Identification of metabolic components of carotid plaque in high-risk patients utilizing liquid chromatography-tandem mass spectrometry.

OBJECTIVE: Carotid atherosclerosis is a chronic progressive vascular disease that can be complicated by stroke in severe cases. Prompt diagnosis and treatment of high-risk patients are quite difficult due to the lack of reliable clinical biomarkers. This study aimed to explore potential plaque metabolic markers of stroke-prone risk and relevant targets for pharmacological intervention. METHOD: Carotid intima and plaque sample tissues were obtained from 20 patients with cerebrovascular symptoms of carotid origin. An untargeted metabolomics approach based on liquid chromatography-tandem mass spectrometry was utilized to characterize the metabolic profiles of the tissues. Multivariate and univariate analysis tools were used. RESULTS: A total of 154 metabolites were significantly altered in carotid plaque when compared with thickened intima. Of these, 62 metabolites were upregulated, whereas 92 metabolites were downregulated. Support vector machines identified the 15 most important metabolites, such as N-(cyclopropylmethyl)-N'-phenylurea, 9(S)-HOTrE, ACar 12:2, quinoxaline-2,3-dithiol, and l-thyroxine, as biomarkers for high-risk plaques. Metabolic pathway analysis showed that abnormal purine and nucleotide metabolism, amino acid metabolism, glutathione metabolism, and vitamin metabolism may contribute to the occurrence and progression of carotid atherosclerotic plaque. CONCLUSIONS: Our study identifies the biomarkers and related metabolic mechanisms of carotid plaque, which is stroke-prone, and provides insights and ideas for the precise prevention and targeted intervention of the disease.

Polymorphism rs3733591 of the SLC2A9 gene and metabolic syndrome affect gout risk in Taiwan Biobank subjects.

Background: Over the past few decades, gout and diseases like metabolic syndrome (MetS) have become more prevalent. Attempts have been made in Taiwan to identify the genes responsible for gout. A few gene loci, among them SLC2A9, have been identified using Taiwan Biobank (TWB) data. We, therefore, examined whether MetS could also account for the association between polymorphism SLC2A9 rs3733591 and gout. Methods: The final analysis consisted of 73,558 subjects, of whom 2,709 had gout. To estimate the likelihood of gout occurrence based on rs3733591 and MetS, we used logistic regression models. Results: Rs3733591-TC + CC compared to TT genotype was associated with gout (OR, 1.15; 95% CI, 1.06-1.25). Also associated with gout was MetS (OR, 1.21; 95% CI, 1.10-1.33). A significant interaction was seen between rs3733591 and MetS (p-value = 0.039). Using rs3733591-TT/no MetS as the reference group, the ORs (95% CI) for gout was 1.24 (1.11-1.38) for TC + CC/no MetS, 1.35 (1.17-1.56) for TT/MetS, and 1.39 (1.22-1.58) for TC + CC/MetS. However, subgroup analysis defined by sex showed no significant associations in women. Conclusion: In summary, metabolic syndrome and SLC2A9 rs3733591 genotypes were interactively associated with gout in Taiwanese men, but not women.

Alpha-lipoic acid (ALA) ameliorates early brain injury after subarachnoid hemorrhage in Sprague-Dawley (SD) rats via inhibiting STING-NLRP3 inflammatory signaling.

Neuroinflammation is intimately associated with poor prognosis in patients with subarachnoid hemorrhage (SAH). Alpha-lipoic acid (ALA), a disulfide antioxidant, has been shown to be neuroprotective in an in vivo model of neurological injury; however, the role of ALA in SAH has never been evaluated. In this study, the Sprague-Dawley rats SAH model was induced by endovascular perforation method. ALA was transplanted intravenously into rats, and SR-717, a stimulator of interferon genes (STING) agonist, was injected intraperitoneally. The effects of ALA on early brain injury were assayed by neurological score, hematoxylin and eosin staining and Nissl staining. Immunohistochemistry staining and Western blotting were used to analyze various proteins. ALA significantly reduced STING- NLRP3 protein expression and decreased cell death, which in turn mitigated the neurobehavioral dysfunction following SAH. Furthermore, coadministration of ALA and SR-717 promoted STING-NLRP3 signaling pathway activation following SAH, which reversed the inhibitory effect of ALA on STING-NLRP3 protein activation and increased the neurological deficits. In conclusion, ALA may be a promising therapeutic strategy for alleviating early brain injury after SAH.

Effects of an intraoperative intravenous Bolus Dose of Dexmedetomidine on postoperative catheter-related bladder discomfort in male patients undergoing transurethral resection of bladder tumors: a randomized, double-blind, controlled trial.

PURPOSE: To investigate whether the effect of intravenous bolus doses of dexmedetomidine on postoperative catheter-related bladder discomfort (CRBD) was dose-dependent in male patients undergoing transurethral resection of bladder tumors (TURBT). METHODS: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR 2,000,034,657, date of registration: July 14, 2020). Adult male patients were randomized to one of four groups: placebo (Group C); dexmedetomidine 0.2 µg/kg (Group D 0.2); dexmedetomidine 0.5 µg/kg (Group D 0.5); or dexmedetomidine 1 µg/kg (Group D 1). The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 6, 24, and 48 h postoperatively. RESULTS: The incidence of moderate-to-severe CRBD was significantly lower in Group D 0.5 and Group D 1 than in Group C at 0 h (13% vs. 40%, P = 0.006; 8% vs. 40%, P = 0.001), 1 h (15% vs. 53%, P < 0.001; 13% vs. 53%, P < 0.001), and 6 h (10% vs. 32%, P = 0.025; 8% vs. 32%, P = 0.009) postoperatively. Compared with baseline, both the MAP and HR were significantly lower in Group D 1 at 1 min ([94 ± 15] vs. [104 ± 13] mm Hg, P = 0.003; [64 ± 13] vs. [73 ± 13] bpm, P = 0.001) and 30 min ([93 ± 10] vs. [104 ± 13] mm Hg, P < 0.001; [58 ± 9] vs. [73 ± 13] bpm, P < 0.001) postextubation. CONCLUSION: The effect of intravenous bolus doses of dexmedetomidine on postoperative CRBD was dose-independent, whereas intravenous administration of 0.5 µg/kg dexmedetomidine reduced the early postoperative incidence of CRBD with minimal side effects. TRIAL REGISTRATION: Clinical trial number and registry URL: ChiCTR 2,000,034,657, http://www.chictr.org.cn , date of registration: July 14, 2020.

Knockdown of sortilin improves the neurological injury and regional cerebral blood flow in rats after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a severe subtype of stroke. Sortilin protein is elevated in cerebrospinal fluid (CSF) of SAH patients. This study explored the mechanism of sortilin in SAH. SAH model was established by occipital cisternal blood injection. Neurological evaluation was performed on SAH rats using the Gracia scoring system and beam-balance tests. Regional cerebral blood flow (rCBF) and intracranial pressure (ICP) changes were measured using a laser Doppler blood flow monitor and an intraparenchymal Camino ICP probe. The correlation between rCBF changes and neurological deficit was analyzed using the Spearman method. Sortilin protein level in rat cerebral cortex and CSF was detected by Western blot. The Garcia score and beam-balance score of rats at 1, 12, 24, 48, and 72 h after SAH were lowered. Blood clots were observed on the ventral surface of the brain in SAH rats, around Willis ring, and ventral surface of brain stem, but no blood clots were found in the control group. At 1, 12, 24, 48, and 72 h after SAH in rats, the severity of SAH was aggravated, rCBF was decreased, and ICP was increased. The changes of rCBF in rat cerebral cortex at 1 and 72 h after SAH were correlated with the Garcia score. Sortilin was highly expressed in the cerebral cortex and CSF of SAH rats. Knockdown of sortilin improved the neurological injury and rCBF in rats. Sortilin was highly expressed in the cerebral cortex and CSF of SAH rats. Sortilin silencing improved neurological injury and CBF in rats.

Design, synthesis and antitumour evaluation of novel anthraquinone derivatives.

We report the design, synthesis, and biological evaluation of 13 new and 1 known anthraquinone derivatives which exerted cytotoxicity against PC3, A549 and NTUB1 cell lines. The results indicate that, among these 14, compounds-1 and 14 showed the highest growth inhibitory effect on NTUB1 and PC3 cells, respectively. Compound-1 at lower doses targets DNA, induces DNA damage and subsequently triggers G2/M arrest and apoptotic cell death at 24 h. Previously we reported that 14 induced PC3 cell autophagy and in treated PC3 cells, cleaved caspase-3 and cleaved PARP, and survivin did not increase and increase, respectively. The autophagic and necrotic cell deaths mediated by 14-triggered ROS generation. Our study is the first to investigate the biological mechanism of 14 action in detail. We find that when 14 was co-administrated with Bafilomycin A1 (BAF) in PC3 cells, rapid necrotic cell death occurred with no cleaved caspase-3 and cleaved PARP activation and increasing the expression of survivin. We further show that necrotic signaling in these cells coincided with production of reactive oxygen species. In the present study, we developed methods to synthesize five new 14 analogues for studing the structure-activity relationships. This study could provide valuable sight to find new antitumor agents for cancer therapy.

Clinical predictors and impact of bacteremia in cirrhotic patients with acute skin and skin structure infection.

OBJECTIVE: Acute bacterial skin and skin structure infection (ABSSSI) is a common cause of acute admissions in patients with cirrhosis worldwide, but the disease is not well-understood epidemiologically with respect to factors that determine positive blood cultures or patient mortality. The aim of this study was to understand the utility of blood cultures and the association between bacteremia and mortality in cirrhotic patients with ABSSSI. We conducted a retrospective study to investigate factors associated with positive blood cultures and mortality in cirrhotic patients with ABSSSI. METHODS: A retrospective cohort study of hospitalized adult cirrhotic patients with ABSSSI was conducted in a tertiary hospital in Taiwan between March 2015 and December 2016. RESULTS: A total of 122 hospitalized cirrhotic patients with ABSSSI were included. The overall mortality rate was 9% (11/122), and 23 patients had positive blood culture results. Comorbidities that were significant risk factors for a positive blood culture included diabetes mellitus, acute kidney injury (AKI), and acute-on-chronic liver failure (ACLF). Significant risk factors evident in laboratory evaluations included higher model for end-stage liver disease (MELD) score, higher serum lactate, and lower serum albumin level. Bacteremia was also a significant factor associated with mortality. CONCLUSION: A blood culture should be considered for cirrhotic patients with ABSSSI with diabetes mellitus, AKI, ACLF or those exhibiting abnormal albumin, lactate levels, or high MELD score because of the positive correlation between bacteremia and mortality.

The Relationship Between Fluid Accumulation in Ultrasonography and the Diagnosis and Prognosis of Patients with Necrotizing Fasciitis.

Necrotizing fasciitis is a severe soft-tissue infection with a high mortality rate. There is little literature on the relationship between the ultrasonographic finding of fluid accumulation along the deep fascia and the diagnosis and prognosis of necrotizing fasciitis. This retrospective study showed that when fluid accumulation was present along the deep fascia, patients with clinically suspected necrotizing fasciitis had a higher probability of having necrotizing fasciitis. The ultrasonographic finding of fluid accumulation with a cutoff point of more than 2 mm of depth had the best accuracy (72.7%) for diagnosing necrotizing fasciitis. In regard to the prognosis of necrotizing fasciitis, when fluid accumulation was present along the deep fascia, patients with necrotizing fasciitis had a longer length of hospital stay and were at risk of amputation or mortality. Ultrasonography is a point-of-care imaging tool that facilitates the diagnosis and prognosis of necrotizing fasciitis.

Lactate on emergency department arrival as a predictor of in-hospital mortality in necrotizing fasciitis: a retrospective study.

BACKGROUND: Hyperlactatemia is known to be associated with adverse outcome in critical illness. In this study, we attempted to identify if hyperlactatemia on emergency department (ED) arrival is a reliable predictor for in-hospital mortality in necrotizing fasciitis (NF) patients. METHOD: A prospective cohort study of hospitalized patients with NF was conducted in two tertiary teaching hospitals in Taiwan between March 2010 and March 2018. Blood samples were collected in the ED upon arrival, and the lactate levels were determined. Sequential organ failure assessment (SOFA) scores were calculated during the first 24 h after admission. All collected data were statistically analyzed. RESULT: Of the 707 NF patients, 40 (5.66%) died in the hospital. The median (interquartile range) blood lactate level in all NF patients was 3.6 mmol/l (2.2-4.8). The blood lactate level upon ED arrival was significantly associated with mortality (odds ratio [OR] = 1.35; 95% confidence interval [CI], 1.30-1.46; P < 0.001), even after adjustment for age and SOFA score (OR = 1.27; P < 0.001). Multivariate regression analysis showed that a high blood lactate level (OR = 1.17; 95% CI, 1.07-1.29; P = 0.001) and a high SOFA score (OR = 1.15; 95% CI, 1.11-1.20; P < 0.001) were independent risk factors for in-hospital mortality in NF. Blood lactate achieved an area under-the-receiver-operating-characteristic curve (AUC) of 0.79 (P < 0.001) for predicting mortality that was similar to that of SOFA score (AUC = 0.82; P < 0.001). Blood lactate displayed a sensitivity of 62% and a specificity of 86% in predicting mortality at the optimal cutoff value of 5.80 mmol/l. CONCLUSION: In necrotizing fasciitis patients, hyperlactatemia on ED arrival is independently associated with in-hospital mortality. NF patients with hyperlactatemia on ED arrival should be closely monitored for signs of deterioration and consider early and aggressive intervention to prevent mortality.

Discovering a Racemate Polycyclic Prenylated Acylphloroglucinol with Unprecedented Skeleton by an ESI-LCMS Analytical Approach.

By an ESI-LC/MS analytical method, a racemate 1 consisting of a pair of unprecedented phloroglucinol enantiomers with a 5/6/5/5/6 fused ring system, (-)-garcinielliptone HG [((-)-1a] and (+)-garcinielliptone HH [(+)-1b], was obtained from the isolates of a CH2Cl2 extract of Garcinia subelliptica (heartwood). The gross structure of 1 was elucidated by spectroscopic methods and X-ray single-crystal diffraction data. The absolute configurations of 1a and 1b were unequivocally assigned by analysis on the calculated and experimental circular dichroism spectra and X-ray single-crystal diffraction data.

Diagnostic Performance of Initial Serum Albumin Level for Predicting In-Hospital Mortality among Necrotizing Fasciitis Patients.

BACKGROUND: Hypoalbuminemia is known to be associated with adverse outcomes in critical illness. In this study, we attempted to identify whether hypoalbuminemia on emergency department (ED) arrival is a reliable predictor for in-hospital mortality in necrotizing fasciitis (NF). METHOD: A retrospective cohort study of hospitalized adult patients with NF was conducted in a tertiary teaching hospital in Taiwan between March 2010 and March 2018. Blood samples were collected in the ED upon arrival, and serum albumin levels were determined. We evaluated the predictive value of serum albumin level at ED presentation for in-hospital mortality. All collected data were statistically analyzed. RESULT: Of the 707 NF patients, 40 (5.66%) died in the hospital. The mean serum albumin level was 3.1 ± 0.9 g/dL and serum albumin levels were significantly lower in the non-survivor group than in the survivor group (2.8 ± 0.7 g/dL vs. 3.5 ± 0.8 g/dL). In the multivariable logistic regression model, albumin was significantly associated with in-hospital mortality (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.88⁻0.96, p < 0.001). The area under-the-receiver-operating-characteristic curve (AUC) for in-hospital survival was 0.77 (95% CI 0.72⁻0.82) and corresponding sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratio were 66%, 74%, 33%, 88%, 2.25, and 0.48, respectively. High sensitivity (96%) for survival was shown at albumin level of 4.0 g/dL and high specificity (91%) for mortality was shown at a level of 2.5 g/dL. CONCLUSION: Initial serum albumin levels strongly predicted in-hospital mortality among patients with necrotizing fasciitis. NF patients with hypoalbuminemia on ED arrival should be closely monitored for signs of deterioration and early and aggressive intervention should be considered to prevent mortality.

Risk factors for mortality in the late amputation of necrotizing fasciitis: a retrospective study.

Background: Necrotizing fasciitis (NF) is a rapidly progressive infectious disease that primarily involves the fascia and subcutaneous tissue. If not promptly treated, it can lead to morbidity as well as mortality. It can affect any part of the body, most commonly the extremities. Early and aggressive surgical treatment is the proper way of management. The purpose of this study was to identify the risk factors for mortality in late amputation among NF patients that may be used in routine clinical practice to prevent mortality. Methods: A retrospective cohort study of hospitalized patients with NF was conducted in a tertiary teaching hospital in Taiwan between March 2015 and March 2018. All collected data were statistically analyzed. Results: A total of 582 patients with NF were included; 35 of them had undergone amputation (7 primary and 28 late amputations), with a 6% amputation rate. Thirteen amputated patients still died eventually (all in the late amputation group). Significant risk factors for mortality identified in the late amputation group included hemorrhagic bullae (p = 0.001, OR 4.7, 95% confidence interval (CI) 2.68-8.69), peripheral vascular disease (p < 0.001, OR 3.2, 95% CI 1.12-10.58), bacteremia (p = 0.021, OR 2.87, 95% CI 2.07-5.96), and Laboratory Risk Indicator of Necrotizing Fasciitis (LRINEC) score > 8 (p < 0.001, OR 1.97, 95% CI 1.28-4.61). Vibrio vulnificus was the main causative organism based on our study, but the microbiology results showed no significant correlation. Conclusion: NF patients with hemorrhagic bullae, comorbidity with peripheral vascular disease, presence of bacteremia, or LRINEC score > 8 should receive early and primary amputation in order to prevent mortality.

Autophagy mediates cytotoxicity of human colorectal cancer cells treated with garcinielliptone FC.

The tautomeric pair of garcinielliptone FC (GFC) is a novel tautomeric pair of polyprenyl benzophenonoid isolated from the pericarps of Garcinia subelliptica Merr. (G. subelliptica, Clusiaceae), a tree with abundant sources of polyphenols. Our previous report demonstrated that GFC induced apoptosis on various types of human cancer cell lines including chemoresistant human colorectal cancer HT-29 cells. In the present study, we observed that many autophagy-related genes in GFC-treated HT-29 cells were up- and down-regulated using a cDNA microarray containing oncogenes and kinase genes. GFC-induced autophagy of HT-29 cells was confirmed by observing the formation of acidic vesicular organelles, LC3 puncta, and double-membrane autophagic vesicles using flow cytometry, confocal microscopy, and transmission electron microscopy, respectively. Inhibition of AKT/mTOR/P70S6K signaling as well as formation of Atg5-Atg12 and PI3K/Beclin-1 complexes were observed using Western blot. Administration of autophagy inhibitor (3-methyladenine and shRNA Atg5) and apoptosis inhibitor Z-VAD showed that the GFC-induced autophagy was cytotoxic form and GFC-induced apoptosis enhanced GFC-induced autophagy. Our data suggest the involvement of autophagy and apoptosis in GFC-induced anticancer mechanisms of human colorectal cancer.

18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts.

Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18ß-glycyrrhetinic acid (18ß-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18ß-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18ß-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18ß-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18ß-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18ß-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18ß-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.

Therapeutic Benefits of Mesenchymal Stromal Cells in a Rat Model of Hemoglobin-Induced Hypertensive Intracerebral Hemorrhage.

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-1ß and TNF-α). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

Photoprotective Effects of Cycloheterophyllin against UVA-Induced Damage and Oxidative Stress in Human Dermal Fibroblasts.

Ultraviolet (UV) radiation, particularly ultraviolet A (UVA), is known to play a major role in photoaging of the human skin. Many studies have demonstrated that UV exposure causes the skin cells to generate reactive oxygen species and activates the mitogen-activated protein kinase (MAPK) pathway. Previous studies have also demonstrated that cycloheterophyllin has an antioxidant effect and can effectively scavenge free radicals. Extending the aforementioned investigations, in this study, human dermal fibroblasts were used to investigate the protective effect of cycloheterophyllin against UV-induced damage. We found that cycloheterophyllin not only significantly increased cell viability, but also attenuated the phosphorylation of MAPK after UVA exposure. Furthermore, cycloheterophyllin could reduce hydrogen peroxide (H2O2) generation and down-regulate H2O2-induced MAPK phosphorylation. In the in vivo studies, the topical application of cycloheterophyllin before UVA irradiation significantly decreased trans-epidermal water loss (TEWL), erythema, and blood flow rate. These results indicate that cycloheterophyllin is a photoprotective agent that inhibits UVA-induced oxidative stress and damage, and could be used in the research on and prevention of skin photoaging.

Low p21 level is necessary for the suppressive effects of micoRNA-31 on glioma cell migration and invasion.

MicroRNAs (miRNAs), a kind of endogenous non-coding RNAs, regulate gene expression through binding to the 3'-untranslational region (UTR) of target messenger RNAs (mRNAs) and act as endogenous agents of RNA interference, resulting in either mRNA degradation or translational repression. MiR-31 has been demonstrated to be associated with the development and progression of glioma. However, the underlying molecular mechanism remains largely unclear. In the present study, we demonstrated that miR-31 only inhibited the cell migration and invasion, as well as the expression of a known miR-31 target oncogene radixin, in U251 glioma cells that expressed low level of p21; however, miR-31 showed no above effects on glioma SHG44 cells that highly expressed p21. Moreover, upregulation of p21 in U251 cells reversed the suppressive effects of miR-31 on the cell migration and invasion, suggesting that low p21 level is necessary for the miR-31-mediated inhibitory effects on glioma. Furthermore, analysis for 35 glioma specimens showed that the expression of radixin was negatively correlated with the miR-31 level in glioma tissues with low p21 expression; however, no such correlation was found in glioma tissues with high p21 level, further supporting that the low p21 level is necessary for the suppressive effect of miR-31 on the expression of its target oncogenes. In summary, our study demonstrates that the suppressive effect of miR-31 on glioma cell migration and invasion is p21-dependent, and suggests that miR-31 may be used for the treatment of patients with p21-deficent glioma.

Triterpenoids and an alkamide from Ganoderma tsugae.

Ganoderma tsugae is a medicinal mushroom. In a continual study on the bioactive constituents of this fungus, a new lanostanoid, 3ß-acetoxy-16α-hydroxy-24ξ-methyl-5α-lanosta-8,25-dien-21-oic acid, named tsugaric acid F (1) and a novel palmitamide, N-(3'α,4'ß-dihydroxy-2'ß-(hydroxymethyl)-1'ß-(cyclobutyl)palmitamide (2) were isolated and characterized from the fruit bodies of G. tsugae, and three novel seco-lanostanoids, 3,4-seco-8α,9α-epoxy-5α-lanosta-21-oic acid 3,4 lactone (5), 3,4-seco-5ß-lanosta-7,9(11),4(29)-trien-3,21-dioic acid-3-methyl ester (6), 3,4-seco-5ß-lanosta-7,9(11),4(29)-trien-3,21-dioic acid (7), and a known compound, 3-oxo-5α-lanosta-8-en-21-oic acid (4) were prepared from 3. The structures of new compounds, 1, 2, 5-7 were determined by spectroscopic methods. Compounds 1 and 4 showed inhibitory effects on xanthine oxidase (XO) with an IC50 values of 313.3 ± 80.0 and 43.9 ± 29.9 µM, respectively when 7 exhibited potent inhibitory effect on superoxide anion generation in rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB) with an IC50 values of 1.3 ± 0.2 µM. Compounds 4-7 showed weak cytotoxic activities against PC3 cells. These results indicated that 4 and 7 may be used as cancer chemopreventive agents.

MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson's Disease by Targeting to Bim.

Parkinson's disease (PD) is the most prevalent movement disorder characterized by selective loss of midbrain dopaminergic (DA) neurons. MicroRNA-124 (miR-124) is abundantly expressed in the DA neurons and its expression level decreases in the 1-methyl-4-pheny-1, 2, 3, 6-tetrahydropyridine (MPTP) model of PD. However, whether the upregulation of miR-124 could attenuate neurodegeneration remains unknown. Here, we employed miR-124 agomir and miR-124 mimics to upregulate miR-124 expression in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y cells, respectively. We found that loss of DA neurons and striatal dopamine in MPTP-treated mice was significantly reduced by upregulating miR-124. In addition, we identified a target of miR-124, Bim that mediated the neuroprotection of miR-124. Indeed, treatment of miR-124 agomir in MPTP-treated mice inhibited Bim expression, thus suppressing Bax translocation to mitochondria. Moreover, impaired autophagy process in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y cells characterized as autophagosomes (AP) accumulation and lysosomal depletion were alleviated by the upregulation of miR-124. Taken together, these results indicate that upregulation of miR-124 could regulate apoptosis and impaired autophagy process in the MPTP model of PD, thus reducing the loss of DA neurons.

The application of data mining techniques to oral cancer prognosis.

This study adopted an integrated procedure that combines the clustering and classification features of data mining technology to determine the differences between the symptoms shown in past cases where patients died from or survived oral cancer. Two data mining tools, namely decision tree and artificial neural network, were used to analyze the historical cases of oral cancer, and their performance was compared with that of logistic regression, the popular statistical analysis tool. Both decision tree and artificial neural network models showed superiority to the traditional statistical model. However, as to clinician, the trees created by the decision tree models are relatively easier to interpret compared to that of the artificial neural network models. Cluster analysis also discovers that those stage 4 patients whose also possess the following four characteristics are having an extremely low survival rate: pN is N2b, level of RLNM is level I-III, AJCC-T is T4, and cells mutate situation (G) is moderate.