Cholangiocarcinoma (CCA) is a severe malignancy usually producing a poor prognosis and high mortality rate. MicroRNAs (miRNAs) have been reported in association with CCA; however, the role miR‐329 ...plays in the CCA condition still remains unclear. Therefore, this study was conducted to explore the underlying mechanism of which miR‐329 is influencing the progression of CCA. This work studied the differential analysis of the expression chips of CCA obtained from the Gene Expression Omnibus database. Next, to determine both the expression and role of pituitary tumor transforming gene‐1 (PTTG1) in CCA, the miRNAs regulating PTTG1 were predicted. In the CCA cells that had been intervened with miR‐329 upregulation or inhibition, along with PTTG1 silencing, expression of miR‐329, PTTG1, p‐p38/p38, p‐ERK5/ERK5, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bcl‐2‐associated X protein (Bax), B‐cell CLL/lymphoma 2 (Bcl‐2), and caspase‐3 were determined. The effects of both miR‐329 and PTTG1 on cell proliferation, cell‐cycle distribution, and apoptosis were also assayed. The miR‐329 was likely to affect the CCA development through regulation of the PTTG1‐mediated mitogen‐activated protein kinase (MAPK) signaling pathway. The miR‐329 targeted PTTG1, leading to inactivation of the MAPK signaling pathway. Upregulation of miR‐329 and silencing of PTTG1 inhibited the CCA cell proliferation, induced cell‐cycle arrest, and subsequently promoted apoptosis with elevations in Bax, cleaved caspase‐3, and total caspase‐3, but showed declines in PCNA, Cyclin D1, and Bcl‐2. Moreover, miR‐329 was also found to suppress the tumor growth by downregulation of PTTG1. To summarize, miR‐329 inhibited the expression of PTTG1 to inactivate the MAPK signaling pathway, thus suppressing the CCA progression, thereby providing a therapeutic basis for the CCA treatment.
To summarize, miR‐329 inhibited the expression of pituitary tumor transforming gene‐1 to inactivate the mitogen‐activated protein kinase signaling pathway, thus suppressing the cholangiocarcinoma (CCA) progression, thereby providing a therapeutic basis for CCA treatment.
Hepatocellular carcinoma (HCC) is a common malignant gastrointestinal tumor. There are currently few clinical diagnostic and prognostic markers for HCC. LncRNA cancer susceptibility candidate 9 ...(CASC9) is a long-chain non-coding RNA discovered in recent years, and previous studies have found that lncRNA CASC9 participates in the occurrence and development of HCC, but its clinical value remains unclear.
To determine the expression of lncRNA CASC9 in HCC and its diagnostic and prognostic value.
Data on CASC9 expression in patients with HCC were collected from the Cancer Genome Atlas (TCGA) database to analyze the relationship between CASC9 and patient survival. A total of 80 HCC patients treated in The First Affiliated Hospital of Guangxi Medical University from May 2012 to January 2014 were enrolled in the patient group, and 50 healthy subjects were enrolled in the control group during the same period. CASC9 expression in the two groups was determined using quantitative real-time polymerase chain reaction, and its diagnostic and prognostic value was analyzed based on the CASC9 data and pathological data in these HCC patients. The relationship between CASC9 and patient survival was assessed during the 5-year follow-up period.
Analysis of data from TCGA database revealed that control samples showed significantly lower CASC9 expression than carcinoma tissue samples (
< 0.001); the low CASC9 expression group had a higher survival rate than the high CASC9 expression group (
= 0.011), and the patient group showed significantly increased expression of serum CASC9, with the area under the curve (AUC) of 0.933. CASC9 expression was related to tumor size, combined hepatitis, tumor, node, metastasis (TNM) staging, lymph node metastasis, differentiation and alpha fetoprotein, and the high CASC9 expression group showed lower 1-year, 3-year and 5-year survival rates than the low CASC9 expression group (all
< 0.05). Multivariate Cox regression analysis revealed that TNM staging, lymph node metastasis, differentiation, alpha fetoprotein and CASC9 were independent factors affecting the prognosis of patients. Stage I+II patients with lymph node metastasis, low differentiation, and alpha fetoprotein > 200 ng/mL had a poor 5-year survival rate.
High CASC9 expression is beneficial in the prognosis of HCC patients. CASC9 is expected to be a potential diagnostic and prognostic indicator of HCC.
During reprogramming, there is exchange of histone H1c and the oocyte-specific linker histone, and H1c may play a critically important role in the reprogramming process of somatic cell nuclear ...transfer (SCNT). The aim of the present study was to investigate the role of the H1c gene in SCNT reprogramming in Chinese swamp buffalo (Bubalus bubalis) using RNA interference (RNAi). Chinese swamp buffalo H1c gene sequences were obtained and H1c-RNAi vectors were designed, synthesised and then transfected into a buffalo fetal skin fibroblast cell line. Expression of H1c was determined by real-time polymerase chain reaction to examine the efficiency of vector interference. These cells were then used as a nuclear donor for SCNT so as to observe the further development of SCNT embryos. Inhibition of H1c gene expression in donor cells significantly improved the developmental speed of embryos from the 1-cell to 8-cell stage. Furthermore, compared with the control group, inhibition of H1c gene expression significantly reduced the blastocyst formation rate. It is concluded that linker histone H1c is very important in SCNT reprogramming in Chinese swamp buffalo. Correct expression of the H1c gene plays a significant role in preimplantation embryonic development in B. bubalis.
Non-alcoholic steatohepatitis (NASH) is a common liver disease in the western world. The mechanisms behind NASH formation are poorly understood, but there may be multiple targets considering the ...disease’s multifactorial nature. To explore the genes related to the pathogenesis of NASH, we downloaded clinical data and gene expression of NASH patients from the Gene Expression Omnibus database (GEO). We identified 281 genes with a common expression in two NASH-related datasets (GSE89632 and GSE83452), suggesting that they may be related to NASH. Further study showed that
Angptl4
,
Foxo1
, and
Ttc39B
might be essential for NASH progression, and these have been poorly studied. Therefore, we explored their roles in NASH. Our data show that these genes participate in the development of NASH through lipid metabolism. This suggests that the three genes can be used as therapeutic targets in NASH.
AIMS: Grassland conversion to cropland (GCC) may result in loss of a large amount of soil organic carbon (SOC). However, the assessment of such loss of SOC still involves large uncertainty due to ...shallow sampling depth, soil bulk density estimation and spatial heterogeneity. Our objectives were to quantify changes in SOC, soil total nitrogen (STN) and C:N ratio in 0–100 cm soil profile after GCC and to clarify factors influencing the SOC change. METHODS: A nest-paired sampling design was used in six sites along a temperature gradient in Northeast China. RESULTS: SOC change after GCC ranged from −17 to 0 Mg ha⁻¹ in 0–30 cm soil layer, recommended by IPCC, across the six sites, but ranged from −30 to 7 Mg ha⁻¹ when considering 0–100 cm. We found a linear relationship between SOC change in 30–100 cm and that in 0–30 cm profile (ΔC₃₀₋₁₀₀ = 0.35ΔC₀₋₃₀, P < 0.001), suggesting that SOC change in 0–100 cm was averagely 35 % higher than that in 0–30 cm. The change in STN showed a similar pattern to SOC, and soil C:N ratio did not change at most of sites. On the other hand, SOC loss after GCC was greater in soils with higher initial SOC content or in croplands without applying chemical fertilizers. Furthermore, SOC loss after GCC decreased with falling mean annual temperature (MAT), and even vanished in the coldest sites. CONCLUSIONS: The magnitude of SOC loss following GCC in Northeast China is lower than the global average value, partly due to low MAT here. However, the current low SOC loss can be intensified by remarkable climate warming in this region.
The FcγRs found on macrophages (Ms) and dendritic cells (DCs) efficiently facilitate the presentation or cross-presentation of immune-complexed Ags to T cells. We found that the MHC class I-related ...neonatal FcR for IgG (FcRn) in both Ms and DCs failed to have a strong effect on the cross-presentation of immune complex (IC) OVA Ag to CD8(+) T cells. Interestingly, endosomal FcRn enhanced the presentation of the monomeric OVA-IC to CD4(+) T cells robustly, whereas FcRn in phagosomes exerted distinctive effects on Ag presentation between Ms and DCs. The presentation of phagocytosed OVA-ICs to CD4(+) T cells was considerably enhanced on wild-type versus FcRn-deficient Ms, but was not affected in FcRn-deficient DCs. This functional discrepancy was associated with the dependence of IgG-FcRn binding in an acidic pH. Following phagocytosis, the phagosomal pH dropped rapidly to <6.5 in Ms but remained in the neutral range in DCs. This disparity in pH determined the rate of degradation of phagocytosed ICs. Thus, our findings reveal that FcRn expression has a different effect on Ag processing and presentation of ICs to CD4(+) T cells in the endosomal versus phagosomal compartments of Ms versus DCs.
A series of tetracyclic diterpenoids bearing α-methylenelactone group were synthesized from stevioside. Some of them exhibited significant cytotoxicity against all the six tumor cell lines with the ...IC50 values ranging from 0.09 to 5.71μM.
A series of tetracyclic diterpenoids bearing the α-methylenelactone group have been synthesized and screened for their in vitro anti-tumor activities against six human cancer cell lines. The results showed that compounds 1c, 2a and 2b exhibited significant cytotoxicity superior to the positive control doxorubicin hydrochloride against MDA-MB-231, K562 and HepG2 cell lines. In particular, compound 2b was identified as the most promising anticancer agent against HepG2 cells with IC50 value of 0.09μM.
Inhibitor of dsRNA-dependent protein kinase (PKRI) and medroxyprogesterone acetate (MPA) improve cancer cachexia via different mechanisms. We aimed to compare these two drugs, alone or in ...combination, in cancer cachexia in mice. Forty male BABL/c mice aged 6-8 weeks were randomly divided into PKRI, MPA, PKRI+MPA, placebo, and healthy control groups. The first 4 groups were injected with colon-26 adenocarcinoma and fed for 12 days and then treated with PKRI and MPA alone or in combination for 7 days. Body weight, tumor volume, wet weight of gastrocnemius muscle, serum levels of nutritional markers and cytokines were measured. The tumor growth (volume and weight) of mice treated with PKRI, MPA alone or PKRI+MPA was slower than that of placebo group. Wet weight of gastrocnemius muscle was significantly higher in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). All tumor-bearing mice had a significantly lower level of blood glucose, higher level of serum triglyceride and lower level of serum albumin compared with healthy control (P<0.001). However, PKRI, MPA and PKRI+MPA groups had a significant higher level of blood glucose and lower level of serum triglyceride compared with placebo group (P<0.001). All tumor bearing mice had a significant higher level of serum TNF-α, IL-1 and IL-6 compared with healthy control (P<0.001). Serum level of TNF-α and IL-6 was significantly lower in PKRI and PKRI+MPA-treated than in placebo animals (P<0.01). PKRI alone and combination therapy with PKRI and MPA reduce tumor growth and may alleviate cachexia.
The soft coral Sinularia microclavata collected from the bay of Sanya, Hainan Island, China, yielded a new diterpenoid, microclavatin (1), and a known cembranolide, capillolide (2). The structure of ...compound 1 was determined on the basis of spectroscopic methods and X-ray single-crystal diffraction analysis. Microclavatin (1) showed cytotoxic activities against tumor cell lines KB and MCF with IC50 values of 5.0 and 20.0 microg/mL, respectively, and capillolide (2) showed potent cytotoxic activity against tumor cell lines (A-549) with an IC50 value of 0.5 microg/mL.
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