Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) poses a significant health challenge in modern societies due to shifts in lifestyle and dietary habits. Its complexity stems from genetic predisposition, environmental influences, and metabolic factors. Epigenetic processes govern various cellular functions such as transcription, chromatin structure, and cell division. In NAFLD, these epigenetic tendencies, especially the process of histone methylation, are intricately intertwined with fat accumulation in the liver. Histone methylation is regulated by different enzymes like methyltransferases and demethylases and influences the expression of genes related to adipogenesis. While early-stage NAFLD is reversible, its progression to severe stages becomes almost irreversible. Therefore, early detection and intervention in NAFLD are crucial, and understanding the precise role of histone methylation in the early stages of NAFLD could be vital in halting or potentially reversing the progression of this disease.

[Effects of dexmedetomidine on the proliferation, invasiveness and tumorigenesis of human prostate cancer PC3 cells and its action mechanism].

OBJECTIVE: To investigate the effects of dexmedetomidine (Dex) on the proliferation, invasiveness and tumorigenesis of human PCa PC3 cells and its action mechanism. METHODS: We treated human PCa PC3 cells with Dex at 0 µmol/L (the control group), 1 µmol/L (Dex group 1), 2 µmol/L (Dex group 2), and 5 µmol/L (Dex group 3). After 24, 48 and 72 hours of treatment, we examined the proliferation, apoptosis and invasiveness of the cells using cell counting kit-8 (CCK8), flow cytometry and Transwell assay respectively, measured the tumorigenicity of the transplanted tumors in the nude mice, and determined the expressions of mitogen-activated protein kinase (MAPK) signaling pathway-related proteins in the cells by Western blot. RESULTS: After treatment, the A value of the PC3 cells was significantly increased in all the four groups (P < 0.05). Compared with the control group, the three Dex groups showed a decrease in the A value, an elevated rate of apoptotic cells (P < 0.05), an increased number of membrane-penetrating cells (P < 0.05), reduced volume of the transplanted tumors (P < 0.05), and down-regulated expressions of phosphorylated extracellular signal-regulated kinase (p-ERK) / ERK and phosphorylated c-Jun N-terminal kinase (p-JNK) / JNK (P < 0.05) with the increased dose of Dex. The volume of the transplanted tumors in the nude mice was increased in all the four groups in a time-dependent manner (P < 0.05). CONCLUSION: Dex inhibits the proliferation and invasiveness, promotes the apoptosis, and reduces the tumorigenicity of human PCa PC3 cells by decreasing the phosphorylation of ERK and JNK in the MAPK signaling pathway.

Structures and In Vitro Antihepatic Fibrosis Activities of Prenylated Dihydrostilbenes and Flavonoids from Glycyrrhiza uralensis Leaves.

Glycyrrhiza uralensis is the major plant source of licorice. This study was to identify bioactive compounds from the plant's leaves in order to make better use of its aerial part. An ethanol extract of the leaves was subjected to repeated chromatography to yield 15 compounds. The structures were determined to be three novel dihydrostilbenes, based on their various spectroscopic data-glycypytilbene A (1), glycydipytilbene (2), and glycypytilbene B (3)-and 12 known compounds, α,α'-dihydro-3,5,4'-trihydroxy-4,3'-diisopentenylstilbene (4), α,α'-dihydro-3,5,3',4'-tetrahydroxy-2,5'-diisopentenylstilbene (5), 6-prenyleriodictyol (6), 5'-prenyleriodictyol (7), 6-prenylquercetin-3-Me ether (8), 5'-prenylquercetin (9), 6-prenylquercetin (10), 6-prenylnaringenin (11), 3'-prenylnaringenin (12), sigmoidin C (13), 8-[(E)-3-hydroxymethyl-2- butenyl]-eriodictyol (14), and quercetin-3-Me ether (15). Most of these chemical constituents inhibited α-glucosidase activity, with the two prenylated quercetin derivatives (9 to 10) being the greatest active (IC50 < 4.0 µg/mL). Compounds 1, 3 to 4, 6 to 7, 9 to 12 impeded the growth of human hepatic stellate cells, with the prenylated flavonoids (6 to 7, 9 to 12) being more robust than their unprenylated counterparts. PRACTICAL APPLICATIONS: This study found that Glycyrrhiza uralensis leaves contain prenylated dihydrostilbenes and flavonoids with inhibiting effects on α-glucosidase and on the proliferation of human hepatic stellate cells, which should prompt the development of G. uralensis leaves for healthy products with anti-diabetic or liver fibrosis-preventing effects.

Identification and Enrichment of α-Glucosidase-Inhibiting Dihydrostilbene and Flavonoids from Glycyrrhiza uralensis Leaves.

To exploit Glycyrrhiza uralensis resources, we examined the bioactive constituents of G. uralensis leaves. Seven chemical components were isolated by repeat column chromatography, and using spectroscopic methods, their structures were determined to be a novel prenylated dihydrostilbene, α,α'-dihydro-3,5,3',4'-tetrahydroxy-2,5'-diprenylstilbene (1); a methylated flavonoid, quercetin-3-Me ether (4); and 5 prenylated flavonoids: 5'-prenylquercetin (3), 8-[(E)-3-hydroxymethyl-2-butenyl]eriodictyol (7), 6-prenyleriodictyol (5), 5'-prenyleriodictyol (6), and 6-prenylquercetin-3-Me ether (2). Compounds 1-7 and their unprenylated counterparts, glycosides, and other related compounds (8-13) were quantitatively analyzed. Using a macroporous resin column, most of these compounds could be enriched in the 40% to 60% ethanol-eluted fractions. Compounds 1-7 showed strong radical scavenging activity toward DPPH, and most of them demonstrated greater inhibitory activity against α-glucosidase than their unprenylated counterparts.

[Electrophysiological effects of ischemia/reperfusion (I/R) on pacemaker cells in guinea-pig left ventricular outflow tract and the effects of antiarrhythmic drugs treatment].

OBJECTIVE: To investigate the electrophysiological effects of ischemia/reperfusion (I/R) on the spontaneous slow response action potentials in guinea-pig left ventricular outflow tract and the effects of antiarrhythmic drugs onI/R. METHODS: The action potentials of pacemaker cells in guinea-pig left ventricular outflow tract were recorded by conventional intracellular microelectrode technique. The influences of ischemia(I) 10 min, reperfusion(R) 2 min, and R 15min on the spontaneous slow response potentials were investigated. The effects of lidocaine, propafenone, amiodarone, verapamil, adenosine, and sodium nitroprusside (SNP) on I/R were also studied. Electrophysiological parameters were examined:velocity of diastolic depolarization(VDD), rate of pacemaker firing(RPF), maximal diastolic potential(MDP), maximal rate of depolarization(Vmax), amplitude of action potential(APA), 50% and 90% of duration of action potential(APD50 and APD90). RESULTS: ①In I 10 min group, the values of VDD, RPF, Vmax and APA were decreased markedly compared with control group (P<0.05, P<0.01).In R 2 min group, VDD and RPF were increased significantly(P<0.01), MDP was increased notably(P<0.05), APD50 and APD90 were shortened significantly compared with I 10 min and control group. Vmax was increased markedly vs control group(P<0.05). APA was decreased notably vs I 10 min group (P<0.05), but was increased markedly vs control group(P<0.05). In R 15 min group, the action potentials recovered gradually to the levels of control group. ② Compared with I 10 min/R 2 min group, 1 µmol/L lidocaine, 10 µmol/L propafenone, 1 µmol/L amiodarone, 1 µmol/L verapamil, 50 µmol/L adenosine, and 10 µmol/L SNP decreased VDD and RPF significantly. CONCLUSIONS: I/R injury can trigger abnormal spontaneous activities of guinea-pig left ventricular outflow tract.The electrophysiological effects of I/R injury on left ventricular outflow tract can be treated by antiarrhythmic drugs.

Transvenous treatment of complex cavernous dural arteriovenous fistulae with Onyx and coils.

Transvenous embolization has become the treatment of choice for such lesions We evaluated Onxy for patients with cavernous dural arteriovenous fistulae (CDAVFs) who underwent transvenous embolization via different transvenous approaches. Case records of six patients with symptomatic CDAVFs, treated between October 2006 and November 2007 were reviewed. A total of seven transvenous procedures were performed in the six patients with CDAVFs. All the patients with CDAVFs of the cavernous sinus were symptom free following embolization. The approach via the internal jugular vein and the inferior petrosal sinus was possible in four of the six patients, with complete occlusion of the fistula. In the remaining two patients, the approach was via the facial vein. Transient bradyarrythmia without morbidity was the only complication in two patients.