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Shikonin, an herbal naphthoquinone, demonstrates a broad spectrum of pharmacological properties. Owing to increasingly adverse environmental conditions, human skin is vulnerable to harmful influences from dust particles. This study explored the antioxidant capabilities of shikonin and its ability to protect human keratinocytes from oxidative stress induced by fine particulate matter (PM2.5). We found that shikonin at a concentration of 3 µM was nontoxic to human keratinocytes and effectively scavenged reactive oxygen species (ROS) while increasing the production of reduced glutathione (GSH). Furthermore, shikonin enhanced GSH level by upregulating glutamate-cysteine ligase catalytic subunit and glutathione synthetase mediated by nuclear factor-erythroid 2-related factor. Shikonin reduced ROS levels induced by PM2.5, leading to recovering PM2.5-impaired cellular biomolecules and cell viability. Shikonin restored the GSH level in PM2.5-exposed keratinocytes via enhancing the expression of GSH-synthesizing enzymes. Notably, buthionine sulphoximine, an inhibitor of GSH synthesis, diminished effect of shikonin against PM2.5-induced cell damage, confirming the role of GSH in shikonin-induced cytoprotection. Collectively, these findings indicated that shikonin could provide substantial cytoprotection against the adverse effects of PM2.5 through direct ROS scavenging and modulation of cellular antioxidant system.
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Runt domain transcription factor 3 (RUNX3) suppresses many different cancer types and is disabled by mutations, epigenetic repression, or cytoplasmic mislocalization. In this study, we investigated whether oxidative stress is associated with RUNX3 accumulation from the nucleus to the cytoplasm in terms of histone modification. Oxidative stress elevated histone deacetylase (HDAC) level and lowered that of histone acetyltransferase. In addition, oxidative stress decreased the expression of mixed lineage leukemia (MLL), a histone methyltransferase, but increased the expression of euchromatic histone-lysine N-methyltransferase 2 (EHMT2/G9a), which is also a histone methyltransferase. Moreover, oxidative stress-induced RUNX3 phosphorylation, Src activation, and Jun activation domain-binding protein 1 (JAB1) expression were inhibited by knockdown of HDAC and G9a, restoring the nuclear localization of RUNX3 under oxidative stress. Cytoplasmic RUNX3 localization was followed by oxidative stress-induced histone modification, activated Src along with RUNX3 phosphorylation, and induction of JAB1, resulting in RUNX3 inactivation.
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SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.
Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.
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Animales , Ratones , Piperidonas/administración & dosificación , Pirimidinas/administración & dosificación , Té , Extractos Vegetales/administración & dosificación , Tacrolimus/toxicidad , Enfermedades Renales/tratamiento farmacológico , Piperidonas/farmacología , Pirimidinas/farmacología , Extractos Vegetales/farmacología , Sustancias Protectoras , Sinergismo Farmacológico , Inmunosupresores/toxicidad , Riñón/efectos de los fármacos , Enfermedades Renales/inducido químicamenteRESUMEN
BACKGROUND/AIM: Melanoma is a prevalent malignant tumor that arises from melanocytes. The treatment of malignant melanoma has become challenging due to the development of drug resistance. It is, therefore, imperative to identify novel therapeutic drug candidates for controlling malignant melanoma. Naringenin is a flavonoid abundant in oranges and other citrus fruits and recognized for its numerous medicinal benefits. The objective of the study was to assess the anti-carcinogenic potential of naringenin by evaluating its ability to regulate the cellular production of reactive oxygen species (ROS) and its effect on mitochondrial function and apoptosis in melanoma cells. MATERIALS AND METHODS: Cell viability, intracellular ROS levels, cell apoptosis, and mitochondrial functions were evaluated. RESULTS: Naringenin decreased melanoma cell viability and triggered generation of ROS, leading to cell apoptosis. In addition, it stimulated mitochondrial damage in melanoma cells by elevating the levels of Ca2+ and ROS in the mitochondria and decreasing cellular ATP. Naringenin stimulated the expression of proapoptotic proteins, including phospho p53, B-cell lymphoma-2 (Bcl-2)-associated X protein, cleaved caspase-3, and cleaved caspase-9, in melanoma cells in a time-dependent manner. Furthermore, it reduced the expression of the anti-apoptotic protein Bcl-2. Naringenin triggered cell apoptosis by phosphorylating c-Jun N-terminal kinase and stimulating cellular autophagy. CONCLUSION: Naringenin caused oxidative stress and mitochondrial damage, and activated autophagy in melanoma cells, leading to cell apoptosis. These findings indicate the potential of naringenin as a new therapeutic candidate for melanoma.
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Flavanonas , Melanoma , Humanos , Especies Reactivas de Oxígeno/metabolismo , Melanoma/patología , Línea Celular Tumoral , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Potencial de la Membrana MitocondrialRESUMEN
SUMMARY: To evaluate the anti-cancer effects of yeast extract on resistant cells, autophagy and necroptosis were investigated in 5-fluorouracil (5-FU)-resistant colorectal cancer cells. Further underlying characteristics on drug resistance were evaluated, focused on ERK-RSK-ABCG2 linkage. SNU-C5 and 5-FU resistant SNU-C5 (SNU-C5/5-FUR) colorectal cancer cells were adopted for cell viability assay and Western blotting to examine the anti-cancer effects of yeast extract. Yeast extract induced autophagy in SNU-C5 cells with increased Atg7, Atg12-5 complex, Atg16L1, and LC3 activation (LC3-II/LC3-I), but little effects in SNU-C5/5-FUR cells with increased Atg12-5 complex and Atg16L1. Both colorectal cancer cells did not show necroptosis after yeast extract treatment. Based on increased ABCG2 and RSK expression after yeast extract treatment, drug resistance mechanisms were further evaluated. As compared to wild type, SNU-C5/5-FUR cells showed more ABCG2 expression, less RSK expression, and less phosphorylation of ERK. ABCG2 inhibitor, Ko143, treatment induces following changes: 1) more sensitivity at 500 mM 5-FU, 2) augmented proliferation, and 3) less phosphorylation of ERK. These results suggest that protective autophagy in SNU-C5/5-FUR cells with increased ABCG2 expression might be candidate mechanisms for drug resistance. As the ERK responses were different from each stimulus, the feasible mechanisms among ERK-RSK-ABCG2 should be further investigated in 5-FU-resistant CRC cells.
Para evaluar los efectos anticancerígenos del extracto de levadura en células resistentes, se investigaron la autofagia y la necroptosis en células de cáncer colorrectal resistentes al 5-fluorouracilo (5-FU). Además se evaluaron otras características subyacentes de la resistencia a los medicamentos centrándose en el enlace ERK-RSK-ABCG2. Se usaron células de cáncer colorrectal SNU-C5 (SNU-C5/5-FUR) resistentes a SNU-C5 y 5- FU para el ensayo de viabilidad celular y la transferencia Western para examinar los efectos anticancerígenos del extracto de levadura. El extracto de levadura indujo autofagia en células SNU-C5 con mayor activación de Atg7, complejo Atg12-5, Atg16L1 y LC3 (LC3-II/LC3-I), pero pocos efectos en células SNU-C5/5-FUR con aumento de Atg12-5 complejo y Atg16L1. Ambas células de cáncer colorrectal no mostraron necroptosis después del tratamiento con extracto de levadura. Se evaluaron los mecanismos de resistencia a los medicamentos. en base al aumento de la expresión de ABCG2 y RSK después del tratamiento con extracto de levadura.En comparación con las de tipo salvaje, las células SNU-C5/5-FUR mostraron más expresión de ABCG2, menos expresión de RSK y menos fosforilación de ERK. El tratamiento con inhibidor de ABCG2, Ko143, induce los siguientes cambios: 1) más sensibilidad a 5-FU 500 mM, 2) proliferación aumentada y 3) menos fosforilación de ERK. Estos resultados sugieren que la autofagia protectora en células SNU-C5/5-FUR con mayor expresión de ABCG2 podría ser un mecanismo candidato para la resistencia a los medicamentos. Como las respuestas de ERK fueron diferentes de cada estímulo, los mecanismos factibles entre ERK-RSK- ABCG2 deberían investigarse más a fondo en células CCR resistentes a 5-FU.
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Autofagia , Extractos Vegetales/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Antineoplásicos/farmacología , Levaduras , Células Tumorales Cultivadas , Supervivencia Celular/efectos de los fármacos , Western Blotting , Resistencia a Antineoplásicos , Proteínas Quinasas S6 Ribosómicas 90-kDa , Electroforesis , Fluorouracilo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , NecroptosisRESUMEN
Cancer stem cells (CSCs) are known to be a major cause of metastasis, resistance and recurrence. Spheroid formation is one of the methods used to recruit CSCs utilizing an anchorage-independent environment in vitro. It was aimed to investigate the availability of spheroid formation culture methods in the research field of CSCs and resistance using 5-fluorouracil (5-FU)-resistant colorectal cancer cells. The wild type SNU-C5 and 5-FU-resistant SNU-C5 (SNU-C5/5-FUR) cells were cultured as usual (monolayer), and in 3-dimensional non-adhesive environments supplemented with fetal bovine serum (FBS) or growth factors, respectively. The characteristics of the spheroids were evaluated by morphometry, cell viability assay, western blotting, immunocytochemistry and enzyme-linked immunosorbent assay. Spheroid formation was induced in an environment supplemented with FBS, while SNU-C5/5-FUR cells only formed spheres in media supplemented with GFs. Sphere-formed cells showed slower cell proliferation than cells from monolayer, which coincided with an increased level of p21 and a decreased level of ß-catenin. Markers for CSCs and drug resistance were not significantly changed after spheroid formation. Sphere-formed cells showed significantly increased levels of soluble E-cadherin, particularly in the environment supplemented with FBS. These results suggested that spheroid formation may be related to soluble E-cadherin, but is not related to CSCs or resistance markers.
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Benzimidazole anthelmintic agents have been recently repurposed to overcome cancers resistant to conventional therapies. To evaluate the anti-cancer effects of benzimidazole on resistant cells, various cell death pathways were investigated in 5-fluorouracil-resistant colorectal cancer cells. The viability of wild-type and 5-fluorouracil-resistant SNU-C5 colorectal cancer cells was assayed, followed by Western blotting. Flow cytometry assays for cell death and cell cycle was also performed to analyze the anti-cancer effects of benzimidazole. When compared with albendazole, fenbendazole showed higher susceptibility to 5-fluorouracil-resistant SNU-C5 cells and was used in subsequent experiments. Flow cytometry revealed that fenbendazole significantly induces apoptosis as well as cell cycle arrest at G2/M phase on both cells. When compared with wild-type SNU-C5 cells, 5-fluorouracil-resistant SNU-C5 cells showed reduced autophagy, increased ferroptosis and ferroptosis-augmented apoptosis, and less activation of caspase-8 and p53. These results suggest that fenbendazole may be a potential alternative treatment in 5-fluorouracil-resistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.
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The Hsp70-binding protein 1 (HspBP1) belongs to a family of co-chaperones that regulate Hsp70 activity and whose biological significance is not well understood. In the present study, we show that when HspBP1 is either knocked down or overexpressed in BRCA1-proficient breast cancer cells, there were profound changes in tumorigenesis, including anchorage-independent cell growth in vitro and in tumor formation in xenograft models. However, HspBP1 did not affect tumorigenic properties in BRCA1-deficient breast cancer cells. The mechanisms underlying HspBP1-induced tumor suppression were found to include interactions with BRCA1 and promotion of BRCA1-mediated homologous recombination DNA repair, suggesting that HspBP1 contributes to the suppression of breast cancer by regulating BRCA1 function and thereby maintaining genomic stability. Interestingly, independent of BRCA1 status, HspBP1 facilitates cell survival in response to ionizing radiation (IR) by interfering with the association of Hsp70 and apoptotic protease-activating factor-1. These findings suggest that decreased HspBP1 expression, a common occurrence in high-grade and metastatic breast cancers, leads to genomic instability and enables resistance to IR treatment.
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Neoplasias de la Mama , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis/genética , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Reparación del ADN , Femenino , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Reparación del ADN por RecombinaciónRESUMEN
The amyloid hypothesis has been considered a major explanation of the pathogenesis of Alzheimer disease. However, failure of phase III clinical trials with anti-amyloid-beta monoclonal antibodies reveals the need for other therapeutic approaches to treat Alzheimer disease. Compared to its relatively short history, optogenetics has developed considerably. The expression of microbial opsins in cells using genetic engineering allows specific control of cell signals or molecules. The application of optogenetics to Alzheimer disease research or clinical approaches is increasing. When applied with gamma entrainment, optogenetic neuromodulation can improve Alzheimer disease symptoms. Although safety problems exist with optogenetics such as the use of viral vectors, this technique has great potential for use in Alzheimer disease. In this paper, we review the historical applications of optogenetic neuromodulation with gamma entrainment to investigate the mechanisms involved in Alzheimer disease and potential therapeutic strategies.
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SUMMARY: Fetal-type variant of the posterior cerebral artery is a relatively common variant of the cerebral arterial circle (circle of Willis), but concurrent cerebral pathologies have not been well reported. We describe a case of fetal-type variant of the posterior cerebral artery and concurrent bilateral cerebral infarctions in the territories of the middle cerebral artery in a 78-year-old Korean male cadaver. Fetal-type variant of the posterior cerebral artery was found the right cerebral arterial circle, arose from the internal carotid artery with larger diameter than the pre-communicating segment from the basilar artery. Histopathological examination revealed that left supramarginal gyrus and right infraparietal lobule showed characteristic cerebral infarctions with chronological changes, respectively. Knowledge on the variation in the posterior cerebral artery combined with clinical features including cerebral infarction plays a pivotal role to anatomists and clinicians.
RESUMEN: La variante de tipo fetal de la arteria cerebral posterior es una variante relativamente común del círculo arterial cerebral (polígono de Willis) de arterial cerebral, pero las patologías cerebrales concurrentes no han sido bien informadas. Describimos un caso de variante de tipo fetal de la arteria cerebral posterior e infartos cerebrales bilaterales concurrentes en los territorios de la arteria cerebral media en un cadáver masculino coreano de 78 años. La variante de tipo fetal de la arteria cerebral posterior se encontró en la parte de derecha del círculo arterial cerebral, surgido de la arteria carótida interna con mayor diámetro que el segmento precomunicante de la arteria basilar. El examen histopatológico reveló que el giro supramarginal izquierdo y el lóbulo infraparietal derecho mostraban infartos cerebrales característicos con cambios cronológicos, respectivamente. El conocimiento sobre la variación en la arteria cerebral posterior combinado con las características clínicas, incluido el infarto cerebral es fundamental para los anatomistas y los médicos.
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Humanos , Masculino , Anciano , Infarto Cerebral/etiología , Infarto Cerebral/patología , Círculo Arterial Cerebral/anomalías , Arteria Cerebral Posterior/anomalías , CadáverRESUMEN
Objective: To investigate a feasible candidate for an appropriate cell line for the orthotopic renal cell carcinoma (RCC) model. Methods: Normal human proximal tubule cells (HK-2) and RCC cells were used for MTT assay, Western blotting, sphere-forming assay, and orthotopic injection of BALB/c-nude mice. Immunohistochemistry was adopted in tissue arrays and orthotopic tumors. Results: Primary RCC cells showed resistance to a GPX4 inhibitor compared to HK-2 and to metastatic RCC cells, Caki-1. Caki-2 and SNU-333 cells showed resistance to ferroptosis via increased GPX4 and FTH1, respectively. RCC cells showed increased αSMA, in which Caki-2 and SNU-333 cells exhibited different epithelial-mesenchymal transition and cancer stem cell markers. Caki-1 and SNU-333 cells formed spheres in vitro and orthotopic tumor masses in vivo. The injected SNU-333 tumor only showed high intensities of CD10 and PAX8, markers of renal origin. Conclusion: SNU-333 cell line exhibited resistance via iron metabolism and stemness, and had tumor-initiating capacities in vitro and in vivo. These results suggest that among the cells tested, SNU-333 cells were the most promising for the establishment of an orthotopic RCC model for further researches.
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Carcinoma de Células Renales/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Neoplasias Renales/patología , Animales , Biomarcadores de Tumor , Carcinoma de Células Renales/tratamiento farmacológico , Supervivencia Celular , Ferroptosis/genética , Humanos , Inmunohistoquímica , Neoplasias Renales/tratamiento farmacológico , Masculino , Ratones , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonica A. Berger, also known as Wa-song in Korea, has traditionally been used as a folk medicine, but the potential anti-cancer effects of aqueous extract of Orostachys japonica (OJe) have not yet been thoroughly investigated. AIM OF THE STUDY: To evaluate the anti-cancer effects of OJe, its possible mechanisms of action were investigated in 5-fluorouracil (5-FU) resistant SNU-C5/5-FUR colorectal cancer cells. MATERIALS AND METHODS: The functional compounds of OJe were identified with high performance liquid chromatography. The anti-cancer effects of OJe in SNU-C5/5-FUR cells were investigated by a cell viability assays, flow cytometry analysis, and a subcutaneous xenograft model employing BALB/c-nude mice. Possible signalling pathways were assayed with Western blotting. RESULTS: OJe (250 µg/ml) showed anti-cancer effects in SNU-C5/5-FUR cells, that were mediated via apoptosis as well as cell cycle arrest at the G0/G1 phase. Gallic acid and (-)-epicatechin, the major functional components of OJe, induced cell cycle arrest. OJe treatment (250 mg/kg, p.o.) produced a significant anti-proliferative effect in the xenograft model via decreased ß-catenin/GSK3ß and increased p27 expression. OJe treatment significantly activated ERK and p38 both in vitro and in vivo. CONCLUSIONS: These results suggest that OJe has anti-proliferative effects on 5-FU-resistant colorectal cancer cells via regulation of MAPK signalling pathways.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Crassulaceae/química , Fluorouracilo/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Humanos , Ratones , Ratones Desnudos , Extractos Vegetales/química , Distribución Aleatoria , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The abalone aquaculture industry in South Korea has grown rapidly since the 2000s. In this study, we investigated the sedimentary pollution at four major abalone farms responsible for ~60% of all South Korean abalone produced. We also surveyed the current statuses of cage facilities, abalone mass mortality, and current velocities within and outside farm cages. The concentrations of total organic carbon in the study area were 7.92 ± 2.09 mg g-1, indicating a mild level of sedimentary pollution. We observed higher mortality rates in rectangular-shaped shelter cages than in triangular shelters. With increases in the number and size of abalone farming facilities, current velocities inside the cages declined by an average of 45% relative to those outside the cages, leading to poor habitat conditions for farmed abalone. Our results provide insights into the current status of the benthic environments and major causes of mass mortality in the abalone farms of South Korea.
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Gastrópodos , Hidrodinámica , Animales , Acuicultura , Granjas , República de CoreaRESUMEN
PURPOSE: From the evolutionary myology, the additional tendon of the extensor hallucis longus (EHL) muscle represents the sample of a new acquisition. We aimed to determine whether the insertion pattern of the EHL muscle differs in Koreans according to demographic populations, especially between Jeju islanders and the Korean Peninsula inhabitants. METHODS: We used 69 Korean cadavers and classified the tendinous insertion of the EHL muscle as Pattern I, Pattern II, and Pattern III. The ratio of each Pattern in adult cadaveric samples was compared between demographic populations. RESULTS: The proportion of Pattern I, Pattern II, and Pattern III of the EHL muscle was 30.43, 63.77, and 5.80%, respectively, further divided into 18.00 vs. 36.04%, 72.00 vs. 60.47%, 10.00 vs. 3.49% in Jeju islanders vs. peninsular Koreans. There was a considerable difference in the insertion patterns of the EHL muscle in each regional group (p = 0.032), but not in each gender, age, and body sides of lower limbs. CONCLUSION: The findings of this study indicate that there was a higher incidence of the accessory tendon(s) of the EHL muscle in Koreans and the distributed insertion patterns of the EHL muscle was significantly different between Jeju islanders and peninsular Koreans.
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Variación Anatómica , Hallux/anatomía & histología , Músculo Esquelético/anatomía & histología , Tendones/anatomía & histología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cadáver , Disección , Femenino , Geografía , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Adulto JovenRESUMEN
The microbiome has recently become a key interest for cancer research. Anti-tumor effects of reinforced clostridium media (RCM) were investigated for all ingredients of RCM, which showed that yeast extract could be a candidate for this phenomenon. MTT assay, cell counting, cell death analysis, cell cycle analysis, and Western blotting were done on colorectal cancer cells with or without 5-fluorouracil resistance (SNU-C5 and SNU-C5/5-FUR). Yeast extract treatment showed dose- and time-dependent anti-tumor effects on SNU-C5 and SNU-C5/5-FUR. Anti-tumor effects were related to G0/G1 phase arrest with increased p21, reactive oxygen species scavenger activities, and decreased free iron. Yeast extract treatment significantly increased apoptosis, which was effectively blocked with the PARP inhibitor. Anti-tumor effects of yeast extract were correlated with the increased phosphorylation of p38 and p53. These results suggest that yeast extract might inhibit the proliferation of colorectal cancer cells via the activation of the p38-p53-p21 cascade.
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Antineoplásicos/farmacología , Apoptosis , Puntos de Control del Ciclo Celular , Neoplasias Colorrectales/tratamiento farmacológico , Mezclas Complejas/farmacología , Levaduras/química , Antimetabolitos Antineoplásicos/farmacología , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Fluorouracilo/farmacología , Humanos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Levaduras/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Adrenal cystic lymphangiomas are extremely rare entities that are often identified incidentally, with less than 60 cases reported to date. We found a protruding ovoid mass consisting of a multiloculated cystic lesion within right adrenal gland in the cadaver of a 75-year-old Korean man. The epithelial cells lining the adrenal cyst were diffusely positive for cluster of differentiation 31 and podoplanin, and negative for pan-cytokeratin. The histopathological diagnosis confirmed a cystic lymphangioma arising from the adrenal gland. Post-mortem findings of the present case are discussed based on the clinicopathological features of adrenal cystic lymphangiomas.
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The microbiome has recently attracted research interest in a variety of subjects, including cancer. In the present study, it was determined that reinforced clostridium media (RCM) for microbiome culture, exerts antitumor effects on renal cell carcinoma cells when compared to the microbiome 'X'. The antitumor effects of RCM were investigated for all ingredients of RCM, and the results revealed that yeast extract could be a candidate for the ingredient driving this phenomenon. Further experiments including MTT assay, cell counting, cell death analysis, cell cycle analysis and western blotting were conducted with yeast extract on renal cell carcinoma cells (Caki1 and Caki2) and normal human proximal tubular cells (HK2). As a result, yeast extract exhibited dosedependent antitumor effects on Caki1 and Caki2, but only slight effects on HK2. In addition, yeast extract only exhibited slight effects on necrosis, autophagy, or apoptosis of Caki1 and Caki2. Yeast extract produced cell cycle arrest with an increased G0/G1 fraction and a decreased S fraction, and this was considered to be related to the decreased cyclin D1. Although yeast extract treatment increased antioxidant activities, the antitumor effects of yeast extract were also related to iron metabolism, based on the decreased transferrin receptor and increased ferritin. In addition, decreased GPX4 may be related to irondependent cell death, particularly in Caki2. These results revealed that yeast extract may inhibit proliferation of renal cell carcinoma cells by regulating iron metabolism. Since an increased iron requirement is a classic phenomenon of cancer cells, yeast extract may be a candidate for adjuvant treatment of renal cell carcinoma.
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Antineoplásicos/farmacología , Carcinoma de Células Renales/terapia , Medios de Cultivo/farmacología , Hierro/metabolismo , Neoplasias Renales/terapia , Levaduras/química , Antineoplásicos/química , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/microbiología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medios de Cultivo/química , Microbioma Gastrointestinal , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/microbiología , Levaduras/fisiologíaRESUMEN
The Original article has conflicts between the figure and explanations.
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Many anatomical variants on the sternocleidomastoid muscle have been reported. In this study, supernumerary clavicular heads of sternocleidomastoid muscle in a Korean female cadaver were bilaterally displayed. The observed supernumerary heads were classified as follows: one sterno-mastoid, one cleido-occipital and one cleido-mastoid on the right side, and one sterno-mastoid-occipital, four cleido-occipitals, and one cleido-mastoid on the left side. The sterno-mastoid and sterno-mastoid-occipital and the cleido-occipital made the superficial layer of the sternocleidomastoid muscle, while others made deep layer. We discussed clinical relevance and developmental basis of these muscular variations important for clinicians and anatomists.
Asunto(s)
Variación Anatómica , Músculos del Cuello/anomalías , Cadáver , Clavícula/anatomía & histología , Femenino , Humanos , Apófisis Mastoides/anatomía & histología , Persona de Mediana Edad , República de Corea , Esternón/anatomía & histologíaRESUMEN
Norgalanthamine has been shown to possess hair-growth promoting effects, including increase in hair-fiber length in cultured rat vibrissa follicles and increase in dermal papilla cell (DPC) proliferation. However, the intracellular mechanisms that underlie the action of norgalanthamine in DPCs have not been investigated. In this study, we addressed the ability of norgalanthamine to trigger anagen-activating signaling pathways in DPCs. Norgalanthamine significantly increased extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at 0.1 µM, a concentration at which DPC proliferation was also induced. Furthermore, the increases in norgalanthamine-induced ERK 1/2 activation and subsequent DPC proliferation were suppressed by the mitogen-activated protein kinase/ERK kinase (MEK) 1/2 inhibitor, U0126. A 0.1 µM dose of norgalanthamine also increased phosphorylation of AKT, which was followed by an increase in glycogen synthase kinase 3ß phosphorylation and nuclear translocation of ß-catenin. In addition, LY294002, a phosphatidylinositol 3 kinase (PI3K) inhibitor, blocked the effect of norgalanthamine on DPC proliferation. These results suggest that norgalanthamine can stimulate the anagen phase of the hair cycle in DPCs via activation of the ERK 1/2, PI3K/AKT, and Wnt/ß-catenin pathways.