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1.
Bioelectromagnetics ; 43(5): 336-346, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35544783

RESUMEN

A large number of studies on the biological effects of microwaves are carried out using rodents and cells, but the conditions are difficult to control, and the irradiation period is short; the results obtained have always been controversial and difficult to reproduce. In this study, we expose nematodes to an electromagnetic environment for a long-term and multigeneration period to explore the possible biological effects. Wild-type N2 strains of Caenorhabditis elegans are exposed to 9.4 GHz microwaves at a specific adsorption rate of 4 W/kg for 10 h per day from L1 larvae to adults. Then, adult worms are washed off, and the laid eggs are kept to hatch L1 larvae, which are continuously exposed to microwaves until passing through 20 generations. The worms of the 10th, 15th, and 20th generations are collected for index detection. Interestingly, we found that the fecundity of C. elegans decreased significantly in the exposed group from the 15th generation. At the same time, we found that the growth of C. elegans decreased, motility decreased, and oxidative stress occurred in the exposed group from the 10th generation, which may play roles in the decreased spawning in worms. We preliminarily believe that the microwave energy received by worms leads to oxidative stress, which causes a decrease in the spawning rate, and the underlying mechanism needs to be further studied. © 2022 Bioelectromagnetics Society.


Asunto(s)
Caenorhabditis elegans , Microondas , Animales , Caenorhabditis elegans/efectos de la radiación , Fenómenos Electromagnéticos
2.
Bioelectromagnetics ; 43(1): 5-13, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34962293

RESUMEN

Because of the extensive application of electromagnetic technology, its health impact on humans has attracted widespread attention. Due to the lack of a model organism with a stable response to electromagnetic waves, the research conclusions on the biological effects of electromagnetic waves have been vague. Therefore, the aim of this study was to investigate the effects of irradiation by pulsed 9.4 GHz high-power microwaves with a peak power density of 2126 W/cm2 using Caenorhabditis elegans. The development, movement, egg production, ROS, and lifespan of C. elegans were detected at different times after irradiation with different repetitive frequencies of 10, 20, and 50 Hz for 30 min. The results indicated that no obvious changes in basic life indices were induced compared with the sham radiation group, but the survival rate of positive control was significantly decreased compared with other groups, which is of interest for microwave protection research based on C. elegans and provides data for updating safety standards with respect to pulsed high-peak power microwave. © 2021 Bioelectromagnetics Society.


Asunto(s)
Caenorhabditis elegans , Microondas , Animales , Fenómenos Electromagnéticos , Humanos
3.
Integr Cancer Ther ; 20: 15347354211031650, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34261372

RESUMEN

BACKGROUND: Traditional Chinese medicine (TCM) is widely integrated into cancer care in China. An overview in 2011 identified 2384 randomized and non-randomized controlled trials (RCTs, non-RCTs) on TCM for cancer published in the Chinese literature. This article summarizes updated evidence of RCTs on TCM for cancer care. METHODS: We searched 4 main Chinese databases: China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed, and Wanfang. RCTs on TCM used in cancer care were analyzed in this bibliometric study. RESULTS: Of 5834 RCTs (477 157 cancer patients), only 62 RCTs were indexed in MEDLINE. The top 3 cancers treated were lung, stomach, and breast cancer. About 4752 RCTs (81.45%) tested TCM combined with conventional treatment, and 1082 RCTs (18.55%) used TCM alone for treating symptoms and side-effects. Herbal medicine was the most frequently used TCM modality (5087 RCTs; 87.20%). The most frequently reported outcome was symptom improvement (3712 RCTs; 63.63%) followed by quality of life (2725 RCTs; 46.71%), and biomarkers (2384 RCTs; 40.86%). The majority of RCTs (4051; 69.44%) concluded there were beneficial effects using either TCM alone or TCM plus conventional treatment compared with conventional treatment. CONCLUSION: Substantial randomized trials demonstrated different types/stages of cancer were treated by various TCM modalities, alone or in combination with conventional medicine. Further evaluation on the effects and safety of TCM modalities focusing on outcomes such as quality of life is required.


Asunto(s)
Neoplasias de la Mama , Medicamentos Herbarios Chinos , China , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Medicina Tradicional China , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
Neurotox Res ; 39(4): 1160-1170, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33826131

RESUMEN

Copper oxide nanoparticles (CuONPs) are widely used in pharmaceutical, food, and textile industries. They have been shown to cause lung, liver, and kidney damage. However, whether an intratracheal instillation of CuONPs would affect the brain and its underlying mechanisms remain poorly studied. In this study, healthy C57BL/6J male mice were equally subdivided into control group, low-dose (30 µg/animal), medium-dose (50 µg/animal), and high-dose (100 µg/animal) CuONPs-treated groups. Mice were subjected to acute exposure of CuONPs via intratracheal instillation. Brain histopathology, inflammatory factors, oxidative stress markers, and mitochondrial function-related protein expression were determined. Our results demonstrated that CuONPs caused a dose-dependent brain damage in mice. Histopathological changes in the brain, elevation of inflammatory factors (Tnf, Il-6), and significant alterations in oxidative stress markers were also observed after treatment with CuONPs. Intriguingly, we did not observe infiltration of macrophage cell. Moreover, Tim23, TFAM, and MFN2 protein expression levels showed the decreasing trend after treatment with CuONPs. Taken together, these results indicate that pulmonary exposure to CuONPs induces pathological damage, inflammation, oxidative stress, and mitochondrial dysfunction in the cerebral cortex, suggesting that neurotoxicity caused by pulmonary exposure of CuONPs needs more attention from the public and relevant departments.


Asunto(s)
Cobre/toxicidad , Pulmón/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Tráquea/efectos de los fármacos , Animales , Cobre/administración & dosificación , Relación Dosis-Respuesta a Droga , Pulmón/metabolismo , Masculino , Nanopartículas del Metal/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Tráquea/metabolismo
5.
Trials ; 22(1): 85, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482853

RESUMEN

BACKGROUND: Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease and a leading cause of death worldwide. The clinical utility of commonly used lipid-lowering drugs such as statins and fibrates is sometimes limited by the occurrence of various adverse reactions. Recently, berberine (BBR) has received increasing attention as a safer and more cost-effective option to manage dyslipidemia. Thus, a high-quality randomized controlled trial to evaluate the efficacy and safety of BBR in the treatment of dyslipidemia is deemed necessary. METHODS/DESIGN: This is a randomized, double-blind, and placebo-controlled clinical trial. A total of 118 patients with dyslipidemia will be enrolled in this study and randomized into two groups at a ratio of 1:1. BBR or placebo will be taken orally for 12 weeks. The primary outcome is the percentage of low-density lipoprotein cholesterol reduction at week 12. Other outcome measures include changes in other lipid profiles, high sensitivity C-reactive protein, blood pressure, body weight, Bristol Stool Chart, traditional Chinese medicine symptom form, adipokine profiles, and metagenomics of intestinal microbiota. Safety assessment includes general physical examination, blood and urine routine test, liver and kidney function test, and adverse events. DISCUSSION: This trial may provide high-quality evidence on the efficacy and safety of BBR for dyslipidemia. Importantly, the findings of this trial will help to identify patient and disease characteristics that may predict favorable outcomes of treatment with BBR and optimize its indication for clinical use. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021361 . Registered on 17 February 2019.


Asunto(s)
Berberina , Medicamentos Herbarios Chinos , Dislipidemias , Berberina/efectos adversos , Manejo de Datos , Método Doble Ciego , Dislipidemias/diagnóstico , Dislipidemias/tratamiento farmacológico , Humanos , Medicina Tradicional China , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
6.
J Integr Neurosci ; 19(4): 679-685, 2020 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-33378842

RESUMEN

Postoperative cognitive dysfunction is a common neurological complication, characterized by impaired learning and memory, that occurs after anesthesia and surgery, especially in elderly patients. The traditional Chinese medicine baicalin is known to have neuroprotective effects. Therefore, we have investigated whether baicalin can improve postoperative cognitive impairment in aged rats after splenectomy. A total of 60 Sprague Dawley rats were randomly divided, equally, into the splenectomy, sham operation (Sham), low-dose baicalin (Baicalin A), medium-dose baicalin (Baicalin B), and high-dose baicalin (Baicalin C) groups. Splenectomy was performed under anesthesia in all groups except for the Sham group, in which an appropriate concentration of saline was administered. The effects of baicalin on learning and memory were examined by the Y-maze behavioral experiments. Although splenectomy had a negative effect on cognitive function in the acute phase, all the rats spontaneously recovered on a postoperative day seven. Nonetheless, in the acute phase, the medium and high doses of baicalin slightly alleviated these effects of the procedure. The protein expression of the inflammatory cytokines tumor necrosis factor-α, Interleukin-6, and Interleukin-1ß was assessed using enzyme-linked immunosorbent assay. Their levels were elevated in the acute phase but were returned to normal with the medium and high dose of baicalin. Real-time PCR analysis of the mRNA expression of the N-methyl-D-aspartic acid receptor TNF-α, which is known to be involved in long-term potentiation, revealed that baicalin promoted its transcription. Thus, the findings indicate that baicalin may improve postoperative cognitive memory dysfunction in postoperative cognitive dysfunction in rats via anti-inflammatory mechanisms and pathways that involve N-methyl-D-aspartate receptor 2B subunit.


Asunto(s)
Envejecimiento , Antiinflamatorios no Esteroideos/farmacología , Flavonoides/farmacología , Inflamación/prevención & control , Aprendizaje por Laberinto/efectos de los fármacos , Complicaciones Cognitivas Postoperatorias/prevención & control , Esplenectomía/efectos adversos , Enfermedad Aguda , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Conducta Animal/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Flavonoides/administración & dosificación , Inflamación/etiología , Inflamación/inmunología , Inflamación/metabolismo , Masculino , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/inmunología , Complicaciones Cognitivas Postoperatorias/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
7.
Int J Mol Med ; 46(5): 1783-1793, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32901861

RESUMEN

Phosphorus reduction can prevent against vascular calcification (VC) in chronic kidney disease (CKD), but the mechanisms underlying its actions remain unclear. The aim of the present study was to determine the effect of a fortified phosphorus­lowing treatment on VC in CKD. Serum levels of creatinine, blood urea nitrogen (BUN), fibroblast growth factor 23 (FGF23), calcium and phosphorus, and the plasma levels of parathyroid hormone (PTH) were determined in an animal model of CKD treated with or without lanthanum. Haematoxylin and eosin (H&E) staining was performed to examine the structure of kidney tissues. Western blot analysis was performed to compare the levels of total­ (t­) extracellular signal­related kinase (ERK) and phospho­ (p­)ERK among the different experimental groups to investigate the effect of FGF23 on p­ERK expression. In the animal model, administration of adenine increased the serum levels of creatinine, BUN, FGF23 and phosphorus but decreased the serum levels of calcium. In addition, adenine treatment increased the plasma levels of PTH. H&E staining showed that lanthanum treatment did not alter the severity of renal cortex injury. Furthermore, the levels of t­ERK levels did not notably differ between the Adenine­free, Adenine­vehicle and Adenine­lanthanum groups, whereas the levels of p­ERK and aortic calcium in the Adenine­vehicle group were significantly upregulated. In addition, ectopic overexpression of FGF23 increased the levels of p­ERK, Msx2 and Osx in a dose­dependent manner. Furthermore, a total of 48 patients were enrolled in the present study. In the fortified group, the serum levels of FGF23, phosphorus and PTH were significantly reduced, whereas the serum levels of calcium were significantly increased, indicating an enhanced preventative effect in the fortified group. The results of the present study suggest that FGF23 may be used as a therapeutic target in the management and prevention of VC in CKD.


Asunto(s)
Factores de Crecimiento de Fibroblastos/metabolismo , Lantano/farmacología , Fósforo/metabolismo , Sustancias Protectoras/farmacología , Insuficiencia Renal Crónica/tratamiento farmacológico , Calcificación Vascular/tratamiento farmacológico , Animales , Nitrógeno de la Urea Sanguínea , Calcio/metabolismo , Creatinina/sangre , Modelos Animales de Enfermedad , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/metabolismo , Calcificación Vascular/sangre , Calcificación Vascular/metabolismo
8.
J Clin Lab Anal ; 34(9): e23376, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32537819

RESUMEN

BACKGROUND: The prevalence of vitamin D deficiency and insufficiency is extremely high in pregnant women worldwide. However, the association between single nucleotide polymorphisms (SNPs) in vitamin D metabolic pathway genes and 25-hydroxyvitamin D (25(OH)D) concentration among Chinese pregnant women is seldom reported. The risk of adverse neonatal outcomes due to maternal vitamin D deficiency has not been well investigated. METHODS: A total of 815 pregnant women and 407 infants were enrolled in this study. Serum 25(OH)D concentration was detected. DNA was extracted from the maternal blood for genotyping genetic SNPs in vitamin D pathway. An XGBoost model was established based on SNPs combined with external variables. RESULTS: Mean serum 25(OH)D level was 15.67 ± 7.98 ng/mL among the pregnant women. Seventy-five percent of pregnant women had 25(OH)D deficiency in China. SNPs of GC (rs17467825, rs4588, rs2282679, rs2298850, and rs1155563) were significantly associated with maternal 25(OH)D concentration. The influence of variants of rs17467825, rs4588, rs2282679, and rs2298850 on maternal 25(OH)D might be modified by vitamin D supplementation and sunshine exposure. An XGBoost model was established for monitoring 25(OH)D status in pregnant women and provided clinical advice to reduce the risk of 25(OH)D deficiency. Mothers with 25(OH)D deficiency hinted a risk for macrosomia. CONCLUSION: A high prevalence of vitamin D deficiency in China has been confirmed. A clinical model was established to guide pregnant women to supplement vitamin D according to genotype. Furthermore, we suggest the effect of maternal vitamin D status on the risk of macrosomia.


Asunto(s)
Complicaciones del Embarazo , Deficiencia de Vitamina D , Proteína de Unión a Vitamina D/genética , Adulto , China , Suplementos Dietéticos , Femenino , Humanos , Lactante , Polimorfismo de Nucleótido Simple/genética , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/genética , Vitamina D , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/genética , Adulto Joven
9.
J Tradit Chin Med ; 36(5): 596-605, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-29933194

RESUMEN

OBJECTIVE: To compare the clinical efficacy of Traditional Chinese Medicine (TCM) to Western Medicine in the treatment of primary Sjögren's syndrome (pSS). METHODS: We collected randomized controlled trials of TCM vs Western Medicine for the treatment of pSS in Chinese and foreign databases. The study quality was evaluated as suggested in the Cochrane Handbook. The Meta-analysis was performed using Review Manager 5.0 statistical software. RESULTS: A total of 31 randomized controlled trials with 2137 cases were retrieved. The efficiencies of TCM and control treatments were 87.18% and 65.63% , respectively. The results of heterogeneity tests showed that the data were homogeneous (P = 0.83), thus a fixed effects model was used for analysis. The results revealed an odds ratio of 3.74 with a 95% confidence interval of 2.99-4.69. The overall effectiveness value was 11.48 (P < 0.000 01). These results suggest the efficacy of TCM therapy for pSS better than Western Medicine. CONCLUSION: Although our findings reveal that the TCM treatment of pSS had significant advantages over its counterpart, there were some flaws in the studies included. The findings warrant further investigation.


Asunto(s)
Medicamentos Herbarios Chinos/administración & dosificación , Síndrome de Sjögren/tratamiento farmacológico , Humanos , Medicina Tradicional China , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
Food Funct ; 5(9): 2243-51, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25058795

RESUMEN

Kang-fu-ling (KFL) is a polybotanical dietary supplement with antioxidant properties. This study aimed to evaluate the potential protective effects of KFL on cognitive deficit induced by high-power microwave (HPM) and the underlying mechanism for this neuroprotection. The electron spin resonance technique was employed to evaluate the free radical scavenging activity of KFL in vitro and KFL exhibited scavenging hydroxyl radical activity. KFL at doses of 0.75, 1.5 and 3 g kg(-1) and vehicle were administered orally once daily for 14 days to male Wistar rats after being exposed to 30 mW cm(-2) HPM for 15 minutes. KFL reversed HPM-induced memory loss and the histopathological changes in hippocampus of rats. In addition, KFL displayed a protective effect against HPM-induced oxidative stress and activated the nuclear factor-E2-related factor 2 (Nrf2) and its target genes in the hippocampus of rats. The Nrf2-antioxidant response element (ARE) signaling pathway may be involved in the neuroprotective effects of KFL against HPM-induced oxidative stress. In summary, the dietary supplement KFL is a promising natural complex, which ameliorates oxidative stress, with neuroprotective effects against HPM.


Asunto(s)
Antioxidantes/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Microondas/efectos adversos , Fármacos Neuroprotectores/administración & dosificación , Animales , Suplementos Dietéticos/análisis , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/efectos de la radiación , Masculino , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Wolfiporia
11.
PLoS One ; 9(7): e101532, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24992449

RESUMEN

BACKGROUND: The prevention and treatment of Microwave-caused cardiovascular injury remains elusive. This study investigated the cardiovascular protective effects of compound Chinese medicine "Kang Fu Ling" (KFL) against high power microwave (HPM)-induced myocardial injury and the role of the mitochondrial permeability transition pore (mPTP) opening in KFL protection. METHODS: Male Wistar rats (100) were divided into 5 equal groups: no treatment, radiation only, or radiation followed by treatment with KFL at 0.75, 1.5, or 3 g/kg/day. Electrocardiography was used to Electrophysiological examination. Histological and ultrastructural changes in heart tissue and isolated mitochondria were observed by light microscope and electron microscopy. mPTP opening and mitochondrial membrane potential were detected by confocal laser scanning microscopy and fluorescence analysis. Connexin-43 (Cx-43) and endothelial nitric oxide synthase (eNOS) were detected by immunohistochemistry. The expression of voltage-dependent anion channel (VDAC) was detected by western blotting. RESULTS: At 7 days after radiation, rats without KFL treatment showed a significantly lower heart rate (P<0.01) than untreated controls and a J point shift. Myocyte swelling and rearrangement were evident. Mitochondria exhibited rupture, and decreased fluorescence intensity, suggesting opening of mPTP and a consequent reduction in mitochondrial membrane potential. After treatment with 1.5 g/kg/day KFL for 7 d, the heart rate increased significantly (P<0.01), and the J point shift was reduced flavorfully (P<0.05) compared to untreated, irradiated rats; myocytes and mitochondria were of normal morphology. The fluorescence intensities of dye-treated mitochondria were also increased, suggesting inhibition of mPTP opening and preservation of the mitochondrial membrane potential. The microwave-induced decrease of Cx-43 and VDAC protein expression was significantly reversed. CONCLUSION: Microwave radiation can cause electrophysiological, histological and ultrastructural changes in the heart. KFL at 1.5 g/kg/day had the greatest protective effect on these cardiovascular events. mPTP plays an important role in the protective effects of KFL against microwave-radiation-induced myocardial injury.


Asunto(s)
Medicamentos Herbarios Chinos/química , Lesiones Cardíacas/prevención & control , Microondas , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Conexina 43/metabolismo , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Lesiones Cardíacas/etiología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/ultraestructura , Miocardio/metabolismo , Miocardio/ultraestructura , Miocitos Cardíacos/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Canales Aniónicos Dependientes del Voltaje/metabolismo , Wolfiporia
12.
Int J Mol Sci ; 14(10): 20326-39, 2013 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-24129171

RESUMEN

MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play important roles in gene expressions at transcriptional and post-transcriptional stages in mammalian brain. So far, a growing number of porcine miRNAs and their function have been identified, but little is known regarding the porcine developing hypothalamus and pituitary. In the present study, Solexa sequencing analysis showed 14,129,397 yielded reads, 6,680,678 of which were related to 674 unique miRNAs. After a microarray assay, we detected 175 unique miRNAs in the hypothalamus, including 136 previously known miRNAs and 39 novel candidates, while a total of 140 miRNAs, including 104 known and 36 new candidate miRNAs, were discovered in pituitary. More importantly, 37 and 30 differentially expressed miRNAs from several developmental stages of hypothalamus and pituitary were revealed, respectively. The 37 differentially expressed miRNAs in hypothalamus represented 6 different expression patterns, while the 30 differentially expressed miRNAs in pituitary represented 7 different expression patterns. To clarify potential target genes and specific functions of these differentially expressed miRNAs in hypothalamus and pituitary, TargetScan and Gorilla prediction tools were then applied. The current functional analysis showed that the differentially expressed miRNAs in hypothalamus and pituitary shared many biological processes, with the main differences being found in tissue-specific processes including: CDP-diacylglycerol biosynthetic/metabolic process; phosphatidic acid biosynthetic/metabolic process; energy reserve metabolic process for hypothalamus; adult behavior; sterol transport/homeostasis; and cholesterol/reverse cholesterol transport for pituitary. Overall, this study identified miRNA profiles and differentially expressed miRNAs among various developmental stages in hypothalamus and pituitary and indicated miRNA profiles change with age and brain location, enhancing our knowledge about spatial and temporal expressions of miRNAs in the porcine developing brain.


Asunto(s)
Hipotálamo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Hipófisis/metabolismo , Transcriptoma/genética , Animales , Perfilación de la Expresión Génica , Porcinos
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