Kctd17-mediated Chop degradation promotes adipogenic differentiation.

Obesity is commonly associated with excessive adipogenesis, a process by which preadipocytes undergo differentiation into mature adipocytes; however, the mechanisms underlying adipogenesis are not completely understood. Potassium channel tetramerization domain-containing 17 (Kctd17) belongs to the Kctd superfamily and act as a substrate adaptor of the Cullin 3-RING E3 ubiquitin ligase, which is involved in a wide variety of cell functions. However, its function in the adipose tissue remains largely unknown. Here, we found that Kctd17 expression levels were increased in white adipose tissue, especially in adipocytes, in obese mice compared to lean control mice. Gain or loss of function of Kctd17 in preadipocytes inhibited or promoted adipogenesis, respectively. Furthermore, we found that Kctd17 bound to C/EBP homologous protein (Chop) to target it for ubiquitin-mediated degradation, and this process was likely associated with increased adipogenesis. In conclusion, these data suggest that Kctd17 plays an important role in adipogenesis and can be a novel therapeutic target for obesity.

Compositional dependence of Co- and Mo-supported beta zeolite for selective one-step hydrotreatment of methyl palmitate to produce bio jet fuel range hydrocarbons.

For producing a drop-in bio jet fuel, one-step hydrotreatment, which includes deoxygenation, isomerization and cracking in one step, is essential to overcome the typical biofuel drawbacks due to high oxygen content, out of jet fuel range hydrocarbons, and low isomerization degree. Herein, Co- or/and Mo-supported Beta(25) zeolites with various Co/Mo ratios were prepared as transition metal-supported zeolite catalysts without the need for sulfidation of conventional transition metal catalysts. Based on the catalyst characterization, the Co/Mo ratio alters the metal phase with the appearance of CoMoO4 and the altered Co metal phase strongly influences the acidic properties of Beta(25) by the formation of Lewis (L) acid sites with different strengths as Co3O4 and CoMoO4 for strong and weak L acid sites, respectively. The catalytic activities were investigated for hydrotreatment of methyl palmitate as a biofuel model compound of fatty acid methyl esters. Primarily, Co is required for deoxygenation and Mo suppresses overcracking to enhance the yield of jet fuel range hydrocarbons. The Co/Mo ratio plays an important role to improve the C8-C16 selectivity by modifying the acidic properties to inhibit excessive cracking. Co5Mo10/Beta(25) achieved the best catalytic performance with the conversion of 94.2%, C8-C16 selectivity of 89.7 wt%, and high isomer ratio of 83.8% in organic liquid product. This unique modification of acidic properties will find use in the design of optimal transition metal-supported zeolite catalysts for selective one-step hydrotreatment to produce bio jet fuel range hydrocarbons.

Effects of human collagen α-1 type I-derived proteins on collagen synthesis and elastin production in human dermal fibroblasts.

Collagen type I is the most abundant form of collagen in human tissues, and is composed of two identical α-1 type I chains and an α-2 type I chain organized in a triple helical structure. A previous study has shown that human collagen α-2 type I (hCOL1A2) promotes collagen synthesis, wound healing, and elastin production in normal human dermal fibroblasts (HDFs). However, the biological effects of human collagen α-1 type I (hCOL1A1) on various skin properties have not been investigated. Here, we isolate and identify the hCOL1A1-collagen effective domain (CED) which promotes collagen type I synthesis. Recombinant hCOL1A1-CED effectively induces cell proliferation and collagen biosynthesis in HDFs, as well as increased cell migration and elastin production. Based on these results, hCOL1A1-CED may be explored further for its potential use as a preventative agent against skin aging. [BMB Reports 2021; 54(6): 329-334].

Synthesis of aminoalkyl-substituted aurone derivatives as acetylcholinesterase inhibitors.

Alzheimer's disease (AD), a progressive and neurodegenerative disorder of the brain, is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, aurone derivatives were designed and synthesized as AChE inhibitors based on the lead structure of sulfuretin. Of those synthesized, compound 10d showed ca. 1700-fold and 6-fold higher AChE inhibitory activity than sulfuretin and galantamine, respectively. This compound also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2mg/kg.

Comparison of choroidal thickness in patients with diabetes by spectral-domain optical coherence tomography.

PURPOSE: To evaluate choroidal thickness in diabetes patients using spectral-domain optical coherence tomography. METHODS: We examined 203 eyes of 203 diabetic participants and 48 eyes of 48 healthy controls. The choroidal thickness at the foveal lesion was measured by enhanced-depth imaging optical coherence tomography. The participants were grouped according to diabetic retinopathy grade: no diabetic change, mild-to-moderate or severe non-proliferative, or proliferative diabetic retinopathy. The study parameters included history, age, axial length, intraocular pressure, central retinal thickness, fasting glucose, and blood pressure. RESULTS: The subfoveal choroidal thickness was thinner in eyes with non-proliferative or proliferative diabetic retinopathy than in normal eyes (p < 0.01). However, there was no difference between eyes with non-proliferative and proliferative diabetic retinopathy or between eyes with no diabetic change and the controls. Eyes exhibiting macular edema showed no significant difference in choroidal thickness compared with eyes having normal macular contours. CONCLUSIONS: The central choroid is thinner when eyes show diabetic changes on the retina. However, the presence of diabetic macular edema or proliferative change is not associated with more pronounced choroidal thinning.

Comparison of intravitreal bevacizumab alone or combined with triamcinolone versus triamcinolone in diabetic macular edema: a randomized clinical trial.

PURPOSE: To compare the effect of an intravitreal injection of bevacizumab alone (IVB) or combined with triamcinolone (IVB/IVT) versus triamcinolone (IVT) in patients with diabetic macular edema (DME). METHODS: In this randomized three-arm clinical trial, eligible eyes were assigned randomly to one of the three study arms: the IVB group, 2 injections of 1.25 mg of bevacizumab with 6-week intervals; the IVB/IVT group, 1.25 mg of IVB with 2 mg of IVT, and the IVT group, 2 mg of IVT. The clinical course of best-corrected visual acuity and central macular thickness by optical coherence tomography was monitored for up to 12 months after the initial injection. RESULTS: One hundred eleven eyes of 105 patients with DME completed 12 months of follow-up. The IVB/IVT group and the IVT group showed better visual acuity and reduced central macular thickness at 6 weeks and 3 months, compared with the IVB group (p = 0.041, p = 0.02 at 6 weeks; p = 0.045, p = 0.043 at 3 months, respectively). However, no significant difference in visual acuity and central macular thickness was observed between the three groups at 12 months (p = 0.088, p = 0.132, respectively). The frequency of retreatment was lower in the IVB/IVT and IVT groups during the 12-month period (p < 0.001). No significant differences in visual acuity or central macular thickness were observed between the IVB/IVT and IVT groups during the follow-up. CONCLUSION: IVB/IVT and IVT showed more pronounced effects during the earlier postinjection period. However, levels of visual acuity or central macular thickness at 12 months were comparable in the three study groups. No beneficial effect of the combination injection was observed.

Synthesis of aurones and their inhibitory effects on nitric oxide and PGE2 productions in LPS-induced RAW 264.7 cells.

Sulfuretin is one of major constituents of Rhus verniciflua that exerts anti-inflammatory activities. Some of aurones were synthesized as sulfuretin derivatives and evaluated for their abilities to inhibit NO and PGE(2) production in LPS-induced RAW 264.7 cells in order to reveal the relationship. Of the aurones synthesized in the present study, 2h and 2i, which possess C-6 hydroxyl group in A-ring and methoxy substituents in B-ring, more potently inhibited NO and PGE(2) production and were less cytotoxic than sulfuretin.

Concentration of cytokines in the aqueous humor of patients with central serous chorioretinopathy.

PURPOSE: To evaluate the levels of aqueous humor cytokines in the eyes of patients with central serous chorioretinopathy (CSC) before an intravitreal injection of bevacizumab. METHODS: In a prospective interventional trial, 20 eyes of 20 patients with symptomatic CSC of at least 3 months duration and 20 eyes of 20 patients with cataract as control were included. Eyes with CSC received a single intravitreal injection of bevacizumab (1.25 mg/0.05 mL). Aqueous humor samples were collected from patients and controls. Multiplex bead assays were used for measurement of cytokines, including vascular endothelial growth factor and platelet-derived growth factor. RESULTS: Similar vascular endothelial growth factor levels and significantly decreased platelet-derived growth factor levels were measured in the aqueous humor of eyes from patients with CSC compared with controls (P = 0.172 and P = 0.004, respectively). There was a significant inverse correlation between the vascular endothelial growth factor and platelet-derived growth factor in patients (r = -0.555; P = 0.026). Interleukin 6, interleukin 8, and monocyte chemoattractant protein-1 were detectable, but not significantly different between the patients and controls. CONCLUSION: The results of the current study suggest that platelet-derived growth factor contributes to the pathogenesis of CSC; however, the roles of vascular endothelial growth factor in CSC are unclear and warrant further investigation.

Stenotrophomonas daejeonensis sp. nov., isolated from sewage.

A Gram-stain-negative, motile, aerobic bacterial strain, designated MJ03(T), was isolated from sewage and was characterized taxonomically by using a polyphasic approach. Comparative 16S rRNA gene sequence analysis showed that strain MJ03(T) belongs to the family Xanthomonadaceae, class Gammaproteobacteria, and was related most closely to Stenotrophomonas acidaminiphila AMX 19(T) (97.9  % sequence similarity), Stenotrophomonas humi R-32729(T) (97.1  %), Stenotrophomonas nitritireducens L2(T) (96.9  %), Stenotrophomonas maltophila ATCC 13637(T) (96.8  %) and Stenotrophomonas terrae R-32768(T) (96.7  %). The G+C content of the genomic DNA of strain MJ03(T) was 64.7 mol%. The detection of a quinone system with ubiquinone Q-8 as the predominant component and a fatty acid profile with iso-C15:0, iso-C11:0, iso-C14:0, iso-C17:1ω9c, iso-C11:0 3-OH and iso-C13:0 3-OH as major components supported the affiliation of strain MJ03(T) to the genus Stenotrophomonas. However, levels of DNA-DNA relatedness between strain MJ03(T) and the type strains of five closely related species of the genus Stenotrophomonas ranged from 11 to 34  %, showing clearly that the isolate represents a novel genospecies. Strain MJ03(T) could be differentiated clearly from its phylogenetic neighbours on the basis of several phenotypic, genotypic and chemotaxonomic features. Therefore, strain MJ03(T) is considered to represent a novel species of the genus Stenotrophomonas, for which the name Stenotrophomonas daejeonensis sp. nov. is proposed. The type strain is MJ03(T) (=KCTC 22451(T) =JCM 16244(T)).

Aqueous humor and plasma levels of vascular endothelial growth factor and interleukin-8 in patients with central serous chorioretinopathy.

PURPOSE: The purpose of this study was to determine aqueous vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in patients with central serous chori-oretinopathy (CSC) before a single intravitreal bevacizumab injection. METHODS: Twelve eyes with symptomatic CSC were included. Samples from patients with cataracts served as controls. The levels of VEGF and IL-8 concentrations were measured in aqueous humor and plasma by multiplex bead assays. RESULTS: All patients with CSC showed an improvement in visual acuity and resolved neurosensory detachment after intravitreal bevacizumab injection. The aqueous humor levels of VEGF and IL-8 were not significantly increased in patients with CSC compared with the healthy control group (18.2 ± 24.8 vs. 35.3 ± 28.5 pg/mL, P > 0.05; 2.3 ± 0.4 vs. 2.8 ± 0.3 pg/mL, P > 0.05, respectively). The plasma levels of VEGF and IL-8 in patients with CSC were not different from those in the healthy control group. CONCLUSION: Vascular endothelial growth factor and IL-8 were not increased in the aqueous humor and plasma of patients with CSC. The effect of intravitreal bevacizumab injection as a treatment for CSC must be fully understood, and the true effect of anti-VEGF treatment in patients with CSC remains to be elucidated.

The effect of intravitreal bevacizumab in patients with acute central serous chorioretinopathy.

PURPOSE: To evaluate the effect of intravitreal bevacizumab injection (IVBI) in acute central serous chorioretinopathy (CSC) patients. METHODS: Patients with acute CSC received IVBI (1.25 mg/0.05 mL) or observation by randomization. Twelve eyes in each group completed 6 months of regular follow-up and were ultimately included in this study. Each patient was assessed using best corrected visual acuity measurements, fluorescein angiography, and optical coherence tomography at baseline and had regular follow-ups after treatment. RESULTS: All patients showed improvements in visual acuity and fluorescein angiographic leakage and had resolution of their neurosensory detachment following treatment. There were no significant differences in visual acuity, central retinal thickness, or remission duration between the IVBI group and the control group at baseline or after treatment (p>0.05). CONCLUSIONS: Intravitreal bevacizumab showed no positive effect in acute CSC patients compared to the observation group, and there were no adverse effects of treatment. Further investigation will be helpful to understand this therapy in patients with CSC.

Sulfuretin isolated from heartwood of Rhus verniciflua inhibits LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines expression via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells.

It has been reported that Rhusverniciflua exhibits anti-inflammatory, anti-oxidant and anti-cancer activities. However, little is known about biological activity of sulfuretin, a flavonoid isolated from R.verniciflua. In the present study, we investigated the anti-inflammatory effect and the underlying molecular mechanisms of sulfuretin in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Sulfuretin dose-dependently reduced the productions of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) induced by LPS. Consistent with these findings, sulfuretin significantly suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-alpha, and IL-1 beta. In addition, sulfuretin attenuated LPS-induced DNA binding and the transcriptional activities of nuclear factor-kappa B (NF-kappaB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa B-alpha (I kappaB-alpha) and consequently by decreased nuclear translocation of p65 subunit of NF-kappaB. Furthermore, pretreatment with sulfuretin significantly inhibited the LPS-stimulated activation of I kappaB kinase beta (IKK beta). Taken together, these results suggest that the anti-inflammatory effect of sulfuretin in LPS-treated RAW 264.7 macrophages is associated with the suppression of NF-kappaB transcriptional activity via the inhibitory regulation of IKKbeta phosphorylation.

Pegylated-interferon-associated retinopathy in chronic hepatitis patients.

PURPOSE: To investigate the clinical features of pegylated-interferon (PEG-IFN)-associated retinopathy in chronic hepatitis patients. METHODS: We examined a consecutive case series of 46 patients who were treated with PEG-IFN for chronic hepatitis C or B between October 2007 and September 2008. All patients underwent regular ophthalmologic examinations every 3 weeks during the 6 months after treatment. RESULTS: Ten of the 46 patients (21.73%) developed retinal abnormalities. PEG-IFN-associated retinopathy occurred a mean of 7.25 +/- 10.28 weeks after treatment and manifested itself as cotton wool spots and retinal hemorrhages. All patients, except for 1 with a retinal vein occlusion, recovered without cessation of treatment. CONCLUSIONS: PEG-IFN-associated retinopathy in chronic hepatitis patients was reversible, and patients recovered without visual complications; however, 1 patient did present with an irreversible visual impairment. This type of retinopathy is usually asymptomatic, and clinicians should closely observe patients for 3 months after treatment.