Mapping of the methylation pattern of the hMSH2 promoter in colon cancer, using bisulfite genomic sequencing

The detailed methylation status of CpG sites in the promoter region of hMSH2 gene has yet not to be reported. We have mapped the complete methylation status of the hMSH2 promoter, a region that contains 75 CpG sites, using bisulfite genomic sequencing in 60 primary colorectal cancers. And the expression of hMSH2 was detected by immunohistochemistry. The hypermethylation of hMSH2 was detected in 18.33% (11/60) of tumor tissues. The protein of hMSH2 was detected in 41.67% (25/60) of tumor tissues. No hypermethylation of hMSH2 was detected in normal tissues. The protein of hMSH2 was detected in all normal tissues. Our study demonstrated that hMSH2 hypermethylation and protein expression were associated with the development of colorectal cancer

Standard metabolic rate predicts growth trajectory of juvenile Chinese crucian carp (Carassius auratus) under changing food availability

Phenotypic traits vary greatly within populations and can have a significant influence on aspects of performance. The present study aimed to investigate the effects of individual variation in standard metabolic rate (SMR) on growth rate and tolerance to food-deprivation in juvenile crucian carp (Carassius auratus) under varying levels of food availability. To address this issue, 19 high and 16 low SMR (individuals were randomly assigned to a satiation diet for 3 weeks, whereas another 20 high and 16 low SMR individuals were assigned to a restricted diet (approximately 50% of satiation) for the same period. Then, all fish were completely food-deprived for another 3 weeks. High SMR individuals showed a higher growth rate when fed to satiation, but this advantage of SMR did not exist in food-restricted fish. This result was related to improved feeding efficiency with decreased food intake in low SMR individuals, due to their low food processing capacity and maintenance costs. High SMR individuals experienced more mass loss during food-deprivation as compared to low SMR individuals. Our results here illustrate context-dependent costs and benefits of intraspecific variation in SMR whereby high SMR individuals show increased growth performance under high food availability but had a cost under stressful environments (i.e., food shortage)

Expressions and clinic significance of miRNA-143, miRNA- 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer tissues

Purpose: To search for novel biomarkers for early diagnosis of cervical cancer, as well as novel therapeutic target for cervical cancer.Methods: A total of 96 cervical tissue specimens were collected from patients in the Second Affiliated Hospital of Zhengzhou University, out of which 10 were normal control. The remaining specimens (86) were cervical cancer specimens and were divided into 4 groups (A - D) based on tumor-biomarker levels of CA125 and SCC. Quantitative real-time polymerase chain reaction technology (qRT-PCR) was used to detect the expressions of miRNA-143, miRNA-34A, miRNA-944, miRNA-101 and miRNA-218 in the cervical cancer tissues.Results: The levels of CA125 (U/mL) and SCC (ug/L) expressed in normal control group and groups A - D were 11.75 and 0.73 (n = 10), 382 and 2.72 (n = 25), 912.9 and 3.93 (n = 21), 1675 and 5.87 (n = 29), and 2120 and 6.66 (n = 11), respectively. Furthermore, qRT-PCR results showed that the expressions of miRNA-944 and miRNA-218 in cervical cancer tissues were markedly up-regulated compared to normal control tissues (p < 0.01). In contrast, the expression level of miRNA-143, miRNA-34A, and miRNA-101 were significantly decreased (p < 0.01).Conclusion: The biomarkers, miRNA-143, miRNA-34A, miRNA-944, miRNA-101 and miRNA-218, can be considered novel for early diagnosis of cervical cancer.Keywords: Cervical cancer, Biomarkers, miRNA-143, miRNA-34A, miRNA-944, miRNA-101, miRNA- 21

Effect of polygonimitin C on bone formation and resorption in human osteoblast-like MG63 cells

Purpose: To investigate the effect of polygonimitin C (PC) on bone formation and resorption in human osteoblast-like MG63 cells.Methods: MG63 cells were treated with PC at doses of 0, 20, 40 or 80 μg/mL for 48 h, with an untreated group as control. The effect of PC on alkaline phosphatase (ALP) activity in MG63 cells was investigated by p-nitrophenyl phosphate disodium hexahydrate assay. Western blot assay was used to evaluate the effect of PC on the expressions of osterix (OSX), bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (RUNX-2), osteocalcin (OC), fibronectin (FN), type I collagen (COL I), osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) proteins in MG63 cells.Results: ALP relative activity in MG63 cells treated with PC at 20, 40 or 80 μg/mL (123.58, 137.74 or 159.62 %, respectively) was significantly (p < 0.05 or 0.01) higher than that in control group (99.37 %). Expressions of OSX, BMP-2, RUNX-2, OC, FN, COL I and OPG proteins in MG63 cells treated with PC at 20, 40 or 80 μg/mL were significantly (p < 0.01) higher than those in control group. However, there were no statistically significant differences in RANKL protein expression between PC-treated MG63 cells and control group.Conclusion: These results show that PC exerts protective effects against osteoporosis by promoting bone formation and inhibiting bone resorption. Thus, PC may be useful in the development of new antiosteoporosis drugs.Keywords: Polygonimitin C, MG63 cells, Bone formation, Bone resorption, Osteoporosi

Ethyl 3-{5-[(diethyl­amino)meth­yl]isoxazol-3-yl}-2-phenyl­pyrazolo[1,5-a]pyridine-5-carboxyl­ate

In the title compound, C24H26N4O3, the pyrazolo[1,5-a]pyridine ring system makes dihedral angles of 38.130 (3) and 30.120 (3)°, respectively, with the isoxazole and phenyl rings. In the crystal, two mol­ecules are linked by a pair of C—H⋯N hydrogen bonds, forming a centrosymmetric dimer. A weak intra­molecular C—H⋯O inter­action is also present

Isospin dependence of projectile-like fragment production at intermediate energies

The cross sections of fragments produced in 140 $A$ MeV $^{40,48}$Ca + $^9$Be and $^{58,64}$Ni + $^9$Be reactions are calculated by the statistical abration-ablation(SAA) model and compared to the experimental results measured at the National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University. The fragment isotopic and isotonic cross section distributions of $^{40}$Ca and $^{48}$Ca, $^{58}$Ni and $^{64}$Ni, $^{40}$Ca and $^{58}$Ni, and $^{48}$Ca and $^{64}$Ni are compared and the isospin dependence of the projectile fragmentation is studied. It is found that the isospin dependence decreases and disappears in the central collisions. The shapes of the fragment isotopic and isotonic cross section distributions are found to be very similar for symmetric projectile nuclei. The shapes of the fragment isotopic and isotonic distributions of different asymmetric projectiles produced in peripheral reactions are found very similar. The similarity of the distributions are related to the similar proton and neutron density distributions inside the nucleus in framework of the SAA model.Comment: 7 pages, 4 figures; to be published in Phys Rev

The Effectiveness and Safety of Total Glucosides of Paeony in Primary Sjögren's Syndrome: A Systematic Review and Meta-Analysis

Objective: To assess the effectiveness and safety of the total glucosides of paeony (TGP) on the treatment of primary Sjögren's syndrome (pSS) by conducting a meta-analysis.Methods: Eight databases were searched from their inception to December 10, 2018 for randomized controlled trials (RCTs). The Revman 5.3 software was used for this meta-analysis.Results: Nine RCTs which included 770 participants were identified. Pooled results showed that significant difference in Schirmer's test (P < 0.00001) comparing TGP with placebo (PBO). However, the pooled results displayed significant differences in salivary flow rate, Schirmer's test, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), serum γ-globulin, immunoglobulin G (IgG), IgA, IgM, and effective rate (P ≤ 0.01) in the co-administration of TGP with immunosuppressant (IS) compared with IS alone. Subgroup analyses revealed both heterogeneities in ESR and serum γ-globulin were eliminated, showing combined intervention of TGP + IS being more advantageous than single usage of IS (P < 0.00001). However, the advantage varied among three subgroups and showed a gradual weakening over time. Furthermore, our results showed statistical significance in Schirmer's test (P = 0.0006), when hydroxychloroquine (HCQ) was jointly applied, but not in the case of combined TGP with methotrexate (MTX) (P = 0.41). For the safety analysis, the most common adverse events (AEs) were diarrhea or gastrointestinal discomfort, and no severe AEs were reported in TGP group. Meanwhile, six trials showed statistically insignificant differences between TGP + IS and IS in AEs (P = 0.76).Conclusions: Improving the lacrimal gland secretion (Schirmer's test) is the prominent function of TGP compared with PBO. TGP + IS can improve the clinical symptoms, such as lacrimal and salivary gland secretion function (Schirmer's test, salivary flow rate), inflammatory indices (ESR, CRP, and RF) and immunoglobulins (γ-globulin, IgG, IgA, and IgM) on the basis of IS monotherapy. In addition, TGP has an acceptable safety profile and AEs were not increased when TGP combined with IS in pSS. Therefore, TGP can be considered to be a potentially valid and safe drug for the treatment of pSS in the clinic. In view of the limitations of the included trials, the potential beneficial effectiveness and safety of TGP need additional high-quality, multi-center, and large-scale RCTs to assess its use in pSS treatment

Gemcitabine enhances cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling

Pancreatic cancer, one of the most lethal cancers, has very poor 5-year survival partly due to gemcitabine resistance. Recently, it was reported that chemotherapeutic agents may act as stressors to induce adaptive responses and to promote chemoresistance in cancer cells. During long-term drug treatment, the minority of cancer cells survive and acquire an epithelial-mesenchymal transition phenotype with increased chemo-resistance and metastasis. However, the short-term response of most cancer cells remains unclear. This study aimed to investigate the short-term response of pancreatic cancer cells to gemcitabine stress and to explore the corresponding mechanism. Our results showed that gemcitabine treatment for 24 hours enhanced pancreatic cancer cell invasion. In gemcitabine-treated cells, HAb18G/CD147 was up-regulated; and HAb18G/CD147 down-regulation or inhibition attenuated gemcitabine-enhanced invasion. Mechanistically, HAb18G/CD147 promoted gemcitabine-enhanced invasion by activating the EGFR (epidermal growth factor receptor)-STAT3 (signal transducer and activator of transcription 3) signaling pathway. Inhibition of EGFR-STAT3 signaling counteracted gemcitabine-enhanced invasion, and which relied on HAb18G/CD147 levels. In pancreatic cancer tissues, EGFR was highly expressed and positively correlated with HAb18G/CD147. These data indicate that pancreatic cancer cells enhance cell invasion via activating HAb18G/CD147-EGFR-pSTAT3 signaling. Our findings suggest that inhibiting HAb18G/CD147 is a potential strategy for overcoming drug stress-associated resistance in pancreatic cancer