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1.
Oncol Lett ; 27(5): 211, 2024 May.
Article in English | MEDLINE | ID: mdl-38572064

ABSTRACT

The present retrospective study investigated the clinical features and prognosis of secondary hematological malignancies (SHMs) in patients with sarcoma at Korea Cancer Center Hospital (Seoul, South Korea). Patients who had been diagnosed with SHMs after having received treatment for sarcoma between January 2000 and May 2023 were enrolled. Clinical data were collected from the patients' medical records. Clinical characteristics were analyzed, including SHM incidence, type and prognosis. Of 2,953 patients with sarcoma, 18 (0.6%) were diagnosed with SHMs. Their median age at the time of sarcoma diagnosis was 39.5 (range, 9-72) years, and 74% (n=14) of these patients were male. The histological features of sarcoma varied, with osteosarcoma diagnosed in nine patients (50%). All patients with sarcoma underwent surgical treatment, and 16 (88.8%) received chemotherapy. The most common type of SHMs was acute myeloid leukemia (n=6; 33.3%), followed by myelodysplastic syndrome (n=5; 27.7%). The median latency period between the sarcoma diagnosis and SHM identification was 30 (range, 11-121) months. A total of 13 (72.2%) patients received treatment for the SHM. The median overall survival after SHM diagnosis was 15.7 (range, 0.4-154.9) months. The incidence of SHMs in sarcoma in the present study was consistent with that reported previously. The presence of SHMs was associated with a poor patient prognosis, especially if treatment for SHMs was not administered.

2.
J Ethnopharmacol ; 330: 118270, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38685368

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Cheonwangbosimdan (CWBSD), a herbal medicine traditionally used for anxiety, insomnia, depression, and heart palpitations, has been reported to have anti-anxiety, antidepressant, cognitive improvement, and neuroprotective effects. AIM OF THE STUDY: The purpose of this study was to determine if CWBSD could affect post-traumatic stress disorder (PTSD)-like behaviors because it has prioritized clinical use over mechanism study. MATERIALS AND METHODS: A single prolonged stress (SPS) mouse model, a well-established animal model of PTSD, was used to investigate whether standardized CWBSD could mitigate PTSD-like behaviors through robust behavioral tests, including the elevated plus-maze test and marble burying test for measuring anxiety-like behaviors, the splash test, forced swimming test, and tail suspension test for evaluating depression-like behaviors, and the Y-maze test and novel object recognition test for assessing cognitive function. Additionally, a fear extinction test was employed to determine whether CWBSD might reverse fear memory extinction deficits. Amygdala tissue was isolated from SPS-treated mouse brain and subjected to Western blotting or quantitative PCR to explore mechanisms by which CWBSD could mitigate PTSD-like behaviors. RESULTS: CWBSD ameliorated emotional impairments and cognitive dysfunction in an SPS-induced PTSD-like mouse model. It also mitigated deficits in abnormal fear memory extinction. Protein expression levels of N-methyl-D-aspartate (NMDA) receptor subunit 2B (GluN2B) and phosphorylation levels of Ca2+/calmodulin-dependent protein kinase II in the amygdala were increased in SPS model mice and normalized by CWBSD. Additionally, co-administration of CWBSD and GluN2B-containing NMDA receptor antagonist, ifenprodil, at each sub-effective dose promoted fear memory extinction. CONCLUSIONS: CWBSD can alleviate SPS-induced PTSD-like behaviors by normalizing GluN2B-containing NMDA receptor activity in the amygdala. Therefore, CWBSD could be a promising candidate for PTSD treatment with fewer adverse effects and better efficacy than existing therapies.


Subject(s)
Behavior, Animal , Disease Models, Animal , Receptors, N-Methyl-D-Aspartate , Stress Disorders, Post-Traumatic , Animals , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/psychology , Stress Disorders, Post-Traumatic/metabolism , Male , Mice , Behavior, Animal/drug effects , Mice, Inbred C57BL , Fear/drug effects , Amygdala/drug effects , Amygdala/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Anxiety/drug therapy , Anxiety/psychology
3.
J Ethnopharmacol ; 327: 118063, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38493906

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Moutan cortex (MC), the root bark of Paeonia suffruticosa Anderws (Paeoniaceae), has been historically employed in traditional herbal medicine for addressing women's ailments by replenishing kidney Yin. AIM OF THE STUDY: We aimed to explore if paeonol, an active constituent of MC, could ameliorate neuropsychiatric symptoms, such as anxiety, depression, and cognitive impairments, associated with post-menopausal syndrome (PMS) in an ovariectomized (OVX) mouse model. MATERIALS AND METHODS: The experimental design comprised 6 groups, including a sham group, OVX group, paeonol administration groups (3, 10 or 30 mg/kg, p.o.), and an estradiol (E2)-treated positive control group. Behavioral tests including the open field, novel object recognition, Y-maze, elevated plus-maze, splash, and forced swimming tests were conducted. In addition, we investigated the effets of paeonol on the phosphorylated levels of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), as well as on the expression levels of G protein-coupled receptor (GPR30) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus. RESULTS: Paeonol treatment (10 and 30 mg/kg, p.o.) effectively reversed the cognitive decline in OVX mice, measured by the novel object recognition and Y-maze tests, similar to that in the positive control group. Additionally, it alleviated anxiety- and depressive-like behaviors, as evaluated by the elevated plus-maze test, splash test, and forced swimming test. Paeonol restored GPR30 expression levels in the prefrontal cortex and hippocampus, mirroring the effects of E2 administration. Furthermore, it reversed the reduced expression levels of the PI3K-Akt-mTOR signaling pathway in the prefrontal cortex and hippocampus and increased BDNF expression in the hippocampus of OVX mice. CONCLUSION: This research suggests that paeonol would be beneficial for alleviating PMS-associated cognitive impairment, anxiety and depression.


Subject(s)
Acetophenones , Brain-Derived Neurotrophic Factor , Postmenopause , Mice , Humans , Female , Animals , Brain-Derived Neurotrophic Factor/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Hippocampus , TOR Serine-Threonine Kinases/metabolism , Mammals/metabolism
4.
Article in English | MEDLINE | ID: mdl-38467326

ABSTRACT

Post-traumatic stress disorder (PTSD) is a mental illness that can occur in individuals who have experienced trauma. Current treatments for PTSD, typically serotonin reuptake inhibitors, have limited effectiveness for patients and often cause serious adverse effects. Therefore, a novel class of treatment with better pharmacological profile is necessary. D-Pinitol has been reported to be effective for depression and anxiety disorders, but there are no reports associated with PTSD. In the present study, we investigated the effects of D-pinitol in a mouse model of PTSD induced by a single prolonged stress (SPS) protocol. We examined the therapeutic effects of D-pinitol on emotional and cognitive impairments in the SPS mouse model. We also investigated the effects of D-pinitol on fear memory formation. Mineralocorticoid receptor transactivation assay, Western blot, and quantitative PCR were employed to investigate how D-pinitol exerts its pharmacological activities. D-Pinitol ameliorated PTSD-like behaviors in a SPS mouse model. D-Pinitol also normalized the increased mRNA expression levels and protein levels of the mineralocorticoid receptor in the amygdala. A mineralocorticoid receptor agonist reversed the effects of D-pinitol on fear extinction and recall, and the antagonistic property of D-pinitol against the mineralocorticoid receptor was confirmed in vitro. Our findings suggest that D-pinitol could serve as a potential therapeutic agent for PTSD due to its antagonistic effect on the mineralocorticoid receptor.


Subject(s)
Inositol/analogs & derivatives , Stress Disorders, Post-Traumatic , Mice , Humans , Animals , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/psychology , Fear/physiology , Extinction, Psychological , Receptors, Mineralocorticoid/metabolism , Receptors, Mineralocorticoid/therapeutic use , Disease Models, Animal , Stress, Psychological/psychology
5.
Chem Biodivers ; 21(4): e202301115, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38334224

ABSTRACT

In this study, three diterpenoids (1-3), including one known compound (1), were isolated from the fruits of Vitex rotundifolia and their structures were determined via spectroscopic analysis. In lipopolysaccharide-stimulated RAW264.7 cells, these compounds dose-dependently decreased the intracellular reactive oxygen species levels and nitric oxide production compared to those in the control cells. At 25 µM/mL, these compounds also diminished the protein expression of the pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6, with compound 3 exhibiting the most potent inhibitory effect.


Subject(s)
Diterpenes , Vitex , Vitex/chemistry , Antioxidants/pharmacology , Salt-Tolerant Plants/metabolism , Anti-Inflammatory Agents/pharmacology , Diterpenes/pharmacology , Diterpenes/chemistry , Nitric Oxide/metabolism , Lipopolysaccharides/pharmacology , Nitric Oxide Synthase Type II/metabolism
6.
J Ginseng Res ; 48(1): 59-67, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38223823

ABSTRACT

Background: Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid ß (Aß) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of Panax ginseng and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of P. ginseng extract. Methods: We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aß25-35 peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting. Results: We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca2+/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brain-derived neurotrophic factor (BDNF) expression levels in Aß25-35 peptide-treated mice were modulated by sub-chronic administration of panaxcerol D. Conclusion: Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aß accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of P. ginseng for improving cognitive function.

7.
Aging Dis ; 15(1): 115-152, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37307828

ABSTRACT

As a recently discovered waste removal system in the brain, cerebral lymphatic system is thought to play an important role in regulating the homeostasis of the central nervous system. Currently, more and more attention is being focused on the cerebral lymphatic system. Further understanding of the structural and functional characteristics of cerebral lymphatic system is essential to better understand the pathogenesis of diseases and to explore therapeutic approaches. In this review, we summarize the structural components and functional characteristics of cerebral lymphatic system. More importantly, it is closely associated with peripheral system diseases in the gastrointestinal tract, liver, and kidney. However, there is still a gap in the study of the cerebral lymphatic system. However, we believe that it is a critical mediator of the interactions between the central nervous system and the peripheral system.


Subject(s)
Central Nervous System , Lymphatic System , Brain/physiology , Homeostasis
8.
Clin Cancer Res ; 30(1): 127-138, 2024 01 05.
Article in English | MEDLINE | ID: mdl-37931242

ABSTRACT

PURPOSE: Medullary thyroid carcinoma (MTC) presents a distinct biological context from other thyroid cancers due to its specific cellular origin. This heterogeneous and rare tumor has a high prevalence of advanced diseases, making it crucial to address the limited therapeutic options and enhance complex clinical management. Given the high clinical accessibility of methylation information, we construct the largest MTC methylation cohort to date. EXPERIMENTAL DESIGN: Seventy-eight fresh-frozen MTC samples constituted our methylation cohort. The comprehensive study process incorporated machine learning, statistical analysis, and in vitro experiments. RESULTS: Our study pioneered the identification of a three-class clustering system for risk stratification, exhibiting pronounced epigenomic heterogeneity. The elevated overall methylation status in MTC-B, combined with the "mutual exclusivity" of hypomethylated sites displayed by MTC-A and MTC-C, distinctively characterized the MTC-specific methylation pattern. Integrating with the transcriptome, we further depicted the features of these three clusters to scrutinize biological properties. Several MTC-specific aberrant DNA methylation events were emphasized in our study. NNAT expression was found to be notably reduced in poor-prognostic MTC-C, with its promoter region overlapping with an upregulated differentially methylated region. In vitro experiments further affirmed NNAT's therapeutic potential. Moreover, we built an elastic-net logistic regression model with a relatively high AUC encompassing 68 probes, intended for future validation and systematic clinical application. CONCLUSIONS: Conducting research on diseases with low incidence poses significant challenges, and we provide a robust resource and comprehensive research framework to assist in ongoing MTC case inclusion and facilitate in-depth dissection of its molecular biological features.


Subject(s)
Carcinoma, Neuroendocrine , Thyroid Neoplasms , Humans , DNA Methylation , Thyroid Neoplasms/pathology , Carcinoma, Neuroendocrine/pathology
9.
Behav Brain Res ; 461: 114836, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38145873

ABSTRACT

Alzheimer's disease (AD) is characterized by cognitive impairment. It is common in the elderly. Etiologically, dysfunction of cholinergic neurotransmitter system is prominent in AD. However, disease modifying drug for AD is still unavailable. We hypothesized that krill oil and modified krill oil containing 20 % lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA, LPC20K) could play a crucial role in AD by improving cognitive functions measured by several behavioral tests. We found that LPC20K could ameliorate short-term, long-term, spatial, and object recognition memory under cholinergic hypofunction states. To find the underlying mechanism involved in the effect of LPC20K on cognitive function, we investigated changes of signaling molecules using Western blotting. Expression levels of protein kinase C zeta (PKCζ) and postsynaptic density protein 95 (PSD-95), and phosphorylation levels of extracellular signal-regulated kinase (ERK), Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), and cAMP response element-binding protein (CREB) were significantly increased in LPC20K-administered group compared to those in the memory impairment group. Moreover, the expression levels of BDNF were temporally increased especially 6 or 9 h after administration of LPC20K compared with the control group. These results suggest that LPC20K could ameliorate memory impairment caused by hypocholinergic state by enhancing the expression levels of PKCζ and PSD-95, and phosphorylation levels of ERK, CaMKⅡ and CREB and increasing BDNF expression levels. Therefore, LPC20K could be used as a dietary supplement against cognitive impairment observed in diseases such as AD with a hypocholinergic state.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Euphausiacea , Humans , Animals , Aged , Scopolamine/pharmacology , Euphausiacea/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Maze Learning , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Memory Disorders/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Cholinergic Agents/pharmacology , Hippocampus/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism
10.
Phys Chem Chem Phys ; 26(1): 635, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38058216

ABSTRACT

Correction for 'Structural, electronic, optical, elastic, thermodynamic and thermal transport properties of Cs2AgInCl6 and Cs2AgSbCl6 double perovskite semiconductors using a first-principles study' by Keqing Zhang et al., Phys. Chem. Chem. Phys., 2023, 25, 31848-31868, https://doi.org/10.1039/d3cp03795a.

11.
Phys Chem Chem Phys ; 25(46): 31848-31868, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-37968998

ABSTRACT

In this study, we employ the framework of first-principles density functional theory (DFT) computations to investigate the physical, electrical, bandgap and thermal conductivity of Cs2AgInCl6-CAIC (type I) and Cs2AgSbCl6-CASC (type II) using the GGA-PBE method. CAIC possesses a direct band gap energy of 1.812 eV, while CASC demonstrates an indirect band gap energy of 0.926 eV. The CAIC and CASC exhibit intriguingly reduced thermal conductivity, which can be attributed to the notable reduction in their respective Debye temperatures, measuring 182 K and 135 K, respectively. The Raman active modes computed under ambient conditions have been compared with real-world data, showing excellent agreement. The thermal conductivity values of CAIC and CASC compounds exhibit quantum mechanical characteristics, with values of 0.075 and 0.25 W m-1 K-1, respectively, at 300 K. It is foreseen that these outcomes will generate investigations concerning phosphors and diodes that rely on single emitters, with the aim of advancing lighting and display technologies in the forthcoming generations.

13.
Biomed Pharmacother ; 168: 115639, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37812895

ABSTRACT

Haloperidol, one of the representative typical antipsychotics, is on the market for schizophrenia but shows severe adverse effects such as extrapyramidal symptoms (EPS) or cognitive impairments. Oleanolic acid (OA) is known to be effective for tardive dyskinesia which is induced by long-term treatment with L-DOPA. This study aimed to investigate whether OA could ameliorate EPS or cognitive impairment induced by haloperidol. The balance beam, catalepsy response, rotarod and vacuous chewing movement (VCM) tests were performed to measure EPS and the novel object recognition test was used to estimate haloperidol-induced cognitive impairment. Levels of dopamine and acetylcholine, the phosphorylation levels of c-AMP-dependent protein kinase A (PKA) and its downstream signaling molecules were measured in the striatum. OA significantly attenuated EPS and cognitive impairment induced by haloperidol without affecting its antipsychotic properties. Valbenazine only ameliorated VCM. Also, OA normalised the levels of dopamine and acetylcholine in the striatum which were increased by haloperidol. Furthermore, the increased phosphorylated PKA, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) levels and c-FOS expression level induced by haloperidol were significantly decreased by OA in the striatum. In addition, cataleptic behaviour of haloperidol was reversed by sub-effective dose of H-89 with OA. These results suggest that OA can alleviate EPS and cognitive impairment induced by antipsychotics without interfering with antipsychotic properties via regulating neurotransmitter levels and the PKA signaling pathway in the striatum. Therefore, OA is a potential candidate for treating EPS and cognitive impairment induced by antipsychotics.


Subject(s)
Antipsychotic Agents , Oleanolic Acid , Mice , Animals , Haloperidol/adverse effects , Antipsychotic Agents/adverse effects , Dopamine , Acetylcholine , Signal Transduction
14.
Life Sci ; 333: 122147, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37802198

ABSTRACT

AIMS: Menopause is a natural process in women that can lead to post-menopausal syndrome with symptoms such as hot flushes, weight gain, anxiety, cognitive decline, and depression. Hormonal replacement therapy is commonly prescribed. However, it has serious adverse effects. Herbal medicinal products and isoflavones are used as alternatives. D-Pinitol found in Pinaceae and Fabaceae families has anti-inflammatory and antioxidant effects. However, it has not received as much attention as isoflavones. In this study, we investigated whether D-pinitol could alleviate post-menopausal symptoms using an ovariectomized (OVX) mouse model. MAIN METHODS: Female ICR mice were divided into six groups: sham (vehicle), OVX (vehicle), OVX + D-pinitol (10, 30, 100 mg/kg, p.o.), and OVX + estradiol (0.5 mg/kg, s.c.). Treatment with vehicle, D-pinitol, and estradiol began at seven weeks post ovariectomy. We employed several behavioral tests, hot-flush test, and Western blot analysis. KEY FINDINGS: We found that D-pinitol treatment (30, 100 mg/kg, p.o.) reversed cognitive dysfunction in OVX mice (novel object recognition and Y-maze test). Additionally, D-pinitol alleviated anxiety-like behaviors (elevated plus-maze) and reversed depressive-like behaviors (splash test, tail suspension test). It also normalized increased basal tail skin temperature in OVX mice. Moreover, D-pinitol administration reversed decreased expression of ERß and synaptophysin and phosphorylation of ERK and PI3K-Akt-GSK-3ß induced by OVX in the hippocampus and prefrontal cortex. SIGNIFICANCE: These findings indicate that D-pinitol might be a promising candidate for treating post-menopausal symptoms by increasing ERß and synaptophysin expression levels and activation of ERK or PI3K-Akt-GSK-3ß signaling pathway, at least in part.


Subject(s)
Isoflavones , Postmenopause , Humans , Mice , Female , Animals , Glycogen Synthase Kinase 3 beta , Synaptophysin/pharmacology , Proto-Oncogene Proteins c-akt , Estrogen Receptor beta , Phosphatidylinositol 3-Kinases , Mice, Inbred ICR , Estradiol/pharmacology , Isoflavones/pharmacology , Ovariectomy/adverse effects
15.
Radiat Oncol ; 18(1): 156, 2023 Sep 22.
Article in English | MEDLINE | ID: mdl-37736735

ABSTRACT

PURPOSE: This study evaluated the treatment outcomes of spine stereotactic body radiation therapy (SBRT) in sarcoma patients. MATERIALS AND METHODS: A total of 44 sarcoma patients and 75 spinal lesions (6 primary tumors, 69 metastatic tumors) treated with SBRT were retrospectively reviewed between 2006 and 2017. The median radiation dose was 33 Gy (range, 18-45 Gy) in 3 fractions (range, 1-5) prescribed to the 75% isodose line. RESULTS: The median follow-up duration was 18.2 months. The 1-year local control was 76.4%, and patients treated with single vertebral body were identified as a favorable prognostic factor on multivariate analyses. Progression-free survival at 1 year was 31.9%, with the interval between initial diagnosis and SBRT and extent of disease at the time of treatment being significant prognostic factors. The 1-year overall survival was 80.5%, and PTV and visceral metastases were independently associated with inferior overall survival. CONCLUSION: SBRT for spinal sarcoma is effective in achieving local control, particularly when treating a single vertebral level with a limited extent of disease involvement, resulting in an excellent control rate. The extent of disease at the time of SBRT is significantly correlated with survival outcomes and should be considered when treating spine sarcoma.


Subject(s)
Neoplasms, Second Primary , Radiosurgery , Sarcoma , Soft Tissue Neoplasms , Humans , Retrospective Studies , Treatment Outcome , Sarcoma/radiotherapy , Sarcoma/surgery
16.
Z Naturforsch C J Biosci ; 78(11-12): 399-407, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-37703186

ABSTRACT

Melanogenesis is the process where skin pigment melanin is produced through tyrosinase activity. Overproduction of melanin causes skin disorders such as freckles, spots, and hyperpigmentation. Myricetin 3-O-galactoside (M3G) is a dietary flavonoid with reported bioactivities. M3G was isolated from Limonium tetragonum and its anti-melanogenic properties were investigated in α-melanocyte stimulating hormone-stimulated B16F10 melanoma cells. The in vitro anti-melanogenic capacity of M3G was confirmed by inhibited tyrosinase and melanin production. M3G-mediated suppression of melanogenic proteins, tyrosinase, microphthalmia-associated transcription factor (MITF), and tyrosinase-related proteins (TRP)-1 and TRP-2, were confirmed by mRNA and protein levels, analyzed by RT-qPCR and Western blot, respectively. Furthermore, M3G suppressed Wnt signaling through the inhibition of PKA phosphorylation. M3G also suppressed the consequent phosphorylation of CREB and nuclear levels of MITF. Analysis of MAPK activation further revealed that M3G increased the activation of ERK1/2 while p38 and JNK activation remained unaffected. Results showed that M3G suppressed melanogenesis in B16F10 cells by decreasing tyrosinase production and therefore inhibiting melanin formation. A possible action mechanism was the suppression of CREB activation and upregulation of ERK phosphorylation which might cause the decreased nuclear levels of MITF. In conclusion, M3G was suggested to be a potential nutraceutical with anti-melanogenic properties.


Subject(s)
Melanoma, Experimental , Melanoma , Animals , Monophenol Monooxygenase , Melanins/metabolism , MAP Kinase Signaling System , alpha-MSH/pharmacology , alpha-MSH/metabolism , Flavonoids/pharmacology , Galactosides , Melanoma, Experimental/metabolism , Cell Line, Tumor
17.
Phytother Res ; 37(12): 5904-5915, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37654104

ABSTRACT

Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D-pinitol could ameliorate schizophrenia-like behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D-pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D-pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D-pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D-pinitol. Single administration of D-pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D-Pinitol also reversed social behavior deficits and cognitive impairments induced by MK-801 without causing any motor coordination deficits. Furthermore, D-pinitol reversed increased expression levels of pNF-kB induced by MK-801 treatment and consequently increased expression levels of TNF-α and IL-6 in the prefrontal cortex. These results suggest that D-pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down-regulating transcription factor NF-κB and pro-inflammatory cytokines in the prefrontal cortex.


Subject(s)
Cognitive Dysfunction , Schizophrenia , Mice , Animals , Dizocilpine Maleate/adverse effects , Reflex, Startle/physiology , Schizophrenia/chemically induced , Schizophrenia/drug therapy , Schizophrenia/metabolism , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy
18.
West J Nurs Res ; 45(10): 878-884, 2023 10.
Article in English | MEDLINE | ID: mdl-37614166

ABSTRACT

BACKGROUND: Nurses suffer a certain degree of work alienation (a psychological state in which employees feel separated from their jobs because the jobs do not meet the needs of employees or do not match their expectations). It is necessary to identify predictors of work alienation and find effective interventions. OBJECTIVE: To explore the influence of organizational climate and job stress on work alienation among nurses in emergency departments. METHODS: This was a cross-sectional study conducted from June to August 2022. A convenience sampling method was adopted to invite 342 nurses from emergency departments in 12 tertiary public hospitals in 4 cities in China. Data were collected using self-reported questionnaires on organizational climate, job stress, and work alienation. Path analysis implemented by IBM AMOS 21.0 was used to explore the associations among organizational climate, job stress, and work alienation. RESULTS: Job stress can positively affect work alienation among nurses in emergency departments (ß = 0.44, P < .01). Organizational climate can directly and negatively affect work alienation (ß = -0.33, P < .01); it can also negatively and indirectly affect work alienation through job stress (ß = -0.20, 95% confidence interval: -0.252 to -0.146). CONCLUSIONS: Job stress partially mediated the effect of organizational climate on work alienation among nurses in emergency departments. The findings provided a valuable perspective on predictors of work alienation among emergency department nurses.


Subject(s)
Nurses , Occupational Stress , Humans , Cross-Sectional Studies , Emotions , Emergency Service, Hospital
19.
Eur J Pharmacol ; 956: 175954, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37541369

ABSTRACT

Oleanolic acid (OA) and ursolic acid (UA) are structural isomeric triterpenoids. Both triterpenoids have been reported to be able to improve depression. However, no studies have compared their effects in the same system. Whether OA or UA could ameliorate depression-like behaviors in maternal separation (MS)-induced depression-like model was investigated. MS model is a well-accepted mouse model that can reflect the phenotype and pathogenesis of depression. Depression is a mental illness caused by neuroinflammation or changes in neuroplasticity in certain brain regions, such as the prefrontal cortex and hippocampus. Depression-like behaviors were measured using splash test or forced swimming test. In addition, anxiety-like behaviors were also measured using the open field test or elevated plus-maze test. MS-treated female mice showed greater depression-like behaviors than male mice, and that OA improved several depression-like behaviors, whereas UA only relieved anxiety-like behavior of MS-treated mice. Microglial activation, expression levels of TNF-α, and mRNA levels of IDO1 were increased in the hippocampi of MS-treated female mice. However, OA and UA treatments attenuated such increases. In addition, expression levels of synaptophysin and PSD-95 were decreased in the hippocampi of MS-treated female mice. These decreased expression levels of synaptophysin were reversed by both OA and UA treatments, although decreased PSD-95 expression levels were only reversed by OA treatment. Our findings suggest that MS cause depression-like behaviors through female-specific neuroinflammation, changes of tryptophan metabolism, and alterations of synaptic plasticity. Our findings also suggest that OA could reverse MS-induced depression-like behaviors more effectively than UA.


Subject(s)
Depression , Oleanolic Acid , Mice , Animals , Male , Female , Depression/etiology , Oleanolic Acid/pharmacology , Oleanolic Acid/therapeutic use , Synaptophysin/metabolism , Neuroinflammatory Diseases , Maternal Deprivation , Hippocampus , Ursolic Acid
20.
ACS Appl Mater Interfaces ; 15(36): 42424-42438, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37647534

ABSTRACT

We herein report for the first time a simple environmentally friendly hydrothermal method for one-step synthesis of fragment-reduced graphene oxide (FrGO) under mild conditions without the addition of reducing agents, and we applied it as an electrode material for a supercapacitor. The characterization results show that the introduction of Al2O3 as a spacer and HCl as an etchant results in a macroporous/mesoporous structure, increases the fragmentation of the FrGO microtopography, shortens the electron/ion transport path, and increases the contact between the electrode material and the electrolyte. Compared to the traditional hydrothermal reduced graphene materials, FrGO shows a larger specific capacitance. The results indicate that suitable hydrothermal temperature and time can effectively promote the retention of more oxygen-containing functional groups on the graphene surface. The first-principles density functional theory (DFT) calculation results show that the electrostatic potential in carbonyl group graphene is more negative, favored by the H+ adsorption, and provides the system with a pseudocapacitive effect. Under optimized conditions, FrGO (1:4, 180 °C, 3 h) exhibits 417 F/g at 1 A/g with an outstanding capacitance retention of 78.51% at 50 A/g and exhibits remarkable stability over 20 000 charge/discharge cycles. The proposed FrGO-based synthesis method can be used to guide the development of electrode materials for various supercapacitor devices.

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