Search Results (12)

Diabetes is a prevalent and debilitating metabolic disorder affecting a large population worldwide. The condition is characterized by insulin resistance and impaired function of pancreatic β-cells, leading to elevated blood glucose levels. In this study, the antidiabetic effects of Erigeron annuus extract (EAE) on zebrafish with damaged pancreatic islets caused by insulin resistance were investigated. The study utilized the zebrafish model to monitor live pancreatic islets. RNA sequencing was also conducted to determine the mechanism by which EAE exerts its antidiabetic effect. The results showed that EAE was effective in recovering reduced islets in excess insulin-induced zebrafish. The effective concentration at 50% (EC₅₀) of EAE was determined to be 0.54 μg/mL, while the lethal concentration at 50% (LC₅₀) was calculated as 202.5 μg/mL. RNA sequencing indicated that the mode of action of EAE is related to its ability to induce mitochondrial damage and suppress endoplasmic reticulum stress. The findings of this study demonstrate the efficacy and therapeutic potential of EAE in treating insulin resistance in zebrafish. The results suggest that EAE may offer a promising approach for the management of diabetes by reducing mitochondrial damage and suppressing endoplasmic reticulum stress. Further research is required to establish the clinical application of EAE in diabetic patients. Full article

Traditional tissue-based assessments of genomic alterations in castration-resistant prostate cancer (CRPC) can be challenging. To evaluate the real-world clinical utility of liquid biopsies for the evaluation of genomic alterations in CRPC, we preemptively collected available plasma samples and archival tissue samples from patients that were being treated for clinically confirmed CRPC. The cell-free DNA (cfDNA) and tumor tissue DNA were analyzed using the AlphaLiquid^®100-HRR panel. Plasma samples from a total of 87 patients were included in this study. Somatic mutations from cfDNA were detected in 78 (89.7%) patients, regardless of the presence of overt metastasis or concomitant treatment given at the time of plasma sample collection. Twenty-three patients were found to have known deleterious somatic or germline mutations in HRR genes from their cfDNA. Archival tissue samples from 33 (37.9%) patients were available for comparative analysis. Tissue sequencing was able to yield an NGS result in only 51.5% of the tissue samples. The general sensitivity of cfDNA for detecting somatic mutations in tissues was 71.8%, but important somatic/germline mutations in HRR genes were found to have a higher concordance (100%). Liquid biopsies can be a reasonable substitute for tissue biopsies in CRPC patients when evaluating genomic alterations. Full article

Sensorineural hearing loss (SNHL) is a common condition that results from the loss of function of hair cells, which are responsible for converting sound into electrical signals within the cochlea and auditory nerve. Despite the prevalence of SNHL, a universally effective treatment has yet to be approved. To address this absence, the present study aimed to investigate the potential therapeutic effects of TS, a combination of Cuscutae Semen and Rehmanniae Radix Preparata. To this end, both in vitro and in vivo experiments were performed to evaluate the efficacy of TS with respect to SNHL. The results showed that TS was able to protect against ototoxic neomycin-induced damage in both HEI-OC1 cells and otic hair cells in zebrafish. Furthermore, in images obtained using scanning electron microscopy (SEM), an increase in the number of kinocilia, which was prompted by the TS treatment, was observed in the zebrafish larvae. In a noise-induced hearing loss (NIHL) mouse model, TS improved hearing thresholds as determined by the auditory brainstem response (ABR) test. Additionally, TS was found to regulate several genes related to hearing loss, including Trpv1, Cacna1h, and Ngf, as determined by quantitative real-time polymerase chain reaction (RT-PCR) analysis. In conclusion, the findings of this study suggest that TS holds promise as a potential treatment for sensorineural hearing loss. Further research is necessary to confirm these results and evaluate the safety and efficacy of TS in a clinical setting. Full article

Recently, semiconductor wastewater treatment has received much attention due to the emergence of environmental issues. Acid-resistant coatings are essential for metal prefilters used in semiconductor wastewater treatment. Perfluoroalkoxy alkane is mainly used as an acid-resistant coating agent, since PFA has inherent superhydrophobicity, water permeability is lowered. To solve this problem, the surface of the PFA-coated metal mesh was treated via an oxyfluorination method in which an injected mixed gas of fluorine and oxygen reacted with the surface functional groups. Surface analysis, water contact angle measurement, and water permeability tests were performed on the surface-treated PFA-coated mesh. Consequently, the superhydrophobic surface was effectively converted to a hydrophobic surface as the PFA coating layer was surface-modified with C-O-OH functional groups via the oxyfluorination reaction. As a result of using simulation solutions that float silica particles of various sizes, the permeability and particle removal rate of the surface-modified PFA-coated stainless-steel mesh were improved compared to those before surface modification. Therefore, the oxyfluorination treatment used in this study was suitable for improving the filtration performance of SiO₂ microparticles in the PFA-coated stainless-steel mesh. Full article

Metabolic syndrome has become a global health care problem since it is rapidly increasing worldwide. The search for alternative natural supplements may have potential benefits for obesity and diabetes patients. Diospyros kaki fruit extract and its oligosaccharides, including gentiobiose, melibiose, and raffinose, were examined for their anti-insulin resistance and obesity-preventing effect in zebrafish larvae. The results show that D. kaki oligosaccharides improved insulin resistance and high-fat-diet-induced obesity in zebrafish larvae, evidenced by enhanced β-cell recovery, decreased abdominal size, and reduced the lipid accumulation. The mechanism of the oligosaccharides, molecular docking, and enzyme activities of PTP1B were investigated. Three of the oligosaccharides had a binding interaction with the catalytic active sites of PTP1B, but did not show inhibitory effects in an enzyme assay. The catalytic residues of PTP1B were typically conserved and the cellular penetration of the cell membrane was necessary for the inhibitors. The results of the mechanism of action study indicate that D. kaki fruit extract and its oligosaccharides affected gene expression changes in inflammation- (TNF-α, IL-6, and IL-1β), lipogenesis- (SREBF1 and FASN), and lipid-lowering (CPT1A)-related genes. Therefore, D. kaki fruit extract and its oligosaccharides may have a great potential for applications in metabolic syndrome drug development and dietary supplements. Full article

The electric double-layer capacitor (EDLC) has attracted attention by using activated carbon (AC) as an active electrode material with a high power density and high cost-efficiency in industrial applications. The EDLC has been actively developed over the past decade to improve the power density and capacitance. Extensive studies on EDLCs have been conducted to investigate the relation of EDLC capacitance to the physical properties of AC, such as the specific surface area, pore type and size, and electrical conductivity. In this study, EDLC was fabricated with AC, and its capacitance was evaluated with the physical properties of AC. The AC was prepared using petroleum-based pitch synthesized using pyrolysis fuel oil (PFO) with polyethylene terephthalate (PET). The AC based on PFO and PET (PPAC) exhibited high specific surface area and low micropore fraction compared to the PFO-based AC without PET addition (PAC). Furthermore, the reduction of the EDLC capacitance of PPAC was smaller than that of PAC, as the scan rate was increased from 5 to 100 mV s−1. It was determined that the minor reduction of capacitance with an increase in the scan rate resulted from the development of 4 nm-sized mesopores in PPAC. In addition, a comprehensive correlation of EDLC capacitance with various physical properties of ACs, such as specific surface area, pore characteristics, and electrical conductivity, was established. Finally, the optimal properties of AC were thereupon derived to improve the EDLC capacitance. Full article

Cancer-associated thrombosis is the second-leading cause of mortality in patients with cancer and presents a poor prognosis, with a lack of effective treatment strategies. NAD(P)H quinone oxidoreductase 1 (NQO1) increases the cellular nicotinamide adenine dinucleotide (NAD⁺) levels by accelerating the oxidation of NADH to NAD⁺, thus playing important roles in cellular homeostasis, energy metabolism, and inflammatory responses. Using a murine orthotopic 4T1 breast cancer model, in which multiple thrombi are generated in the lungs at the late stage of cancer development, we investigated the effects of regulating the cellular NAD⁺ levels on cancer-associated thrombosis. In this study, we show that dunnione (a strong substrate of NQO1) attenuates the prothrombotic state and lung thrombosis in tumor-bearing mice by inhibiting the expression of tissue factor and formation of neutrophil extracellular traps (NETs). Dunnione increases the cellular NAD⁺ levels in lung tissues of tumor-bearing mice to restore the declining sirtuin 1 (SIRT1) activity, thus deacetylating nuclear factor-kappa B (NF-κB) and preventing the overexpression of tissue factor in bronchial epithelial and vascular endothelial cells. In addition, we demonstrated that dunnione abolishes the ability of neutrophils to generate NETs by suppressing histone acetylation and NADPH oxidase (NOX) activity. Overall, our results reveal that the regulation of cellular NAD⁺ levels by pharmacological agents may inhibit pulmonary embolism in tumor-bearing mice, which may potentially be used as a viable therapeutic approach for the treatment of cancer-associated thrombosis. Full article

We evaluated the expression of PDLIM2 in human kidney cancer cell lines from primary or metastatic origins and found that PDLIM2 expression was highly elevated in metastatic kidney cancers. We evaluated the effect of PDLIM2 inhibition by RNA interference method. PDLIM2 knockdown showed the decreased proliferation and metastatic character in human metastatic kidney cancer cells. By repeated round of orthotopic injection of RenCa mouse kidney cancer cell line, we obtained metastatic prone mouse kidney cancer cell lines. PDLIM2 expression was highly expressed in these metastatic prone cells comparing parental cells. In addition, we evaluated the in vivo efficacy of PDLIM2 knockout on the tumor formation and metastasis of kidney cancer cells using a PDLIM2 knockout mice. The experimental metastasis model with tail vein injection and orthotopic metastasis model injected into kidney all showed reduced lung metastasis cancer formation in PDLIM2 knockout mice comparing control Balb/c mice. Overall, our findings indicate that PDLIM2 is required for cancer formation and metastasis in metastatic kidney cancer, indicating that PDLIM2 may be a new therapeutic target for metastatic kidney cancer. Full article

Kidney cancer is one of the most difficult cancers to treat by targeted and radiation therapy. Therefore, identifying key regulators in this cancer is especially important for finding new drugs. We focused on androgen receptor (AR) regulation by its epigenetic co-regulator lysine-specific histone demethylase 1 (LSD1) in kidney cancer development. LSD1 knock-down in kidney cancer cells decreased expression of AR target genes. Moreover, the binding of AR to target gene promoters was reduced and histone methylation status was changed in LSD1 knock-down kidney cancer cells. LSD1 knock-down also slowed growth and decreased the migration ability of kidney cancer cells. We found that pargyline, known as a LSD1 inhibitor, can reduce AR activity in kidney cancer cells. The treatment of kidney cancer cells with pargyline delayed growth and repressed epithelial–mesenchymal transition (EMT) markers. These effects were additively enhanced by co-treatment with the AR inhibitor enzalutamide. Down-regulation of LSD1 in renal cancer cells (RCC) attenuated in vivo tumor growth in a xenograft mouse model. These results provide evidence that LSD1 can regulate kidney cancer cell growth via epigenetic control of AR transcription factors and that LSD1 inhibitors may be good candidate drugs for treating kidney cancer. Full article

Histone demethylase KDM7A regulates many biological processes, including differentiation, development, and the growth of several cancer cells. Here, we have focused on the role of KDM7A in bladder cancer cells, especially under drug-resistant conditions. When the KDM7A gene was knocked down, bladder cancer cell lines showed impaired cell growth, increased cell death, and reduced rates of cell migration. Biochemical studies revealed that KDM7A knockdown in the bladder cancer cells repressed the activity of androgen receptor (AR) through epigenetic regulation. When we developed a cisplatin-resistant bladder cancer cell line, we found that AR expression was highly elevated. Upon treatment with TC-E 5002, a chemical inhibitor of KDM7A, the cisplatin-resistant bladder cancer cells, showed decreased cell proliferation. In the mouse xenograft model, KDM7A knockdown or treatment with its inhibitor reduced the growth of the bladder tumor. We also observed the upregulation of KDM7A expression in patients with bladder cancer. The findings suggest that histone demethylase KDM7A mediates the growth of bladder cancer. Moreover, our findings highlight the therapeutic potential of the KMD7A inhibitor, TC-E 5002, in patients with cisplatin-resistant bladder cancer. Full article

The association between acute kidney injury (AKI) and long-term renal function after radical nephrectomy has not been evaluated fully. We reviewed 558 cases of radical nephrectomy. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria. Values of estimated glomerular filtration rate (eGFR) were collected up to 36 months (median 35 months) after surgery. The primary outcome was new-onset chronic kidney disease (CKD) stage 3a or higher or all-cause mortality within three years after nephrectomy. The functional change ratio (FCR) of eGFR was defined as the ratio of the most recent GFR (24–36 months after surgery) to the new baseline during 3–12 months. A multivariable Cox proportional hazard regression analysis for new-onset CKD and a multivariable linear regression analysis for FCR were performed to evaluate the association between AKI and long-term renal outcomes. A correlation analysis was performed with the serum creatinine ratio and used to determine AKI and FCR. AKI occurred in 43.2% (n = 241/558) and our primary outcome developed in 40.5% (n = 226/558) of patients. The incidence of new-onset CKD was significantly higher in patients with AKI than those without at all follow-up time points after surgery. The Cox regression analysis showed a graded association between AKI and our primary outcome (AKI stage 1: Hazard ratio 1.71, 95% confidence interval 1.25–2.32; AKI stage 2 or 3: Hazard ratio 2.72, 95% confidence interval 1.78–4.10). The linear regression analysis for FCR showed that AKI was significantly associated with FCR (β = −0.168 ± 0.322, p = 0.011). There was a significant negative correlation between the serum creatinine ratio and FCR. In conclusion, our analysis demonstrated a robust and graded association between AKI after radical nephrectomy and long-term renal functional deterioration. Full article

A flexible asymmetric supercapacitor (ASC) with high electrochemical performance was constructed using reduced graphene oxide (rGO)-wrapped redox-active metal oxide-based negative and positive electrodes. Thin layered rGO functionality on the positive and the negative electrode surfaces has promoted the feasible surface-active sites and enhances the electrochemical response with a wide operating voltage window. Herein we report the controlled growth of rGO-wrapped tubular FeMoO₄ nanofibers (NFs) via electrospinning followed by surface functionalization as a negative electrode. The tubular structure offers the ultrathin-layer decoration of rGO inside and outside of the tubular walls with uniform wrapping. The rGO-wrapped tubular FeMoO₄ NF electrode exhibited a high specific capacitance of 135.2 F g⁻¹ in Na₂SO₄ neutral electrolyte with an excellent rate capability and cycling stability (96.45% in 5000 cycles) at high current density. Meanwhile, the hydrothermally synthesized binder-free rGO/MnO₂ nanorods on carbon cloth (rGO-MnO₂@CC) were selected as cathode materials due to their high capacitance and high conductivity. Moreover, the ASC device was fabricated using rGO-wrapped FeMoO₄ on carbon cloth (rGO-FeMoO₄@CC) as the negative electrode and rGO-MnO₂@CC as the positive electrode (rGO-FeMoO₄@CC/rGO-MnO₂@CC). The rationally designed ASC device delivered an excellent energy density of 38.8 W h kg⁻¹ with a wide operating voltage window of 0.0–1.8 V. The hybrid ASC showed excellent cycling stability of 93.37% capacitance retention for 5000 cycles. Thus, the developed rGO-wrapped FeMoO₄ nanotubes and MnO₂ nanorods are promising hybrid electrode materials for the development of wide-potential ASCs with high energy and power density. Full article