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1.
Phytomedicine ; 128: 155449, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518644

RESUMEN

BACKGROUND: Peucedanum japonicum Thunb. (PJ) is a vegetable widely consumed in East Asia and is known to have anticancer and anti-inflammatory effects. However, the effect of PJ on muscle atrophy remains elusive. PURPOSE: This study aimed to investigate the effect of PJ and its active compound on dexamethasone (DEX)-induced muscle atrophy. METHODS: We performed qualitative and quantitative analysis of PJ using ultra-performance liquid chromatography-mass spectrometry tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. The efficacy of PJ and its main compound 4-caffeoylquinic acid (CQA) on muscle atrophy was evaluated in DEX-induced myotube atrophy and DEX-induced muscle atrophy in mouse myoblasts (C2C12) and C57BL/6 mice, in vitro and in vivo, respectively. RESULTS: The UPLC-MS/MS and HPLC data showed that the concentration of 4-CQA in PJ was 18.845 mg/g. PJ and 4-CQA treatments significantly inhibited DEX-induced myotube atrophy by decreasing protein synthesis and glucocorticoid translocation to the nucleus in C2C12 myotubes. In addition, PJ enhanced myogenesis by upregulating myogenin and myogenic differentiation 1 in C2C12 cells. PJ supplementation effectively increased muscle function and mass, downregulated atrogenes, and decreased proteasome activity in C57BL/6 mice. Additionally, PJ effectively decreased the nuclear translocation of forkhead transcription factor 3 alpha by inhibiting glucocorticoid receptor. CONCLUSION: Overall, PJ and its active compound 4-CQA alleviated skeletal muscle atrophy by inhibiting protein degradation. Hence, our findings present PJ as a potential novel pharmaceutical candidate for the treatment of muscle atrophy.


Asunto(s)
Apiaceae , Dexametasona , Ratones Endogámicos C57BL , Atrofia Muscular , Extractos Vegetales , Ácido Quínico/análogos & derivados , Animales , Atrofia Muscular/inducido químicamente , Atrofia Muscular/tratamiento farmacológico , Dexametasona/farmacología , Ratones , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apiaceae/química , Masculino , Línea Celular , Espectrometría de Masas en Tándem , Fibras Musculares Esqueléticas/efectos de los fármacos , Ácido Quínico/farmacología , Cromatografía Líquida de Alta Presión , Miogenina/metabolismo
2.
BMC Cancer ; 23(1): 734, 2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37553666

RESUMEN

BACKGROUND: For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC. METHODS: This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2-4 weeks in the TNT group and 6-10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life, and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate. DISCUSSION: The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients. TRIAL REGISTRATION: Cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Terapia Neoadyuvante/métodos , Capecitabina/uso terapéutico , Resultado del Tratamiento , Estudios Prospectivos , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estadificación de Neoplasias , Neoplasias del Recto/patología , Quimioradioterapia/métodos , República de Corea/epidemiología , Fluorouracilo , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
3.
Food Nutr Res ; 672023.
Artículo en Inglés | MEDLINE | ID: mdl-37152296

RESUMEN

Background: Euonymus alatus (Thunb.) Siebold (EA) is a medicinal plant used in some Asian countries to treat various diseases, including cancer, hyperglycemia, diabetes, urticaria, dysmenorrhea, and arthritis. Owing to the wide range of pharmacological applications of EA, various roles of EA are being studied. Objective: We evaluated the immune-enhancing effect of EA treatment in a cyclophosphamide (Cy)-induced immunosuppressed rat model. Design: We analyzed the immune enhancement effect of EA on macrophages by western blotting. In addition, cell viability and natural killer (NK) cell activity were analyzed in splenocytes following EA treatment. For in vivo studies, analysis of weekly body weight, spleen weight, immune cell count, cytokine levels, and spleen histological findings was performed following EA administration in Cy-induced immunocompromised rats. Results: EA significantly increased cell viability and phospho-nuclear factor-kappa B and phospho-extracellular signal-regulated kinase protein levels in the macrophages. EA significantly increased NK cell activity in splenocytes compared with the control group. In Cy-induced immunosuppressed rats, EA administration increased spleen tissue weight and the contents of leukocytes, lymphocytes, granulocytes, intermediate cells, and plasma cytokines (tumor necrosis factor-α and interferon-γ). In addition, improvement in the damaged spleen tissue was observed. Conclusions: These findings confirm that EA exerts an immune-enhancing effect, thereby suggesting its potential as an immunostimulatory agent or functional food.

4.
Vet Res Commun ; 47(3): 1629-1640, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36977954

RESUMEN

The effects of probiotics supplementation on the reproductive function have been evaluated in many species, but no study has evaluated the changes in the gut microbiome along with the sperm quality changes simultaneously. This study evaluated the effects of dietary supplementation with probiotics on the gut microbiome, sperm quality and gene expression, along with possible correlations between these parameters in dogs. The dogs were supplemented with Lactobacillus rhamnosus for six weeks, and fecal and semen samples were collected at 0, 3, and 6 weeks. Fecal samples were assessed using 16S Metagenomic Sequencing for gut microbiome analysis; and semen samples were analyzed using computer-assisted sperm analysis, DNA and acrosome integrity assessment, viability and morphology assessment, and real-time PCR. The analyses suggested that probiotic supplementation improved kinematic parameters, viability, DNA and acrosome integrity, and morphology of sperms. The mRNA levels of genes associated with fertility, DNA repair and integrity, and antioxidation were also upregulated. The sperm parameters were positively correlated with the relative abundance of Actinobacteria, Allobaculum, Phascolarctobacterium and Catenibacterium, and negatively correlated with Faecalibacterium and Streptococcus. Taken together, the sperm quality enhancement through the gut-testis axis may be due to a change in the gut microorganisms populations.


Asunto(s)
Suplementos Dietéticos , Microbioma Gastrointestinal , Lactobacillus , Probióticos , Espermatozoides , Animales , Perros , Espermatozoides/citología , Espermatozoides/fisiología , Probióticos/administración & dosificación , Análisis de Semen/veterinaria , Masculino , Heces/microbiología
5.
Nutrients ; 15(3)2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36771397

RESUMEN

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host-microbiome crosstalk in IDA.


Asunto(s)
Anemia Ferropénica , Microbioma Gastrointestinal , Deficiencias de Hierro , Microbiota , Humanos , Femenino , Anemia Ferropénica/complicaciones , Anemia Ferropénica/tratamiento farmacológico , Hierro/uso terapéutico
6.
Molecules ; 28(2)2023 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-36677905

RESUMEN

Periodontitis is caused by pathogens in the oral cavity. It is a chronic infectious disease that causes symptoms including gingival bleeding and tooth loss resulting from the destruction of periodontal tissues coupled with inflammation. Dendropanax morbiferus H.Lév (DM) is a natural product that exhibits various biological activities with few side effects. In this study, the potential of DM leaf hot-water extracts (DMWE) as a treatment for periodontitis was determined and its anti-oxidant and anti-inflammatory effects were evaluated. Compounds in DMWE were identified by high-performance liquid chromatography (HPLC) and nitric oxide (NO) and prostaglandin E2 (PGE2) production was measured in RAW 264.7 cells. We measured the gingival index and gingival sulcus depth, and micro-CT was performed in vivo using a ligature-induced periodontitis rat model, which is similar to human periodontitis. The DMWE-treated group exhibited a decrease in cytokine concentration and relieved the gingival index and gingival sulcus depth compared with the periodontitis-induced control group. In addition, micro-CT and histological analysis revealed that DMWE exhibited anti-inflammatory effects and improved alveolar bone loss in periodontitis-induced rats. These findings suggest that DMWE has excellent anti-oxidant and anti-inflammatory effects that protect and prevent periodontal tissue damage and tooth loss caused by the inflammatory response.


Asunto(s)
Pérdida de Hueso Alveolar , Periodontitis , Pérdida de Diente , Ratas , Humanos , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Pérdida de Diente/complicaciones , Pérdida de Diente/tratamiento farmacológico , Modelos Animales de Enfermedad , Periodontitis/patología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/patología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
7.
Cells ; 11(16)2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-36010621

RESUMEN

Radiation-induced enteritis is frequently observed following radiotherapy for cancer or occurs due to radiation exposure in a nuclear accident. The loss of the epithelial integrity leads to 'leaky gut', so recovery of damaged epithelium is an important strategy in therapeutic trials. Centella asiatica (CA), a traditional herbal medicine, is widely used for wound healing by protecting against endothelial damage. In this study, we investigated the radio-mitigating effect of CA, focusing on the crosstalk between endothelial and epithelial cells. CA treatment relieved radiation-induced endothelial dysfunction and mitigated radiation-induced enteritis. In particular, treatment of the conditioned media from CA-treated irradiated endothelial cells recovered radiation-induced epithelial barrier damage. We also determined that epidermal growth factor (EGF) is a critical factor secreted by CA-treated irradiated endothelial cells. Treatment with EGF effectively improved the radiation-induced epithelial barrier dysfunction. We also identified the therapeutic effects of CA-induced endothelial paracrine in a radiation-induced enteritis mouse model with epithelial barrier restoration. Otherwise, CA treatment did not show radioprotective effects on colorectal tumors in vivo. We showed therapeutic effects of CA on radiation-induced enteritis, with the recovery of endothelial and epithelial dysfunction. Thus, our findings suggest that CA is an effective radio-mitigator against radiation-induced enteritis.


Asunto(s)
Centella , Enteritis , Traumatismos por Radiación , Animales , Células Endoteliales , Enteritis/tratamiento farmacológico , Enteritis/etiología , Factor de Crecimiento Epidérmico/farmacología , Ratones , Fitoterapia , Traumatismos por Radiación/tratamiento farmacológico
8.
Proc Natl Acad Sci U S A ; 119(33): e2117904119, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35939684

RESUMEN

Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous Lactobacillus spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of Lactobacilli that is markedly reduced. Exposing infected human BECs to L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load. The adherence of Lactobacilli to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D-mediated UPEC killing was diminished in germ-free mice and type I IFN receptor-deficient mice. Secreted metabolites of L. crispatus seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of Lactobacilli into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.


Asunto(s)
Antibiosis , Infecciones por Escherichia coli , Interferón Tipo I , Lactobacillus crispatus , Vejiga Urinaria , Infecciones Urinarias , Escherichia coli Uropatógena , Animales , Terapia Biológica , Catepsina D/metabolismo , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/terapia , Femenino , Humanos , Inmunidad Innata , Interferón Tipo I/inmunología , Lactobacillus crispatus/fisiología , Masculino , Ratones , Vejiga Urinaria/inmunología , Vejiga Urinaria/microbiología , Infecciones Urinarias/inmunología , Infecciones Urinarias/microbiología , Infecciones Urinarias/terapia , Escherichia coli Uropatógena/crecimiento & desarrollo
9.
Diabetes Metab J ; 46(5): 677-688, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35124687

RESUMEN

BACKGROUND: Neonatal porcine pancreatic cell clusters (NPCCs) have been proposed as an alternative source of ß cells for islet transplantation because of their low cost and growth potential after transplantation. However, the delayed glucose lowering effect due to the immaturity of NPCCs and immunologic rejection remain as a barrier to NPCC's clinical application. Here, we demonstrate accelerated differentiation and immune-tolerant NPCCs by in vitro chemical treatment and microencapsulation. METHODS: NPCCs isolated from 3-day-old piglets were cultured in F-10 media and then microencapsulated with alginate on day 5. Differentiation of NPCCs is facilitated by media supplemented with activin receptor-like kinase 5 inhibitor II, triiodothyronine and exendin-4 for 2 weeks. Marginal number of microencapsulated NPCCs to cure diabetes with and without differentiation were transplanted into diabetic mice and observed for 8 weeks. RESULTS: The proportion of insulin-positive cells and insulin mRNA levels of NPCCs were significantly increased in vitro in the differentiated group compared with the undifferentiated group. Blood glucose levels decreased eventually after transplantation of microencapsulated NPCCs in diabetic mice and normalized after 7 weeks in the differentiated group. In addition, the differentiated group showed nearly normal glucose tolerance at 8 weeks after transplantation. In contrast, neither blood glucose levels nor glucose tolerance were improved in the undifferentiated group. Retrieved graft in the differentiated group showed greater insulin response to high glucose compared with the undifferentiated group. CONCLUSION: in vitro differentiation of microencapsulated immature NPCCs increased the proportion of insulin-positive cells and improved transplant efficacy in diabetic mice without immune rejection.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Islotes Pancreáticos , Alginatos/metabolismo , Alginatos/farmacología , Animales , Animales Recién Nacidos , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/cirugía , Exenatida/farmacología , Insulina/metabolismo , Ratones , ARN Mensajero/metabolismo , ARN Mensajero/farmacología , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Porcinos , Trasplante Heterólogo , Triyodotironina/metabolismo , Triyodotironina/farmacología
10.
Nutrients ; 14(2)2022 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-35057420

RESUMEN

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30-40 years, who were randomly assigned to two groups-a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.


Asunto(s)
Dieta Saludable/etnología , Dieta Saludable/métodos , Dislipidemias/dietoterapia , Índice Glucémico , Obesidad/dietoterapia , Adulto , Colesterol/sangre , Dieta para Diabéticos/etnología , Dieta para Diabéticos/métodos , Dieta con Restricción de Grasas/etnología , Dieta con Restricción de Grasas/métodos , Dislipidemias/sangre , Dislipidemias/etiología , Ingestión de Energía , Femenino , Humanos , Resistencia a la Insulina , Obesidad/sangre , Obesidad/complicaciones , República de Corea , Resultado del Tratamiento , Triglicéridos/sangre
11.
Pediatr Rheumatol Online J ; 19(1): 100, 2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34193198

RESUMEN

BACKGROUND: Dermatomyositis is an inflammatory muscle disease caused by immune-mediated muscle injury, and central core disease (CCD) is a congenital myopathy associated with disturbed intracellular calcium homeostasis and excitation-contraction coupling. To date, CCD has not been reported to have autoantibodies or coexist with inflammatory myopathy. CASE PRESENTATION: Here, we described the case of a 25-year-old woman who had progressive proximal muscle weakness, myalgia, pruritic macular rash, skin ulcers, and calcinosis. Dermatomyositis was initially suspected based on the clinical symptoms accompanied by elevated muscle enzyme levels, electromyography abnormalities, and a positive antinuclear antibody test. However, the patient's muscle biopsy revealed the characteristic findings of both dermatomyositis and CCD, suggesting that dermatomyositis occurred in this patient with previously asymptomatic CCD. The patient did not have any pathogenic gene mutations associated with congenital myopathy, including RYR1 and SEPN1 in targeted next-generation sequencing. She received high-dose glucocorticoid therapy and azathioprine with a significant improvement in muscle strength. CONCLUSIONS: We present a case of rare coexistence of dermatomyositis and CCD. Clinicians should be aware that patients with CCD may have inflammatory myopathy that responds well to immunosuppressive therapy.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Dermatomiositis/etiología , Miopatía del Núcleo Central/complicaciones , Adulto , Enfermedades Autoinmunes/genética , Femenino , Humanos , Miopatía del Núcleo Central/genética
12.
Children (Basel) ; 8(5)2021 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-34063250

RESUMEN

OBJECTIVES: We determined whether glycerin enemas were appropriately prescribed in pediatric fecal impaction patients using the Leech score and identified factors that influenced the prescription of glycerin enemas in the pediatric emergency department (PED). METHODS: We included patients who received a glycerin enema at the PED of a tertiary teaching hospital. We divided the study subjects into two groups on the basis of their Leech scores: an appropriate enema group (Leech score ≥ 8), and an inappropriate enema group (Leech score < 8). Logistic regression was performed to determine the factors associated with glycerin enema administration. RESULTS: The data of 998 patients, including 446 patients in the inappropriate enema group (Leech score 5.2 ± 1.7) and 552 patients in the appropriate enema group (Leech score 10.1 ± 1.7), were analyzed. A discharge diagnosis of fecal impaction was observed significantly more frequently (57.1%) in the appropriate enema group, and nonspecific abdominal pain (8.3%) and acute gastroenteritis (40.8%) were diagnosed significantly more frequently in the inappropriate enema group (p < 0.05). Constipation (2.8%) and irritability (3.0%) were slightly more common in the appropriate enema group than in the inappropriate enema group (p < 0.05). According to multiple logistic regression, subjects aged 2-8 years (2-4 years, OR 4.24; 4-8 years, OR 2.83), with vomiting (OR 1.72), with irritability (OR 4.52), and with a prolonged last defecation day (OR 1.2) were most likely to receive appropriate enema administration (p < 0.05). CONCLUSION: The results showed that in those aged 2-8 years, with vomiting and irritability, and with a prolonged last defecation day, an enema was generally administered appropriately.

13.
Laryngoscope ; 131(10): 2332-2340, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34156095

RESUMEN

OBJECTIVES/HYPOTHESIS: Tinnitus can develop due to, or be aggravated by, stress in a rat model. To investigate stress as a possible causal factor in the development of tinnitus, we designed an animal study that included tinnitus behavior and excitatory/inhibitory neurotransmitter expression after noise exposure as well as restraint stress. STUDY DESIGN: An experimental animal study. METHODS: Wistar rats were grouped according to single or double exposure to noise and restraint stress. The noise exposure (NE) group was subjected to 110 dB sound pressure level (SPL) of 16 kHz narrow-band noise (NBN) for 1 hour, and the restraint stress (RS) group was restrained for 1 hour with or without noise exposure. Gap prepulse inhibition of the acoustic startle (GPIAS) reflex was measured at an NBN of 16 kHz to investigate tinnitus development. Various immunohistopathologic and molecular biologic studies were undertaken to evaluate possible mechanisms of tinnitus development after noise and/or restraint stress. RESULTS: The RS-only group showed a reduced GPIAS response, which is a reliable sign of tinnitus development. In the double-stimulus groups, more tinnitus-development signs of reduced GPIAS responses were observed. The expression of γ-aminobutyric acid A receptor α1 (GABAAR α1) in the hippocampus decreased in the NE│RS group. Increased N-methyl-d-aspartate receptor1 intensities in the NE│RS group and decreased GABAAR α1 intensities in the RS and NE│RS groups were observed in the CA3 region of the hippocampus. CONCLUSIONS: Tinnitus appeared to develop after stress alone in this animal study. An imbalance in excitatory and inhibitory neurotransmitters in the hippocampus may be related to the development of tinnitus after acute NE and/or stress. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2332-2340, 2021.


Asunto(s)
Región CA3 Hipocampal/patología , Ruido/efectos adversos , Estrés Psicológico/complicaciones , Acúfeno/etiología , Estimulación Acústica/efectos adversos , Estimulación Acústica/métodos , Animales , Modelos Animales de Enfermedad , Humanos , Masculino , Ratas , Receptores de GABA-A/análisis , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/análisis , Receptores de N-Metil-D-Aspartato/metabolismo , Reflejo de Sobresalto , Estrés Psicológico/psicología , Acúfeno/diagnóstico , Acúfeno/patología , Acúfeno/psicología
14.
Artículo en Inglés | MEDLINE | ID: mdl-33936244

RESUMEN

Venous insufficiency results from several factors responsible for the progression of inflammation and oxidative damage of veins. Recently, natural extracts have been proposed for the treatment of venous insufficiency, but their efficacies have not been fully elucidated. In the present study, we evaluate the combinatorial effects on anti-inflammatory and anti-vascular leakage potential of mixed compositions containing different proportions of Centella asiatica extract (CE) and Vitis vinifera L. leaf extract (VVE) using an inflammation model of lipopolysaccharide- (LPS-) stimulated RAW264.7 cells and various vascular permeability models in mice (acetic-acid-induced peritoneal vascular model, mustard-oil-stimulated ear vascular model, and carrageenan-induced paw edema model). Pretreatment of CE and VVE in a 1 : 3 combination dose dependently inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) through downregulation of the nuclear factor-κB (NF-κB) pathway in LPS-stimulated RAW264.7 macrophages. In vascular permeability-related mouse models, pretreatment with the CE-VVE 1 : 3 combination significantly reduced the permeability of peritoneal or ear veins caused by acetic acid and mustard oil, respectively. Furthermore, pretreatment of the CE-VVE 1 : 3 combination ameliorated inflammation and edema of the hind paw caused by carrageenan injection. Thus, the combination of CE and VVE showed significant anti-inflammatory qualities and anti-vascular leakage effects. These findings indicate that an optimal combination of CE and VVE may have a more synergistic effect than that of CE or VVE alone as a putative agent against vascular incompetence.

15.
Ecotoxicol Environ Saf ; 219: 112318, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33993091

RESUMEN

Curcumin exhibited numerous key activities including antioxidant, anti-inflammatory, and immunostimulatory effects in fish. This study evaluated the protective effects of curcumin (CUR) against lead (Pb)-induced toxicities in fish. Healthy Cyprinus carpio L. individuals were segregated into control, Pb only, Pb+CUR, and CUR only groups. Pb groups were exposed to 1 mg L -1 of Pb, and CUR groups were fed a basal diet supplemented with 15 g kg-1 of CUR. After eight weeks, growth performance, Pb accumulation in tissues, various haemato-biochemical parameters, immune responses, and cytokine gene expression were measured. Dietary CUR effectively decreased Pb accumulation in tissues and increased the survival of Pb-exposed fish. Co-treatment with Pb and CUR reversed alterations in haemato-biochemical parameters, ameliorated Pb-induced oxidative stress, enhanced immune responses, and restored intestinal enzymatic activities. Dietary CUR reversed changes in intestinal microbiota in Pb-exposed fish. Pb-induced upregulation of NF-κBp65 and HSP70 was inhibited by dietary CUR. CUR supplementation upregulated the mRNA levels of SOD, Nrf2, IL-10, and CYP450 1A and attenuated Pb-induced degradation of I κB-α mRNA levels. Overall, CUR antagonizes Pb-induced negative impacts in fish. Thus, dietary CUR had several beneficial effects on immune responses, decreased Pb accumulation in tissues, and reversed Pb-induced oxidative stress in fish. Therefore, CUR plays a protective role in Pb-induced immune toxicity in fish, and, as such, may be suitable as an aqua feed additive for use in carp aquaculture.


Asunto(s)
Antioxidantes/farmacología , Carpas/fisiología , Curcumina/farmacología , Plomo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Alimentación Animal/análisis , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Acuicultura , Carpas/metabolismo , Citocinas , Dieta , Suplementos Dietéticos/análisis , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Intoxicación por Plomo/veterinaria
16.
Food Chem ; 353: 129463, 2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-33743428

RESUMEN

Codium fragile (CF) is a type of green algae consumed as kimchi in Asia. UPLC-QTOF-MS/MS analysis showed that CF contain lysophosphatidyl choline, canthaxanthin, retinoic acid, α-tocopherol, and unsaturated fatty acids, which reportedly improve skeletal muscle health. However, the effect of CF on skeletal muscle mass and function remains to be elucidated. In mice fed with CF extracts, exercise endurance and muscle weight increased. CF extracts enhanced protein synthesis and myogenic differentiation through the mTORC1 pathway. CF extracts also promoted oxidative muscle fiber formation and mitochondrial biogenesis through the PGC-1α-related signaling pathway. Upregulation of PGC-1α by CF extracts was abolished by EX527 SIRT1 inhibitor treatment. Changed signaling molecules in the CF extracts were partially regulated by canthaxanthin, a new compound in CF extracts, suggesting that canthaxanthin contribute synergistically to the effect of CF extracts. Therefore, CF is a potential food source for sport nutrition or prevention of sarcopenia.


Asunto(s)
Chlorophyta/química , Músculo Esquelético/efectos de los fármacos , Resistencia Física/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Cantaxantina/análisis , Carbazoles/farmacología , Masculino , Ratones Endogámicos C57BL , Músculo Esquelético/fisiología , Tamaño de los Órganos/efectos de los fármacos , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Condicionamiento Físico Animal/fisiología , Resistencia Física/fisiología , Extractos Vegetales/análisis , Algas Marinas/química , Transducción de Señal/efectos de los fármacos , Espectrometría de Masas en Tándem , Regulación hacia Arriba/efectos de los fármacos
17.
Poult Sci ; 100(2): 1291-1298, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33518086

RESUMEN

The effects of commercial vegetable oils and duck skin on quality characteristics of a reduced-fat duck meat emulsion were examined. The cooking loss, emulsion stability, and hardness were lower for emulsions preemulsified with vegetable oils and duck skin (P < 0.05) than for the control. Storage modulus (G') and loss modulus (G″) of reduced-fat duck meat emulsions treated with corn, grape seed, soy, and olive oils were similar to the values of control; the highest G' and G″ values were reported for the reduced-fat duck meat emulsion treated with coconut oil. Myofibril protein solubility was the highest for the reduced-fat duck meat emulsion treated with coconut oil and duck skin (P < 0.05). Replacing of pork back fat with different vegetable oils for emulsification may impart superior quality to reduced-fat duck meat emulsion. We recommend preemulsion with vegetable oils and duck skin to enhance the quality characteristics of reduced-fat duck meat emulsion.


Asunto(s)
Grasas de la Dieta/clasificación , Productos de la Carne , Aceites de Plantas , Animales , Rastreo Diferencial de Calorimetría , Dieta con Restricción de Grasas/métodos , Patos , Emulsiones , Ácidos Grasos/análisis , Manipulación de Alimentos , Humanos , Productos de la Carne/análisis , Productos de la Carne/normas , Aceites de Plantas/análisis , Porcinos , Viscosidad
18.
Phytomedicine ; 81: 153424, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33278782

RESUMEN

BACKGROUD: Exposure to high-dose radiation, such as after a nuclear accident or radiotherapy, elicits severe intestinal damage and is associated with a high mortality rate. In treating patients exhibiting radiation-induced intestinal dysfunction, countermeasures to radiation are required. In principle, the cellular event underlying radiation-induced gastrointestinal syndrome is intestinal stem cell (ISC) apoptosis in the crypts. High-dose irradiation induces the loss of ISCs and impairs intestinal barrier function, including epithelial regeneration and integrity. Notch signaling plays a critical role in the maintenance of the intestinal epithelium and regulates ISC self-renewal. Ghrelin, a hormone produced mainly by enteroendocrine cells in the gastrointestinal tract, has diverse physiological and biological functions. PURPOSE: We investigate whether ghrelin mitigates radiation-induced enteropathy, focusing on its role in maintaining epithelial function. METHODS: To investigate the effect of ghrelin in radiation-induced epithelial damage, we analyzed proliferation and Notch signaling in human intestinal epithelial cell. And we performed histological analysis, inflammatory response, barrier functional assays, and expression of notch related gene and epithelial stem cell using a mouse model of radiation-induced enteritis. RESULTS: In this study, we found that ghrelin treatment accelerated the reversal of radiation-induced epithelial damage including barrier dysfunction and defective self-renewing property of ISCs by activating Notch signaling. Exogenous injection of ghrelin also attenuated the severity of radiation-induced intestinal injury in a mouse model. CONCLUSION: These data suggest that ghrelin may be used as a potential therapeutic agent for radiation-induced enteropathy.


Asunto(s)
Ghrelina/farmacología , Enfermedades Intestinales/tratamiento farmacológico , Mucosa Intestinal/citología , Receptores Notch/metabolismo , Células Madre/efectos de la radiación , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Línea Celular , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Humanos , Enfermedades Intestinales/etiología , Enfermedades Intestinales/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de la radiación , Masculino , Ratones Endogámicos C57BL , Traumatismos por Radiación , Protectores contra Radiación/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Células Madre/efectos de los fármacos , Células Madre/patología , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/efectos de la radiación
19.
Prev Nutr Food Sci ; 25(2): 173-183, 2020 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-32676469

RESUMEN

Endothelial cell injury caused by oxidative stress is a critical factor in the initial stage of vascular diseases. Thus, identification of more effective antioxidants is a promising strategy to protect against endothelial cell injury. Recently, synergistic effects between phytochemicals have received renewed attention for their role in the treatment of various diseases. Vitis vinifera L. and Centella asiatica are well-known medicinal plants with various biological effects. However, the combination of the two has not previously been studied. Here, we investigated the effects of V. vinifera L. leaf and C. asiatica extract combination (VCEC), a standardized herbal blend comprising V. vinifera L. leaf extract (VE) and C. asiatica extract (CE), for its antioxidant activity and for the protection of endothelial cells against hydrogen peroxide (H2O2)-mediated oxidative damage in human umbilical vein endothelial cells (HUVECs). VCEC showed higher antioxidant activity than VE or CE in oxygen radical antioxidant capacity assays. In HUVECs, VCEC significantly suppressed increases in the production of intracellular reactive oxygen species, decreased levels of nitric oxide and vascular endothelial-cadherin, and increased endothelial hyperpermeability triggered by H2O2. Treatment with VE or CE alone ameliorated HUVEC injury in a pattern similar to VCEC, although their effects were significantly weaker than VCEC. Overall, VCEC exhibited a substantial synergistic effect on protecting endothelial cells against oxidative damage through its antioxidant activity. Therefore, VCEC could be developed as a potential agent for reducing the risk of vascular diseases related to oxidative stress.

20.
Cryobiology ; 95: 90-96, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32504620

RESUMEN

Oxidative stress is one of the major issues associated with cryopreservation because it causes a marked reduction in the post-thaw quality of semen. This study investigated the ability of kinetin to preserve the structural and functional integrity of dog sperm during cryopreservation. Pooled ejaculates were divided into 5 equal aliquots, diluted with buffer 2 supplemented with different concentrations of kinetin (0, 25, 50, 100, and 200 µM), and finally cryopreserved. The optimal concentration of kinetin was 50 µM based on the significantly improved (P < 0.05) motion characteristics and viability of post-thaw sperm samples. Moreover, kinetin-supplemented samples exhibited significantly higher (P < 0.05) sperm counts with the intact plasma membrane, normal acrosomes, mitochondria, and chromatin than control. The beneficial effects of kinetin were also reflected by the significant increase in the expression levels of anti-apoptotic (B-cell lymphoma, BCL2) and protamine-related genes (protamine 2, PRM2; protamine 3, PRM3), and decrease in the expression of pro-apoptotic (BCL2-associated X, BAX) and mitochondrial reactive oxygen species-modulating genes (ROS modulator 1, ROMO1) in kinetin-supplemented sperm samples than in control. The results demonstrated that supplementation of buffer 2 with 50 µM kinetin is ideal for reducing the magnitude of oxidative damage during semen cryoprocessing and improving the post-thaw quality of dog semen.


Asunto(s)
Preservación de Semen , Animales , Criopreservación/métodos , Suplementos Dietéticos , Perros , Humanos , Cinetina , Masculino , Proteínas de la Membrana , Proteínas Mitocondriales , Análisis de Semen , Preservación de Semen/veterinaria , Motilidad Espermática , Espermatozoides
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