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1.
Biomol Ther (Seoul) ; 32(2): 231-239, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38296651

RESUMO

Methyl anthranilate (MA) is a botanical fragrance used in food flavoring with unexplored potential in anti-pigment cosmetics. MA dose-dependently reduced melanin content without affecting cell viability, inhibited dendrite elongation and melanosome transfer in the co-culture system of human melanoma cells (MNT-1) and human keratinocyte cell line (HaCaT), and downregulated melanogenic genes, including tyrosinase, tyrosinase-related protein 1 and 2 (TRP-1, TRP-2). Additionally, MA decreased cyclic adenosine monophosphate (cAMP) production and exhibited a significant anti-pigmentary effect in Melanoderm™. These results suggest that MA is a promising anti-pigmentary agent for replacing or complementing existing anti-pigmentary cosmetics.

2.
Int J Mol Sci ; 24(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38069092

RESUMO

While fibrinolytic enzymes and thrombolytic agents offer assistance in treating cardiovascular diseases, the existing options are associated with a range of adverse effects. In our previous research, we successfully identified ficin, a naturally occurring cysteine protease that possesses unique fibrin and fibrinogenolytic enzymes, making it suitable for both preventing and treating cardiovascular disorders linked to thrombosis. Papain is a prominent cysteine protease derived from the latex of Carica papaya. The potential role of papain in preventing fibrino(geno)lytic, anticoagulant, and antithrombotic activities has not yet been investigated. Therefore, we examined how papain influences fibrinogen and the process of blood coagulation. Papain is highly stable at pH 4-11 and 37-60 °C via azocasein assay. In addition, SDS gel separation electrophoresis, zymography, and fibrin plate assays were used to determine fibrinogen and fibrinolysis activity. Papain has a molecular weight of around 37 kDa, and is highly effective in degrading fibrin, with a molecular weight of over 75 kDa. Furthermore, papain-based hemostatic performance was confirmed in blood coagulation tests, a blood clot lysis assay, and a κ-carrageenan rat tail thrombosis model, highlighting its strong efficacy in blood coagulation. Papain shows dose-dependent blood clot lysis activity, cleaves fibrinogen chains of Aα, Bß, and γ-bands, and significantly extends prothrombin time (PT) and activated partial thromboplastin time (aPTT). Moreover, the mean length of the infarcted regions in the tails of Sprague-Dawley rats with κ-carrageenan was shorter in rats administered 10 U/kg of papain than in streptokinase-treated rats. Thus, papain, a cysteine protease, has distinct fibrin and fibrinogenolytic properties, suggesting its potential for preventing or treating cardiovascular issues and thrombosis-related diseases.


Assuntos
Carica , Cisteína Proteases , Hemostáticos , Trombose , Ratos , Animais , Fibrinolíticos/farmacologia , Fibrinolíticos/química , Látex/química , Papaína , Anticoagulantes , Carragenina , Ratos Sprague-Dawley , Trombose/tratamento farmacológico , Fibrinogênio , Fibrina/química
3.
Biol Reprod ; 109(6): 851-863, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37669128

RESUMO

Male contraceptive development has included use of testosterone (T) with or without a progestin or the use of a single molecule such as progestogenic androgens (PA) for suppression of testicular T production. Expanding upon the vast amount of data accumulated from nortestosterone (NT), NT analogs, and their prodrugs, a new series of PA, the C7 methyl, and ethyl α-substituted T analogs 7α-Methyltestosterone (7α-MT) and 7α-Ethyltestosterone (7α-ET), respectively, were hypothesized and designed to have superior androgenic and progestogenic activities when compared with parent T. Results from androgen receptor and progesterone receptor competitive binding and transcriptional activation assays showed favorable activities for these T analogs. Additionally, 7α-MT and 7α-ET were shown to be active substrates for aromatase in vitro, mitigating a potential negative impact on bone mineral density with long-term use. In conjunction with this observation, the diminished metabolism of these T analogs by 5α-reductase may reduce potential concerns for prostatic growth. In the Hershberger in vivo rat bioassay, 7α-MT and 7α-ET showed superior androgenic and anabolic activities as compared with T. These C7 α-substituted T analogs also showed clear progestogenic activity in the McPhail bioassay which evaluated endometrial glandular arborization in a rabbit model. The discovery of aromatizable molecules with reduced metabolism by 5α-reductase that have androgenic, anabolic, and progestogenic properties indicates that the core and/or prodrugs of 7α-MT and 7α-ET are promising molecules for further development as male contraceptive PAs.


Assuntos
Anticoncepcionais Masculinos , Nandrolona , Pró-Fármacos , Masculino , Ratos , Coelhos , Animais , Humanos , Androgênios/farmacologia , Androgênios/metabolismo , Testosterona , Progestinas/farmacologia , Nandrolona/farmacologia , Nandrolona/metabolismo , Metiltestosterona , Anticoncepção , Anticoncepcionais Masculinos/farmacologia
4.
Sensors (Basel) ; 23(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37420709

RESUMO

In indoor environments, estimating localization using a received signal strength indicator (RSSI) is difficult because of the noise from signals reflected and refracted by walls and obstacles. In this study, we used a denoising autoencoder (DAE) to remove noise in the RSSI of Bluetooth Low Energy (BLE) signals to improve localization performance. In addition, it is known that the signal of an RSSI can be exponentially aggravated when the noise is increased proportionally to the square of the distance increment. Based on the problem, to effectively remove the noise by adapting this characteristic, we proposed adaptive noise generation schemes to train the DAE model to reflect the characteristics in which the signal-to-noise ratio (SNR) considerably increases as the distance between the terminal and beacon increases. We compared the model's performance with that of Gaussian noise and other localization algorithms. The results showed an accuracy of 72.6%, a 10.2% improvement over the model with Gaussian noise. Furthermore, our model outperformed the Kalman filter in terms of denoising.


Assuntos
Algoritmos , Fenômenos Biológicos , Razão Sinal-Ruído , Distribuição Normal
5.
Nat Commun ; 14(1): 3779, 2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37355655

RESUMO

Colloidal Ag(In,Ga)S2 nanocrystals (AIGS NCs) with the band gap tunability by their size and composition within visible range have garnered surging interest. High absorption cross-section and narrow emission linewidth of AIGS NCs make them ideally suited to address the challenges of Cd-free NCs in wide-ranging photonic applications. However, AIGS NCs have shown relatively underwhelming photoluminescence quantum yield (PL QY) to date, primarily because coherent heteroepitaxy has not been realized. Here, we report the heteroepitaxy for AIGS-AgGaS2 (AIGS-AGS) core-shell NCs bearing near-unity PL QYs in almost full visible range (460 to 620 nm) and enhanced photochemical stability. Key to the successful growth of AIGS-AGS NCs is the use of the Ag-S-Ga(OA)2 complex, which complements the reactivities among cations for both homogeneous AIGS cores in various compositions and uniform AGS shell growth. The heteroepitaxy between AIGS and AGS results in the Type I heterojunction that effectively confines charge carriers within the emissive core without optically active interfacial defects. AIGS-AGS NCs show higher extinction coefficient and narrower spectral linewidth compared to state-of-the-art heavy metal-free NCs, prompting their immediate use in practicable applications including displays and luminescent solar concentrators (LSCs).


Assuntos
Luminescência , Nanopartículas , Fótons , Software
6.
Int J Mol Sci ; 24(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37108207

RESUMO

Glycine max Merr. (GM) is a functional food that provides many beneficial phytochemicals. However, scientific evidence of its antidepressive and sedative activities is scarce. The present study was designed to investigate the antidepressive and calmative effects of GM and its biologically active compound, genistein (GE), using electroencephalography (EEG) analysis in an electric foot shock (EFS)-stressed rat. The underlying neural mechanisms of their beneficial effects were determined by assessing corticotropin-releasing factor (CRF), serotonin (5-HT), and c-Fos immunoreactivity in the brain using immunohistochemical methods. In addition, the 5-HT2C receptor binding assay was performed because it is considered a major target of antidepressants and sleep aids. In the binding assay, GM displayed binding affinity to the 5-HT2C receptor (IC50 value of 14.25 ± 11.02 µg/mL). GE exhibited concentration-dependent binding affinity, resulting in the binding of GE to the 5-HT2C receptor (IC50, 77.28 ± 26.57 mg/mL). Administration of GM (400 mg/kg) increased non-rapid eye movement (NREM) sleep time. Administration of GE (30 mg/kg) decreased wake time and increased rapid eye movement (REM) and NREM sleep in EPS-stressed rats. In addition, treatment with GM and GE significantly decreased c-Fos and CRF expression in the paraventricular nucleus (PVN) and increased 5-HT levels in the dorsal raphe in the brain. Overall, these results suggest that GM and GE have antidepressant-like effects and are effective in sleep maintenance. These results will benefit researchers in developing alternatives to decrease depression and prevent sleep disorders.


Assuntos
Hormônio Liberador da Corticotropina , Transtornos do Sono-Vigília , Ratos , Animais , Hormônio Liberador da Corticotropina/farmacologia , Genisteína/farmacologia , Genisteína/uso terapêutico , Serotonina/metabolismo , Receptor 5-HT2C de Serotonina , Sono , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Eletroencefalografia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etiologia
7.
Antioxidants (Basel) ; 11(8)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35892650

RESUMO

Recently, the impacts of 5G electromagnetic radiation (EMR) with 28 GHz on human health have been attracting public attention with the advent of 5G wireless communication. Here, we report that 5G (28 GHz) EMR can attenuate the skin pigmentation in murine melanoma cells (B16F10) and a 3D pigmented human epidermis model (Melanoderm™). B16 cells were exposed to 5G (28 GHz) with or without α-MSH for 4 h per day. Interestingly, 5G attenuated α-MSH-induced melanin synthesis. Fontana-Masson staining confirmed that the dendritic formation of α-MSH stimulated B16 cells was diminished by 5G exposure. To confirm the anti-melanogenic effect of 5G EMR, MelanoDerm™ was irradiated with 5G at a power intensity of 10 W/m2 for 4 h a day for 16 days and melanin distribution was detected with Fontana-Masson staining, which supported the anti-melanogenic effect of 5G EMR. Consistently, 5G EMR suppressed α-MSH induced upregulation of melanogenic enzymes; tyrosinase, TRP-1, and TRP-2. Of note, 5G EMR attenuated ROS production stimulated by α-MSH and H2O2, suggesting that 5G EMR may dissipate ROS generation, which is pivotal for the melanin synthesis. Collectively, we demonstrated that 5G EMR can attenuate skin pigmentation by attenuating ROS generation.

8.
Curr Issues Mol Biol ; 44(3): 1407-1416, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35723317

RESUMO

(1) Background: Three isolated compounds from Physalis alkekengi var. franchetii (PAF) have been investigated to possess a variety of biological activities. Their structures were elucidated by spectroscopic analysis (Ultraviolet (UV), High-resolution electrospray mass spectrometry (HR-ESI-Ms), and their anti-inflammatory effects were evaluated in vitro; (2) Methods: To investigate the mechanisms of action of PAF extracts and their isolated compounds, their anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). RAW 264.7 cells were treated with different concentrations of Physalis alkekengi var. franchetii three isolated compounds of PAF for 30 min prior to stimulation with or without LPS for the indicated times. The inflammatory cytokines, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were determined using reverse transcription-polymerase chain (RT-PCR); (3) Results Treatment of RAW 264.7 cells with LPS alone resulted in significant increases in inflammatory cytokine production as compared to the control group (p < 0.001). However, with the treatment of isophysalin B 100 µg/mL, there was a significant decrease in the mRNA expression levels of TNF-α in LPS-stimulated raw 264.7 cells (p < 0.001). With treatment of physalin 1−100 µg/mL, there was a markedly decrease in the mRNA expression levels of TNF-α in LPS stimulated raw 264.7 (p < 0.05). Moreover, TNF-α mRNA (p < 0.05) and IL-1ß mRNA (p < 0.001) mRNA levels were significantly suppressed after treatment with 3',7-dimethylquercetin in LPS stimulated Raw 264.7 cells; (4) Conclusions: These findings suggest that three isolated compounds from can suppress inflammatory responses in LPS stimulated macrophage.

9.
Korean J Radiol ; 22(12): 2073-2081, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34719891

RESUMO

Deep learning-based applications have great potential to enhance the quality of medical services. The power of deep learning depends on open databases and innovation. Radiologists can act as important mediators between deep learning and medicine by simultaneously playing pioneering and gatekeeping roles. The application of deep learning technology in medicine is sometimes restricted by ethical or legal issues, including patient privacy and confidentiality, data ownership, and limitations in patient agreement. In this paper, we present an open platform, MI2RLNet, for sharing source code and various pre-trained weights for models to use in downstream tasks, including education, application, and transfer learning, to encourage deep learning research in radiology. In addition, we describe how to use this open platform in the GitHub environment. Our source code and models may contribute to further deep learning research in radiology, which may facilitate applications in medicine and healthcare, especially in medical imaging, in the near future. All code is available at https://github.com/mi2rl/MI2RLNet.


Assuntos
Aprendizado Profundo , Radiologia , Bases de Dados Factuais , Humanos , Radiologistas , Software
10.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201391

RESUMO

Hyper-activated melanocytes are the major cause of skin hyper-pigmentary disorders, such as freckles and melasma. Increasing efforts have been made to search for materials with depigmenting activity to develop functional cosmetics. As a result, numerous materials have been reported to have depigmenting activity but some of them are known to cause unwanted side effects. Consequently, anti-pigmentary natural compounds without concern of toxicity are in great demand. Virtually all sorts of natural sources have been investigated to find anti-pigmentary natural compounds. This review summarizes recently reported anti-pigmentary natural compounds and their mode of action from the ocean, plants, and bacteria.


Assuntos
Produtos Biológicos/farmacologia , Fitoterapia/métodos , Transtornos da Pigmentação/tratamento farmacológico , Extratos Vegetais/farmacologia , Pigmentação da Pele/efeitos dos fármacos , Humanos
11.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066270

RESUMO

With the rapid growth of the wireless communication industry, humans are extensively exposed to electromagnetic fields (EMF) comprised of radiofrequency (RF). The skin is considered the primary target of EMFs given its outermost location. Recent evidence suggests that extremely low frequency (ELF)-EMF can improve the efficacy of DNA repair in human cell-lines. However, the effects of EMF-RF on DNA damage remain unknown. Here, we investigated the impact of EMF-long term evolution (LTE, 1.762 GHz, 8 W/kg) irradiation on DNA double-strand break (DSB) using the murine melanoma cell line B16 and the human keratinocyte cell line HaCaT. EMF-LTE exposure alone did not affect cell viability or induce apoptosis or necrosis. In addition, DNA DSB damage, as determined by the neutral comet assay, was not induced by EMF-LTE irradiation. Of note, EMF-LTE exposure can attenuate the DNA DSB damage induced by physical and chemical DNA damaging agents (such as ionizing radiation (IR, 10 Gy) in HaCaT and B16 cells and bleomycin (BLM, 3 µM) in HaCaT cells and a human melanoma cell line MNT-1), suggesting that EMF-LTE promotes the repair of DNA DSB damage. The protective effect of EMF-LTE against DNA damage was further confirmed by attenuation of the DNA damage marker γ-H2AX after exposure to EMF-LTE in HaCaT and B16 cells. Most importantly, irradiation of EMF-LTE (1.76 GHz, 6 W/kg, 8 h/day) on mice in vivo for 4 weeks reduced the γ-H2AX level in the skin tissue, further supporting the protective effects of EMF-LTE against DNA DSB damage. Furthermore, p53, the master tumor-suppressor gene, was commonly upregulated by EMF-LTE irradiation in B16 and HaCaT cells. This finding suggests that p53 plays a role in the protective effect of EMF-LTE against DNA DSBs. Collectively, these results demonstrated that EMF-LTE might have a protective effect against DNA DSB damage in the skin, although further studies are necessary to understand its impact on human health.


Assuntos
Quebras de DNA de Cadeia Dupla , Campos Eletromagnéticos , Queratinócitos/efeitos da radiação , Melanoma/prevenção & controle , Substâncias Protetoras , Radiação Ionizante , Ondas de Rádio , Animais , Apoptose , Sobrevivência Celular , Reparo do DNA , Humanos , Técnicas In Vitro , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Melanoma/etiologia , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL
12.
J Nanosci Nanotechnol ; 21(7): 3819-3823, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33715698

RESUMO

This study focuses on analyzing the effects of the SiO2/Al2O3 ratio of a support on the physico-chemical properties of bead-type CoMo/HZSM-5 catalysts and on the catalytic performance during the hydrocracking reaction of PFO. CoMo/HZSM-5 catalysts were prepared by an incipient wetness method. Subsequently, binder-added catalysts were molded into the bead type catalysts. The N2 adsorption-dersorption results clearly indicate that the nanoporous structure was well developed in the bead-type CoMo/HZSM-5 catalyst. The CoMo/HZSM-5(30) catalyst not only possessed the highest number of acid sites but also showed the highest ratio of strong acid to weak acid sites. Moreover, the Lewis acid/Brönsted acid site ratio is highest with the CoMo/HZSM-5(30) catalysts. A hydrocracking reaction of PFO over the bead-type CoMo/HZSM-5 catalysts was conducted at 400 °C and under 40 atm in a fixed-bed reactor. The bead-type CoMo/HZSM-5(30) catalyst showed the highest BTXE yield with a sum of BTXE outcome of 43.0% in the catalytic cracking reaction of PFO, which is attributed to the synergistic combination of suitable acidity and hierarchical porosity.

13.
J Ginseng Res ; 45(1): 98-107, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33437161

RESUMO

BACKGROUND: Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Panax ginseng Meyer. METHODS: An endophytic fungus, Penicillium sp. SNF123 was isolated from the root of P. ginseng, from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm. RESULTS: Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT-PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue. CONCLUSION: This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of P. ginseng, can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with P. ginseng for cosmetic ingredients.

14.
Int J Mol Sci ; 22(1)2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33375304

RESUMO

With the rapid growth of wireless communication devices, the influences of electromagnetic fields (EMF) on human health are gathering increasing attention. Since the skin is the largest organ of the body and is located at the outermost layer, it is considered a major target for the health effects of EMF. Skin pigmentation represents one of the most frequent symptoms caused by various non-ionizing radiations, including ultraviolet radiation, blue light, infrared, and extremely low frequency (ELF). Here, we investigated the effects of EMFs with long-term evolution (LTE, 1.762 GHz) and 5G (28 GHz) bandwidth on skin pigmentation in vitro. Murine and Human melanoma cells (B16F10 and MNT-1) were exposed to either LTE or 5G for 4 h per day, which is considered the upper bound of average smartphone use time. It was shown that neither LTE nor 5G exposure induced significant effects on cell viability or pigmentation. The dendrites of MNT-1 were neither lengthened nor regressed after EMF exposure. Skin pigmentation effects of EMFs were further examined in the human keratinocyte cell line (MNT-1-HaCaT) co-culture system, which confirmed the absence of significant hyper-pigmentation effects of LTE and 5G EMFs. Lastly, MelanoDerm™, a 3D pigmented human epidermis model, was irradiated with LTE (1.762 GHz) or 5G (28 GHz), and image analysis and special staining were performed. No changes in the brightness of MelanoDerm™ tissues were observed in LTE- or 5G-exposed tissues, except for only minimal changes in the size of melanocytes. Collectively, these results imply that exposure to LTE and 5G EMFs may not affect melanin synthesis or skin pigmentation under normal smartphone use condition.


Assuntos
Campos Eletromagnéticos , Queratinócitos/efeitos da radiação , Melanócitos/efeitos da radiação , Ondas de Rádio , Pigmentação da Pele/efeitos da radiação , Animais , Proliferação de Células , Humanos , Técnicas In Vitro , Queratinócitos/citologia , Queratinócitos/metabolismo , Melaninas/metabolismo , Melanócitos/citologia , Melanócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
15.
Mol Cancer Ther ; 19(3): 858-867, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31941722

RESUMO

Prodrugs are harmless until activated by a bacterial or viral gene product; they constitute the basis of gene-delivered prodrug therapies called GDEPT, which can kill tumors without major side effects. Previously, we utilized the prodrug CNOB (C16H7CIN2O4; not clinically tested) and enzyme HChrR6 in GDEPT to generate the drug MCHB (C16H9CIN2O2) in tumors. Extracellular vesicles (EVs) were used for directed gene delivery and HChrR6 mRNA as gene. Here, the clinical transfer of this approach is enhanced by: (i) use of CB1954 (tretazicar) for which safe human dose is established; HChrR6 can activate this prodrug. (ii) EVs delivered in vitro transcribed (IVT) HChrR6 mRNA, eliminating the potentially harmful plasmid transfection of EV producer cells we utilized previously; this has not been done before. IVT mRNA loading of EVs required several steps. Naked mRNA being unstable, we ensured its prodrug activating functionality at each step. This was not possible using tretazicar itself; we relied instead on HChrR6's ability to convert CNOB into MCHB, whose fluorescence is easily visualizable. HChrR6 mRNA-translated product's ability to generate fluorescence from CNOB vicariously indicated its competence for tretazicar activation. (iii) Systemic IVT mRNA-loaded EVs displaying an anti-HER2 single-chain variable fragment ("IVT EXO-DEPTs") and tretazicar caused growth arrest of human HER2+ breast cancer xenografts in athymic mice. As this occurred without injury to other tissues, absence of off-target mRNA delivery is strongly indicated. Many cancer sites are not amenable for direct gene injection, but current GDEPTs require this. In circumventing this need, a major advance in GDEPT applicability has been accomplished.


Assuntos
Proteínas de Bactérias/genética , Neoplasias da Mama/terapia , Vesículas Extracelulares/metabolismo , Técnicas de Transferência de Genes , Terapia Genética , Pró-Fármacos/farmacologia , RNA Mensageiro/administração & dosagem , Animais , Apoptose , Proteínas de Bactérias/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células , Vesículas Extracelulares/genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor ErbB-2/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
J Dermatol Sci ; 97(2): 101-108, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31892452

RESUMO

BACKGROUND: Rab27a, Mlph, and MyoVa form a tripartite complex and relate to melanosome distribution. Melanophilin (Mlph) acts as a linker protein between Rab27a and MyoVa. The biological activity and function of 16-kauren on the expression of Mlph has not yet been studied. OBJECTIVE: We examined the effect of 16-kauren on melanosome transport and skin pigmentation. METHODS: Murine Melan-a melanocytes and SP-1 keratinocytes were used for in vitro analysis. Western blot analysis, quantitative real-time polymerase chain reaction, luciferase assay and immunohistochemical staining in 3D pigmented human skin model were performed. RESULTS: We found that 16-kauren inhibits melanosome transport in Melan-a melanocytes without affecting melanin synthesis. Treatment with 16-kauren reduced melanophilin (Mlph), a key protein in melanosome transport, in Melan-a melanocytes, at both the protein and mRNA levels while it did not affect the expression of Rab27a and MyoVa, the other two key proteins for melanosome transport. Notably, the expression of melanogenic proteins, including tyrosinase, trp1, trp2, and MITF, was not affected by 16-kauren. However, 16-kauren attenuated melanosome distribution in co-culture of Melan-a melanocytes and SP-1 keratinocytes as well as in Melan-a monolayer culture. In further confirmation of the depigmenting effects of 16-kauren on Melanoderm™, a 3D pigmented human skin model, treatment with 16-kauren for 12 days increased the brightness of the tissue as determined by lightness value and reduced the distribution of melanosomes as shown in histological examination. CONCLUSION: These results demonstrated that 16-kauren is a selective modulator of a melangenic target, Mlph expression, and can be employed as a new depigmenting strategy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Diterpenos do Tipo Caurano/farmacologia , Melanócitos/efeitos dos fármacos , Melanossomas/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos , Animais , Asteraceae/química , Linhagem Celular Tumoral , Técnicas de Cocultura , Regulação para Baixo/efeitos dos fármacos , Queratinócitos , Antígeno MART-1/genética , Antígeno MART-1/metabolismo , Melaninas/biossíntese , Melanócitos/citologia , Melanócitos/metabolismo , Melanossomas/metabolismo , Camundongos
17.
Biomed Res Int ; 2019: 5705232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612144

RESUMO

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.


Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Panax/química , Serotonina/metabolismo , Animais , Antidepressivos/química , Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Depressão/genética , Depressão/fisiopatologia , Transtorno Depressivo/genética , Transtorno Depressivo/fisiopatologia , Modelos Animais de Doenças , Elevação dos Membros Posteriores/métodos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Ratos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Natação
18.
Biomed Res Int ; 2019: 5815604, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380432

RESUMO

BACKGROUND: Sasa quelpaertensis Nakai extract (SQE) or dwarf bamboo has been extensively investigated for its antioxidant and anti-inflammatory effects; however, no previous study assessed its effect as an antidepressant agent. Therefore, this study was designed to examine the effect of oral SQE administration in ameliorating menopausal depressive symptoms and to evaluate its mechanisms in ovariectomized rats with repeated stress. METHODS: All experimental groups except normal group underwent ovariectomy and then immobilization for 14 consecutive days. During these 2 weeks, two rat groups received SQE (100 and 300 mg/kg orally) and their cutaneous body temperature was measured. The tail suspension test (TST) and forced swim test (FST) were performed in order to evaluate depression-like behavior. Additionally, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were carried out to evaluate the central monoaminergic neurotransmitter levels and activity. RESULTS: Oral SQE (100 mg/kg) administration had reduced immobility time in TST and FST. Additionally, the SQE 100 and 300 mg/kg administration had decreased the cutaneous body temperature in the rats compared to those without treatment. In ELISA analysis, the SQE 100 group expressed elevated levels of serotonin and dopamine in the hypothalamus, prefrontal cortex, and hippocampus. Antityrosine hydroxylase (anti-TH) antibodies showed a tremendous increase in the density of TH positive cells in the locus coeruleus (LC) region of the SQE 100 group. Likewise, the SQE 100 elevated the number of tryptophan hydroxylase (TPH) and protein kinase C (PKC) immunoreactive cell counts and density in the hypothalamic region. CONCLUSION: These results suggested that the oral SQE administration induced the antidepressant-like effect in the ovariectomized rats with repeated stress via upregulating the levels of serotonin and dopamine through enhancing the expression of TH, TPH, and PKC in many brain areas.


Assuntos
Antidepressivos/química , Depressão/tratamento farmacológico , Extratos Vegetais/química , Sasa/química , Animais , Antidepressivos/farmacologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Elevação dos Membros Posteriores/métodos , Humanos , Ovariectomia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos , Natação
19.
J Infect Chemother ; 25(11): 909-912, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31239194

RESUMO

NDM-4-producing Klebsiella pneumoniae (NDM-4-KP) was detected from the patient who had previously been injured and hospitalized for 5 days in Vietnam in a neurosurgical intensive care unit (NSICU) of a Korean tertiary-care hospital in December 2016. He admitted with ventilator-associated pneumonia and NDM-4-KP was isolated, which was subsequently detected in two other NSICU patients. All NDM-4-KP isolates from patient and environmental surveillance cultures were sequence type 11. Colonization of three patients persisted for 5-12 months. Dedicated environmental cleaning was added to single room isolation of NDM-4-KP patients and universal chlorhexidine bathing, and no further transmission of NDM-4-KP occurred. This is the first report of NDM-4-KP in a Korean hospital where a patient with a history of hospitalization abroad was the index case initiating an outbreak involving three patients. The spread of newly introduced CPE was controlled using a bundle of infection control.


Assuntos
Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/metabolismo , beta-Lactamases/metabolismo , Adulto , Proteínas de Bactérias/metabolismo , Humanos , Controle de Infecções/métodos , Masculino , República da Coreia , Vietnã
20.
Uisahak ; 28(1): 89-138, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31092805

RESUMO

This paper examines WHO's involvement in South Korea within the context of the changing organization of public health infrastructure in Korea during the years spanning from the end of the Japanese occupation, through the periods of American military occupation and the Korean War, and to the early years of the Park Chung Hee regime in the early 1960s, in order to demonstrate how tuberculosis came to be addressed as a public health problem. WHO launched several survey missions and relief efforts before and during the Korean War and subsequently became deeply involved in shaping government policy for public health through a number of technical assistance programs, including a program for tuberculosis control in the early 1960s. This paper argues that the principal concern for WHO was to start rebuilding the public health infrastructure beyond simply abolishing the remnants of colonial practices or showcasing the superiority of American practices vis-à-vis those practiced under a Communist rule. WHO consistently sought to address infrastructural problems by strengthening the government's role by linking the central and regional health units, and this was especially visible in its tuberculosis program, where it attempted to take back the responsibilities and functions previously assumed by voluntary organizations like the Korea National Tuberculosis Administration (KNTA). This interest in public health infrastructure was fueled by WHO's discovery of a cost-effective, drug-based, and communityoriented horizontal approach to tuberculosis control, with a hope that these practices would replace the traditional, costly, disease-specific, and seclusion-oriented vertical approach that relied on sanatoria. These policy imperatives were met with the unanticipated regime change from a civilian to a military government in 1961, which created an environment favorable for the expansion of the public health network. Technology and politics were intricately intertwined in the emergence of a new infrastructure for public health in Korea, as this case of tuberculosis control illustrates.


Assuntos
Controle de Doenças Transmissíveis/história , Saúde Pública/história , Tuberculose/prevenção & controle , Organização Mundial da Saúde , Controle de Doenças Transmissíveis/métodos , História do Século XX , Saúde Pública/instrumentação , Saúde Pública/métodos , República da Coreia
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