Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the ...clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1β (IL-1β) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1β levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in healthy volunteers. Empagliflozin induced marked reduction in both urinary and serum mtND-1 and mtCOX-3 copy numbers, as well as in urinary IL-1β. Empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response in T2DM patients. This would explain the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
(UCW) is one of the most representative standardized herbal drugs for the treatment of central nervous system diseases, including mood disorders, and has been used for over 600 years in Korea and ...China. In spite of the long clinical application of UCW, no experimental evidence for its use against depressive disorders exists. Here, we performed an animal study to investigate the anti-depressive effect of UCW and the underlying mechanisms.
A social isolation-induced depressive-like model was produced using C57BL/6J male mice by housing the mice individually for 31 days, and the mice underwent daily oral administration of distilled water, UCW (100, 200, 400 mg/kg) or fluoxetine (20 mg/kg) during the final 17 days. A tail suspension test (TST), forced swimming test (FST), and open field test (OFT) were used to explore the effects of UCW on depressive-like behaviors. 5-Hydroxytryptamine (5-HT) was measured in the dorsal raphe nuclei (DRN) using immunofluorescence. The serum corticosterone level was measured with its receptor and catecholamine, along with cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus.
Social isolation stress effectively induced depressive-like behaviors, and UCW treatment significantly improved the symptoms of depressive-like behavior in the FST, TST, and OFT. The isolation stress-induced depletion of 5-HT was significantly ameliorated by UCW treatment. UCW also attenuated the activation of the glucocorticoid receptor (GR) and the elevated serum corticosterone level, as well as the hippocampal levels of dopamine and norepinephrine. Dexametasone-derived translocation of GR was inhibited by UCW treatment in PC12 cells and HT22 cells. In addition, alterations of tryptophan hydroxylase 2 (TPH2), BDNF, and CREB in the protein analyses were notably regulated by UCW treatment.
These results provide animal-based evidence for the anti-depressive effect of UCW, and its underlying mechanisms may involve regulating the serotonergic system, the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophin.
The low-temperature processing of transparent electrodes on polymer substrates is an increasingly important issue in lightweight and flexible optoelectronic devices and low-temperature processing is ...essential since most polymer substrates cannot withstand high temperatures. We analyzed the electrical and optical characteristics of indium tin oxide (ITO) films according to the various crystallization conditions and confirmed that the low-temperature crystallized ITO has a rhombohedral structure. The ultrathin ITO films were crystallized at a temperature of 250 °C, which is lower than the glass transition temperature of polyimide substrates, and a hybrid transparent electrode with a metal mesh was formed. Our hybrid transparent electrode had a high transmittance of 77.4% and a low sheet resistance of 6.3 Ω/sq. After 1000 bending cycles at a bending radius of 6 mm, the hybrid transparent electrode maintained a sheet resistance of 6.5 Ω/sq. We applied rhombohedral ITO to the device rather than the commonly used cubic ITO, and as a result, it showed excellent electrical properties and better bending-stress stability.
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•Rhombohedral ITO thin films were grown using low-temperature crystallization.•Hybrid transparent electrodes were fabricated using ultrathin ITO and copper mesh via low-temperature crystallization.•The sheet resistance and bending stability of the flexible transparent electrodes were greatly improved.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aim
Cardiac involvement is the main prognostic determinant in AL amyloidosis. We sought to determine the prognostic significance of longitudinal change of left ventricular (LV) global longitudinal ...strain (GLS) in cardiac light chain (AL) amyloidosis patients undergoing chemotherapy.
Methods and Result
We retrospectively investigated 117 cardiac AL amyloidosis patients who underwent chemotherapy from 2005 to 2019. All patients underwent comprehensive 2D conventional transthoracic echocardiography at baseline and after completion of first-line chemotherapy. Speckle tracking analysis of images was performed offline. Absolute value of LV GLS was expressed as LV GLS and change of LV GLS after chemotherapy was expressed as Δ LV GLS. Clinical outcomes including cardiac response and all-cause mortality were analyzed.
Baseline clinical and echocardiographic parameters were similar in patients with and without CR. Δ LV GLS significantly differed between the CR and non-CR groups (0.4 ± 2.8% in the CR group vs. −0.6 ± 2.5% in the non-CR group,
P
-value = 0.046). Δ LV GLS showed satisfactory predictive performance for all-cause mortality (cut-off value = 0.8%, AUC 0.643, 95% CI 0.537–0.748). Adding Δ LV GLS to the Mayo stage + pre-chemotherapy LV GLS model showed incremental prognostic value (C-index: 0.637 vs. 0.708; Relative Integrated Discrimination Index 0.07,
P
-value = 0.003; Net Reclassification Improvement 0.54,
P-
value < 0.001). Δ LV GLS showed good correlation with cardiac response (AUC 0.820, 95% CI 0.737–0.904).
Conclusion
In cardiac amyloidosis patients who underwent chemotherapy, longitudinal change of LV GLS after chemotherapy showed significant association with overall survival as well as cardiac response.
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•Glutamate leads to neuroexcitotoxicity in HT22 cells, hippocampal neuron cell line.•ALE notably prevented the glutamate-induced neuronal cell death.•ALE inhibited the ...glutamate-induced intracellular ROS generation and Ca2+ influx.•ALE remarkably prevented the glutamate-induced depletion of BDNF.•ALE exerts inhibitory property against neuroexcitotoxicity via calpain pathway.
An imbalance between excitatory and inhibitory neurotransmitters is known to induce neuronal excitotoxicity which is a major cause of neurodegenerative disorders. Excessive glutamate concentration leads to the neuronal death by increasing oxidative stress and affecting the apoptotic signaling pathway. We investigated the anti-excitotoxic effects and associated working mechanisms of 30% ethanol extract of Aquilariae Lignum (ALE) against hippocampal neuronal death by glutamate. HT22 cells were treated with glutamate (20 mM) for 24 h following pretreatment with ALE (5, 10, 25 μg/mL). Cell viability, biochemical analysis, flow chemistry, and Western blotting assays were performed.
Glutamate treatment substantially increased the intracellular level of reactive oxygen species (ROS) and Ca2+ influx into the cell, which were followed by apoptosis. ALE pretreatment, however, significantly attenuated these excitotoxicity-related features according to the results of Annexin V analysis and the lactate dehydrogenase assay, in which the calpain pathway (in a caspase 3-independent manner) may be involved. ALE pretreatment also significantly attenuated the glutamate-induced activation of both inflammation-associated molecules (extracellular signal–regulated kinase, c-Jun N-terminal kinases and p38) and death-related molecules (p53, apoptosis-inducing factor). The inactivation of brain-derived neurotrophic factor (BDNF) was restored by ALE pretreatment.
Our results verified that A. Lignum has potential neuroprotective effects on glutamate-induced excitotoxicity in hippocampal neuron cells, and its underlying mechanism may involve the regulation of ROS-mediated cell death pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Immediate breast reconstruction with tissue expander in breast cancer patients who were expected to receive adjuvant therapy, such as chemotherapy or radiotherapy, has been a topic of debate. ...Postoperative complications from tissue expander procedures can delay the timing of adjuvant treatment and subsequently increase the probability of recurrence. The purpose of this study was to identify the impact of chemotherapy and radiotherapy on postoperative complications in patients who underwent immediate reconstruction (IR) using tissue expander.
We conducted a retrospective study of 1081 breast cancer patients who underwent mastectomy and IR using tissue expander insertion between 2012 and 2017 in Samsung Medical Center. The patients were divided into two groups based on complications (complication group vs. no complication group). Complication group was regarded to have surgical removal or conservative treatment based on clinical findings such as infection, capsular contracture, seroma, hematoma, rupture, malposition, tissue viability, or cosmetic problem. The complication group had 59 patients (5.5%) and the no complication group had 1022 patients (94.5%).
In univariate analysis, adjuvant radiotherapy and adjuvant chemotherapy were significantly associated with postoperative complications. In multivariate analysis, however, only higher pathologic N stage was significantly associated with postoperative complications (p < 0.001). Chemotherapy (p = 0.775) or radiotherapy (p = 0.825) were not risk factors for postoperative complications.
IR with tissue expander after mastectomy may be a treatment option even when the patients are expected to receive adjuvant chemotherapy or radiotherapy. These results will aid patients who are concerned about the complications of IR caused by chemotherapy or radiotherapy determine whether or not to have IR.
Patients were selected and registered retrospectively, and medical records were evaluated.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present study investigated the prognostic role of adjuvant systemic chemotherapy in patients with node negative, T1c triple negative breast cancer (TNBC) from a nationwide cohort. In addition, ...the prognostic effect between 3 different chemotherapy regimens were compared in node-negative T1c TNBC patients by subgroup analysis.
From the Korean breast cancer registry database, 1,151 T1c node negative TNBC patients were included in this study. Patients were categorized into four treatment groups according to chemotherapy regimen: (1) no chemotherapy, (2) adriamycin plus cyclophosphamide (AC), (3) adriamycin/epirubicin plus cyclophosphamide plus 5-FU (FAC/FEC), and (4) cyclophosphamide plus 5-FU plus methotrexate (CMF). Overall survival (OS) was evaluated between each patient group.
Of the 1,151 T1c node negative TNBC patients, 1,006 received adjuvant chemotherapy, while 145 received no chemotherapy. Among the patients receiving adjuvant chemotherapy the distribution of regimens was: 586 AC, 168 FAC/FEC (126 FAC, 42 FEC), and 252 CMF. The mean follow-up time of the full study cohort was 87.98 ± 33.56 months (range = 6-192 months). Patients in the no chemotherapy group showed significantly worse OS compared to each chemotherapy regimen group. However, when OS was compared between each chemotherapy regimen, no significant difference was found.
This study showed that adjuvant systemic chemotherapy improved OS in T1c node negative TNBC patients, regardless of chemotherapy between AC, FAC/FEC, and CMF regimens.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The carbon materials receive considerable attention, due to their wide application potentials in energy conversion and storage. Stemming from their low standard oxidation potential (0.207 V versus ...SHE), the carbon corrosion is thermodynamically favored. Hence, mitigating this unwelcomed phenomenon is of paramount importance, due to the subsequent deactivation or peeling off caused by carbon corrosion. However, to the best of our knowledge, there are no systematically studied experiments on the stability of edge-oxygenated groups on graphitic carbon frameworks, since it is difficult to control the edges with unitary group by traditional strong oxidation method. Here, we adopt a pre-activated method to decorate the edges with targeted functional groups, such as (G)C–H, (G)C–OH, (G)C–O–C(G), (G)C–COO–C(G), (G)C–COOH. Our experiments and DFT calculations demonstrate that the in-plane etheric rings exhibit the highest stability against both electrochemical and chemical corrosions. The findings will be a guide to design carbon-based catalysts with high stability.
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•Edge-selectively oxygenated groups on graphitic carbon frameworks were designed to minimize electrochemical corrosion.•Edge-selectively oxygenated groups on graphitic carbon frameworks were realized by a pre-activated method.•Among numerous edge-oxygenated groups, edge etheric rings ((G)C-O-C(G)) exhibited the highest electrochemical/chemical stabilities.•Among edge-oxygenated groups edge-carboxylic acids ((G)C-COOH) showed the poorest electrochemical/chemical stabilities.•Gaining a better understanding of how edge chemistry affects the stability of graphitic carbon materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mouse bone marrow-derived clonal mesenchymal stem cells (mcMSCs), which were originated from a single cell by a subfractionation culturing method, are recognized as new paradigm for stem cell therapy ...featured with its homogenous cell population. Next to proven therapeutic effects against pancreatitis, in the current study we demonstrated that mcMSCs showed significant therapeutic effects in dextran sulfate sodium (DSS)-induced experimental colitis model supported with anti-inflammatory and restorative activities. mcMSCs significantly reduced the disease activity index (DAI) score, including weight loss, stool consistency, and intestinal bleeding and significantly increased survival rates. The pathological scores were also significantly improved with mcMSC. We have demonstrated that especial mucosal regeneration activity accompanied with significantly lowered level of apoptosis as beneficiary actions of mcMSCs in UC models. The levels of inflammatory cytokines including TNF-α, IFN-γ, IL-1β, IL-6, and IL-17 were all significantly concurrent with significantly repressed NF-κB activation compared to the control group and significantly decreased infiltrations of responsible macrophage and neutrophil. Conclusively, our findings provide the rationale that mcMSCs are applicable as a potential source of cell-based therapy in inflammatory bowel diseases, especially contributing either to prevent relapse or to accelerate healing as solution to unmet medical needs in IBD therapy.
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