Serine/Threonine Kinase (STK) 33 promotes the proliferation and metastasis of human esophageal squamous cell carcinoma via inflammation-related pathway.

The serine/threonine kinase (STK) 33 plays a key role in cancer cell proliferation and metastasis. Abnormal STK33 expression is closely related to malignancy of numerous cancers. This study suggests the important role of STK33 in the pathogenesis and metastatic progression of esophageal squamous cell carcinoma (ESCC). STK33 expression in human ESCC tissues was detected by immunohistochemical technique. Further, we analyzed the relationship between STK33 and clinical and pathological factors as well as the prognosis of patients. ECa109 cell line was cultured and transfected with STK33-RNAi lentiviral vector to perform Hochest33342 & PI and metastasis experiments. The TCGA database was used to analyze the STK33 expression level in ESCC. All statistical analyses were performed in SPSS 23.0 software. Differences with P < 0.05 were considered statistically significant. In human ESCC specimens, STK33 was overexpressed and associated with poor prognosis. Silencing STK33 expression suppressed ESCC proliferation, migration, invasion, and tumor growth. STK33 also mediated angiogenesis, TGFß, and inflammatory response in ESCC. Mechanistic investigations revealed that STK33 regulates ESCC through multiple complex pathways. Dysregulated STK33 signaling promotes ESCC growth and progression. Thus, our findings identified STK33 as a candidate treatment target that improves ESCC therapy.

TRIM4 Expression Related to Malignant Progression and Cisplatin Resistance in Osteosarcoma.

Osteosarcoma (OS) is a high-grade intraosseous malignancy. Twenty to thirty percent of OS patients react poorly to standard therapy with a combination of surgical resection and chemotherapy. It is necessary to find molecules that play an important role in this. This study explored the role of TRIM4 in OS chemotherapy sensitivity and malignant progression. The expression of TRIM4 in OS tissues and cells was examined by RT-qPCR, immunohistochemical staining, and western blot. Specific siRNA was transfected into U2-OS and SAOS2 cells to target TRIM4. Cell biological behavior was examined by CCK-8, Transwell, and flow cytometry experiments. Cisplatin-resistant SAOS2 (SAOS2-Cis-R) cells were established, and the effect of TRIM4 expression on the cisplatin response of SAOS2 cells was tested. Knockdown of TRIM4 significantly inhibited the proliferation, migration, and invasion of U2-OS and SAOS2 cells and induced apoptosis. TRIM4 expression was significantly higher in chemotherapy-resistant OS tissues compared to chemotherapy-sensitive OS tissues. Furthermore, the expression of TRIM4 in SAOS2-Cis-R cells was significantly increased compared to parental SAOS2 cells. Moreover, overexpression of TRIM4 enhanced cisplatin resistance in parental SAOS2 cells, while the downregulation of TRIM4 expression enhanced cisplatin sensitivity of SAOS2-Cis-R cells. High TRIM4 expression might be associated with malignant progression and poor response to chemotherapy response of OS. Targeting TRIM4 may be beneficial for OS treatment or combination therapy.

Antagonistic MADS-box transcription factors SEEDSTICK and SEPALLATA3 form a transcriptional regulatory network that regulates seed oil accumulation.

Transcriptional regulation is essential for balancing multiple metabolic pathways that influence oil accumulation in seeds. Thus far, the transcriptional regulatory mechanisms that govern seed oil accumulation remain largely unknown. Here, we identified the transcriptional regulatory network composed of MADS-box transcription factors SEEDSTICK (STK) and SEPALLATA3 (SEP3), which bridges several key genes to regulate oil accumulation in seeds. We found that STK, highly expressed in the developing embryo, positively regulates seed oil accumulation in Arabidopsis (Arabidopsis thaliana). Furthermore, we discovered that SEP3 physically interacts with STK in vivo and in vitro. Seed oil content is increased by the SEP3 mutation, while it is decreased by SEP3 overexpression. The chromatin immunoprecipitation, electrophoretic mobility shift assay, and transient dual-luciferase reporter assays showed that STK positively regulates seed oil accumulation by directly repressing the expression of MYB5, SEP3, and SEED FATTY ACID REDUCER 4 (SFAR4). Moreover, genetic and molecular analyses demonstrated that STK and SEP3 antagonistically regulate seed oil production and that SEP3 weakens the binding ability of STK to MYB5, SEP3, and SFAR4. Additionally, we demonstrated that TRANSPARENT TESTA 8 (TT8) and ACYL-ACYL CARRIER PROTEIN DESATURASE 3 (AAD3) are direct targets of MYB5 during seed oil accumulation in Arabidopsis. Together, our findings provide the transcriptional regulatory network antagonistically orchestrated by STK and SEP3, which fine tunes oil accumulation in seeds.

Combination of clinical, radiomic, and "delta" radiomic features in survival prediction of metastatic gastroesophageal adenocarcinoma.

Objectives: To identify combined clinical, radiomic, and delta-radiomic features in metastatic gastroesophageal adenocarcinomas (GEAs) that may predict survival outcomes. Methods: A total of 166 patients with metastatic GEAs on palliative chemotherapy with baseline and treatment/follow-up (8-12 weeks) contrast-enhanced CT were retrospectively identified. Demographic and clinical data were collected. Three-dimensional whole-lesional radiomic analysis was performed on the treatment/follow-up scans. "Delta" radiomic features were calculated based on the change in radiomic parameters compared to the baseline. The univariable analysis (UVA) Cox proportional hazards model was used to select clinical variables predictive of overall survival (OS) and progression-free survival (PFS) (p-value <0.05). The radiomic and "delta" features were then assessed in a multivariable analysis (MVA) Cox model in combination with clinical features identified on UVA. Features with a p-value <0.01 in the MVA models were selected to assess their pairwise correlation. Only non-highly correlated features (Pearson's correlation coefficient <0.7) were included in the final model. Leave-one-out cross-validation method was used, and the 1-year area under the receiver operating characteristic curve (AUC) was calculated for PFS and OS. Results: Of the 166 patients (median age of 59.8 years), 114 (69%) were male, 139 (84%) were non-Asian, and 147 (89%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median PFS and OS on treatment were 3.6 months (95% CI 2.86, 4.63) and 9 months (95% CI 7.49, 11.04), respectively. On UVA, the number of chemotherapy cycles and number of lesions at the end of treatment were associated with both PFS and OS (p < 0.001). ECOG status was associated with OS (p = 0.0063), but not PFS (p = 0.054). Of the delta-radiomic features, delta conventional HUmin, delta gray-level zone length matrix (GLZLM) GLNU, and delta GLZLM LGZE were incorporated into the model for PFS, and delta shape compacity was incorporated in the model for OS. Of the treatment/follow-up radiomic features, shape compacity and neighborhood gray-level dependence matrix (NGLDM) contrast were used in both models. The combined 1-year AUC (Kaplan-Meier estimator) was 0.82 and 0.81 for PFS and OS, respectively. Conclusions: A combination of clinical, radiomics, and delta-radiomic features may predict PFS and OS in GEAs with reasonable accuracy.

Demographics, pattern of practice and clinical outcomes in rectal squamous cell carcinoma.

AIM: The aim of this study was to describe the baseline clinical features, treatment patterns and outcomes in rectal squamous cell carcinoma (SCC). METHOD: This is a retrospective study of patients with rectal SCC treated at the Princess Margaret Cancer Centre (Toronto, Canada) between 1 January 1995 and 31 December 2020. Clinical factors associated with locoregional failure (LRF), distant metastases (DM), disease-free survival (DFS) and overall survival (OS), such as age, sex, HIV status, T-category, nodal status, grade and primary treatment, were investigated with univariate analysis (UVA). RESULTS: Twenty nine patients with rectal SCC were analysed with a median follow-up of 7.4 years (range 0.3-20.4 years). The median age at diagnosis was 52 years, with the majority presenting with clinical T3 disease or higher (n = 21, 72%) and positive regional lymph nodes (n = 16, 55%), while more than quarter of patients (28%) had metastatic disease. Definitive chemoradiation was the treatment modality of choice in more than half of all cases (n = 17, 59%) with a response rate of 100%. The 10-year cumulative incidence of LRF and DM was, respectively, 12% (95% CI 1.8%-32.9%) and 31% (95% CI: 12.0%-52.6%). The 5- and 10-year OS was 82% (95% CI 66.1%-100%). UVA revealed a trend towards an association of male gender (hazard ratio = 4.65, 95% CI 0.9%-24.1; p = 0.067) and primary surgical treatment (hazard ratio = 0.76, 95% CI 0.09-6.34; p = 0.061) with DFS. CONCLUSION: Definitive chemoradiation is an effective and preferred treatment for rectal SCC allowing for sphincter preservation with complete clinical response observed in all patients.

Acetaminophen changes the RNA m6A levels and m6A-related proteins expression in IL-1ß-treated chondrocyte cells.

BACKGROUND: Acetaminophen is commonly recommended for the early analgesia of osteoarthritis. However, the molecular mechanism by which it acts remains unknown. The aim of this study is to investigate the effect of acetaminophen on inflammation and extracellular matrix degradation in human chondrocytes, and the possible molecular mechanisms involved in its effect. METHODS: The normal chondrocyte cell line C28/I2 was treated with interleukin-1ß to mimic the inflammatory state. Acetaminophen and the methylation inhibitor (cycloleucine) were used to treat interleukin-1ß-induced C28/I2 cells. The expression of RNA N6-methyladenosine -related proteins was detected by RT-qPCR and western blot. The total RNA N6-methyladenosine level was measured by dot blot analysis and enzyme linked immunosorbent assay. The levels of interleukin-6, interleukin-8 and anti-tumor necrosis factor-α were measured by enzyme linked immunosorbent assay. The extracellular matrix synthesis and degradation were examined by western blot. RESULTS: After interleukin-1ß stimulated C28/I2 cells, the intracellular RNA N6-methyladenosine level increased, and the expression of regulatory proteins also changed, mainly including the increased expression of methyltransferase like 3 and the downregulated expression of AlkB family member 5. The use of cycloleucine inhibited interleukin-1ß-induced inflammation and extracellular matrix degradation by inhibiting RNA N6-methyladenosine modification. In contrast, acetaminophen treatment counteracted interleukin-1ß-induced changes in RNA N6-methyladenosine levels and regulatory protein expression. Furthermore, acetaminophen treatment of interleukin-1ß-induced C28/I2 cells inhibited the secretion of interleukin-6, interleukin-8 and anti-tumor necrosis factor-α, down-regulated the expression of matrix metalloproteinase-13 and Collagen X, and up-regulated the expression of collagen II and aggrecan. In addition, AlkB family member 5 overexpression activated interleukin-1ß-induced chondrocyte viability and suppressed inflammation and extracellular matrix degradation. CONCLUSION: Acetaminophen affects inflammatory factors secretion and extracellular matrix synthesis of human chondrocytes by regulating RNA N6-methyladenosine level and N6-methyladenosine-related protein expression. Stimulation of the normal chondrocyte cell line C28/I2 with the cytokine IL-1ß (10 µM) mimics the inflammatory state in vitro. Acetaminophen (Ace, 50 µg/mL) changes the m6A related proteins expression and the total RNA m6A levels in IL-1ß-treated chondrocyte cells. Furthermore, regulation of RNA m6A levels (by methylation inhibitor Cyc and/or Ace) affects IL-1ß-induced inflammatory cytokines secretion and extracellular matrix synthesis in C28/I2 cells.

Nasopharyngeal Carcinoma Radiomic Evaluation with Serial PET/CT: Exploring Features Predictive of Survival in Patients with Long-Term Follow-Up.

PURPOSE: We aim determine the value of PET and CT radiomic parameters on survival with serial follow-up PET/CT in patients with nasopharyngeal carcinoma (NPC) for which curative intent therapy is undertaken. METHODS: Patients with NPC and available pre-treatment as well as follow up PET/CT were included from 2005 to 2006 and were followed to 2021. Baseline demographic, radiological and outcome data were collected. Univariable Cox proportional hazard models were used to evaluate features from baseline and follow-up time points, and landmark analyses were performed for each time point. RESULTS: Sixty patients were enrolled, and two-hundred and seventy-eight (278) PET/CT were at baseline and during follow-up. Thirty-eight percent (38%) were female, and sixty-two patients were male. All patients underwent curative radiation or chemoradiation therapy. The median follow-up was 11.72 years (1.26-14.86). Five-year and ten-year overall survivals (OSs) were 80.0% and 66.2%, and progression-free survival (PFS) was 90.0% and 74.4%. Time-dependent modelling suggested that, among others, PET gray-level zone length matrix (GLZLM) gray-level non-uniformity (GLNU) (HR 2.74 95% CI 1.06, 7.05) was significantly associated with OS. Landmark analyses suggested that CT parameters were most predictive at 15 month, whereas PET parameters were most predictive at time points 3, 6, 9 and 15 month. CONCLUSIONS: This study with long-term follow up data on NPC suggests that mainly PET-derived radiomic features are predictive for OS but not PFS in a time-dependent evaluation. Furthermore, CT radiomic measures may predict OS and PFS best at initial and long-term follow-up time points and PET measures may be more predictive in the interval. These modalities are commonly used in NPC surveillance, and prospective validation should be considered.

Clinical characteristics of reflux esophagitis among patients with liver cirrhosis: a case-control study.

BACKGROUND: Reflux esophagitis (RE) can cause esophageal varices bleeding and largely reduce life quality of liver cirrhosis (LC) patients. AIMS: To clarify the prevalence, severity and risk factors of RE among LC patients. METHODS: A case-control study that enrolled 420 endoscopy-confirmed LC patients with RE as a case cohort and 409 LC patients without RE as a control group was conducted. Logistic regression was used to determine the risk factors for RE among LC patients. RESULTS: The 10-year cumulative incidence rate of RE was 4.79% among the LC patients. The severity of RE among the LC patients was higher than that among the non-LC patients (p<.05). The LC patients with RE patients were older (56 years vs. 53 years) and had higher rates of male patients (77.14% vs. 65.77%), smoking (46.90% vs. 32.76%), alcohol intake (50.24% vs. 41.08%), past endoscopic variceal ligation (EVL) (9.05% vs. 4.65%), endoscopic injection sclerotherapy (EIS) (16.19% vs. 2.69%), hiatus hernia (7.14% vs. 0.13%) and portal vein thrombosis (PVT) (14.05% vs. 4.01%). Logistic regression demonstrated that hiatus hernia, past EIS, PVT, smoking, white blood cell count, age, spleen thickness and platelet (PLT) count were risk factors for RE among the LC patients. CONCLUSIONS: Patients with LC tended to have severer RE than non-LC patients. The special risk factors of RE among LC patients included past EIS and PVT, which deserved extra attention for hepatologists as well as gastroenterologists to prevent.

Integrative iTRAQ-based proteomic and transcriptomic analysis reveals the accumulation patterns of key metabolites associated with oil quality during seed ripening of Camellia oleifera.

Camellia oleifera (C. oleifera) is one of the four major woody oil-bearing crops in the world and has relatively high ecological, economic, and medicinal value. Its seeds undergo a series of complex physiological and biochemical changes during ripening, which is mainly manifested as the accumulation and transformation of certain metabolites closely related to oil quality, especially flavonoids and fatty acids. To obtain new insights into the underlying molecular mechanisms, a parallel analysis of the transcriptome and proteome profiles of C. oleifera seeds at different maturity levels was conducted using RNA sequencing (RNA-seq) and isobaric tags for relative and absolute quantification (iTRAQ) complemented with gas chromatography-mass spectrometry (GC-MS) data. A total of 16,530 transcripts and 1228 proteins were recognized with significant differential abundances in pairwise comparisons of samples at various developmental stages. Among these, 317 were coexpressed with a poor correlation, and most were involved in metabolic processes, including fatty acid metabolism, α-linolenic acid metabolism, and glutathione metabolism. In addition, the content of total flavonoids decreased gradually with seed maturity, and the levels of fatty acids generally peaked at the fat accumulation stage; these results basically agreed with the regulation patterns of genes or proteins in the corresponding pathways. The expression levels of proteins annotated as upstream candidates of phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) as well as their cognate transcripts were positively correlated with the variation in the flavonoid content, while shikimate O-hydroxycinnamoyltransferase (HCT)-encoding genes had the opposite pattern. The increase in the abundance of proteins and mRNAs corresponding to alcohol dehydrogenase (ADH) was associated with a reduction in linoleic acid synthesis. Using weighted gene coexpression network analysis (WGCNA), we further identified six unique modules related to flavonoid, oil, and fatty acid anabolism that contained hub genes or proteins similar to transcription factors (TFs), such as MADS intervening keratin-like and C-terminal (MIKC_MADS), type-B authentic response regulator (ARR-B), and basic helix-loop-helix (bHLH). Finally, based on the known metabolic pathways and WGCNA combined with the correlation analysis, five coexpressed transcripts and proteins composed of cinnamyl-alcohol dehydrogenases (CADs), caffeic acid 3-O-methyltransferase (COMT), flavonol synthase (FLS), and 4-coumarate: CoA ligase (4CL) were screened out. With this exploratory multiomics dataset, our results presented a dynamic picture regarding the maturation process of C. oleifera seeds on Hainan Island, not only revealing the temporal specific expression of key candidate genes and proteins but also providing a scientific basis for the genetic improvement of this tree species.

Type 2 diabetes mellitus increases liver transplant-free mortality in patients with cirrhosis: A systematic review and meta-analysis.

BACKGROUND: The impact of type 2 diabetes mellitus (T2DM) on the prognosis and complications of liver cirrhosis is not fully clarified. AIM: To clarify the mortality and related risk factors as well as complications in cirrhotic patients with T2DM. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from their inception to December 1, 2020 for cohort studies comparing liver transplant-free mortality, hepatocellular carcinoma (HCC), ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy (HE) in cirrhotic patients with vs without T2DM. Odds ratios (ORs) were combined by using fixed-effects or random-effects models with RevMan software. RESULTS: The database search generated a total of 17 cohort studies that met the inclusion criteria. Among these studies, eight reported the risk of mortality, and eight reported the risk of HCC. Three studies provided SBP rates, and two documented ascites rates. Four articles focused on HE rates, and three focused on variceal bleeding rates. Meta-analysis indicated that T2DM was significantly associated with an increased risk of liver transplant-free mortality [OR: 1.28, 95% confidence intervals (CI): 1.16-1.41, P < 0.0001] and HCC incidence (OR: 1.82, 95%CI: 1.32-2.51, P = 0.003). The risk of SBP was not significantly increased (OR: 1.16 95%CI: 0.86-1.57, P = 0.34). Additionally, T2DM did not significantly increase HE (OR: 1.31 95%CI: 0.97-1.77, P = 0.08), ascites (OR: 1.11 95%CI: 0.84-1.46, P = 0.46), and variceal bleeding (OR: 1.34, 95%CI: 0.99-1.82, P = 0.06). CONCLUSION: The findings suggest that cirrhotic patients with T2DM have a poor prognosis and high risk of HCC. T2DM may not be associated with an increased risk of SBP, variceal bleeding, ascites, or HE in cirrhotic patients with T2DM.

Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray.

Galanin receptor1 (GalR1) transcript levels are elevated in the rat ventral periaqueductal gray (vPAG) after chronic mild stress (CMS) and are related to depression-like behavior. To explore the mechanisms underlying the elevated GalR1 expression, we carried out molecular biological experiments in vitro and in animal behavioral experiments in vivo. It was found that a restricted upstream region of the GalR1 gene, from -250 to -220, harbors an E-box and plays a negative role in the GalR1 promoter activity. The transcription factor Scratch2 bound to the E-box to down-regulate GalR1 promoter activity and lower expression levels of the GalR1 gene. The expression of Scratch2 was significantly decreased in the vPAG of CMS rats. Importantly, local knockdown of Scratch2 in the vPAG caused elevated expression of GalR1 in the same region, as well as depression-like behaviors. RNAscope analysis revealed that GalR1 mRNA is expressed together with Scratch2 in both GABA and glutamate neurons. Taking these data together, our study further supports the involvement of GalR1 in mood control and suggests a role for Scratch2 as a regulator of depression-like behavior by repressing the GalR1 gene in the vPAG.

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome.

Objective: The main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population. Methods: Patients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome. Results: In total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease. Conclusion: We present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.

Virus-Mediated Overexpression of ETS-1 in the Ventral Hippocampus Counteracts Depression-Like Behaviors in Rats.

ETS-1 is a transcription factor that is a member of the E26 transformation-specific (ETS) family. Galanin receptor 2 (GalR2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of GalR2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress (CMS) decreased the expression of both ETS-1 and GalR2 in the ventral hippocampus of rats. Meanwhile, we demonstrated that overexpression of ETS-1 increased the expression of GalR2 in primary hippocampal neurons. Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2) of GalR2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats, which might be mediated by increasing the level of GalR2 and its downstream p-ERK1/2 in the ventral hippocampus.

The Biological Significance and Regulatory Mechanism of c-Myc Binding Protein 1 (MBP-1).

Alternatively translated from the ENO gene and expressed in an array of vertebrate and plant tissues, c-Myc binding protein 1 (MBP-1) participates in the regulation of growth in organisms, their development and their environmental responses. As a transcriptional repressor of multiple proto-oncogenes, vertebrate MBP-1 interacts with other cellular factors to attenuate the proliferation and metastasis of lung, breast, esophageal, gastric, bone, prostrate, colorectal, and cervical cancer cells. Due to its tumor-suppressive property, MBP-1 and its downstream targets have been investigated as potential prognostic markers and therapeutic targets for various cancers. In plants, MBP-1 plays an integral role in regulating growth and development, fertility and abiotic stress responses. A better understanding of the functions and regulatory factors of MBP-1 in plants may advance current efforts to maximize plant resistance against drought, high salinity, low temperature, and oxidative stress, thus optimizing land use and crop yields. In this review article, we summarize the research advances in biological functions and mechanistic pathways underlying MBP-1, describe our current knowledge of the ENO product and propose future research directions on vertebrate health as well as plant growth, development and abiotic stress responses.

The antioxidant activity and genotoxicity of isogarcinol.

The antioxidant activity and genotoxicity of isogarcinol were assessed by several in vitro tests. Its IC50 values for DPPH and ABTS were 36.3 ±â€¯3.35 µM and 16.6 ±â€¯3.98 µM, respectively, which were all lower than those of VC and BHT. Isogarcinol had no cyctotoxic or promotional activities at 1-10 µM in the CCK-8 assay, and negligible genotoxic effects at 50-500 µM on HepG2 cells by the single-cell gel electrophoresis assay. Pre-incubation of the cells with 0.5-1.5 µM isogarcinol, before exposure to H2O2, significantly increased cell viability in a concentration-dependent manner. Isogarcinol also reduced intercellular reactive oxygen species accumulation, lactate dehydrogenase release and malondialdehyde levels, and increased superoxide dismutase activity and glutathione levels. Western-blot analysis revealed that it up-regulated pro-caspase-3 and reduced cleaved caspase-3 during H2O2-induced oxidative stress. All the above results indicate that isogarcinol promises to be useful as a natural antioxidant.

Cordycepin induces apoptosis in human bladder cancer cells via activation of A3 adenosine receptors.

Bladder cancer is a neoplasm originated from bladder epithelial cells. The therapy for bladder cancer is so far not satisfactory. In this study, we examined the effects of Cordyceps militaris hot water extracts containing cordycepin on human bladder cells. Cordyceps militaris hot water extracts containing cordycepin was used to treat human T24 bladder carcinoma cells, and we found that Cordyceps militaris hot water extracts containing cordycepin decreased T24 cell survival in a dose-dependent manner, which was seemingly mediated by activation of A3 adenosine receptor and the subsequent inactivation of Akt pathways, resulting in increases in cleaved Caspase-3 and apoptosis. Overexpression of A3 adenosine receptor in T24 cells mimicked the effects of Cordyceps militaris hot water extracts, while A3 adenosine receptor depletion abolished the effects of Cordyceps militaris hot water extracts containing cordycepin. Together, these data suggest that Cordyceps militaris hot water extracts containing cordycepin may be a promising treatment for bladder cancer via A3 adenosine receptor activation.