Association between decreased ipsilateral renal function and aggressive behavior in renal cell carcinoma.

BACKGROUND: To assess prognostic value of pre-operative ipsilateral split renal function (SRF) on disease-free survival (DFS) and its association with aggressive pathological features in renal cell carcinoma (RCC) patients.  METHODS: We examined patients registered in SNUG-RCC-Nx who underwent partial or radical nephrectomy at Seoul National University Hospital between January 1, 2010 and December 31, 2020. Patients with the following criteria were excluded from the study. 1) non-kidney origin cancer or benign renal tumor, 2) no pre-operative Tc 99 m-DTPA renal scan, 3) single kidney status or previous partial or radical nephrectomy, and 4) bilateral renal mass. Finally, 1,078 patients were included. RESULTS: Among 1,078 patients, 899 (83.4%) showed maintained ipsilateral SRF on DTPA renal scan; 179 patients (16.6%) showed decreased SRF. The decreased SRF group showed significantly large tumor size (maintained vs. decreased SRF; 3.31 ± 2.15 vs. 6.85 ± 3.25, p < 0.001), high Fuhrman grade (grade 3-4) (41.7% vs. 55.6%, p < 0.001), and high T stage (T stage 3-4) (9.0% vs. 20.1%, p < 0.001). Pathological invasive features, including invasion of the renal capsule, perirenal fat, renal sinus fat, vein, and collecting duct system, were associated with low SRF of the ipsilateral kidney. Univariate Cox regression analysis identified higher SSIGN (The stage, size, grade, and necrosis) score and decreased ipsilateral SRF as significant risk factors, while multivariate analysis showed SSIGN (5-7) (hazard ratio [HR] 11.9, p < 0.001) and SSIGN (8-10) (HR 69.2, p < 0.001) were significantly associated with shortened DFS, while decreased ipsilateral SRF (HR 1.75, p = 0.065) showed borderline significance. Kaplan-Meier analysis showed that decreased ipsilateral SRF (< 45%) group had shorter DFS than the other group (median DFS: 90.3 months vs. not reached, p < 0.001). CONCLUSIONS: Among unilateral RCC patients, those with low ipsilateral SRF showed poor prognosis with pathologically invasive features. Our novel approach may facilitate risk stratification in RCC patients, helping formulate a treatment strategy.

Advanced Electron Paramagnetic Resonance Studies of a Ternary Complex of Copper, Amyloid-ß, and a Chemical Regulator.

Although there has been extensive effort to develop chemical regulators, progress has been static, in part because of these regulators' unclear mechanisms. Here, we report using advanced electron paramagnetic resonance (EPR) spectroscopy to obtain the first molecular-level structural information regarding a ternary complex of CuII-amyloid-ß (Aß) with a chemical regulator that can specifically modulate Cu-induced Aß aggregation. Our advanced EPR spectroscopic results revealed that a chemical regulator (1) for CuII-Aß1-16 disrupted the coordination environment of CuII in Aß, resulting in the detachment of the primary amine at the N-terminal and a carbonyl group between Asp1 and Ala2 from the CuII center and the subsequent formation of a ternary complex, chemical regulator-CuII-Aß1-16. Therefore, our results demonstrate how a chemical regulator interacts with metal-Aß at the molecular level. These findings provide novel insight into working mechanisms and thereby contribute to the establishment of a rational design for chemical regulators of metal-Aß complexes.

Cell-Penetrating Cross-ß Peptide Assemblies with Controlled Biodegradable Properties.

Although self-assembled peptide nanostructures (SPNs) have shown potential as promising biomaterials, there is a potential problem associated with the extremely slow hydrolysis rate of amide bonds. Here, we report the development of cell-penetrating cross-ß SPNs with a controllable biodegradation rate. The designed self-assembling ß-sheet peptide incorporating a hydrolyzable ester bond (self-assembling depsipeptide; SADP) can be assembled into bilayer ß-sandwich one-dimensional (1D) fibers similarly to conventional ß-sheet peptides. The rate of hydrolysis can be controlled by the pH, temperature, and structural characteristics of the ester unit. The 1D fiber of the SADP transforms into vesicle-like 3D structures when the hydrophilic cell-penetrating peptide segment is attached to the SADP segment. Efficient cell internalization of the 3D nanostructures was observed, and we verified the intracellular degradation and disassembly of the biodegradable nanostructures. This study illustrates the potential of biodegradable cross-ß SPNs and provides a valuable toolkit that can be used with self-assembling peptides.

Simultaneous Stabilization and Multimerization of a Peptide α-Helix by Stapling Polymerization.

Maintaining specific conformations of peptide ligands is crucial for improving the efficacy of biological interactions. Here, a one-pot polymerization strategy for stabilizing the α-helical conformation of peptides while simultaneously constructing multimeric ligands is presented. The new method, termed stapling polymerization, uses radical polymerization between acryloylated peptide side chains and vinylic monomers. Studies with model peptides indicate that i, i+7 crosslinking is effective for the helix stabilization, whereas i, i+4 crosslinking is not. The stapling polymerization results in the formation of peptide-polyacrylamide conjugates that include ≈3-16 peptides in a single conjugate. This stapling polymerization provides a simple but powerful methodology to fabricate multimeric α-helices that can further be developed to modulate multivalent biomacromolecular interactions.

Multiplexing natural orientation: oppositely directed self-assembling peptides.

We explore here the possibility that polypeptide chains with directional multiplicity might provide for the control of peptide self-assembly processes. We tested this new possibility using an oppositely directed peptide (ODP) supramolecular system. The ODP could make it possible to form a ßαß motif with antiparallel ß-sheets, which does not exist in nature. Furthermore, the designed ODPs were able to self-assemble into discrete, homogeneous, and structured protein-like controlled nano-objects. ODPs represent a simple but powerful unnatural self-assembling peptide system that can become a basic scaffold for fabricating more complex and elaborate artificial nanostructures.

Effect of ectopic OCT4 expression on canine adipose tissue-derived mesenchymal stem cell proliferation.

Enhancing the proliferative capacity of mesenchymal stem cells (MSCs) is critical for increasing their therapeutic potential in a variety of diseases. We hypothesized that lentivirus-mediated overexpression of canine octamer-binding transcription factor 4 (OCT4) might influence the proliferation of canine adipose tissue-derived MSCs (cATMSCs). cOCT4-cATMSCs were generated by transducing cATMSCs with a cOCT4-lentiviral vector. Increased expression of cOCT4 was confirmed using RT-PCR and immunoblotting. Immunophenotypic characterization using flow cytometry indicated that the CD29, CD44, CD73, CD90, and CD105 surface markers were highly expressed by both cOCT4- and mock-transduced cATMSCs (mock-cATMSCs), whereas the CD31 and CD45 markers were absent. We performed the osteogenic differentiation assay to evaluate the effects of cOCT4 overexpression on the osteogenic differentiation potential of cATMSCs. The results showed that cOCT4-cATMSCs had a much higher potential for osteogenic differentiation than mock-cATMSCs. Next, the proliferative capacities of cOCT4- and mock-cATMSCs were evaluated using a WST-1 cell proliferation assay and trypan blue exclusion. cOCT4-cATMSCs showed a higher proliferative capacity than mock-cATMSCs. Cell cycle analysis indicated that overexpression of cOCT4 in cATMSCs induced an increase in the proportion of cells in S and G2/M phases. Consistent with this, immunoblot analysis showed that cyclin D1 expression was increased in cOCT4-cATMSCs. In conclusion, our results indicate that lentivirus-mediated overexpression of cOCT4 increased the proliferative capacity of cATMSCs. OCT4-mediated enhancement of cell proliferation may be a useful method for expanding MSC population rapidly without loss of stemness.

Reliability and Agreement Assessment of Sarcopenia Diagnosis through Comparison of Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry.

A unified diagnostic criterion has yet to be established for sarcopenia. Therefore, we analyzed the reliability and validity of sarcopenia diagnosis using bioelectrical impedance analysis (BIA) compared with the gold standard, dual-energy X-ray absorptiometry (DEXA), and evaluated the predictive accuracy of BIA for diagnosis. The clinical trial, involving a total of 239 participants, was conducted between December 2018 and September 2019 on healthy volunteers without significant medical histories. The participants underwent health assessments, followed by sequential DEXA and BIA measurements. In both the low and normal appendicular skeletal muscle (ASM) groups, there were significant differences in the right arm, left arm, right leg, left leg, ASM, and ASM index (ASMI) between DEXA and BIA across all age groups (p < 0.05). BIA tended to overestimate compared to DEXA, but ASMI values for males and females were consistent with the criteria for sarcopenia. Bland-Altman analysis showed that each segment in both the low and normal ASM groups fell within the limits of agreement (LOA). The diagnosis of sarcopenia using BIA was significantly different from that using DEXA. However, it exhibited a significantly high correlation, fell within the LOA, and demonstrated high predictive accuracy. BIA can be considered an effective tool for diagnosing sarcopenia.

Inhibition of protein-protein interactions using biodegradable depsipeptide nanoassemblies.

Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome. Optimized SdPNs displayed better tumor targeting and PPI inhibition properties than the comparable small molecule inhibitor in vivo. Kinetics of PPI inhibition for SdPNs were gradual and controllable in contrast to the rapid inhibition kinetics of the small molecule. Because SdPN is modular, any appropriate peptide inhibitor can be incorporated into the platform without concern for the poor pharmacokinetic properties of the peptide.

Key Factors Affecting the Stability of CsPbI3 Perovskite Quantum Dot Solar Cells: A Comprehensive Review.

The power conversion efficiency of CsPbI3 perovskite quantum dot (PQD) solar cells shows increase from 10.77% to 16.2% in a short period owing to advances in material and device design for solar cells. However, the device stability of CsPbI3 PQD solar cells remains poor in ambient conditions, which requires an in-depth understanding of the degradation mechanisms of CsPbI3 PQDs solar cells in terms of both inherent material properties and device characteristics. Along with this analysis, advanced strategies to overcome poor device stability must be conceived. In this review, fundamental mechanisms that cause the degradation of CsPbI3 PQD solar cells are discussed from the material property and device viewpoints. In addition, based on detailed insights into degradation mechanisms in CsPbI3 PQD solar cells, various strategies are introduced to improve the stability of CsPbI3 PQD solar cells. Finally, future perspectives and challenges are presented to achieve highly durable CsPbI3 PQD solar cells. The investigation of the degradation mechanisms and the stability enhancement strategies can pave the way for the commercialization of CsPbI3 PQD solar cells.

Stabilized Perovskite Quantum Dot Solids via Nonpolar Solvent Dispersible Covalent Ligands.

The ligand exchange procedure of CsPbI3 perovskite quantum dots (PQDs) enables the fabrication of thick and conductive PQD solids that act as a photovoltaic absorber for solution-processed thin-film solar cells. However, the ligand-exchanged CsPbI3 PQD solids suffer from deterioration in photovoltaic performance and ambient stability due to the surface traps, such as uncoordinated Pb2+ sites on the PQD surface, which are generated after the conventional ligand exchange process using ionic short-chain ligands dissolved in polar solvents. Herein, a facile surface stabilization is demonstrated that can simultaneously improve the photovoltaic performance and ambient stability of CsPbI3 PQD photovoltaic absorber using covalent short-chain triphenylphosphine oxide (TPPO) ligands dissolved in a nonpolar solvent. It is found that the TPPO ligand can be covalently bound to uncoordinated Pb2+ sites and the nonpolar solvent octane can completely preserve the PQD surface components. Owing to their synergetic effects, the CsPbI3 PQD photovoltaic absorber stabilized using the TPPO ligand solution dissolved in octane exhibit higher optoelectrical properties and ambient stability than the control absorber. Consequently, CsPbI3 PQD solar cells composed of PQD photovoltaic absorbers fabricated via surface stabilization strategy provide an improved power conversion efficiency of 15.4% and an enhanced device stability.

Structural and conformational dynamics of self-assembling bioactive ß-sheet peptide nanostructures decorated with multivalent RNA-binding peptides.

Understanding the dynamic behavior of nanostructural systems is important during the development of controllable and tailor-made nanomaterials. This is particularly true for nanostructures that are intended for biological applications because biomolecules are usually highly dynamic and responsive to external stimuli. In this Article, we investigated the structural and conformational dynamics of self-assembling bioactive ß-sheet peptide nanostructures using electron paramagnetic resonance (EPR) spectroscopy. The model peptide nanostructures are characterized by the cross-ß spine of ß-ribbon fibers and multiple RNA-binding bioactive peptides that constitute the shell of the nanostructures. We found first, that bioactive peptides at the shell of ß-ribbon nanostructure have a mobility similar to that of an isolated monomeric peptide. Second, the periphery of the cross-ß spine is more immobile than the distal part of surface-displayed bioactive peptides. Third, the rotational dynamics of short and long fibrils are similar; that is, the mobility is largely independent of the extent of aggregation. Fourth, peptides that constitute the shell are affected first by the external environment at the initial stage. The cross-ß spine resists its external environment to a certain extent and abruptly disintegrates when the perturbation reaches a certain degree. Our results provide an overall picture of ß-sheet peptide nanostructure dynamics, which should be useful in the development of dynamic self-assembled peptide nanostructures.

Investigation of the Hydration State of Self-Assembled Peptide Nanostructures with Advanced Electron Paramagnetic Resonance Spectroscopy.

Probing the intermolecular interactions and local environments of self-assembled peptide nanostructures (SPNs) is crucial for a better understanding of the underlying molecular details of self-assembling phenomena. In particular, investigation of the hydration state is important to understand the nanoscale structural and functional characteristics of SPNs. In this report, we examined the local hydration environments of SPNs in detail to understand the driving force of the discrete geometric structural self-assembling phenomena for peptide nanostructures. Advanced electron paramagnetic resonance spectroscopy was used to probe the hydrogen bond formation and geometry as well as the hydrophobicity of the local environments at various spin-labeled sites in SPNs. The experimental results supplement the sparse experimental data regarding local structures of SPNs, such as the hydrogen bonding and the hydrophobicity of the local environment, providing important information on the formation of SPNs, which have immense potential for bioactive materials.

Increased genomic damage and vitamin B status in inflammatory bowel disease patients: A case-control, prospective, pilot study.

Vitamin B deficiency in patients with inflammatory bowel disease (IBD) is well-documented; however, few studies have explored genomic damage in patients with IBD using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. This study investigated the frequency of micronuclei (MNi) using the CBMN-Cyt assay and the level of vitamin B in patients with IBD. This prospective study was conducted in 15 patients with ulcerative colitis, 15 patients with Crohn's disease, and 30 healthy controls from one tertiary hospital. Serum vitamin B and homocysteine levels were measured, and the MNi status was analyzed using the CBMN-Cyt assay. The patients with IBD showed significantly lower serum pyridoxine levels and significantly higher homocysteine levels than controls. The frequencies of binucleated cells (BNCs) with MNi, nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) were 8.5 [5.8-13.5], 1.0 [0.0-1.9], and 5.4 [4.3-7.4] for the IBD group, and 5.9 [4.8-7.7], 0.2 [0.0-1.0], and 3.5 [2.9-5.4] for the control group (P = 0.011, P = 0.010, and P = 0.002), respectively. This study suggests that patients with IBD have increased frequencies of MNi and decreased levels of pyridoxine than healthy controls.

Myricetin Induces Apoptosis of Human Anaplastic Thyroid Cancer Cells via Mitochondria Dysfunction.

AIM: Thyroid cancer is the most common endocrine malignancy, with an increasing incidence worldwide. Most thyroid cancers are well differentiated and have a favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies. Anaplastic thyroid cancer (ATC) accounts for 2% of all thyroid cancers, and its median survival rate is low. ATC is responsible for more than one-third of thyroid cancer-related deaths. Myricetin is a flavonol compound found in walnuts, herbs, and various berries and is known to induce apoptotic death of various types of cancer cells. However, an anticancer effect of myricetin against human anaplastic thyroid cancer (HATCs) cells has not been demonstrated. MATERIALS AND METHODS: In the present study, the anticancer effects and mechanism of action of myricetin were examined using SNU-80 HATC cells. SNU-80 HATC cells were treated with various concentrations of myricetin and compared with untreated controls. RESULTS: Myricetin significantly reduced HATC cell proliferation, by approximately 70%. A substantial proportion of dead cells exhibited arrest in the sub-G1 phase. Myricetin also exhibited cytotoxicity and induced DNA condensation in SNU-80 HATC cells in a dose-dependent manner. The mechanism of myricetin-induced cell death involved an increase in the activation of caspase cascades and the Bax:Bcl-2 ratio at a concentration of 100 µM. Myricetin also induced the release of apoptosis-inducing factor (AIF) from mitochondria into the cytosol and altered the mitochondrial membrane potential. CONCLUSION: Our results indicate that myricetin is a potent inducer of HATC cell death and may thus prove useful in the development of therapeutic agents for HATC.

Sensitive and Selective Detection of HIV-1 RRE RNA Using Vertical Silicon Nanowire Electrode Array.

In this study, HIV-1 Rev response element (RRE) RNA was detected via an Au-coated vertical silicon nanowire electrode array (VSNEA). The VSNEA was fabricated by combining bottom-up and top-down approaches and then immobilized by artificial peptides for the recognition of HIV-1 RRE. Differential pulse voltammetry (DPV) analysis was used to measure the electrochemical response of the peptide-immobilized VSNEA to the concentration and types of HIV-1 RRE RNA. DPV peaks showed linearity to the concentration of RNA with a detection limit down to 1.513 fM. It also showed the clear different peaks to the mutated HIV-1 RRE RNA. The high sensitivity and selectivity of VSNEA for the detection of HIV-1 RRE RNA may be attributed to the high surface-to-volume ratio and total overlap diffusion mode of ions of the one-dimensional nanowire electrodes.

Transdermal delivery of mixnoxidil with block copolymer nanoparticles.

We evaluated the effect of hydrodynamic size of self-assembled nanoparticles on skin penetration of minoxidil in vitro and in vivo. Self-assembled 40- and 130-nm nanoparticles, both containing minoxidil, were prepared by solvent evaporation of poly(-caprolactone)-block-poly(ethyleneglycol) and were applied onto the skin of both hairy and hairless guinea pigs in the Franz diffusion cell. In hairy guinea pig skin, the permeation of the minoxidil that incorporated in 40-nm nanoparticles was 1.5-fold higher in the epidermal layer and 1.7-fold higher in the receptor solution than that of 130-nm nanoparticles. Nanoparticle size dependence on the permeation behavior of minoxidil was not observed for hairless guinea pig skin in either the epidermal layer or the receptor solution. Phospholipid liposomes and ethanol-water admixture, on the other hand, containing the same amount of minoxidil did not show differences in the amount of permeation irrespective of the existence of hair follicles. Confocal microscopy coupled with in vivo and in vitro skin permeation results demonstrated that nanoparticles containing solutes penetrated mainly via shunt routes like hair follicles, resulting in skin absorption of solutes.

Chemical-mechanical characteristics of crushed oyster-shell.

Enormous amount of oyster-shell waste has been illegally disposed at oyster farm sites along the southern coast of Korea. To seek for a possibility to recycle the waste as construction materials, chemical and mechanical characteristics of crushed oyster-shell were investigated. Chemical and microstructure analyses showed that oyster-shells are predominantly composed of calcium carbonate with rare impurities. Compressive strength tests for soil mortar specimens with varying blending ratio of cement, water, sand, and oyster-shell were compared with normal cement mortar. There was no significant reduction in the compressive strength up to 40% of dosages of oyster-shell instead of sand. The experimental results demonstrate that oyster-shells can be resources of pure calcareous materials and effective in replacement of sand, indicating promising reusable construction materials.

Enhanced proliferation and differentiation of Oct4- and Sox2-overexpressing human adipose tissue mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are attractive candidates for clinical repair or regeneration of damaged tissues. Oct4 and Sox2, which are essential transcription factors for pluripotency and self-renewal, are naturally expressed in MSCs at low levels in early passages, and their levels gradually decrease as the passage number increases. Therefore, to improve MSC proliferation and stemness, we introduced human Oct4 and Sox2 for conferring higher expansion and differentiation capabilities. The Oct4-IRES-Sox2 vector was transfected into human adipose tissue MSCs (ATMSCs) by liposomal transfection and used directly. Oct4 and Sox2 were successfully transfected into ATMSCs, and we confirmed maintenance of MSC surface markers without alterations in both red fluorescent protein (RFP) (control) and Oct4/Sox2-ATMSCs. Enhanced proliferative activity of Oct4/Sox2-ATMSCs was shown by WST-1 assay, and this result was further confirmed by cell counting using trypan blue exclusion for a long period. In addition, FACs cell cycle analysis showed that there was a reduction in the fraction of Oct4/Sox2-ATMSCs in G1 with a concomitant increase in the fraction of cells in S, compared with RFP-ATMSCs. Increased levels of cyclin D1 were also seen in Oct4/Sox2-ATMSCs, indicating acceleration in the transition of cells from G1 to S phase. Furthermore, Oct4/Sox2-overexpressing ATMSCs showed higher differentiation abilities for adipocytes or osteoblasts than controls. The markers of adipogenic or osteogenic differentiation were also upregulated by Oct4/Sox2 overexpression. The improvement in cell proliferation and differentiation using Oct4/Sox2 expression in ATMSCs may be a useful method for expanding the population and increasing the stemness of ATMSCs.

Large current difference in Au-coated vertical silicon nanowire electrode array with functionalization of peptides.

Au-coated vertical silicon nanowire electrode array (VSNEA) was fabricated using a combination of bottom-up and top-down approaches by chemical vapor deposition and complementary metal-oxide-semiconductor process for biomolecule sensing. To verify the feasibility for the detection of biomolecules, Au-coated VSNEA was functionalized using peptides having a fluorescent probe. Cyclic voltammograms of the peptide-functionalized Au-coated VSNEA show a steady-state electrochemical current behavior. Because of the critically small dimension and vertically aligned nature of VSNEA, the current density of Au-coated VSNEA was dramatically higher than that of Au film electrodes. Au-coated VSNEA further showed a large current difference with and without peptides that was nine times more than that of Au film electrodes. These results indicate that Au-coated VSENA is highly effective device to detect peptides compared to conventional thin-film electrodes. Au-coated VSNEA can also be used as a divergent biosensor platform in many applications.

Hydrogen peroxide and monoethanolamine are the key causative ingredients for hair dye-induced dermatitis and hair loss.

BACKGROUND: Hair dyes are being commonly used to change the color of hair for cosmetic reason. However, concern is growing over the dermatitis and subsequent hair loss associated with the repeated use of hair dye products, yet the causative ingredients have not been elucidated. OBJECTIVE: Here we investigated hair dye-induced dermatitis and hair loss using in vivo mouse model to uncover the causative ingredients. METHODS: Commercially available hair dye products or combination of the ingredients of hair dye product were applied topically for 3 days on the dorsum of the female C57BL/6 mice and, dermatitis and hair loss were examined. RESULTS: The mice treated with hair dye products exhibited unequivocal signs of hair loss and dermatitis. To find out causative ingredients, combinations of the representative components of hair dye including reducing agents, the mixture of dye and monoethanolamine (MEA), ammonia, and hydrogen peroxide (H(2)O(2)) were applied and thereafter, hair loss and dermatitis were evaluated. All the groups treated with the combinations containing H(2)O(2) and neutralized dye mixture manifested hair loss and dermatitis. Subsequent experiments revealed that H(2)O(2) and MEA synergistically induced hair loss and dermatitis. Histological examination showed that oxidative stress may be the mechanism underlying hair-dye induced dermatitis. Consistently, H(2)O(2) and MEA synergistically induced oxidative stress and cytotoxicity in human keratinocytes. CONCLUSION: These results suggest that H(2)O(2) and MEA may be the key causative ingredients for hair dye-associated dermatitis and hair loss.