WGCNA and transcriptome profiling reveal hub genes for key development stage seed size/oil content between wild and cultivated soybean.

BACKGROUND: Soybean is one of the most important oil crops in the world. The domestication of wild soybean has resulted in significant changes in the seed oil content and seed size of cultivated soybeans. To better understand the molecular mechanisms of seed formation and oil content accumulation, WDD01514 (E1), ZYD00463 (E2), and two extreme progenies (E23 and E171) derived from RILs were used for weighted gene coexpression network analysis (WGCNA) combined with transcriptome analysis. RESULTS: In this study, both seed weight and oil content in E1 and E171 were significantly higher than those in E2 and E23, and 20 DAF and 30 DAF may be key stages of soybean seed oil content accumulation and weight increase. Pathways such as "Photosynthesis", "Carbon metabolism", and "Fatty acid metabolism", were involved in oil content accumulation and grain formation between wild and cultivated soybeans at 20 and 30 DAF according to RNA-seq analysis. A total of 121 oil content accumulation and 189 seed formation candidate genes were screened from differentially expressed genes. WGCNA identified six modules related to seed oil content and seed weight, and 76 candidate genes were screened from modules and network. Among them, 16 genes were used for qRT-PCR and tissue specific expression pattern analysis, and their expression-levels in 33-wild and 23-cultivated soybean varieties were subjected to correlation analysis; some key genes were verified as likely to be involved in oil content accumulation and grain formation. CONCLUSIONS: Overall, these results contribute to an understanding of seed lipid metabolism and seed size during seed development, and identify potential functional genes for improving soybean yield and seed oil quantity.

Association between Different Types of Tea Consumption and Risk of Gynecologic Cancer: A Meta-Analysis of Cohort Studies.

Plenty of studies have shown that tea has an effect of inhibiting gynecologic tumors. However, there still remained controversy of the association between tea and gynecologic tumors in epidemiological studies. In this study, PubMed, Embase, and Cochrane Database were used to search the literature from 1 January 1960 to 26 December 2022 to investigate the association between tea intake and gynecologic cancer risk. In total, 19 cohort studies with 2,020,980 subjects and 12,155 gynecological tumor cases were retrieved. The pooled relative risk (RR) of gynecologic tumor for tea intake was 1.00 (95% CI: 0.96-1.04). RRs were 0.94 (95% CI: 0.88-1.01) for ovarian cancer, 1.02 (95% CI: 0.97-1.07) for endometrial cancer, and 1.06 (95% CI: 0.91-1.23) for cervical cancer. Subgroup analyses were adopted based on the tea type and geographic location. Interestingly, significant preventive impact of non-herbal tea on ovarian cancer (pooled relative risk: 0.67; 95% CI: 0.55-0.81) was found, especially for black tea (pooled relative risk: 0.64; 95% CI: 0.51-0.80). Dose-response analysis indicated that although it is not statistically significant, a decreasing trend of ovarian cancer risk could be observed when the tea consumption was 1.40 to 3.12 cups/day. In conclusion, our findings suggested that ovarian cancer, but not other gynecologic cancers, could possibly be prevented by drinking non-herbal tea. In addition, the preventive impact of green tea on gynecologic cancer seemed to be relatively weak and needs further cohorts to validate it.

Hyperthermia synergistically enhances antitumor efficacy of PARP inhibitor through impacting homologous recombination repair and oxidative stress in vitro.

Tumors with homologous recombination (HR) deficiency are particularly responsive to PARP inhibitors, however strategies to improve the sensitivity of epithelial ovarian carcinoma (EOC) with sufficient HR abilities still need to be deeply explored. In the present study, we firstly validated that hyperthermia (HT) changed diverse genes and signal pathways related to HR and oxidative stress in HR proficient EOC cells. HT impaired HR efficiency through inhibiting Olaparib (Olap) induced RAD51 foci formation in EOC cells, which was independent of the expression level of RAD51. Combination therapy of HT and Olap synergistically induced oxidative stress and oxidative DNA damage of EOC cells. Furthermore, we revealed that HT and Olap synergistically aggravated double-strand breaks of DNA in EOC cells. Conclusively, our findings confirmed that HT could synergistically enhance HR proficient EOC cells' sensitivity to PARP inhibitor through impairing HR efficiency and increasing oxidative stress.

Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1.

Long noncoding RNAs (lncRNAs) play diverse roles in biological processes, but their expression profiles and functions in cervical carcinogenesis remain unknown. By RNA-sequencing (RNA-seq) analyses of 18 clinical specimens and selective validation by RT-qPCR analyses of 72 clinical samples, we provide evidence that, relative to normal cervical tissues, 194 lncRNAs are differentially regulated in high-risk (HR)-HPV infection along with cervical lesion progression. One such lncRNA, lnc-FANCI-2, is extensively characterized because it is expressed from a genomic locus adjacent to the FANCI gene encoding an important DNA repair factor. Both genes are up-regulated in HPV lesions and in in vitro model systems of HR-HPV18 infection. We observe a moderate reciprocal regulation of lnc-FANCI-2 and FANCI in cervical cancer CaSki cells. In these cells, lnc-FANCI-2 is transcribed from two alternative promoters, alternatively spliced, and polyadenylated at one of two alternative poly(A) sites. About 10 copies of lnc-FANCI-2 per cell are detected preferentially in the cytoplasm. Mechanistically, HR-HPVs, but not low-risk (LR)-HPV oncogenes induce lnc-FANCI-2 in primary and immortalized human keratinocytes. The induction is mediated primarily by E7, and to a lesser extent by E6, mostly independent of p53/E6AP and pRb/E2F. We show that YY1 interacts with an E7 CR3 core motif and transactivates the promoter of lnc-FANCI-2 by binding to two critical YY1-binding motifs. Moreover, HPV18 increases YY1 expression by reducing miR-29a, which targets the 3' untranslated region of YY1 mRNA. These data have provided insights into the mechanisms of how HR-HPV infections contribute to cervical carcinogenesis.

Association between vitamin D/calcium intake and 25-hydroxyvitamin D and risk of ovarian cancer: a dose-response relationship meta-analysis.

BACKGROUND: The association between vitamin D/calcium and risk of ovarian cancer is still a debatable point. The aim of our study was to systematically investigate the association between vitamin D/calcium, and the risk of ovarian cancer and estimate their dose-response association quantitatively. METHODS: PubMed, EMBASE, and Web of Science databases were searched to identify relevant observational studies. Two investigators screened citations and extracted data independently. Data were extracted and the association between vitamin D/calcium and ovarian cancer risk was estimated by calculating pooled relative risks (RRs). Subgroup analyses, publication bias estimation, and dose-response analyses were carried out as well. RESULTS: In total, 21 articles involving 980,008 participants were included in our present study. No significant association was observed between total vitamin D intake and ovarian cancer risk (RR: 1.02; 95% CI, 0.89-1.16, p = 0.81). Further subgroup analysis suggested that neither dietary vitamin D intake (RR: 0.80; 95% CI, 0.62-1.03, p = 0.09) nor supplementary vitamin D intake (RR: 0.98; 95% CI, 0.85-1.13, p = 0.80) was associated with the risk of ovarian cancer. As for calcium, total calcium intake was found to be statistically inversely associated with ovarian cancer risk in case-control studies (RR: 0.73; 95% CI, 0.63-0.86, p < 0.001) but not in cohort studies (RR: 1.05; 95% CI, 0.90-1.24, p = 0.52). Besides, supplementation with calcium plus vitamin D was not effective for the prevention of ovarian cancer (p = 0.98). Of note, dose-response analysis based on cohort studies suggested a potential inverse U-shape relationship between calcium intake (including total calcium and dietary calcium) and ovarian cancer risk, which indicated that low dose of calcium intake might reduce ovarian cancer risk while high dose of calcium intake might not. CONCLUSIONS: Taken together, vitamin D could not decrease the risk of ovarian cancer. The role of calcium intake was not proven for reducing ovarian cancer risk. Besides, no evidence showed combinative use of calcium and vitamin D have additional benefits for ovarian cancer prevention.

Efficacy of hyperthermic intraperitoneal chemotherapy in patients with epithelial ovarian cancer: a meta-analysis.

Objective: The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer (EOC) is still controversial. Present analysis aims to evaluate the survival benefit of HIPEC in treatment of EOC patients. Methods: Articles related to 'HIPEC' and 'ovarian cancer' were comprehensively searched in four databases (PubMed, EMBASE, MEDLINE and Cochrane Library) up to 4 February 2018. Eligible studies were identified depending on the selection criteria. The survival outcome and adverse events were collected. The relationship between HIPEC and survival of EOC was assessed using random-effects models. Results: A total of 1464 patients from 17 trials were subjected to analysis. The pooled results showed that HIPEC significantly improved overall survival (OS, HR = 0.50, 95% CI 0.36-0.69; p = 0.000) and progression-free survival (PFS, HR = 0.57, 95% CI 0.47-0.69; p = 0.000) among EOC patients when compared with no HIPEC controls. Similar results were observed in each year rate of survival. Subgroup analysis didn't lead to the opposite results, except no significant increased 1-year of OS in primary EOC and 1- and 2-year of PFS in recurrent EOC treated with HIPEC were observed. No significant difference existed in the adverse events and mortality between HIPEC and no HIPEC. Conclusions: HIPEC is associated with improved OS and PFS in both primary and recurrent EOC. However, no significant increased 1- and 2-year of PFS were reached in recurrent EOC treated with HIPEC. Further prospective randomized controlled trials are warranted.

Effect of leonurine hydrochloride on endothelin and the endothelin receptor-mediated signal pathway in medically-induced incomplete abortion in rats.

OBJECTIVE: Endothelin (ET) is involved in uterine contractions. Our previous study showed that leonurine hydrochloride (LH) inhibits abnormal bleeding caused by incomplete abortion through an increase in uterine contractions in rats. The present study was conducted to show that LH treatment regulates the ET-mediated signal pathway in abortion in rats. STUDY DESIGN: Early pregnancies in rats had incomplete abortions induced using mifepristone in combination with misoprostol. After the abortions, the rats were treated with LH orally for 7 days and surgery was performed. The sinistro-uterus was dissected for measurement of ET and nitric oxide (NO); the dextro-uterus was stored at -80°C for ET receptor (ETA and ETB) analysis. Myometrial cells from the dextro-uterus were cultured for measurement of phospholipase C (PLC) activity, intra-cellular Ca(2+) concentration ([Ca(2+)]i), and protein kinase C (PKC) activity. RESULTS: In in vivo experiments, LH treatment elevated the ET level and ET/NO ratio in rats with induced abortions and up-regulated ETA mRNA expression (P<0.01 vs. the model group), but there was no change in ETB mRNA. LH significantly increased the [Ca(2+)]i, PLC activity, and relative production of PKC protein in myometrial cells. CONCLUSION: LH increased uterine contractions in rats with incomplete abortions by modulating the ET receptor-mediated signal pathway.

Effects of leonurine hydrochloride on medically induced incomplete abortion in early pregnancy rats.

OBJECTIVES: To determine the effect of leonurine hydrochloride (LH) on abnormal bleeding induced by medical abortion. STUDY DESIGN: Rats had incomplete abortions induced in early pregnancy using mifepristone in combination with misoprostol. After abortion, rats were treated with LH for 7 days, and the duration and volume of uterine bleeding were observed. Approximately 30min after the last treatment, the animals were killed and the uterine shape was observed. The sinistro-uteri were suspended in organ baths to record the contraction curves, including the frequency and tension for 10min; the dextro-uteri were fixed with formaldehyde for pathologic evaluation. In addition, blood samples were collected from the femoral artery for the measurement of estradiol (E2) and progesterone (P) levels by radioimmunoassay. RESULTS: In in vivo experiments, compared with the model group, LH treatment markedly reduced the volume of bleeding and intrauterine residual, and significantly shortened the duration of bleeding. From the contraction curve, LH notably reinforced the frequency and tension of uterine contractions. LH remarkably elevated the serum estradiol level in rats, but had no obvious effect on progesterone level. CONCLUSIONS: LH has an inhibitory effect on bleeding caused by incomplete abortion; the mechanism may be related to up-regulation of the E2 level, leading to an increase in uterine contractions and evacuation of intrauterine residuum.

Progressive miRNA expression profiles in cervical carcinogenesis and identification of HPV-related target genes for miR-29.

miRNAs have the potential to act on diverse downstream genes, and miRNA signatures of HPV-infected tissues may provide insight into HPV-related carcinogenesis. We set out to profile miRNA expression in HPV-infected samples and relate this to histological and grade-specific alterations in the spectrum of cervical carcinogenesis in vivo. A total of 31 miRNAs showed significant and continuous expression along with the progression from normal cervical tissue to cancer, and six of them were validated in 133 samples. By bioinformatics analyses, we established a putative HPV-associated miRNA-mRNA regulatory network, showing that miR-29 is the most highly enriched. We also found that YY1 and CDK6 were both positively correlated with E6/E7 RNA expression and targeted by tumour-suppressive miR-29. Evidence of miR-29 involvement in HPV infection was further verified in patient samples and by various experimental approaches. Taken together, our results suggest that HPVs have oncogenic properties at least in part by reshaping the milieu of cellular miRNAs. miR-29 restrains cell cycle progression and induces apoptosis via YY1 and CDK6 promoting malignant transformation induced by HPV, although the abnormality of miR-29 in HPV-infected cells might be regulated in an indirect way.

[Anti-fertility effect of Tongbi composition and its reversibility in male rats].

OBJECTIVE: To study the anti-fertility effect of maximum-dose Tongbi Composition and its reversibility in male rats. METHODS: Thirty-six male SD rats were equally randomized into a control group and a medication group, the former given normal saline at 10 ml/(kg x d), while the latter treated with Tongbi Composition at 10 g/(kg x d), both for 60 days. Half the rats of each group were sacrificed randomly at the cessation of treatment, and the rest killed at 72 days after it. The relative testis weight, testis volume, sperm concentration and sperm motility were measured, and the pathological changes in the testicular tissue observed under the optical microscope. RESULTS: After 60 days of treatment, no statistically significant differences were found between the two groups in the relative testis weight, testis volume and sperm concentration (P > 0.05) , and the sperm motility of the medication group dropped to zero, but it was restored to normal at 72 days after drug withdrawal. Almost no lesions were observed in the testis tissue of the medication group. CONCLUSION: The short-term use of Tongbi Composition at the maximum clinical dose has an obvious anti-fertility effect, but it is reversible.

Inhibition of acid-sensing ion channels in articular chondrocytes by amiloride attenuates articular cartilage destruction in rats with adjuvant arthritis.

OBJECTIVE: The aim of this study was to examine whether drugs such as amiloride that block acid sensing ion channels (ASICs) could attenuate articular cartilage destruction in adjuvant-induced arthritis (AA). METHODS: Articular chondrocytes were isolated from the normal rats, and intracellular calcium ([Ca(2+)]i) was analyzed with laser scanning confocal microscopy. The cell injury was analyzed with lactate dehydrogenase release assay and electron microscopy. Amiloride or phosphate buffered saline was administered daily to AA rats for 1 week from the time of arthritis onset. Morphology of the articular cartilage was examined by hematoxylin and eosin staining, and Mankin score was calculated. The expression level of type II collagen (COII) and aggrecan mRNA and proteins in the articular cartilage was evaluated by real-time PCR and Western blotting, respectively. RESULTS: The rapid decrease in extracellular pH (6.0) induced a conspicuous increase in [Ca(2+)]i in the articular chondrocytes. Amiloride reduced this increase in [Ca(2+)]i, and inhibited acid-induced articular chondrocyte injury. Amiloride significantly decreased Mankin scores in the articular cartilage in AA rats. COII and aggrecan mRNA and protein expression in the articular cartilage was significantly increased by amiloride. CONCLUSION: These findings represent some experimental evidence of a potential role for ASICs in the pathogenesis of articular cartilage destruction in rheumatoid arthritis.

[Development of intraperitoneally transplantated human ovarian carcinoma model with immune reconstruction in severe combined immunodeficient mice].

OBJECTIVE: To develop an intraperitoneally transplanted human ovarian carcinoma model in humanized severe combined immunodeficient (SCID) mice. METHODS: Twelve CB17SCID mice were randomly divided into 4 groups: group A intraperineally injected with phosphate-buffered saline, group B injected with human ovarian carcinoma cells SKOV3, group C injected with human peripheral blood lymphocyte (PBL) for immune reconstruction, and group D injected with PBL and SKOV3 cells. The behaviors of mice, tumor growth and morphology, human IgG in peripheral blood, cancer antigen 125 (CA125) immunohistochemical staining, tumor infiltrating lymphocyte (TIL), and status of graft versus host disease (GVHD) were detected. RESULTS: The survival period was > 28 days in all groups. The ratio of successful tumor transplantation was 3/3 in groups B and D. The tumor was widespread in peritoneal cavity, mainly in diaphragm, liver, and mesentery, with bloody ascites. The number and size of tumor were less in the humanized group. CA125 expression was positive in primary transplanted tumor cells and SKOV3 cells. IgG was detected in humanized groups (C and D). The level of human IgG was significantly higher in group D than in group C (P < 0.05). TIL infiltration was remarkable in group injected with PBL and SKOV3 cells and failed to be found in group injected with SKOV3 cells. No GVHD was found in all groups. CONCLUSION: An intraperitoneal transplanted human ovarian carcinoma model has been established in humanized SCID mice that simulates the biological behavior of human ovarian carcinoma disseminating intraperitoneally in patients with immune function and may function as an ideal animal model for preclinical research of ovarian carcinoma treatment.