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1.
Int J Radiat Biol ; 100(2): 220-235, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37812149

RESUMEN

PURPOSE: Due to the expanding repertoire of treatment devices that use radiation, the possibility of exposure to both low-dose and high-dose radiation continues to increase. Skin is the outermost part of the body and thus directly exposed to radiation-induced damage. In particular, the skin of diabetes patients is fragile and easily damaged by external stimuli, such as radiation. However, damage and cellular responses induced by ionizing irradiation in diabetic skin have not been explored in detail. In this study, we investigated the effects of several irradiation dose on normal keratinocytes and those from type II diabetes patients, with particular focus on DNA damage. MATERIALS AND METHODS: Cellular responses to low-dose radiation (0.1 Gy) and high-dose radiation (0.5 and 2 Gy) were evaluated. Cell cycle analysis was conducted via flow cytometry and cell viability analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Proteins related to the DNA damage response (DDR) and repair signaling pathways and apoptosis were detected via immunoblot analysis. Apoptosis and cell differentiation were additionally examined in 3D skin organoids using immunohistochemistry. RESULTS: Compared to respective control groups, no significant changes were observed in cell cycle, DDR and repair mechanisms, cell survival, and differentiation in response to 0.1 Gy irradiation in both normal and diabetes type II keratinocytes. On the other hand, the cell cycle showed an increase in the G2/M phase in both cell types following exposure to 2 Gy irradiation. At radiation doses 2 Gy, activation of the DDR and repair signaling pathways, apoptosis, and cell differentiation were increased and viability was decreased in both cell types. Notably, these differences were more pronounced in normal than diabetes type II keratinocytes. CONCLUSIONS: Normal keratinocytes respond more strongly to radiation-induced damage and recovery than diabetes type II keratinocytes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/radioterapia , Queratinocitos/efectos de la radiación , Radiación Ionizante , Dosis de Radiación , Supervivencia Celular/efectos de la radiación , Daño del ADN , Apoptosis/efectos de la radiación , Relación Dosis-Respuesta en la Radiación
2.
Exp Dermatol ; 32(10): 1706-1716, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37421206

RESUMEN

Melanoma is a notoriously radioresistant type of skin cancer. Elucidation of the specific mechanisms underlying radioresistance is necessary to improve the clinical efficacy of radiation therapy. To identify the key factors contributing to radioresistance, five melanoma cell lines were selected for study and genes that were upregulated in relatively radioresistant melanomas compared with radiosensitive melanoma cells determined via RNA sequencing technology. In particular, we focused on cyclin D1 (CCND1), a well known cell cycle regulatory molecule. In radiosensitive melanoma, overexpression of cyclin D1 reduced apoptosis. In radioresistant melanoma cell lines, suppression of cyclin D1 with a specific inhibitor or siRNA increased apoptosis and decreased cell proliferation in 2D and 3D spheroid cultures. In addition, we observed increased expression of γ-H2AX, a molecular marker of DNA damage, even at a later time after γ-irradiation, under conditions of inhibition of cyclin D1, with a response pattern similar to that of radiosensitive SK-Mel5. In the same context, expression and nuclear foci formation of RAD51, a key enzyme for homologous recombination (HR), were reduced upon inhibition of cyclin D1. Downregulation of RAD51 also reduced cell survival to irradiation. Overall, suppression of cyclin D1 expression or function led to reduced radiation-induced DNA damage response (DDR) and triggered cell death. Our collective findings indicate that the presence of increased cyclin D1 potentially contributes to the development of radioresistance through effects on RAD51 in melanoma and could therefore serve as a therapeutic target for improving the efficacy of radiation therapy.


Asunto(s)
Ciclina D1 , Reparación del ADN , Melanoma , Recombinasa Rad51 , Humanos , Apoptosis , Línea Celular Tumoral , Ciclina D1/genética , Ciclina D1/metabolismo , Melanoma/genética , Melanoma/radioterapia , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , Tolerancia a Radiación/genética
3.
Curr Issues Mol Biol ; 45(6): 4875-4890, 2023 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-37367059

RESUMEN

Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis.

4.
Nutrients ; 15(10)2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37242268

RESUMEN

Fibroblast growth factor 21 (FGF21) is a hormone that participates in the regulation of energy homeostasis and is induced by dietary protein restriction. Preclinical studies have suggested that FGF21 induction exerts a protective effect against non-alcoholic fatty liver disease (NAFLD), while human studies have revealed elevated levels of and potential resistance to FGF21 in patients with NAFLD. However, whether the FGF21 pathway also contributes to NAFLD risk at the genetic level remains uncertain. A few attempts to investigate the impact of individual genetic variants at the loci encoding FGF21 and its receptors on NAFLD risk have failed to establish a clear association due to a limited effect size. Therefore, this study aimed to (1) develop a polygenic hazard score (PHS) for FGF21-related loci that are associated with NAFLD risk and (2) investigate the effect of its interaction with protein intake level on NAFLD risk. Data on 3501 participants of the Korean Genome Epidemiology Study (Ansan-Ansung) were analyzed. Eight single-nucleotide polymorphisms of fibroblast growth factor receptors and beta-klotho were selected for PHS determination using forward stepwise analysis. The association between the PHS and NAFLD was validated (p-trend: 0.0171 for men and <0.0001 for women). Moreover, the association was significantly modulated by the protein intake level in all participants as well as women (p-interaction = 0.0189 and 0.0131, respectively) but not in men. In particular, the women with the lowest PHS values and a protein intake lower than the recommended nutrient intake (RNI) exhibited a greater NAFLD risk (HR = 2.021, p-trend = 0.0016) than those with an intake equal to or greater than the RNI; however, those with higher PHS values had a high risk, regardless of protein intake level. These findings demonstrate the contribution of FGF21-related genetic variants and restricted protein intake to NAFLD incidence.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Masculino , Humanos , Adulto , Femenino , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Proteínas en la Dieta/metabolismo , República de Corea/epidemiología , Hígado/metabolismo
5.
Curr Issues Mol Biol ; 45(1): 538-554, 2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36661522

RESUMEN

Periodontitis, a disease caused by inflammation of oral bacteria, contributes to the loss of alveolar bone and destruction of connective tissues. Porphyromonas gingivalis, a Gram-negative bacterium, is known to possess important pathogenic factors for periodontal disease. In this study, we investigated the anti-periodontitis effects of Magnolia kobus extract (MKE) and magnolin as a component of Magnolia kobus (MK) in murine macrophage RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Effects of MKE and magnolin on the mechanism of RAW 264.7 cellular inflammation were determined by analyzing nitric oxide (NO) production and Western blot protein expression (n = 3). MKE/magnolin inhibited NO production without affecting cell survival. MKE/magnolin treatment inhibited LPS-induced pro-inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs such as MMP-1, 3, 8, 9, and 13), and protein levels of inflammatory mediators (such as TNF-α, IL-1ß, and mPGES-1). MKE/magnolin also suppressed NF-κB activation by inhibiting the TLR4 signaling pathway. These findings suggest that MKE has a therapeutic effect on inflammatory periodontal disease caused by oral bacterium P. gingivalis and that magnolin is a major functional component in the anti-inflammatory effect of MKE.

6.
Exp Anim ; 71(1): 109-115, 2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-34707028

RESUMEN

We surveyed mouse microbiological contamination rates by testing rates for common contaminants using serological, culture, and parasitological methods. A total of 21,292 experimentally housed mice from 206 animal facilities, including hospitals, universities, companies, and research institutes, were tested over a 6-year period from 2014 to 2019. The most commonly found contaminants were various species of nonpathogenic protozoa (47.2%). The most common pathogenic bacteria were Staphylococcus aureus (21.2%), Pasteurella pneumotropica (12.5%), and Pseudomonas aeruginosa (5.8%). Mouse hepatitis virus (6.1%) was detected, but no other viral or bacterial pathogens were found. These results establish that the main pathogens that currently contaminate mouse facilities in Korea are opportunistic pathogens and that contamination with important pathogens, such as those in Categories B or C, has decreased.


Asunto(s)
Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Bacterias , Ratones , República de Corea
7.
Molecules ; 26(17)2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34500684

RESUMEN

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.


Asunto(s)
Raíces de Plantas/química , Scrophularia/química , Medicamentos Herbarios Chinos/química
9.
Sci Total Environ ; 755(Pt 2): 143079, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33127129

RESUMEN

Following the construction of eight large weirs in a 200-km section of the Nakdong River, which is a major water source for the region, harmful cyanobacterial blooms have been occurring annually, causing severe problems with water quality. The present study investigated the community structure of harmful cyanobacteria and identified temporal and spatial patterns in harmful cyanobacterial blooms and their dynamic relationships with physicochemical, hydrological, and meteorological variables in the eight weir sections for 6 years from 2013 to 2018. The dominant harmful cyanobacteria in the eight weir sections were Aphanizomenon and Microcystis spp. There was a successional phenomenon wherein Aphanizomenon spp. first bloomed in spring, and then Microcystis spp. bloomed as water temperatures increased. Additionally, the initiation and duration of the blooms of both genera were affected by the timing and volume of heavy rainfall that caused flushing of cyanobacterial biomass, resulting in direct reduction of cyanobacterial growth in all sections. The harmful cyanobacteria of upstream weirs did not affect the biomass of downstream weirs in terms of either growth initiation or time taken to reach peak biomass, despite being physically connected. Owing to the long retention time during the dry season, similar to what occurs in separate reservoirs, the water quality of each weir section, particularly regarding nutrient characteristics and retention time, were the major factors determining the harmful cyanobacterial abundance, resulting in heterogeneous spatial distribution of harmful cyanobacterial blooms in the Nakdong River.


Asunto(s)
Aphanizomenon , Cianobacterias , Microcystis , Lagos , Ríos , Calidad del Agua
10.
Molecules ; 25(22)2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-33238379

RESUMEN

The aim of this study was to determine the anti-osteoarthritic effects of LI73014F2, which consists of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin in a 2:1:2 ratio, in the monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. LI73014F2 was orally administered once per day for three weeks. Weight-bearing distribution and arthritis index (AI) were measured once per week to confirm the OA symptoms. Synovial membrane, proteoglycan layer, and cartilage damage were investigated by histological examination, while synovial fluid interleukin-1ß level was analyzed using a commercial kit. Levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases (MMPs) in the cartilage tissues were investigated to confirm the anti-osteoarthritic effects of LI73014F2. LI73014F2 significantly inhibited the MIA-induced increase in OA symptoms, synovial fluid cytokine, cartilage damage, and expression levels of pro-inflammatory mediators/cytokines and MMPs in the articular cartilage. These results suggest that LI73014F2 exerts anti-osteoarthritic effects by regulating inflammatory cytokines and MMPs in MIA-induced OA rats.


Asunto(s)
Antiinflamatorios/farmacología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Ácido Yodoacético/efectos adversos , Osteoartritis/etiología , Osteoartritis/patología , Extractos Vegetales/farmacología , Animales , Biomarcadores , Citocinas/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Masculino , Metaloproteinasas de la Matriz/metabolismo , Osteoartritis/tratamiento farmacológico , Ratas , Líquido Sinovial/metabolismo
11.
J Korean Med Sci ; 35(26): e225, 2020 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-32627441

RESUMEN

BACKGROUND: Spinal nerve ligation (SNL) model is one of the representative models of the neuropathic pain model. Neuropathic pain in a chronic post-ischemic pain (CPIP) mimics the symptoms of complex regional pain syndrome (CRPS). The administration of polydeoxyribonucleotide (PDRN), which has regenerative and anti-inflammatory effects, has been studied and is used in clinical practice treating various diseases. However, the analgesic effect of PDRN in a neuropathic pain or CRPS model remains unknown. METHODS: PDRN (3.3, 10, and 20 mg/kg) was administered into the subcutaneous (SC) layer of the hind paws of SNL and CPIP models. Mechanical anti-allodynic effects were then investigated using the von Frey test. In the immunohistochemical examination, dorsal root ganglia (DRG) and the spinal cord were harvested and examined for the expression of glial fibrillary acidic protein (GFAP) after the 20 mg PDRN injection. RESULTS: Mechanical allodynia was significantly alleviated by administration of PDRN in SNL and CPIP mice at all of the time point. As the dose of PDRN increased, the effect was greater. The 20 mg PDRN injection was found to have the most effective anti-allodynic effect. The increased expression of GFAP in DRG and the spinal cord of SNL and CPIP model decreased following the administration of PDRN than vehicle. CONCLUSION: SC administration of PDRN results in the attenuation of allodynia and activation of astrocytes in neuropathic pain or CRPS models. We propose that PDRN can have significant potential advantages in neuropathic pain treatment.


Asunto(s)
Síndromes de Dolor Regional Complejo/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Polidesoxirribonucleótidos/uso terapéutico , Animales , Astrocitos/citología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Síndromes de Dolor Regional Complejo/patología , Modelos Animales de Enfermedad , Ganglios Espinales/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Inyecciones Subcutáneas , Masculino , Ratones , Ratones Endogámicos C57BL , Neuralgia/patología , Médula Espinal/metabolismo , Nervios Espinales/cirugía
12.
Rev Sci Instrum ; 91(5): 054106, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32486717

RESUMEN

Existing human lung-mimicking requirements in various radiology application fields have led to the development of many different phantoms. However, most are static apparatus designed for equipment calibration. Although there are a few dynamic phantoms that generate predefined motions, they have complicated mechanisms that hamper even simple modifications for various lung illness simulations. As a result, existing dynamic phantoms in which a target can be embedded normally generate rectilinear target motions with limited displacement. Nevertheless, volume changes in the human lungs during normal respiration are significant, and targets inside the lungs move along various random paths depending on their location, stiffness, and the properties of the surrounding tissues. In the present work, a novel phantom design is introduced and tested. The phantom mimics the human lung motion and its deformation is initiated by a diaphragm movement. The phantom provides a fairly large deformation and the capability to adjust target motion paths. The presented device has a simple mechanism that can be easily modified to generate various pulmonary diseases. To produce a large deformation by diaphragm compressive motion, polyurethane cubic blocks constitute the deformable part of the lung phantom and a tumor made with silicone is inserted in the structure. The assembled lung part is housed within an acrylic case that is filled with water. The phantom system consists of acrylic, plastic, and low-density polyurethane to minimize artifacts when it undergoes computed tomography (CT) scans. The lung part is organized with various density polyurethane blocks, making it possible to produce nonlinear motion paths of the tumor. The lung part is deformed by a silicon film that is driven by external hydraulic pressure. A finite element method simulation and two-dimensional target motion tests were performed to verify phantom performance. The functionality of the proposed phantom system was confirmed in a series of CT images.


Asunto(s)
Pulmón/fisiología , Fenómenos Mecánicos , Movimiento , Fantasmas de Imagen , Radiología/instrumentación , Respiración , Humanos , Pulmón/diagnóstico por imagen
13.
Int J Colorectal Dis ; 35(8): 1537-1548, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32385595

RESUMEN

PURPOSE: An enhanced recovery after surgery (ERAS) protocol for colorectal cancer resection encourages perioperative euvolemic status, and zero-balance fluid therapy is recommended for low-risk patients. Recently, several studies have reported concerns of increased acute kidney injury (AKI) in patients within an ERAS protocol. In the present study, we investigated the impact of intraoperative zero-balance fluid therapy within an ERAS protocol on postoperative AKI. METHODS: Patients who underwent elective surgery for primary colorectal cancer were divided into zero-balance and non-zero-balance fluid therapy groups according to intraoperative fluid amount and balance. After propensity score (PS) matching, 210 patients from each group were selected. Incidences of AKI were compared between the two groups according to the Kidney Disease Improving Global Outcomes criteria. Postoperative kidney functions and surgical outcomes were also compared. RESULTS: AKI was significantly higher in the zero-balance fluid therapy group compared to the non-zero-balance fluid therapy group (21.4% vs. 13.8%, p = 0.040) in PS-matched patients. The decrease in the estimated glomerular filtration rate on the day of surgery was significantly higher in the zero-balance fluid therapy group (- 5.9 mL/min/1.73 m2 vs. - 1.4 mL/min/1.73 m2, p = 0.005). There were no differences in general morbidity or mortality rate, although surgery-related complications were more common in the zero-balance group. CONCLUSIONS: Despite the proven benefits of zero-balance fluid therapy in colorectal ERAS protocols, care should be taken to monitor for postoperative AKI. Further studies regarding the clinical significance of postoperative AKI occurrence and optimised intraoperative fluid therapy are needed in a colorectal ERAS setting.


Asunto(s)
Lesión Renal Aguda , Neoplasias Colorrectales , Recuperación Mejorada Después de la Cirugía , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Neoplasias Colorrectales/cirugía , Fluidoterapia , Humanos , Tiempo de Internación , Complicaciones Posoperatorias/etiología , Puntaje de Propensión , Estudios Retrospectivos
14.
Molecules ; 25(9)2020 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-32349389

RESUMEN

Osteoarthritis (OA) is one of the most well-characterized joint diseases and is associated with chondrocyte inflammation, metalloproteinase upregulation and apoptosis. LI73014F2 is a novel composition prepared from aqueous extract of Terminalia chebula fruit, alcohol extract of Curcuma longa rhizome, and Boswellia serrata extract at 2:1:2 ratio. Earlier studies have shown that LI73014F2 inhibits cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) activities, and attenuates clinical symptoms in OA subjects. In the present study, we evaluated the protective anti-inflammatory and anti-apoptotic effects, as well as the underlying mechanisms, of LI73014F2 in interleukin (IL)-1ß-induced inflammation in human primary chondrocytes. Human chondrocytes were treated with LI73014F2 (0, 12.5, 25 and 50 µg/mL) in IL-1ß (10 ng/mL)-containing chondrocyte growth medium for 24 h. Cell viability was assessed using an MTT assay. The pro-inflammatory mediator, inflammatory cytokines, MMPs, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways protein expression levels were detected by western blot analysis. The results demonstrated that LI73014F2 normalized the expressions of COX-2, mPGES-1, PGE2, 5-LOX, LTB4, IL-1ß, TNFα, IL-6, MMP-2, MMP-3, MMP-9, MMP-13, Bax/Bcl-2, cleaved caspase-9 and -3, cleaved PARP, phospho-NF-κB p65 and phospho-p38 MAPK proteins in IL-1ß-induced primary human chondrocytes. Moreover, the data suggested that LI73014F2 reduced IL-1ß-induced inflammation and apoptosis, at least partially via the inhibition of the NF-κB/MAPK signaling pathway. In conclusion, the present findings provide the molecular basis of the anti-OA efficacy of LI73014F2.


Asunto(s)
Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Condrocitos/efectos de los fármacos , Interleucina-1beta/farmacología , Osteoartritis/tratamiento farmacológico , Extractos Vegetales/farmacología , Araquidonato 5-Lipooxigenasa/metabolismo , Boswellia/química , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Curcuma/química , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Citocinas/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Interleucina-1beta/metabolismo , Leucotrieno B4/metabolismo , Inhibidores de la Lipooxigenasa/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteasas/metabolismo , FN-kappa B/metabolismo , Prostaglandina-E Sintasas/metabolismo , Receptores de Prostaglandina E/metabolismo , Rizoma/química , Terminalia/química
15.
Mol Med Rep ; 20(4): 3448-3455, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31432129

RESUMEN

The aim of the present study was to evaluate the neuroprotective effect of Citrus aurantium extract (CAE) and nobiletin against amyloid ß 1­42 (Aß 1­42)­induced spatial learning and memory impairment in mice. After injecting Aß 1­42 (5 µl/2.5 min, intracerebroventricular injection), amnesic mice were orally administered CAE and nobiletin for 28 days. Memory, spatial and cognitive ability were measured using passive avoidance and a Morris water maze task. Acetylcholinesterase (AchE) activity was investigated in the hippocampus and cortex using commercial kits and the analysis of Bax, Bcl­2, and cleaved caspase­3 protein expression by western blot assays was used to confirm the anti­apoptotic mechanism of CAE and nobiletin. The present study confirmed impairments in learning and memory in the Aß­induced neurodegenerative mice with increased AchE activity in the brain. However, the daily administration of CAE and nobiletin reduced the spatial learning deficits and increased the AchE activity in the cortex and hippocampus. Furthermore, CAE and nobiletin significantly downregulated the Bax and cleaved caspase­3 protein expression and upregulated the Bcl­2 and Bcl­2/Bax expression in the cortex and hippocampus of Aß­treated mice. These results suggest that CAE and nobiletin exert a neuroprotective effect by regulating anti­apoptotic mechanisms, including reduced AchE activity in the cortex and hippocampus of the cognitive deficit mouse model.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Citrus/química , Flavonas/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Fragmentos de Péptidos/metabolismo , Extractos Vegetales/farmacología , Animales , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/fisiopatología , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Ratones , Extractos Vegetales/química
16.
Nutrients ; 11(4)2019 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-31027223

RESUMEN

Over the past decades, periodontitis has become a rising health problem and caused various diseases. In the many studies shows that some extracts and compound to the prevention and treatment of periodontitis. This study focuses on the effects of inhibition of gingival damage and alveolar bone loss. The aim of this study was to evaluate the protective effects of Magnolia biondii extract (MBE) against ligature-induced periodontitis in rats. A ligature was placed around the molar teeth for 8 weeks, and MBE was administered for 8 weeks. Gingival tissue damage and alveolar bone loss were measured by microcomputed tomography (CT) analysis and histopathological examination. Serum Interluekin-1 ß (IL-1ß), tumor necrosis factor-α (TNF-α), cyclooxygenases-2 (COX-2), and receptor activator of nuclear factor-κB ligand (RANKL) levels were investigated using commercial kits to confirm the antiperiodontitis effects of MBE. We confirmed that ligature-induced periodontitis resulted in gingival tissue damage and alveolar bone loss. However, treatment for 8 weeks with MBE protected from periodontal tissue damage and downregulated serum inflammatory cytokine factors and RANKL levels. These results suggest that MBE exerts antiperiodontitis effects by inhibiting gingival tissue destruction and alveolar bone loss through regulation of anti-inflammatory cytokines in periodontitis-induced rats.


Asunto(s)
Antiinflamatorios/uso terapéutico , Magnolia/química , Periodontitis/tratamiento farmacológico , Periodontitis/etiología , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/química , Masculino , Extractos Vegetales/química , Ratas , Microtomografía por Rayos X
17.
Int J Mol Med ; 43(5): 2144-2152, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30896788

RESUMEN

The aim of this study was to investigate the antioxidant and anti­apoptotic activities, as well as the underlying mechanisms of action, of Scrophularia buergeriana (S. buergeriana) extract (SBE) in glutamate­induced SH­SY5Y cell death. The roots of S. buergeriana were extracted with 70% ethanol, and standardized SBE was used in this study. To induce cytotoxicity, the SH­SY5Y cells were exposed to glutamate for 3 h, or pre­treated with SBE for 1 h, and subsequently incubated with glutamate for 3 h. The neuroprotective effects were assessed by measuring cell viability and the total glutathione contents using commercial kits. The antioxidant and anti­apoptotic mechanisms of action of SBE were evaluated by western blot analysis. The results confirmed that glutamate­induced toxicity was caused by reactive oxygen species (ROS) production, leading to oxidative stress and DNA damage, thus leading to cell death. However, treatment of the SH­SY5Y cells with SBE significantly increased the viability of the cells exposed to glutamate by upregulating the levels of antioxidant proteins, such as superoxide dismutase (SOD)1, SOD2 and glutathione peroxidase­1 (GPx­1), and directly enhancing the total glutathione contents. Furthermore, SBE attenuated DNA impairment and decreased B­cell lymphoma-2 (Bcl­2)­associated X protein (Bax), cleaved caspase­3 and cleaved poly(adenosine diphosphate (ADP)­ribose) polymerase (PARP) activation. In addition, SBE upregulated Bcl­2 expression via p38 mitogen­activated protein kinases (MAPKs). On the whole, the findings of this study demonstrated that SBE exerts neuroprotective effects against glutamate­induced cell toxicity through its antioxidant and anti­apoptotic activities.


Asunto(s)
Ácido Glutámico/toxicidad , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Scrophularia/química , Acetilcolinesterasa/metabolismo , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Fragmentación del ADN/efectos de los fármacos , Glutatión/metabolismo , Humanos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
18.
Biol Pharm Bull ; 42(2): 255-260, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30713255

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation, which is the most common form of chronic liver disease. Multiple clinical studies using natural compounds such as flavonoids have been conducted to treat NAFLD. In the present study, the pharmacological effect of Citrus aurantium L. (Rutaceae) peel extract (CAE), which contains over 27% of polymethoxyflavone nobiletin, on NAFLD was evaluated using a high-fat diet (HFD) animal model susceptible to developing NAFLD. C57BL/6 mice were fed an HFD (60% kcal of energy derived from fat) for 8 weeks to induce obesity. Obese mice were randomly allocated to four groups of eight mice each (HFD alone, HFD with silymarin, HFD with 50 mg/kg CAE, and HFD with 100 mg/kg CAE). After 8 weeks of treatment, all mice were euthanized, and plasma and liver tissues were analyzed biochemically and histopathologically. The results indicate that CAE treatment significantly reduced HFD-induced NAFLD, as shown by decreased serum lipid index and prevented liver histopathology. The expression of genes involved in lipid synthesis including free fatty acid (FFA), peroxisome-proliferator-activated receptor γ (PPAR-γ), sterol receptor element binding protein 1c (SREBP-1c), and fatty acid synthesis enzyme was suppressed by CAE treatment. Moreover, compared to untreated mice, CAE-treated HFD mice showed decreased pro-inflammatory cytokine expression. These results demonstrated that CAE prevented HFD-induced NAFLD by reducing plasma levels of triglyceride and cholesterol and de novo lipid synthesis.


Asunto(s)
Citrus/química , Flavonoides/farmacología , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patología , PPAR gamma/biosíntesis , PPAR gamma/genética , Extractos Vegetales/farmacología , Proteínas Quinasas/metabolismo , Distribución Aleatoria , Silimarina/farmacología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/biosíntesis , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Receptor fas/metabolismo
19.
J Clin Med ; 8(1)2019 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-30621004

RESUMEN

Transforaminal epidural injection is used to treat radicular pain. However, there is no objective method of assessing pain relief following transforaminal injection. Perfusion index is a metric for monitoring peripheral perfusion status. This study evaluates the correlation between perfusion index change and analgesic efficacy in transforaminal blocks for lumbosacral radicular pain. We retrospectively analyzed data of 100 patients receiving transforaminal block for lumbosacral radicular pain. We assessed perfusion index before treatment and at 5, 15, and 30 min following the block. We defined responders (group R) and non-responders (group N) as those with ≥50% and <50% pain reduction, respectively, 30 min following block. Clinical data and perfusion index of the groups were analyzed. Ninety-two patients were examined, of whom 57 (61.9%) and 35 (38.0%) patients reported ≥50% and <50% pain reduction, respectively. Group R had a significantly higher perfusion index change ratio 5 min following the block (p = 0.029). A perfusion index change ratio of ≥0.27 was observed in group R (sensitivity, 75.4%; specificity, 51.4%; AUC (area under the curve), 0.636; p = 0.032). A perfusion index change ratio of ≥0.27 at 5 min after block is associated with, but does not predict improvement in, pain levels following lumbosacral transforaminal block.

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