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ABSTRACT: Vitamin D deficiency is common and increases the likelihood of neonatal morbidities in preterm infants. This study assessed vitamin D levels at 1 month of age after 4âweeks of vitamin D supplementation and determined the association between vitamin D levels and neonatal morbidities.This retrospective study included preterm infants with birth weight <1500âg or gestational age <32âweeks born in our hospital between January 2018 and December 2019. They were administered 400 IU of oral vitamin D supplementation after birth according to our policy. The infants were then divided into sufficient (≥20âng/mL) and deficient (<20âng/mL) groups according to their serum vitamin D levels at 1 month of age.The vitamin D deficient and sufficient groups included 49 and 41 patients, respectively. The mean gestational age and birth weight. GHT in the vitamin D deficient group were 29.1â±â2.1âweeks and 1216.1â±â308.1âg, respectively, and 30.0â±â1.7âweeks and 1387.6â±â350.8âg, respectively, in the sufficient group. No significant differences were observed between the 2 groups in demographic and clinical outcomes except for bronchopulmonary dysplasia (BPD), which occurred significantly more often in the vitamin D-deficient group (odds ratio 2.21; 95% confidence interval, 1.85-2.78; Pâ=â.02).The results of our study suggest that vitamin D deficiency at 1 month of age is associated with BPD in preterm infants.
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Displasia Broncopulmonar/etiología , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/administración & dosificación , Vitaminas/administración & dosificación , Adulto , Peso al Nacer , Suplementos Dietéticos , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Estudios Retrospectivos , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Hepatitis B virus (HBV) infectious diseases currently remain incurable due to limitations of conventional antivirals such as incapability of eradicating HBV DNA, prolonged use, drug resistance, and virological relapse. KCT-01, a 30% ethanol extract consisting of Artemisia capillaris, Sanguisorba officinalis, and Curcuma longa, was newly developed. The objective of this study was to investigate pharmacological activities of KCT-01 against HBV using HepG2.2.15 cells and a hydrodynamic injection model. KCT-01 significantly lowered antigen secretion, virion production, and pgRNA synthesis in HepG2.2.15 cells without affecting cell viability. KCT-01 administration also resulted in significant decrease of serum virion production, liver covalently closed circular (ccc) DNA levels, and mRNA synthesis of cytokines in the liver of mice injected with HBV DNA hydrodynamically. Interestingly, coadministration of KCT-01 with entecavir enhanced its in vitro and in vivo antiviral activities. Moreover, safety of KCT-01 was assured up to 5000 mg/kg in rats in both single and repeated-dose preclinical studies. Taken together, our findings demonstrate that KCT-01 is capable of suppressing HBV replication and inflammatory cytokine production in in vitro and in vivo models without showing toxicity, suggesting the potential of using KCT-01 alone or in combination with entecavir as antiviral agent.
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Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays critical roles in the development and progression of hepatocellular carcinoma (HCC). Artemisia capillaris (AC) has been widely used to treat various liver diseases including HCC as a herbal medicine. The effects of AC on IL-6/STAT3 signaling axis in HCC cells and subsequent anticancer activity of AC against HCC were analyzed using HCC cell lines and HBV W4P-LHB-expressing NIH3T3 cell line, which has been shown to gain tumorigenicity by activating IL-6/STAT3 signaling in our previous study. AC extract significantly suppressed the growth and colony formation of HCC cells. In addition, it inhibited the activation of STAT3 by IL-6 and subsequent synthesis of downstream molecules in HCC and W4P-NIH3T3 cells. Consequently, migration of cells was significantly suppressed by the AC extract. Collectively, the findings suggest that AC extract is capable of conferring various antitumor effects against HCC through the modulation of the IL-6/STAT3 pathway. The results provide a basis for the therapeutic use of AC in the treatment of HCC. Identification of the compound responsible for the effect may lead to the development of a novel anticancer agent against HCC.
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Antineoplásicos Fitogénicos/farmacología , Artemisia/química , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Interleucina-6/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones , Células 3T3 NIH , Extractos Vegetales/farmacología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Extracts of Prunella vulgaris have been shown to exert antiestrogenic effects. To identify the compounds responsible for these actions, we isolated the constituents of P. vulgaris and tested their individual antiestrogenic effects. Rosmarinic acid, caffeic acid, ursolic acid (UA), oleanolic acid, hyperoside, rutin and betulinic acid (BA) were isolated from the flower stalks of P. vulgaris var. lilacina Nakai (Labiatae). Among these constituents, UA and BA showed significant antiestrogenic effects, measured as a decrease in the mRNA level of GREB1, an estrogen-responsive protein; the effects of BA were stronger than those of UA. UA and BA were capable of suppressing estrogen response element (ERE)-dependent luciferase activity and expression of estrogen-responsive genes in response to exposure to estradiol, further supporting the suppressive role of these compounds in estrogen-induced signaling. However, neither UA nor BA was capable of suppressing estrogen signaling in cells ectopically overexpressing estrogen receptor α (ERα). Furthermore, both mRNA and protein levels of ERα were reduced by treatment with UA or BA, suggesting that UA and BA inhibit estrogen signaling by suppressing the expression of ERα. Interestingly, both compounds enhanced prostate-specific antigen promoter activity. Collectively, these findings demonstrate that UA and BA are responsible for the antiestrogenic effects of P. vulgaris and suggest their potential use as therapeutic agents against estrogen-dependent tumors.
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Moduladores de los Receptores de Estrógeno/farmacología , Receptor alfa de Estrógeno/antagonistas & inhibidores , Receptor alfa de Estrógeno/metabolismo , Estrógenos/metabolismo , Triterpenos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Moduladores de los Receptores de Estrógeno/aislamiento & purificación , Receptor alfa de Estrógeno/genética , Femenino , Humanos , Células MCF-7 , Masculino , Proteínas de Neoplasias/genética , Triterpenos Pentacíclicos , Fitoterapia , Plantas Medicinales/química , Regiones Promotoras Genéticas , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Prunella/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Transducción de Señal/efectos de los fármacos , Triterpenos/aislamiento & purificación , Ácido Betulínico , Ácido UrsólicoRESUMEN
BACKGROUND: Human respiratory syncytial virus (hRSV) is a leading cause of severe lower respiratory infection and a major public health threat worldwide. To date, no vaccine or effective therapeutic agent has been developed. In a screen for potential therapeutic agents against hRSV, we discovered that an extract of Rosmarinus officinalis exerted a strong inhibitory effect against hRSV infection. Subsequent studies identified carnosic acid as a bioactive constituent responsible for anti-hRSV activity. Carnosic acid has been shown to exhibit potent antioxidant and anti-cancer activities. Anti-RSV activity of carnosic acid was further investigated in this study. METHODS: Effects of extracts from various plants and subfractions from R. officinalis on hRSV replication were determined by microneutralization assay and plaque assay. Several constituents were isolated from ethyl acetate fraction of R. officinalis and their anti-RSV activities were assessed by plaque assay as well as reverse-transcription quantitative PCR to determine the synthesis of viral RNAs. RESULTS: Among the tested bioactive constituents of R. officinalis, carnosic acid displayed the most potent anti-hRSV activity and was effective against both A- and B-type viruses. Carnosic acid efficiently suppressed the replication of hRSV in a concentration-dependent manner. Carnosic acid effectively suppressed viral gene expression without inducing type-I interferon production or affecting cell viability, suggesting that it may directly affect viral factors. A time course analysis showed that addition of carnosic acid 8 hours after infection still effectively blocked the expression of hRSV genes, further suggesting that carnosic acid directly inhibited the replication of hRSV. CONCLUSIONS: The current study demonstrates that carnosic acid, a natural compound that has already been shown to be safe for human consumption, has anti-viral activity against hRSV, efficiently blocking the replication of this virus. Carnosic acid inhibited both A- and B- type hRSV, while it did not affect the replication of influenza A virus, suggesting that its antiviral activity is hRSV-specific. Collectively, this study suggests the need for further evaluation of carnosic acid as a potential treatment for hRSV.
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Abietanos/aislamiento & purificación , Abietanos/farmacología , Antivirales/farmacología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Abietanos/toxicidad , Supervivencia Celular/efectos de los fármacos , Humanos , Pruebas de Neutralización , Extractos Vegetales/toxicidad , Reacción en Cadena en Tiempo Real de la Polimerasa , Virus Sincitial Respiratorio Humano/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rosmarinus/química , Ensayo de Placa ViralRESUMEN
OBJECTIVE: The purpose of this study is to investigate trends in the incidence of subarachnoid hemorrhage (SAH) in South Korea from 2006-2009. METHODS: We used the national health claim database managed by Health Insurance Review and Assessment Service, which contains all hospital records of every Korean citizen. Patients with SAH were defined as International Classification of Diseases-10 codes with a hospitalization period of ≥ 14 days or death within 14 days of hospitalization. We evaluated trends in the incidence of SAH during a 4-year period using the Cochran-Armitage trend test. RESULTS: We identified 35,263 patients with SAH among adult patients (≥ 18 years old) from 2005-2009. Age-adjusted SAH incidence rates decreased from 13.4 in 2006 to 12.4 in 2009/100,000 men (P = 0.0025) and women also showed a decrease from 19.4-17.3/100,000 (P < 0.0001). However, this decreasing pattern was not shown in patients less than 50 years of age. SAH incidence showed gender differences dependent on age; men who were 40 years old or less had a higher incidence than women. CONCLUSIONS: The age-adjusted incidence rates of SAH were slightly decreased in South Korea. Further research should be conducted to identify the clinical risk factors to reduce SAH incidence rates even more, especially in younger people.