UHRF1 is regulated by miR-124-3p and promotes cell proliferation in intrahepatic cholangiocarcinoma

Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is abnormally overexpressed in multiple cancers and closely correlated with tumor-promoting effects, such as high proliferation. However, how UHRF1 functions in intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein, we found that UHRF1 is overexpressed in ICC tissues. Downregulated UHRF1 attenuated the transition of the G1/S cell cycle and then suppressed cell proliferation in vitro and tumor growth in vivo. Moreover, upstream regulators of the UHRF1 expression were predicted, and we found that direct binding of miR-124-3p inhibited the UHRF1 expression. Elevated miR-124-3p suppressed proliferation and led to the arrest of the cell cycle. Furthermore, the expression of UHRF1 was positively correlated with PCNA. Clinically, we showed that elevated UHRF1 was associated with poor prognosis, and served as an independent prognostic factor in ICC patients. Together, these findings demonstrate that UHRF1, regulated by miR-124-3p, acts as a tumor promoter by promoting cell proliferation in ICC.     

High expression of LASS2 is associated with unfavorable prognosis in patients with ovarian cancer

Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), is a gene isolated from a human liver complementary DNA library. In this study, we found that LASS2 protein level was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage and LASS2-negative tumors showed significant association with longer disease-free survival (DFS) and overall survival (OS) in ovarian cancer patients. The heterogeneous expression of LASS2 had been exhibited in diverse ovarian cancer cells. A significantly lower messenger RNA (mRNA) and protein level of LASS2 was seen in 3AO cell compared with those in other types of ovarian cancer cells. Meanwhile, the mRNA and protein levels of LASS2 in ES-2 and NIH:OVCAR-3 cells were obviously higher. LASS2 overexpression in 3AO cell could promote migration, invasion, and metastasis abilities in vitro and in vivo, while LASS2 knockdown in ES-2 and NIH:OVCAR-3 cells had the opposite effects. The oncogenic capacity of LASS2 in ovarian cancer may be mediated by increased expression of YAP/TAZ. It is indicated that lowering the expression of LASS2 is likely to serve as an unprecedented approach for the treatment of ovarian cancer.     

Purple sweet potato color attenuated NLRP3 inflammasome by inducing autophagy to delay endothelial senescence

Autophagy is a vital negative factor regulating cellular senescence. Purple sweet potato color (PSPC), one type of flavonoid, has been demonstrated to suppress endothelial senescence and restore endothelial function in diabetic mice by inhibiting the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. However, the roles of autophagy in the inflammatory response during endothelial senescence are unknown. Here, we found that PSPC augmented autophagy to restrict high-glucose-induced premature endothelial senescence. In addition, PSPC administration impaired endothelium aging in diabetic mice by increasing autophagy. Inhibition of autophagy accelerated endothelial senescence, while enhancement of autophagy delayed senescence. Moreover, deactivation of the NLRP3 inflammasome triggered by PSPC was autophagy-dependent. Autophagy receptor microtubule-associated protein 1 light chain 3 and p62 interacted with the inflammasome component NLRP3, suggesting that autophagosomes target the NLRP3 inflammasome and deliver it to the lysosome for degradation. Altogether, PSPC amplified cellular autophagy, subsequently attenuated NLRP3 inflammasome activity and finally delayed endothelial senescence to ameliorate cardiovascular complication. These results suggest a potential therapeutic target in senescence-related cardiovascular diseases.     

Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart

Many genetic diseases are caused by mutations in cis-acting splicing signals, but few are triggered by defective trans-acting splicing factors. Here we report that tissue-specific ablation of the splicing factor SC35 in the heart causes dilated cardiomyopathy (DCM). Although SC35 was deleted early in cardiogenesis by using the MLC-2v-Cre transgenic mouse, heart development appeared largely unaffected, with the DCM phenotype developing 3-5 weeks after birth and the mutant animals having a normal life span. This nonlethal phenotype allowed the identification of downregulated genes by microarray, one of which was the cardiac-specific ryanodine receptor 2. We showed that downregulation of this critical Ca2+ release channel preceded disease symptoms and that the mutant cardiomyocytes exhibited frequency-dependent excitation-contraction coupling defects. The implication of SC35 in heart disease agrees with a recently documented link of SC35 expression to heart failure and interference of splicing regulation during infection by myocarditis-causing viruses. These studies raise a new paradigm for the etiology of certain human heart diseases of genetic or environmental origin that may be triggered by dysfunction in RNA processing.     

Polyphenols from peanut skins and their free radical-scavenging effects

Separation of the water-soluble fraction of peanut skins led to the isolation of five proanthocyanidins. Based on the spectroscopic investigation and partial acid catalyzed degradation, their structures were determined to be epicatechin-(2beta-->O -->7, 4beta -->6)-[epicatechin-(4beta-->8)]-catechin (1), epicatechin-(2beta-->O -->7, 4beta-->8) epicatechin-(4beta-->8)-catechin-(4alpha-->8)-epicatechin (2), and procyanidins B2 (3), B3 (4) and B4 (5). The absolute configuration of the new compounds was determined from their circular dichroism curves and the (1)H NMR spectra of analysis of flavan-3-ols formed by thiolytic degradation of 1 and 2 in the presence of a chiral dirhodium complex (dirhodium tetra-(R)-(trifluoromethyl) phenyl acetate).     

Equivalent models of indanol isomers adsorption on cellulose tribenzoate

The adsorption isotherm data of (R)- and (S)-1-indanol and of their racemic mixture on cellulose tribenzoate were measured by frontal analysis. The experimental data for each enantiomers were fitted to the single-component bilangmuir isotherm model. The competitive experimental data were fitted to the ideal adsorption solution model (IAS), the real adsorption solution model (RAS), and the bilangmuir thermodynamically consistent model (BTC). The mass transfer kinetic parameters were estimated from systematic comparisons between the experimental single-component band profiles and profiles calculated using the general rate model (GR) of chromatography coupled with the generalized Maxwell-Stefan equation (GMS). The validation of the isotherm model and of the mass transfer kinetic model was made by comparing the experimental band profiles obtained for solutions of the two enantiomers and those calculated with the competitive GR-GMS model. The excellent agreement observed proves that a combination of the BTC isotherm model and the GMS kinetic model, using the best values of the BTC and GMS parameters estimated from single component experiments, allows an excellent prediction of the binary isotherm and the binary mass transfer kinetics.     

Carpal Tunnel Syndrome Assessment with Ultrasonography: Value of Inlet-to-Outlet Median Nerve Area Ratio in Patients versus Healthy Volunteers

Objective

To evaluate the diagnostic value of the Inlet-to-outlet median nerve area ratio (IOR) in patients with clinically and electrophysiologically confirmed carpal tunnel syndrome (CTS).

Methods

Forty-six wrists in 46 consecutive patients with clinical and electrodiagnostic evidence of CTS and forty-four wrists in 44 healthy volunteers were examined with ultrasonography. The cross-sectional area (CSA) of the median nerve was measured at the carpal tunnel inlet (the level of scaphoid-pisiform) and outlet (the level of the hook of the hamate), and the IOR was calculated for each wrist. Ultrasonography and electrodiagnostic tests were performed under blinded conditions. Electrodiagnostic testing combined with clinical symptoms were considered to be the gold standard test. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value between the inlet CSA and IOR.

Results

The study population included 16 men and 30 women (mean age, 45.3 years; range, 18–83 years). The control population included 18 men and 26 women (mean age, 50.4 years; range, 18–79 years). The mean inlet CSA was 8.7 mm² in healthy controls and 14.6mm² in CTS group (P<0.001). The mean IOR in healthy volunteers (1.0) was smaller than that in patients (1.6, P<0.001). Receiver operating characteristic analysis revealed a diagnostic advantage to using the IOR rather than the inlet CSA (P<0.01). An IOR cutoff value of ≥ 1.3 would yield 93% specificity and 91% sensitivity in the diagnosis of CTS.

Conclusion

The IOR of median nerve area promises to be an effective means in the diagnosis of CTS. A large-scale, randomized controlled trial is required to determine how and when this parameter will be used.     

Downregulation of TNIP1 Expression Leads to Increased Proliferation of Human Keratinocytes and Severer Psoriasis-Like Conditions in an Imiquimod-Induced Mouse Model of Dermatitis

Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the TNIP1 gene, which encodes the TNF-α–induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a TNIP1 specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target.