Hydroxysafflor Yellow A (HSYA), which is one of the most important active ingredients of the Chinese herb Carthamus tinctorius L, is widely used in the treatment of cerebrovascular and cardiovascular ...diseases. However, the potential protective effect of HSYA in spinal cord ischemia/reperfusion (I/R) injury is still unknown.
Thirty-nine rabbits were randomly divided into three groups: sham group, I/R group and HSYA group. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, biochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining.
Neurological outcomes in HSYA group were slightly improved compared with those in I/R group. Histopathological analysis revealed that HSYA treatment attenuated I/R induced necrosis in spinal cords. Similarly, alleviated oxidative stress was indicated by decreased malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity after HSYA treatment. Moreover, as seen from TUNEL results, HSYA also protected neurons from I/R-induced apoptosis in rabbits.
These findings suggest that HSYA may protect spinal cords from I/R injury by alleviating oxidative stress and reducing neuronal apoptosis in rabbits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIM: To assess the relationships of final best-corrected visual acuity (BCVA) and the optic nerve structural loss in varying age-cohorts of optic neuritis (ON) patients.
METHODS: This is a ...retrospective, cross-sectional study. Totally 130 ON subjects (200 eyes) without ON onset within 6mo were included, who underwent BCVA assessment, peripapillary retinal nerve fibre layer (pRNFL) and macular segmented layers evaluation by optical coherence tomography (OCT).
RESULTS: For the 0-18y cohort, the final BCVA (logMAR) was significantly better and less frequent recurrences than adult cohorts (P=0.000). The final BCVA (logMAR) in all age-cohorts of the ON patients had negative and linear correlations to the pRNFL thicknesses and macular retinal ganglion cell layer (mRGCL) volumes, when the pRNFL thicknesses were reduced to the thresholds of 57.2-67.5 µm or 0.691-0.737 mm3 in mRGCL volumes, respectively, with the strongest interdependence in the 19-40y cohort. The ON patients from varying age cohorts would be threatened by blindness when their pRNFL thicknesses dropped 36.7-48.3 µm or the mRGCL volumes dropped to 0.495-0.613 mm3.
CONCLUSION: The paediatric ON has best prognosis and young adult ON exhibits perfectly linear correlations of final vision and structural loss. The pRNFL and the mRGCL could be potential structural markers to predict the vision prognosis for varying-age ON patients.
Paclitaxel (PTX) resistance is a major obstacle in the treatment of triple-negative breast cancer (TNBC). Previously, we have reported that interleukin-1 receptor-associated kinase 1 (IRAK1) and its ...downstream pathways are associated with PTX resistance in TNBC cells. In this study, we sought to investigate the combination treatment of ginsenoside panaxatriol (GPT), one of the main active components in
, with PTX on viability and apoptosis of TNBC PTX resistant cells, and explore the role of IRAK1 mediated signaling pathways in the therapeutic effects.
CellTiter-Glo and colony formation assays were used to assess cell viability. Flow cytometry was used to analyze subG1 and apoptosis. Western blot was used to detect expressions of proteins involved in apoptosis and the IRAK1/NF-κB and ERK pathways. The mRNA expression of inflammatory cytokines, S100A7/8/9 and cancer stem cell (CSC)-related genes were examined by qPCR. Stem cells were identified by tumor sphere assay. Cell invasion ability was examined by transwell assay.
We show that GPT inhibits MDA-MB-231 PTX resistant (MB231-PR) cell viability in a dose-dependent manner. When combined with PTX, GPT synergistically causes more cell death, induces subG1 accumulation and cell apoptosis. Besides, up-regulation of BAX/BCL-2 ratio, and down-regulation of MCL-1 are also observed. Moreover, this combination inhibits IRAK1, NF-κB and ERK1/2 activation, and leads to down-regulation of inflammatory cytokines (IL6, IL8, CXCL1, CCL2), S100A7/9 and CSC-related genes (OCT4, SOX2, NANOG, ALDH1, CD44) expression. In addition, the combination treatment suppresses MB231-PR cell invasion ability, and impairs tumor sphere growth both in MB231-PR and SUM159 PTX resistant (SUM159-PR) cells.
Our study demonstrates that GPT can resensitize TNBC PTX resistant cells to PTX by inhibiting the IRAK1/NF-κB and ERK pathways and reducing stem cell characteristics.
Planar solid oxide fuel cell (SOFC) operates at high temperature and requires a good creep strength to ensure the structure integrity. This paper presents a creep and damage analysis of a bonded ...compliant seal (BCS) structure of a planar SOFC considering the effect of as-bonded residual stress and thermal stress, as well as the effect of filler metal and foil thickness. A modified continuum creep-damage model is used in the finite element simulation. It demonstrates that the BCS structure meets the requirement of the long-term operation at the high temperature of 600 °C with an appropriate braze bonding process. The results show that the failure location is not in the region of maximum creep deformation due to the effect of high level multi-axial stress which drastically decreases the multi-axial ductility. Reasonably reducing the thickness of filler metal and foil can decrease the damage of the BCS structure. Based on the consideration of creep and damage, it is proposed that the thickness of filler metal and foil should not exceed 0.1 and 0.05 mm, respectively.
•Creep damage in BCS structure is simulated using a continuum damage model.•The effect of the multi-axial stress on the creep and damage has been considered.•Failure is not located in the region of the maximum creep for the multi-axial effect.•Reducing the thickness of filler metal and foil decreases the creep and damage.•The BCS structure meets the requirement of long-term operation.
Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely ...compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.
Smurf2, one of C2-WW-HECT domain E3 ubiquitin ligases, is closely related to the development and progression in different cancer types, including hepatocellular carcinoma (HCC). This study aims to ...illustrate the expression and molecular mechanism of Smurf2 in regulating the progression of HCC.
The expression of Smurf2 in human HCC and adjacent non-tumor liver specimens was detected using tissue microarray studies from 220 HCC patients who underwent curative resection. The relationships of Smurf2 and HCC progression and survival were analyzed using the chi-square test, Kaplan-Meier analysis, and Cox proportional hazards model. For Smurf2 was low expression in HCC cell lines, Smurf2 overexpression cell lines were established. The effect of Smurf2 on cell proliferation and migration was detected by Cell Counting Kit-8 and colony formation assay, and the epithelial-mesenchymal transition (EMT) markers and its transcription factors were tested by immunoblotting. The interaction and ubiquitination of Smad2 by Smurf2 were detected by co-immunoprecipitation and immunoprecipitation assay. Finally, the effect of Smurf2 on HCC was verified using the mouse lung metastasis model.
Smurf2 was downregulated in HCC tissues compared to that of corresponding non-tumor liver specimens. The low expression of Smurf2 in HCC was significantly associated with macrovascular or microvascular tumor thrombus and the impairment of overall survival and disease-free survival.
and
analysis showed that Smurf2 overexpression decreased the EMT potential of HCC cells by promoting the ubiquitination of Smad2 via the proteasome-dependent degradation pathway.
The expression of Smurf2 was downregulated in HCC specimens and affected the survival of patients. Smurf2 inhibited the EMT of HCC by enhancing Smad2 ubiquitin-dependent proteasome degradation.
•TPS1 and TPS2 are essential for trehalose biosynthesis in F. graminearum.•TPS2 is essential for cell polarity, sporulation and sexual development.•TPS2 is required for virulence, mycotoxin ...biosynthesis and cell wall biosynthesis.•Loss of TPS2 causes changed expression of 1885-specific genes.•TPS1 is dispensable for development and virulence.
Trehalose 6-phosphate synthase (TPS1) and trehalose 6-phosphate phosphatase (TPS2) are required for trehalose biosynthesis in yeast and filamentous fungi, including Fusarium graminearum. Three null mutants Δtps1, Δtps2 and Δtps1–Δtps2, each carrying either a single deletion of TPS1 or TPS2 or a double deletion of TPS1–TPS2, were generated from a toxigenic F. graminearum strain and were not able to synthesize trehalose. In contrast to its reported function in yeasts and filamentous fungi, TPS1 appeared dispensable for development and virulence. However, deletion of TPS2 abolished sporulation and sexual reproduction; it also altered cell polarity and ultrastructure of the cell wall in association with reduced chitin biosynthesis. The cell polarity alteration was exhibited as reduced apical growth and increased lateral growth and branching with increased hyphal and cell wall widths. Moreover, the TPS2-deficient strain displayed abnormal septum development and nucleus distribution in its conidia and vegetative hyphae. The Δtps2 mutant also had 62% lower mycelial growth on potato dextrose agar and 99% lower virulence on wheat compared with the wild-type. The Δtps1, Δtps2 and Δtps1–Δtps2 mutants synthesized over 3.08-, 7.09- and 2.47-fold less mycotoxins, respectively, on rice culture compared with the wild-type. Comparative transcriptome analysis revealed that the Δtps1, Δtps2 and Δtps1–Δtps2 mutants had 486, 1885 and 146 genotype-specific genes, respectively, with significantly changed expression profiles compared with the wild-type. Further dissection of this pathway will provide new insights into regulation of fungal development, virulence and trichothecene biosynthesis.
SUMMARY
Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the ...EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005–2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005–2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005–2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio OR = 0.28, 95% confidence interval 95% CI = 0.13–0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32–0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46–4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21–4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
MicroRNA-124 (miR-124) is abundantly expressed in neurons in the mammalian central nervous system, and plays critical roles in the regulation of gene expression during embryonic neurogenesis and ...postnatal neural differentiation. However, the expression profile of miR-124 after spinal cord injury and the underlying regulatory mechanisms are not well understood. In the present study, we examined the expression of miR-124 in mouse brain and spinal cord after spinal cord injury using in situ hybridization. Furthermore, the expression of miR-124 was examined with quantitative RT-PCR at 1, 3 and 7 days after spinal cord injury. The miR-124 expression in neurons at the site of injury was evaluated by in situ hybridization combined with NeuN immunohistochemical staining. The miR-124 was mainly expressed in neurons throughout the brain and spinal cord. The expression of miR-124 in neurons significantly decreased within 7 days after spinal cord injury. Some of the neurons in the peri-lesion area were NeuN(+)/miR-124(-). Moreover, the neurons distal to the peri-lesion site were NeuN(+)/miR-124(+). These findings indicate that miR-124 expression in neurons is reduced after spinal cord injury, and may reflect the severity of spinal cord injury.
Lysine acetylation and ubiquitination are two primary post-translational modifications (PTMs) in most eukaryotic proteins. Lysine residues are targets for both types of PTMs, resulting in different ...cellular roles. With the increasing availability of protein sequences and PTM data, it is challenging to distinguish the two types of PTMs on lysine residues. Experimental approaches are often laborious and time consuming. There is an urgent need for computational tools to distinguish between lysine acetylation and ubiquitination. In this study, we developed a novel method, called DAUFSA (distinguish between lysine acetylation and lysine ubiquitination with feature selection and analysis), to discriminate ubiquitinated and acetylated lysine residues. The method incorporated several types of features: PSSM (position-specific scoring matrix) conservation scores, amino acid factors, secondary structures, solvent accessibilities, and disorder scores. By using the mRMR (maximum relevance minimum redundancy) method and the IFS (incremental feature selection) method, an optimal feature set containing 290 features was selected from all incorporated features. A dagging-based classifier constructed by the optimal features achieved a classification accuracy of 69.53%, with an MCC of .3853. An optimal feature set analysis showed that the PSSM conservation score features and the amino acid factor features were the most important attributes, suggesting differences between acetylation and ubiquitination. Our study results also supported previous findings that different motifs were employed by acetylation and ubiquitination. The feature differences between the two modifications revealed in this study are worthy of experimental validation and further investigation.
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