

circMTDH.4/miR-630/AEG-1 axis participates in the regulation of proliferation, migration, invasion, chemoresistance, and radioresistance of NSCLC.

Astrocyte elevated gene-1 (AEG-1) plays a critical role in the development, progression, and metastasis of a variety of cancers, including non-small-cell lung cancer (NSCLC). The objective of the current study is to unravel the upstream signaling of AEG-1. A cohort of 28 NSCLC tissues and 30 normal tissues were collected. Quantitative reverse transcription-polymerase chain reaction and Western blotting were used to examine AEG-1, migration, and invasion related markers in NSCLC cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay coupled with colony formation assay were conducted to monitor cell growth. Transwell assay was performed to determine cell migration and invasion. Apoptotic cells were detected by costaining with Annexin-V-fluorescein isothiocyanate and propidium iodide. Immunofluorescent staining was used to observe the levels of migration and invasion related markers. Xenograft models were used to investigate tumor formation in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to determine the interaction between circMTDH.4 and miR-630, as well as the associated between miR-630 and AEG-1. AEG-1 was highly expressed in NSCLC tissues and cell lines. Silencing of AEG-1 inhibited cell proliferation, migration, invasion, and chemoresistance/radioresistance in NCI-H1650 and A549 cells. circMTDH.4 regulated AEG-1 expression via sponging miR-630. Knockdown of circMTDH.4 and/or overexpression of miR-630 inhibited chemoresistance and radioresistance in NSCLC cells, whereas overexpression of AEG-1 or knockdown of miR-630 exerted rescue effects. circMTDH.4/miR-630/AEG-1 axis is responsible for chemoresistance and radioresistance in NSCLC cells.

Small compound bigelovin exerts inhibitory effects and triggers proteolysis of E2F1 in multiple myeloma cells.

Multiple myeloma (MM) is a currently incurable blood cancer. Here we tested the effects of a small compound bigelovin on MM cells, and reported that it caused cell cycle arrest and subsequently induced apoptosis. Bigelovin triggered proteolysis of E2F1, which could be inhibited by caspase inhibitor. To investigate the clinical relevance, the expression of E2F1 in MM specimens was tested, and the results showed that E2F1 was overexpressed in 25-57% of MM patients and was associated with higher International Staging System (ISS) stage. These results suggest that E2F1 may be important for MM pathogenesis, and bigelovin could serve as a lead compound for the development of E2F1 inhibitor.

USP22 acts as an oncogene by the activation of BMI-1-mediated INK4a/ARF pathway and Akt pathway.

Recent studies provided strong support for the view that ubiquitin-specific protease 22 (USP22) plays a central role in cell-cycle progression and also in pathological processes such as oncogenesis. We have recently shown that USP22 levels are elevated in colorectal carcinoma with associated increase in the expression of several cell-cycle-related genes. However, the precise mechanism for these functions of USP22 at molecular level has not been fully elucidated. Currently, we investigated the role of USP22 in human colorectal cancer (CRC). We observed that USP22 expression was statistically significantly correlated positively with that of BMI-1, c-Myc and both, pAkt (Ser473), and pAkt (Thr308), in primary tumor tissues from 43 CRC patients. Down-regulation of USP22 expression in HCT116 colorectal cancer cells by siRNA resulted in the accumulation of cells in the G1 phase of the cell cycle. RNAi-knockdown of USP22 in HCT16 cells also led to the repression of BMI-1 and was accompanied by the up-regulation of p16INK4a and p14ARF, with a consequent decrease in E2F1 and p53 levels. In addition, down-regulation of c-Myc-targeted cyclin D2 was also noticed in cells treated with USP22-siRNA. Furthermore, our results showed that USP22 deletion also caused down-regulation of Akt/GSK3ß activity, which can also contribute to the reduction of cyclin D2. Collectively, our current results suggest that USP22 may act as an oncogene in CRC as it positively regulates cell cycle via both BMI-1-mediated INK4a/ARF pathway and Akt signaling pathway.

SPARC modulates expression of extracellular matrix genes in human trabecular meshwork cells.

PURPOSE: To investigate the effects of secreted protein acidic and rich in cysteine (SPARC) on the expression of components of the extracellular matrix (ECM) in cultured human trabecular meshwork (TM) cells. METHODS: Cultured human trabecular cells were transfected with small interfering RNAs (siRNAs) specific for the human SPARC gene. Protein and mRNA expressions of fibronectin (FN) and the α1chains of collagen I and collagen III were quantified. RESULTS: After silencing of the SPARC gene by transfection of cells with SPARC siRNA, the expression of COL1A1 and COL3A1 mRNAs and proteins was significantly enhanced, as compared to that in the control group (all, p < 0.001). In contrast, SPARC siRNA significantly reduced the expression of FN and SPARC mRNAs and FN protein, as compared to that in the control group (all, p < 0.001.). CONCLUSIONS: SPARC modulates the expression of several ECM genes in cultured human TM cells.

[Expression and prognostic value of M2 macrophages and regulatory T cells in gastric carcinoma tissue].

OBJECTIVE: To explore the prognostic value of M2 macrophages and regulatory T cells(Tregs) in gastric carcinoma. METHODS: Clinicopathological characteristics and follow up data of 135 patients with gastric carcinoma were collected. Patients included were those who underwent D2 radical resection(R0) at Zhongshan Hospital of Fudan University from February 1999 to December 2005. Tissue chips of gastric carcinoma specimen were stained using immunohistochemistry to determine the cells density and number of M2(CD163 positive) and Tregs(Foxp3 positive). RESULTS: The median positive cells density of M2 macrophages and Tregs in tumor tissue were 7.48/HP and 6.33/HP, respectively, higher than that in adjacent tissues(1.37/HP and 2.92/HP, P<0.001). The density of M2 macrophages was positively correlated with that of Treg cells(r=0.415, P<0.001) in tumor tissue. The median survival of patients with low expression of M2 and Tregs(n=43) was significantly longer than those with high expression of the 2 cells(n=45) (99.0 vs. 72.3 months, P<0.05). CONCLUSION: Combined detection of M2 macrophages and Tregs may predict the prognosis of gastric carcinoma.

Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene.

AIM: To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS: We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family, member 1 (ING1) expression. RESULTS: Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentiation and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion, tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION: These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.

Inhibition of survivin expression and mechanisms of reversing drug-resistance of human lung adenocarcinoma cells by siRNA.

BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effects of survivin-specific siRNA on cell proliferation, apoptosis and chemosensitivity to cisplatin in vitro and in vivo and explore the mechanisms about decreasing expression of survivin in reversing cancer cells resistance to chemotherapeutic drug. METHODS: Survivin-specific siRNA was transfected into A549/DDP cells. The expression of survivin and lung resistance-related protein (LRP) mRNA levels were determined by RT-PCR, chemosensitivity of A549/DDP (cisplatin) cells to cisplatin was determined by MTT assay, and apoptosis and cell cycle were determined by flow cytometry (FCM). The protein expression levels of survivin, LRP, cyclin-D(1), caspase-3 and bcl-2 were determined by Western blotting analyses. The effect of survivin siRNA inhibition on tumor growth was studied in athymic nude mice in vivo. RESULTS: Survivin-specific siRNA efficiently down-regulated survivin expression. The cell cycle was arrested at G2/M phase, and apoptosis was obviously found. Inhibition of survivin expression could make the IC50 and drug-resistant index of cisplatin decrease, and enhance the cancer cells sensitivity to cisplatin. After transfection by survivin-specific siRNA, expression of LRP and cyclin-D1 were downregulated, caspase-3 expression was upregulated, bcl-2 expression had no obvious change. The animal experiment confirmed knockdown of survivin could inhibit the tumor growth. CONCLUSIONS: Survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis, inhibit cells proliferation and enhance the chemosensitivity to cisplatin in vitro and in vivo. Suppression of survivin expression helping to reverse drug-resistance may have relationship with downregulation of LRP and upregulation of caspase-3. Anti-tumor strategies based on the inhibition of survivin may be useful in targeting lung adenocarcinomas.

[Expression of MDR1 and KIT in imatinib-resistant gastrointestinal stromal tumor cells].

OBJECTIVE: To explore the relationship between imatinib resistance and genes MDR1 and KIT in gastrointestinal stromal tumor (GIST) cells. METHODS: The MDR1 and KIT mRNA level in GIST882-R and GIST882-S cells were detected by RT-PCR. Immunocytochemistry and Western blot were employed to detect P-gp and CD117 expression in GIST882-R and GIST882-S cells. RESULTS: The relative expression of MDR1 mRNA was 0.321 + or - 0.033 in GIST882-R and 0.157 + or - 0.056 in GIST882-S cells, and the difference was statistically significant (P<0.05). The relative expression of KIT mRNA was 0.389 + or - 0.063 in GIST882-R and 0.339 + or - 0.067 in GIST882-S, and the difference was not statistically significant (P>0.05). The relative density of P-gp was 0.443 + or - 0.058 in GIST882-R and 0.237 + or - 0.094 in GIST882-S, and the difference was statistically significant (P<0.05). The relative density of CD117 was 0.744 + or - 0.123 in GIST882-R and 0.704 + or - 0.094 in GIST882-S, and the difference was not statistically significant (P>0.05). CONCLUSIONS: Over-expression of gene MDR1 may be associated with imatinib resistance in GIST. KIT may not be involved in imatinib resistance.

[Study on the mechanism of imatinib-induced resistance in gastrointestinal stromal tumors].

OBJECTIVE: To investigate the mechanism of imatinib mesylate (IM) induced-resistance in the patients with gastrointestinal stromal tumors (GISTs) and treated with imatinib. METHODS: Eight patients with GIST treated with IM developed secondary IM resistance. A total of 16 tumor samples (pre-IM therapy) and 11 tumor samples (post-IM treatment) were available. Exon 9, 11, 13, and 17 of c-kit gene as well as exon 12 and exon 18 of PDGFRA gene were sequenced. RESULTS: In addition to the changes of baseline genotype, the IM-induced gene changes were concentrated in the kinase domain of c-kit gene in all 8 patients, 2 of them were located in the exon 13 of c-kit gene presenting with V654A, while 6 in exon 17 involving 816 and 820 to 823 codons. CONCLUSION: The mechanism of imatinib mesylate resistance after initial treatment with this agent in gastrointestinal stromal tumors is a novel mutation development in kinase domain of c-kit.

Synergy between proteasome inhibitors and imatinib mesylate in chronic myeloid leukemia.

BACKGROUND: Resistance developed by leukemic cells, unsatisfactory efficacy on patients with chronic myeloid leukemia (CML) at accelerated and blastic phases, and potential cardiotoxity, have been limitations for imatinib mesylate (IM) in treating CML. Whether low dose IM in combination with agents of distinct but related mechanisms could be one of the strategies to overcome these concerns warrants careful investigation. METHODS AND FINDINGS: We tested the therapeutic efficacies as well as adverse effects of low dose IM in combination with proteasome inhibitor, Bortezomib (BOR) or proteasome inhibitor I (PSI), in two CML murine models, and investigated possible mechanisms of action on CML cells. Our results demonstrated that low dose IM in combination with BOR exerted satisfactory efficacy in prolongation of life span and inhibition of tumor growth in mice, and did not cause cardiotoxicity or body weight loss. Consistently, BOR and PSI enhanced IM-induced inhibition of long-term clonogenic activity and short-term cell growth of CML stem/progenitor cells, and potentiated IM-caused inhibition of proliferation and induction of apoptosis of BCR-ABL+ cells. IM/BOR and IM/PSI inhibited Bcl-2, increased cytoplasmic cytochrome C, and activated caspases. While exerting suppressive effects on BCR-ABL, E2F1, and beta-catenin, IM/BOR and IM/PSI inhibited proteasomal degradation of protein phosphatase 2A (PP2A), leading to a re-activation of this important negative regulator of BCR-ABL. In addition, both combination therapties inhibited Bruton's tyrosine kinase via suppression of NFkappaB. CONCLUSION: These data suggest that combined use of tyrosine kinase inhibitor and proteasome inhibitor might be helpful for optimizing CML treatment.

[Detection and clinical significance of plasma vascular endothelial growth factor level in gastrointestinal stromal tumor patients].

OBJECTIVE: To investigate the clinical significance of plasma vascular endothelial growth factor (p-VEGF) levels in gastrointestinal stromal tumor (GIST) patients. METHODS: The p-VEGF levels in 61 primary GIST patients, 18 patients with recurrence or metastasis, and 28 healthy blood donators (as control) were measured by enzyme-linked immunosorbent assay. Paired p-VEGF levels of pre- and post-treatment were obtained from 44 patients. One patient received 22 consecutive detections during the follow up. RESULTS: Primary and recurrent GIST patients had higher p-VEGF levels than healthy controls [(145.31+/-45.58) ng/L, (145.72+/-52.73) ng/L vs (89.86+/-18.30) ng/L] (P<0.01). And there were no significant differences between primary patients and patients with recurrence or metastasis (P>0.05). Significant difference were found in the p-VEGF levels between pre- and post-treatment patients (P<0.01). Post-treatment p-VEGF levels decreased markedly both in 26 primary and 11 recurrent patients [(101.81+/-27.63) ng/L and (112.45+/-38.58) ng/L]. As for the patient with 22 consecutive detections during the follow up, p-VEGF levels the period of were higher before surgery and after recurrence, and lower two months after surgery and during Glivec therapy. CONCLUSIONS: The p-VEGF level of GIST patients is significantly higher than that of healthy people, which will decrease markedly after effective management. Monitoring the p-VEGF level in GIST patients will be helpful to evaluate the therapeutic efficacy and predict the recurrence or metastasis.