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1.
Langmuir ; 40(23): 11873-11887, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38780396

RESUMO

In recent years, organic-inorganic hybrid perovskite materials have become one of the most promising materials in the new generation of solar cells. These perovskites can provide excellent photoelectric properties after a simple fabrication process. Although perovskite solar cells have achieved high power conversion efficiency, instability concerns regarding material exposure to heat, moisture, air, and UV light present hindrances to commercialization. In this study, three kinds of perovskites (MAPbI3, MAPbI3-xBrx, and MAPbI3-xClx) were used to investigate the crystal stability upon exposure to heat and UV light. SEM, XRD, and FTIR were used to observe the surface morphology, crystal structure, and functional groups of the perovskite thin films. XPS was used to examine the surface composition and chemical state of the perovskite thin films under different conditions. Among these three types of perovskites, it was found that the MAPbI3-xBrx crystal demonstrated the best stability. ToF-SIMS was used to confirm the molecular distribution of the MAPbI3-xBrx films upon exposure to heat and UV light at different depths. ToF-SIMS revealed that [Pb]+ and [PbI]+ aggregated at the interface between the perovskite and ITO substrate after 14 days of thermal treatment. On the other hand, [Pb]+ and [PbI]+ were distributed uniformly after 3 days of UV exposure. This study systematically analyzed and revealed the thermal- and UV-induced degradation process of three perovskite films by using surface analysis techniques. It was concluded that bromine-doped perovskite films had better stability, and UV light caused more severe damage than heat.

2.
Aging (Albany NY) ; 16(4): 3612-3630, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38364249

RESUMO

PURPOSE: The age-induced imbalance in ecological niches leads to the loss of GSCs, which is the main reason for ovarian germline senescence. Ginsenoside Rg1 can delay ovarian senescence. Here, we shed light on new insights of ginsenoside Rg1 in regulating the niche to maintain GSCs self-renewal and discussing related molecular mechanisms. METHODS: The differences among GSC number, reproductive capacity of naturally aging female Drosophila after ginsenoside Rg1 feeding were analyzed by immunofluorescence and behavior monitoring. The expressions of the active factors in the niche and the BMP signaling were analyzed through Western blot and RT-qPCR. The target effect was verified in the ECR mutant and combined with the molecular docking. RESULTS: Ginsenoside Rg1 inhibited the age-induced reduction of the GSCs number and restored offspring production and development. Ginsenoside Rg1 promoted the expression of anchor proteins E-cadherin, stemness maintenance factor Nos and differentiation promoting factor Bam, thereby GSCs niche homeostasis was regulated. In addition, ginsenoside Rg1 was bound to the LBD region of the hormone receptor ECR. Ginsenoside Rg1 promotes the regeneration of GSCs by targeting the ECR to increase pSmad1/5/8 expression and thereby activating the BMP signaling pathway. In addition, ginsenoside Rg1 maintenance of niche homeostasis to promote GSCs regeneration is dependent on ECR as demonstrated in ECR mutants. CONCLUSIONS: Ginsenoside Rg1 regulated the ecological niche homeostasis of GSCs and promoted the regeneration of GSCs by targeting the ECR/BMP signaling pathway in hormone-deficient states in aging ovaries. It is of great significance for prolonging fertility potential and delaying ovarian senescence.


Assuntos
Proteínas de Drosophila , Drosophila , Ginsenosídeos , Animais , Feminino , Drosophila/fisiologia , Proteínas de Drosophila/metabolismo , Simulação de Acoplamento Molecular , Células-Tronco/metabolismo , Transdução de Sinais , Hormônios/metabolismo , Células Germinativas
3.
Aging Dis ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38029393

RESUMO

Aging is a natural process that affects all living organisms, including humans. Aging is a complex process that involves the gradual deterioration of various biological processes and systems, including the cardiovascular system. Vascular aging refers to age-related changes in blood vessels. These changes can increase the risk of developing cardiovascular diseases, such as hypertension, atherosclerosis, and stroke. Recently, an exercise-induced muscle factor, irisin, was found to directly improve metabolism and regulate the balance of glucolipid metabolism, thereby counteracting obesity and insulin resistance. Based on a growing body of evidence, irisin modulates vascular aging. Adenosine monophosphate-activated protein kinase (AMPK) serves as a pivotal cellular energy sensor and metabolic modulator, acting as a central signaling cascade to coordinate various cellular processes necessary for maintaining vascular homeostasis. The vascular regulatory effects of irisin are closely intertwined with its interaction with the AMPK pathway. In conclusion, understanding the molecular processes used by irisin to regulate changes in vascular diseases caused by aging may inspire the development of techniques that promote healthy vascular aging. This review sought to describe the impact of irisin on the molecular mechanisms of vascular aging, including inflammation, oxidative stress, and epigenetics, from the perspective of endothelial cell function and vascular macroregulation, and summarize the multiple signaling pathways used by irisin to regulate vascular aging.

4.
Cereb Cortex ; 33(13): 8496-8509, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37092186

RESUMO

The neural basis of configural processing has been extensively studied by exploiting face inversion during recognition, and growing evidence has revealed that word inversion also involves changes in configuration. However, the neural dynamics of face-like inversion effects remain unclear. Here, we tracked the temporal dynamics of neural responses that were sensitive to inversion during Chinese character recognition as they occurred during face recognition using multivariate decoding and temporal generalization analyses. We recorded magnetoencephalography while participants performed a one-back task for faces, compound characters, and simple characters with upright and inverted orientations. We showed that the inversion effect (inverted versus upright) can be decoded at occipitotemporal sensors for all stimulus types over and across time points, with a stronger impact on faces and compound characters than on simple characters. The inversion effect occurred earlier and lasted longer for faces than for characters, and the effect was also stronger for compound characters than for simple characters. Finally, we demonstrated inversion effects in the event-related field for all stimulus types and identified their sources in the ventral occipitotemporal areas. Overall, this study provides novel evidence for the temporal dynamics of the face-like inversion effect occurring during Chinese character recognition.


Assuntos
Reconhecimento Facial , Magnetoencefalografia , Humanos , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa , Face , Reconhecimento Facial/fisiologia
5.
J Ginseng Res ; 46(6): 759-770, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36312736

RESUMO

Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD+-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

6.
Pak J Pharm Sci ; 35(3): 701-710, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35791467

RESUMO

Androgen exposure may be an important factor in promoting the development of polycystic ovary syndrome (PCOS) and disease progression. Bushen Huoxue Formula (BHF), a traditional Chinese medicine, is prescribed in clinical settings as a PCOS remedy, albeit with unclear pharmacological effects on granulosa cells. The present research explores potentially advantageous BHF impacts and whereby BHF alleviates dehydroepiandrosterone (DHEA)-induced inflammation and endocrine disruption. Six chemical components in BHF were identified and fingerprint analysis showed good reproducibility. Using a human granulosa cell line (KGN), BHF effects on cell viability, secretion of steroidogenic and inflammatory factors were evaluated and TLR4/NF-κB pathway expression was examined. Our results demonstrate that BHF treatment of KGN cells in a DHEA-induced inflammatory state led to increased cell viability, decreased testosterone and estradiol production, and decreased CYP19A1 and HSD3B2 mRNA expression. Further experiments revealed that BHF inhibited the expression of pro-inflammatory cytokines and considerably hindered up-regulation in protein levels of TLR4, MyD88, and TRAF6, while inhibiting the activation of NF-κB and phosphorylation of IκBα. Collectively, BHF administration protected granulosa cells from DHEA-induced injuries through down-regulating pro-inflammatory cytokines and blocking the pathway of TLR4/NF-κB. Therefore, BHF hold promise as a therapeutic formulation for preventing androgen induced PCOS.


Assuntos
NF-kappa B , Síndrome do Ovário Policístico , Androgênios/metabolismo , Androgênios/farmacologia , Androgênios/uso terapêutico , Citocinas/metabolismo , Desidroepiandrosterona/metabolismo , Desidroepiandrosterona/farmacologia , Desidroepiandrosterona/uso terapêutico , Medicamentos de Ervas Chinesas , Feminino , Células da Granulosa/metabolismo , Humanos , Inflamação/metabolismo , NF-kappa B/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
7.
J Ginseng Res ; 46(1): 115-125, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35035244

RESUMO

BACKGROUND: Ginsenosides (GS) have potential value as cosmetic additives for prevention of skin photoaging. However, their protective mechanisms against skin barrier damage and their active monomeric constituents are unknown. METHODS: GS monomer types and their relative proportions were identified. A UVB-irradiated BALB/c hairless mouse model was used to assess protective effects of GS components on skin epidermal thickness and transepidermal water loss (TEWL). Skin barrier function, reflected by filaggrin (FLG), involucrin (IVL), claudin-1 (Cldn-1), and aquaporin 3 (AQP3) levels and MAPK phosphorylation patterns, were analyzed in UVB-irradiated hairless mice or HaCaT cells. RESULTS: Total GS monomeric content detected by UPLC was 85.45% and was largely attributed to 17 main monomers that included Re (16.73%), Rd (13.36%), and Rg1 (13.38%). In hairless mice, GS ameliorated UVB-induced epidermal barrier dysfunction manifesting as increased epidermal thickness, increased TEWL, and decreased stratum corneum water content without weight change. Furthermore, GS treatment of UVB-irradiated mice restored protein expression levels and epidermal tissue distributions of FLG, IVL, Cldn-1, and AQP3, with consistent mRNA and protein expression results obtained in UVB-irradiated HaCaT cells (except for unchanging Cldn-1 expression). Mechanistically, GS inhibited JNK, p38, and ERK phosphorylation in UVB-irradiated HaCaT cells, with a mixture of Rg2, Rg3, Rk3, F2, Rd, and Rb3 providing the same protective MAPK pathway inhibition-associated upregulation of IVL and AQP3 expression as provided by intact GS treatment. CONCLUSION: GS protection against UVB-irradiated skin barrier damage depends on activities of six ginsenoside monomeric constituents that inhibit the MAPK signaling pathway.

8.
Neuropsychologia ; 164: 108090, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34801520

RESUMO

This study investigates whether stimulus inversion influences neural responses of Chinese character recognition similarly to its effect on face recognition in category-selective and object-related brain areas using functional magnetic resonance imaging. Participants performed a one-back matching task for simple (one radical) and compound (two radicals) Chinese characters and faces with upright and inverted orientations. Inverted stimuli produced slower response times with stronger activity within the fusiform gyrus (FG) than upright stimuli for faces and Chinese characters. While common inversion-related activation was identified in the left FG among stimulus types, we observed a significant inter-regional correlation between the left FG and the intraparietal sulcus for face inversion. Importantly, analyses of region-of-interest (ROI) multivariate pattern classification showed that classifiers trained on face inversion can decode the representations of character inversion in the character-selective ROI. However, this was not true for face inversion in face-selective ROIs when the classifiers were trained on characters. Similar activity patterns for character and face inversion were observed in the object-related ROIs. We also showed higher decoding accuracy for upright stimuli in the face-selective ROI than in the character-selective ROI but this was not true for inverted ones or when patterns were examined in the object-related ROIs. Together, our results support shared and distinct configural representations for character and face recognition in category-selective and object-related brain areas.


Assuntos
Reconhecimento Facial , China , Face , Humanos , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa/métodos
9.
ACS Omega ; 6(50): 34606-34614, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34963945

RESUMO

Organometal halide perovskites are highly promising materials for photovoltaic applications due to the rapid growth of power conversion efficiency in recent years. However, thermal stability is still a major hurdle for perovskite solar cells toward commercialization. Herein, we first explore the slow thermal response of the CH3NH3PbI3 perovskite crystal investigated via Auger electron spectroscopy (AES). AES image mapping directly observes the evolution of morphology and elemental distribution over time. The AES small spot analysis demonstrates the precise initial degradation position of perovskite with both information regarding physical changes in crystals and chemical changes in elemental bonding at the nanometer scale. X-ray photoelectron spectroscopy (XPS) was used to confirm the surface chemical bonding and composition of the perovskite crystals. This work provides the first insights into the physical and chemical changes of perovskites investigated by AES upon long-term exposure to heat under ambient conditions.

10.
Mol Med Rep ; 24(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34278460

RESUMO

Following the publication of this paper, the authors requested that Daqing Zhao also be included as a joint author for correspondence. The Editor has granted this request, and therefore, the revised information for the corresponding authors is presented as follows (changes highlighted in bold): MANYING WANG1,2*, RUI JIANG1*, JIANZENG LIU2, XIAOHAO XU1, GUANG SUN1, DAQING ZHAO2,3 and LIWEI SUWN1,3. 1Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021; 2Jilin Ginseng Academy, Changchun University of Chinese Medicine; 3Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Changchun, Jilin 130117, P.R. China. Correspondence to: Professor Liwei Sun, Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, 1478 Gongnong Street, Changchun, Jilin 130021, P.R. China. E­mail: sunnylilwei@163.com. Professor Daqing Zhao, Jilin Ginseng Academy, Changchun University of Chinese Medicine, 1035 Boshuo Road, Changchun, Jilin 130117, P.R. China. E­mail: zhaodaqing1963@163.com. All the authors agree to this Corrigendum, and they are grateful to the Editor for allowing this Corrigendum to be published. [the original article was published in Molecular Medicine Reports 23: Article no. 306, 2021; DOI: 10.3892/mmr.2021.11945].

11.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33649814

RESUMO

Muscle atrophy, a side effect from administration of the anti­inflammatory medication dexamethasone (DEX), is preventable by concomitant administration of the major monomeric constituent of Panax ginseng C.A. Meyer, 20(S)­ginsenoside Rg3 (S­Rg3). Putative S­Rg3­associated prevention of DEX­induced muscle atrophy may involve S­Rg3 mitigation of DEX­induced mitochondrial dysfunction. In the present study, MTT assays revealed enhanced cell viability following S­Rg3 treatment of DEX­injured C2C12 myotubes. Subsequent PCR and western blotting results demonstrated S­Rg3­induced reduction of expression of muscle atrophy F­box protein (atrogin­1) and muscle RING­finger protein­1, proteins previously linked to muscle atrophy. Additionally, S­Rg3 treatment of DEX­injured myotubes led to aggregation of Rg3 monomers in cells and dose­dependent increases in cellular mitochondrial basal respiratory oxygen consumption rate and intracellular ATP levels compared with their levels in untreated DEX­injured myotubes. In addition, S­Rg3 treatment significantly reversed DEX­induced reductions of expression of key mitochondrial respiratory electron transport chain subunits of protein complexes II, III and V in DEX­injured myotube cells. Furthermore, S­Rg3 alleviation of mitochondrial dysfunction associated with DEX­induced injury of C2C12 myotubes was linked to S­Rg3­associated decreases in both forkhead box O3 (FoxO3) protein expression and phosphorylation of AMP­activated protein kinase (AMPK). Collectively, these results implicate S­Rg3 modulation of signaling within the AMPK­FoxO3 pathway as a putative mechanism underlying S­Rg3 alleviation of DEX­induced muscle atrophy.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Dexametasona/farmacologia , Proteína Forkhead Box O3/genética , Ginsenosídeos/farmacologia , Mitocôndrias Musculares/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Proteína Forkhead Box O3/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Camundongos , Mitocôndrias Musculares/metabolismo , Modelos Biológicos , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/prevenção & controle , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Transdução de Sinais/genética , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
12.
Int J Biol Macromol ; 165(Pt B): 2219-2230, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33132123

RESUMO

Spectroscopic analysis of HPLC-purified 7.3-kD Acorus tatarinowii Schott root polysaccharide ASP2-1 (FT-IR, NMR) revealed respective monosaccharide proportions of glucose: galactose: arabinose: xylose: galacturonic acid: mannose: rhamnose: glucuronic acid:fucose of 49.1:16.0:11.6:10.2:5.3:2.9:2.2:1.7:0.8. In vitro, ASP2-1 inhibited osteoclastogenesis-associated bone resorption, RANKL-induced osteoclastogenesis and F-actin ring formation and suppressed osteoclastogenesis-associated gene expression (e.g., TRAP, OSCAR, Atp6v0d2, αV, ß3, MMP9 and CtsK) as shown via RT-PCR. ASP2-1-treated RANKL-stimulated bone marrow-derived macrophages exhibited decreased levels of NFATc1 and c-Fos mRNAs and corresponding transcription factor proteins, elevated expression of negative NFATc1 regulators (Mafb, IRF8, Bcl6) and reduced their upstream negative regulator (Blimp1) expression. ASP2-1 inhibition of NFATc1 expression involved PLCγ2-Ca2+ oscillation-calcineurin axis suppression, reflecting suppression of RANKL-induced PLCγ2 activation (and associated Ca2+ oscillation) and calcineurin catalytic subunit PP2BAα expression without inhibiting NF-κB and MAPKs activation or phosphorylation. Staining (H&E, TRAP) and micro-CT assays revealed ASP2-1 attenuated bone destruction and osteoclast over-activation and improved tibia micro-architecture in a murine LPS-induced bone loss model. Thus, ASP2-1 may alleviate inflammatory bone loss-associated diseases.


Assuntos
Acorus/química , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/tratamento farmacológico , Fatores de Transcrição NFATC/metabolismo , Osteogênese/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Actinas/metabolismo , Animais , Biomarcadores/metabolismo , Cálcio/metabolismo , Fenômenos Químicos , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Fosfolipase C gama/metabolismo , Fosforilação/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Ligante RANK/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Biochem Pharmacol ; 180: 114145, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32653593

RESUMO

We previously found that 20(S)-ginsenoside Rg3 (S-Rg3) promotes myoblast differentiation via an unknown mechanism. Here we measured levels of myosin heavy chain (MHC) and myogenin, markers of myoblast differentiation, using Western blot analysis and immunofluorescence staining. Notably, S-Rg3 treatment of C2C12 myoblasts led to increased muscle differentiation and protection from muscle atrophy in a dexamethasone (DEX)-treated C2C12 myotube-based muscle atrophy model. This effect was likely caused by S-Rg3 treatment-induced promotion of Akt/mTOR phosphorylation and inhibition of FoxO3 nuclear transcription. Additionally, S-Rg3 treatment also led to increased fruit fly climbing distances (Drosophila melanogaster) and prevented muscle atrophy in aged fruit flies. Our study provides a mechanistic framework for understanding how S-Rg3 enhances myoblast differentiation and inhibits myotube atrophy through activation of the Akt/mTOR/FoxO3 signaling pathway, as demonstrated in vitro in C2C12 cells and in vivo in fruit flies.


Assuntos
Proteínas de Drosophila/metabolismo , Proteína Forkhead Box O3/metabolismo , Ginsenosídeos/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Atrofia Muscular/metabolismo , Mioblastos/metabolismo , Proteínas Associadas à Matriz Nuclear/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Relação Dose-Resposta a Droga , Drosophila melanogaster , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Mioblastos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
14.
Life Sci ; 254: 117793, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32416164

RESUMO

AIMS: Oxygen and glucose deprivation and reperfusion (OGD/R) injury contributes to the pathophysiology after ischemic stroke, which needs to urgently develop treatment strategies. Previous studies have demonstrated that autophagy in reperfusion period exerted adverse effects on the cerebral ischemic injury. Ginsenoside monomer compound K (CK) is the main intestinal metabolite of ginseng that exerts the pharmacological activities and has a protective effect against cerebral OGD/R injury. However, the specific molecular mechanism of CK protects against OGD/R injury in neurons is still unclear. MATERIALS AND METHODS: In this study, cell viability, reactive oxygen species (ROS) generation, Ca2+ overload, mitochondrial membrane potential depolarization, autophagy and apoptosis were investigated in OGD/R-induced neuronal cells injury after pretreatment with CK and in combination with BML-275 or rapamycin. KEY FINDINGS: Our study found that pretreatment with CK protected neurons against OGD/R injury by increasing cell viability and decreasing the ROS generation, mitochondrial damage, and Ca2+ overload. Moreover, CK cut down autophagy-mediated apoptosis via promoting the process of forming autophagosomes into phagocytic precursors. Furthermore, our study clarified the neuroprotective of CK against OGD/R-induced neural autophagy and apoptosis through the regulation of the AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway. SIGNIFICANCE: Taken together, our study provides credible experimental evidence and explains the potential molecular mechanism of CK as one of the main bioactive ingredients of ginseng for the treatment of cerebral ischemia/reperfusion injury.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Morte Celular Autofágica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Glucose/deficiência , Hipóxia/metabolismo , Traumatismo por Reperfusão/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagossomos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Hipóxia/complicações , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Traumatismo por Reperfusão/complicações , Transdução de Sinais/efeitos dos fármacos
15.
Biomed Res Int ; 2019: 3719643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467885

RESUMO

BACKGROUND: The clinical anti-inflammatory drug dexamethasone (DEX) can cause many side effects such as muscle atrophy for long-term use. Muscle atrophy induced by DEX may be caused by decrease of glucose consumption. Panax ginseng C.A. Meyer was previously considered to be an antiatrophic agent for glucocorticoid- (GC-) treated therapies. As one of the main components, it remains unclear whether ginseng total protein (GP) facilitates recovery from muscle atrophy induced by DEX. METHODS: In this study, GP was extracted and purified with Sephadex-G50. C2C12 myoblasts was induced with 2% horse serum to differentiate into C2C12 myotubes. Cell viability was analyzed by the MTT assay, and Ca2+ concentration was analyzed by a flow cytometer. The release of lactic dehydrogenase (LDH) and the glucose consumption were analyzed by spectrophotometry. The phosphorylation of AMP-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) and the expression of glucose transporter 4 (GLUT4) were analyzed by Western blotting. The phosphorylation of AS160 was quantified by Immunofluorescence staining. RESULTS: We found that GP increased cell viability and increased myotube diameter in high-dose DEX-treated C2C12 myotubes for 24 h, but this activity was not found in the enzymatic hydrolyzed GP group. GP reduced muscle atrophy by decreasing the expression of key proteins such as muscle RING-finger protein-1 and muscle atrophy F-box, reducing the Ca2+ concentration, and decreasing the release of LDH in DEX-injured C2C12 myotubes. Moreover, GP improved glucose consumption and increased the phosphorylation of AMPK, PI3K, Akt, and AS160 and the expression of GLUT4 in DEX-treated C2C12 myotubes. CONCLUSION: The results of this study suggest that GP has effects on recovering DEX-induced muscle atrophy and cell injury, which may improve glucose consumption via the AMPK and PI3K/Akt pathways in high-dose DEX-treated C2C12 myotubes. This study provides in vitro mechanistic insights into the recovery of muscle atrophy with GP treatment.


Assuntos
Glucose/metabolismo , Atrofia Muscular/tratamento farmacológico , Panax/química , Extratos Vegetais/farmacologia , Animais , Dexametasona/toxicidade , Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4 , Humanos , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Mioblastos/efeitos dos fármacos , Mioblastos/patologia , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química
16.
Biochem Pharmacol ; 164: 273-282, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31014753

RESUMO

Resistance to standard induction therapy and relapse remain the primary challenges for improving therapeutic effects in acute myeloid leukemia (AML); thus, novel therapeutic strategies are urgently required. Ataxia telangiectasia and Rad3-related protein (ATR) is a key regulator of different types of DNA damage, which is crucial for the maintenance of genomic integrity. The ATR-selective inhibitor VE-822 has proper solubility, potency, and pharmacokinetic properties. In this study, we investigated the anti-leukemic effects of VE-822 alone or combined with Wee1-selective inhibitor AZD1775 in AML cells. Our results showed that VE-822 inhibited AML cell proliferation and induced apoptosis in a dose-dependent manner. AZD1775 significantly promoted VE-822-induced inhibition of AML cell proliferation and led to a decreased number of cells in the G2/M phase. VE-822 and AZD1775 decreased the protein levels of ribonucleotide reductase M1 (RRM1) and M2 (RRM2) subunits, key enzymes in the synthesis of deoxyribonucleoside triphosphate, which increased DNA replication stress. VE-822 combined with AZD1775 synergistically induced AML cell apoptosis and led to replication stress and DNA damage in AML cell lines. Our study demonstrated that AZD1775 synergistically promotes VE-822-induced anti-leukemic activity in AML cell lines and provides support for clinical research on VE-822 in combination with AZD1775 for the treatment of AML patients.


Assuntos
Apoptose/fisiologia , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas de Ciclo Celular/metabolismo , Dano ao DNA/fisiologia , Isoxazóis/farmacologia , Leucemia Mieloide Aguda/metabolismo , Proteínas Tirosina Quinases/metabolismo , Pirazinas/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas de Ciclo Celular/antagonistas & inibidores , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Leucemia Mieloide Aguda/patologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Células U937
17.
Biomed Pharmacother ; 108: 1751-1758, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372878

RESUMO

Cigarette smoke causes many adverse effects such as inflammation, oxidative stress, and excessive accumulation of the extracellular matrix (ECM). Ginsenoside Rb3 has anti-inflammatory and anti-oxidative effects, which may contribute to delaying the injury caused by cigarette smoke. In this study, we used cigarette smoke extract (CSE) to establish cell injury models in WI-38 human fetal lung fibroblasts and 16HBE human bronchial epithelial cells. Our results showed that Rb3 protected against CSE-induced cytotoxicity in both cell lines. In addition, it significantly inhibited the secretion of inflammatory factors, such as interleukin-8 and tumor necrosis factor alpha, by inhibiting the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB). Moreover, Rb3 pre-treatment led to an increase in the levels of glutathione (GSH) and activities of superoxide dismutase, glutathione peroxidase (GSH-Px), and catalase to reduce the oxidative stress induced by CSE. Additionally, Rb3 decreased the levels of ECM proteins including collagen I (Col I), Col III, and elastin after CSE treatment by inhibiting the expression of transforming growth factor beta 1 (TGF-ß1)-induced vascular endothelial growth factor (VEGF). Our findings suggest that Rb3 prevented CSE-induced inflammation and oxidative stress as well as the excessive accumulation of ECM in WI-38 and 16HBE cells to protect against cell injury by inhibiting the p38 MAPK/NF-κB and TGF-ß1/VEGF pathways. The results of this study may be valuable for the development of Rb3 to combat the damage caused by cigarette smoke.


Assuntos
Fumar Cigarros , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Ginsenosídeos/farmacologia , NF-kappa B/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Ginsenosídeos/química , Humanos , Inflamação/patologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia
18.
Cell Physiol Biochem ; 47(6): 2589-2601, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29996122

RESUMO

BACKGROUND/AIMS: A series of reports revealed that autophagy and apoptosis exerted detrimental effects on the pathology of cardiac ischemia/reperfusion (I/R) injury. Ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has a protective effect against myocardial I/R injury. However, the molecular mechanisms by which CK protects against I/R injury remain unclear. In this study, we hypothesized that the cardioprotective effects of CK against I/R injury are mediated by inhibiting autophagy/apoptosis-related signaling pathways in H9c2 cardiomyocyte cells. METHODS: H9c2 cells were incubated with CK and exposed to I/R. Cell viability and damage was analyzed by MTT and lactate dehydrogenase assays. Reactive oxygen species (ROS) generation, mitochondrial damage, and cell apoptosis were analyzed by flow cytometry and TUNEL staining. The expression of autophagy, apoptosis, and related signaling proteins was analyzed by Western blotting and immunofluorescence staining. RESULTS: CK pretreatment promoted cell viability and attenuated ROS accumulation and intracellular mitochondrial damage induced by I/R injury Moreover, CK reduced autophagy by regulating the formation of phagocytic precursors to autophagosomes and also inhibited apoptosis through a mitochondrial-mediated pathway. Additionally the cardioprotective effect of CK against I/R injury was mainly through the activation of the PI3K-Akt signaling pathway. CONCLUSIONS: CK pretreatment inhibits autophagy-mediated apoptosis induced by I/R injury through the activation of the PI3K-Akt signaling pathway, which reveals that CK may be one of the key bioactive ingredients of ginseng for the treatment of myocardial I/R injury.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ginsenosídeos/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Linhagem Celular , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/patologia
19.
J Craniofac Surg ; 28(6): 1468-1471, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28841595

RESUMO

OBJECTIVE: The aim of this study was to measure palatal bone thickness and select relatively safe regions for mini-implant insertion, and to determine the effect of age and sex on palatal bone thickness and whether there is any difference between right and left sides. MATERIALS AND METHODS: Cone beam computed tomographic (CBCT) evaluation was used on 107 healthy orthodontic patients, including 51 adolescents (12.90 ±â€Š1.71 years) and 56 adults (26.09 ±â€Š4.35 years), who were selected from the Zhongshan Hospital, Fudan University (Shanghai, China). Seventy-two sites of bone thickness were measured in the palate. Intragroup, intergroup, and sex differences were analyzed by repeated measures analysis of variance. RESULTS: Palatal bone thickness exhibited significant differences in 3 anteroposterior areas of the 2 groups. From anterior to posterior region, palatal bone thickness gradually decreased. Meanwhile, on the sagittal plane, palatal bone thickness decreased gradually from reference line 0 to 9 mm among adults, and from reference line 0 to 12 mm among adolescents posterior to the level of the posterior rim of the incisive foramen. However, on the coronal plane, no significant differences were found in the palatal bone thickness among reference lines 2, 4, 6, and 8 mm lateral to the midpalatal suture. Nor were there differences between right and left sides, between adults and adolescents or between males and females. CONCLUSIONS: In terms of bone thickness, the anterior region is relatively safe for orthodontic mini-implant insertion. However, since subjects vary greatly, CBCT scans are needed before undertaking mini-implant insertion.


Assuntos
Procedimentos de Ancoragem Ortodôntica , Palato Duro , Adolescente , Adulto , Feminino , Humanos , Masculino , Palato Duro/anatomia & histologia , Palato Duro/diagnóstico por imagem , Palato Duro/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
J Ginseng Res ; 41(3): 411-418, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28701885

RESUMO

BACKGROUND: Recently, protein from ginseng was studied and used for the treatment of several kinds of diseases. However, the effect of ginseng total protein (GTP) on proliferation and wound healing in fibroblast cells remains unclear. METHODS: In this study, cell viability was analyzed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Cell cycle distribution was analyzed by flow cytometer. The levels of transforming growth factor ß1, vascular endothelial growth factor, and collagens were analyzed by enzyme-linked immunosorbent assay and immunofluorescence staining. The expressions of cyclin A, phosphorylation of extracellular signal-related kinase (p-ERK1/2), and ERK1/2 were analyzed by Western blotting. RESULTS: Our results showed that GTP promoted cell proliferation and increased the percentage of cells in S phase through the upregulation of cyclin A in NIH/3T3 cells. We also found that GTP induced the secretion of type I collagen, and promoted the expression of other factors that regulate the synthesis of collagen such as transforming growth factor ß1 and vascular endothelial growth factor. In addition, the phosphorylation of ERK1/2 at Thr202/Tyr204 was also increased by GTP. CONCLUSION: Our studies suggest that GTP promoted proliferation and secretion of collagen in NIH/3T3 cells by activating the ERK signal pathway, which shed light on a potential function of GTP in promoting wound healing.

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