RESUMEN
Orthodontic tooth movement (OTM) is induced by biomechanical stimuli and facilitated by periodontal tissue remodeling, where multiple immune cells participate in this progression. It has been demonstrated that macrophage is essential for mechanical force-induced tissue remodeling. In this study, we first found that mechanical force significantly induced macrophage proliferation in human periodontal samples and murine OTM models. Yet, how macrophages perceive mechanical stimuli and thereby modulate their biological behaviors remain elusive. To illustrate the mechanisms of mechanical force-induced macrophage proliferation, we subsequently identified Piezo1, a novel mechanosensory ion channel, to modulate macrophage response subjected to mechanical stimuli. Mechanical force upregulates Piezo1 expression in periodontal tissues and cultured bone-marrow-derived macrophages (BMDMs). Remarkably, suppressing Piezo1 with GsMTx4 retarded OTM through reduced macrophage proliferation. Moreover, knockdown of Piezo1 effectively inhibited mechanical force-induced BMDMs proliferation. RNA sequencing was further performed to dissect the underlying mechanisms of Piezo1-mediated mechanotransduction utilizing mechanical stretch system. We revealed that Piezo1-activated AKT/GSK3ß signaling was closely associated with macrophage proliferation upon mechanical stimuli. Importantly, Cyclin D1 (Ccnd1) was authenticated as a critical downstream factor of Piezo1 that facilitated proliferation by enhancing Rb phosphorylation. We generated genetically modified mice in which Ccnd1 could be deleted in macrophages in an inducible manner. Conditional ablation of Ccnd1 inhibited periodontal macrophage proliferation and therefore delayed OTM. Overall, our findings highlight that proliferation driven by mechanical force is a key process by which macrophages infiltrate in periodontal tissue during OTM, where Piezo1-AKT-Ccnd1 axis plays a pivotal role.
Asunto(s)
Ciclina D1 , Canales Iónicos , Macrófagos , Proteínas Proto-Oncogénicas c-akt , Animales , Proliferación Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Humanos , Canales Iónicos/genética , Canales Iónicos/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Mecanotransducción Celular , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Orthodontic tooth movement (OTM), a process of alveolar bone remodelling, is induced by mechanical force and regulated by local inflammation. Bone marrow-derived mesenchymal stem cells (BMSCs) play a fundamental role in osteogenesis during OTM. Macrophages are mechanosensitive cells that can regulate local inflammatory microenvironment and promote BMSCs osteogenesis by secreting diverse mediators. However, whether and how mechanical force regulates osteogenesis during OTM via macrophage-derived exosomes remains elusive. RESULTS: Mechanical stimulation (MS) promoted bone marrow-derived macrophage (BMDM)-mediated BMSCs osteogenesis. Importantly, when exosomes from mechanically stimulated BMDMs (MS-BMDM-EXOs) were blocked, the pro-osteogenic effect was suppressed. Additionally, compared with exosomes derived from BMDMs (BMDM-EXOs), MS-BMDM-EXOs exhibited a stronger ability to enhance BMSCs osteogenesis. At in vivo, mechanical force-induced alveolar bone formation was impaired during OTM when exosomes were blocked, and MS-BMDM-EXOs were more effective in promoting alveolar bone formation than BMDM-EXOs. Further proteomic analysis revealed that ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3) was enriched in MS-BMDM-EXOs compared with BMDM-EXOs. We went on to show that BMSCs osteogenesis and mechanical force-induced bone formation were impaired when UCHL3 was inhibited. Furthermore, mothers against decapentaplegic homologue 1 (SMAD1) was identified as the target protein of UCHL3. At the mechanistic level, we showed that SMAD1 interacted with UCHL3 in BMSCs and was downregulated when UCHL3 was suppressed. Consistently, overexpression of SMAD1 rescued the adverse effect of inhibiting UCHL3 on BMSCs osteogenesis. CONCLUSIONS: This study suggests that mechanical force-induced macrophage-derived exosomal UCHL3 promotes BMSCs osteogenesis by targeting SMAD1, thereby promoting alveolar bone formation during OTM.
Asunto(s)
Células Madre Mesenquimatosas , MicroARNs , Proteína Smad1 , Ubiquitina Tiolesterasa , Diferenciación Celular/fisiología , Macrófagos/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis , Proteómica , Ubiquitina Tiolesterasa/metabolismo , Proteína Smad1/metabolismoRESUMEN
BACKGROUND: Progesterone is widely used to improve the adverse pregnancy outcomes related to vaginal bleeding during early pregnancy. However, the evidence of its effectiveness is equivocal. METHODS: Six thousand six hundred fifteen mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on vaginal bleeding, progesterone administration in early pregnancy were obtained at enrolment. Birth outcomes were obtained from the hospital notes. Body weight of the infants at 12 months of age was collected by telephone interview. Multivariable logistic regression was conducted to estimate the effect of vaginal bleeding and progesterone administration in early pregnancy on birth outcomes and weight status of infants at 12 months of age. RESULTS: 21.4% (1418/6615) participants experienced bleeding in early pregnancy, and 47.5% (674/1418) of them were treated with progesterone. There were no significant associations between progesterone supplementation in early pregnancy and offspring outcomes. Compared to women without bleeding or any therapy, women with bleeding and progesterone therapy experienced increased risk of preterm (OR 1.74, 95% CI 1.21-2.52), and delivering a small-for-gestational-age (SGA) (OR 1.46, 95% CI 1.07-1.98) or low birth weight (LBW) (OR 2.10, 95% CI 1.25-3.51) neonate, and offspring of them had an increased risk of weight for age z-score (WAZ) < -1 at 12 months of age (OR 1.79, 95%CI 1.01-3.19). CONCLUSIONS: Offspring of mothers with bleeding and progesterone therapy were more likely to be a premature, SGA or LBW neonate, and had lower weight at 12 months of age. Progesterone supplementation may have no beneficial effect on improving adverse offspring outcomes related to early vaginal bleeding. TRIAL REGISTRATION: TMCHC was registered at clinicaltrials.gov as NCT03099837 on 4 April 2017.
Asunto(s)
Nacimiento Prematuro , Progesterona , Hemorragia Uterina , Suplementos Dietéticos , Femenino , Retardo del Crecimiento Fetal , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Embarazo , Nacimiento Prematuro/epidemiología , Progesterona/uso terapéutico , Estudios Prospectivos , Hemorragia Uterina/tratamiento farmacológico , Hemorragia Uterina/epidemiologíaRESUMEN
Retention after treatment and effective anchorage control are two essential factors in orthodontics. Our study aimed to explore the effects of fucoidan on orthodontic tooth movement (OTM) and the involvement of macrophages. We established a murine OTM model to test the effect of fucoidan administration. We found that mice injected with fucoidan had a deceleration in OTM and a higher bone mineral density. Moreover, fucoidan increased the proportion of F4/80+ CD206+ macrophages and promoted the messenger RNA expression of Arg-1, CD206, and IL-10 at both in vivo and in vitro levels. In addition, macrophages showed lower expression of TNF-α, IL-1ß, and IL-6 and a decrease in F4/80+ CD11c+ cells. Mechanistically, the level of phosphorylated STAT3 was elevated in unpolarized and restorative macrophages after treatment with fucoidan. Taken together, our findings suggest that fucoidan treatment inhibits OTM and enhances the stability of teeth after movement by promoting restorative macrophages through the STAT3 pathway.
Asunto(s)
Macrófagos/metabolismo , Polisacáridos/farmacología , Factor de Transcripción STAT3/genética , Anomalías Dentarias/tratamiento farmacológico , Animales , Densidad Ósea/genética , Polaridad Celular/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-10/genética , Activación de Macrófagos/efectos de los fármacos , Macrófagos/patología , Ratones , Osteoclastos/efectos de los fármacos , Anomalías Dentarias/genética , Anomalías Dentarias/patología , Técnicas de Movimiento Dental , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Objective To assess the effects of Jianpi Shengxue Granule (JSG) on the fertility and early embryo development in rats. Methods Totally 176 SD rats were stratified by sex, and divided into 4 groups, i.e., the control group, low, medium, high dose JSG treatment groups. Rats in the 3 JSG treatment groups were administered with JSG at 0, 1. 16, 3. 48, 5. 80 g/kg per day by gastrogavage, re- spectively. After 2 weeks of administration for females and 4 weeks of administration for males, males and females were caged in the ratio of 1:1. Females were administered to the gestation day 7. Males were administered for 59 -63 days until the day before anatomy. All parental generations were anatomized to observe signs and morphologies. Pathological examination was performed. General toxicity was detected. The testis and epididymis were weighed. Spermatozoa number was counted from epididymis, and repro- duction toxicity of sperm motility was checked. The numbers of corpus luteum, live fetus, dead fetus, and absorbed fetus were counted. The implantation number was calculated to observe early embryo de- velopment toxicity. Results (1) General toxicity: The body weight growth slowed down in male rats of the high dose JSG treatment group. No abnormality was found in low and medium dose JSG treatment groups. (2)Fertility toxicity: There was no obvious toxic effect on testis, epididymis, and spermatozoa number from epididymis sperm in all JSG treatment groups. (3) Early embryo development toxicity: No significant effect on the formation of early embryos was found in all JSG treatment groups. Conclusions Certain gastrointestinal toxicity of JSG might exist to some extent. The dose for non-adverse effect of JSG on fertility and early embryo development was 3. 38 g/kg per day. No obvious fertility or early embryo development toxicity occurred in each JSG treatment group.
Asunto(s)
Medicamentos Herbarios Chinos , Desarrollo Embrionario , Fertilidad , Motilidad Espermática , Animales , Peso Corporal , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/toxicidad , Desarrollo Embrionario/efectos de los fármacos , Epidídimo , Femenino , Masculino , Tamaño de los Órganos , Ratas , Ratas Sprague-Dawley , Motilidad Espermática/efectos de los fármacos , EspermatozoidesRESUMEN
Osteoporosis is a systemic bone disease characterized by decreased bone mass that is tightly regulated by the coordinated actions of osteoclasts and osteoblasts. Apoptosis as a precise programmed cell death involves a cascade of gene expression events which are mechanistically linked to the regulation of bone metabolism. Nevertheless, the critical biomolecules involved in regulating cell apoptosis in osteoporosis remain unknown. To gain a deeper insight into the relationship between apoptosis and osteoporosis, this study integrated the sequencing results of human samples and using a machine learning workflow to overcome the limitations of a single study. Among all immune cell populations, we assessed the apoptotic level and portrayed the distinct subtypes and lineage differentiation of monocytic cells in osteoporotic tissues. Osteoclasts expressed a higher level of Spermidine/spermine-N1-Acetyltransferase1 (SAT1) during osteoclastogenesis which prevented osteoclasts apoptosis and facilitate osteoporosis progression. In addition, Berenil, one potent SAT1 inhibitor, increased osteoclast apoptosis and reversed the bone loss in the femurs of a murine ovariectomy model. In summary, Berenil promotes osteoclast apoptosis, inhibits the bone resorption and improves the abnormal bone structure in vitro and in vivo models by targeting SAT1, demonstrating its potential as a precise therapeutic strategy for clinical osteoporosis treatment.
Asunto(s)
Acetiltransferasas , Apoptosis , Osteoclastos , Osteoporosis , Apoptosis/efectos de los fármacos , Animales , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoclastos/efectos de los fármacos , Osteoporosis/patología , Osteoporosis/prevención & control , Osteoporosis/metabolismo , Humanos , Femenino , Ratones , Acetiltransferasas/metabolismo , Acetiltransferasas/genética , Ratones Endogámicos C57BL , Resorción Ósea/metabolismo , Resorción Ósea/patología , Resorción Ósea/prevención & control , Ovariectomía , Osteogénesis/efectos de los fármacos , Diferenciación Celular , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: To observe the clinical efficacy of bushen huoxue recipe (BHR) combined estrogen and progesterone in treating premature ovarian failure (POF), and to explore an effective treatment program of POF by integrative medicine. METHODS: Totally 265 POF patients were randomly assigned to 3 groups, i.e., Group I (86 cases, treated by BHR),Group II (88 cases,treated by conjugated estrogens and medroxyprogesterone acetate), and Group III (91 cases,treated by BHR +conjugated estrogens and medroxyprogesterone acetate). The therapeutic course for each group was 6 months. The main symptoms (including menstrual cycle, hectic fever, night sweat, vaginal dryness, and low libido), laboratory indices [including follicle stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), and inhibin B (INH-B)], B-ultrasound indicators (including endometrial thickness, ovarian volume, and antral follicle count), and adverse reactions were observed in the three groups at the end of treatment and 6 months after treatment. RESULTS: Compared with before treatment, the main symptoms, laboratory indices, and B-ultrasound indicators were statistically improved in the three groups at the end of treatment and 6 months after treatment (P <0.05, P <0.01). Better effects were obtained in Group III in improving symptoms of the menstrual cycle, vaginal dryness, and low libido, lowering levels of FSH and LH, elevating levels of E2and INH-B, and ameliorating the endometrial thickness, the ovarian volume, and the antral follicle count (P <0.05, P <0.01). No obvious adverse reaction occurred in the three groups. CONCLUSION: BHR combined estrogen and progesterone showed better clinical efficacy than use of BHR or estrogen/progesterone alone, indicating it was an effective treatment program for POF.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Medicina Integrativa , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Adulto , Estrógenos/uso terapéutico , Femenino , Humanos , Progesterona/uso terapéuticoRESUMEN
During mechanical force-induced alveolar bone remodeling, macrophage-mediated local inflammation plays a critical role. Yet, the detailed heterogeneity of macrophages is still unknown. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages during alveolar bone remodeling. We identified macrophage subclusters with specific gene expression profiles and functions. CellChat and trajectory analysis revealed a central role of the Ccr2 cluster during development, with the CCL signaling pathway playing a crucial role. We further demonstrated that the Ccr2 cluster modulated bone remodeling associated inflammation through an NF-κB dependent pathway. Blocking CCR2 could significantly reduce the Orthodontic tooth movement (OTM) progression. In addition, we confirmed the variation of CCR2+ macrophages in human periodontal tissues. Our findings reveal that mechanical force-induced functional shift of the Ccr2 macrophages cluster mediated by NF-κB pathway, leading to a pro-inflammatory response and bone remodeling. This macrophage cluster may represent a potential target for the manipulation of OTM.
Asunto(s)
Remodelación Ósea/fisiología , Macrófagos/fisiología , Receptores CCR2/genética , Técnicas de Movimiento Dental , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Periodoncio , Análisis de Secuencia de ARN , Transducción de Señal , Análisis de la Célula IndividualRESUMEN
Associations between environmental tobacco smoke (ETS) and the risk of adverse birth outcomes may be confounded. We aimed to clarify the associations of ETS before and during pregnancy with the risk of adverse birth outcomes and determine whether the associations were modified by key potential confounders. A total of 7147 non-smoking mothers from the Tongji Maternal and Child Health Cohort (TMCHC) in Wuhan, China, were included in the final analyses. ETS status was self-reported by pregnant women at their first antenatal care visit before 16 gestational weeks. Information on birth outcomes was extracted from delivery records. Poisson regression was used to identify the association between ETS before and during pregnancy and the risk of adverse birth outcomes. Exposures to ETS before and during pregnancy were reported by 645 (9.0%) and 464 (6.5%) mothers, respectively. Compared with no ETS, continued ETS during pregnancy was associated with an increased risk of preterm birth (PTB) (RR: 1.55, 95% CI: 1.07, 2.25) after adjustment for potential confounders. The association remained consistent in medically indicated PTB and late PTB. The risk of PTB associated with continued ETS during pregnancy was significantly increased in mothers more educated (P for interaction < 0.05). However, the increased risk of low birth weight (LBW) or small for gestational age (SGA) births by ETS during pregnancy was not observed. Exposure to ETS during pregnancy was associated with a higher risk of PTB, but not LBW or SGA births in a Chinese birth cohort.
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Nacimiento Prematuro , Contaminación por Humo de Tabaco , Niño , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Factores de Riesgo , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
AIMS: Iron supplementation has been recommended for healthy pregnancy, but concerns have been raised regarding the potential adverse effects. We sought to examine the impact of periconceptional iron supplement use on subsequent gestational diabetes mellitus (GDM) risk. METHODS: Participants (N = 5101) with information on periconceptional micronutrient supplementation and diagnosis of GDM were involved. Information on iron supplementation and general characteristics were collected at enrollment and follow-up visits. GDM was diagnosed by oral glucose tolerance tests (OGTT) conducted at 24-28 weeks of gestation. Robust Poisson regression model was used to estimate the relative risks (RRs) and 95% confidence intervals (CI) for the effect of iron supplement use on GDM. RESULTS: 10.5% of the participants were diagnosed with GDM and the incidence was significantly higher in users with iron >30 mg/d for more than 3 months (Iron >30-L) than in nonusers. Adjusted RRs (95% CI) were 1.53 (1.21, 1.93) in Iron >30-L group, 1.14 (0.80, 1.61) in users with iron >30 mg/d for<3 months (Iron > 30-S) and 1.15 (0.86, 1.54) in users with iron ≤30 mg/d for any duration (Iron ≤30) respectively, compared to nonusers. This link in Iron >30-L group was even stronger (adjusted RR: 1.70, 95% CI: 1.25, 2.31) when restricting the analysis among primiparous and iron-replete participants without family history of diabetes. There were no significant differences in birth outcomes among groups. CONCLUSIONS: Periconceptional iron supplementation >30 mg/d for long-term was associated with increased GDM risk. The need and safety of prophylactic iron supplement in iron-replete pregnant women should be reconsidered.
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Anemia Ferropénica/prevención & control , Diabetes Gestacional/epidemiología , Hierro/uso terapéutico , Complicaciones Hematológicas del Embarazo/prevención & control , Adulto , Anemia Ferropénica/epidemiología , Quimioprevención/métodos , Quimioprevención/estadística & datos numéricos , China/epidemiología , Estudios de Cohortes , Diabetes Gestacional/etiología , Suplementos Dietéticos , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Fenómenos Fisiologicos Nutricionales Maternos , Embarazo , Complicaciones Hematológicas del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Atención Prenatal/métodos , Atención Prenatal/estadística & datos numéricos , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. OBJECTIVES: We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. METHODS: We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16 weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. RESULTS: The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). CONCLUSIONS: Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.
Asunto(s)
Diabetes Gestacional/prevención & control , Suplementos Dietéticos/efectos adversos , Ferritinas/sangre , Hierro/administración & dosificación , Fenómenos Fisiologicos de la Nutrición Prenatal , Adulto , Estudios de Cohortes , Femenino , Humanos , Hierro/efectos adversos , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: To prevent the rapid spread of COVID-19, the Chinese government implemented a strict lockdown in Wuhan starting on 23 January, 2020, which inevitably led to the changes in indications for the mode of delivery. In this retrospective study, we present the changes in the indications for cesarean delivery (CD) and the birth weights of newborns after the lockdown in Wuhan. METHODS: A total of 3,432 pregnant women in the third trimester of their pregnancies who gave birth in our hospital from 23 January 2019 to 24 March 2020 were selected as the observation group, while 7,159 pregnant women who gave birth from 1 January 2019 to 22 January 2020 were selected as the control group; control group was matched using propensity score matching (PSM). A comparative analysis of the two groups was performed with the chi-square test, t test and rank sum test. RESULTS: The difference in the overall rate of CD between the two groups was not statistically significant (p<0.05). Among the indications for CD, CD on maternal request (CDMR) and fetal distress were also significantly more common in the observation group (p<0.05) than the control group. Furthermore, we found that the weight of newborns was significantly heavier in the observation group than in the control group when considering full-term or close-to-full-term births (p<0.05). CONCLUSIONS: The results may provide useful information to management practices regarding pregnancy and childbirth after lockdown in other cities or countries, enabling better control of the rate of CD due to CDMR, reducing fetal distress, and controlling newborn weight. We recommend that pregnant women pay more attention to controlling the weight of newborns through diet and exercise.
Asunto(s)
Betacoronavirus , Peso al Nacer , Cesárea , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Cuarentena/métodos , Adolescente , Adulto , COVID-19 , China/epidemiología , Infecciones por Coronavirus/virología , Femenino , Sufrimiento Fetal , Humanos , Recién Nacido , Persona de Mediana Edad , Parto Normal , Neumonía Viral/virología , Embarazo , Estudios Retrospectivos , SARS-CoV-2 , Nacimiento a Término , Adulto JovenRESUMEN
PURPOSE: A good number of anticancer studies have focused on the evaluation of plant derived natural products against different types of human cancers. Triterpenes, belonging to terpenoid class of plant secondary metabolites, have been reported to function as potent anticancer agents. The current study was designed to investigate the anticancer potential of Taraxastane against human cervical cancer cells. METHODS: MTT assay and DAPI staining were used for determining the cell viability. DCFH-DA and DiOC6 based estimations were employed for determination of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), respectively. Flow cytometry technique was used for analysis of cell cycle and necrosis. Analysis of cell migration and invasion was performed by wound heal and transwell assays, repectively. Protein expression was analyzed by Western blotting. RESULTS: MTT assay showed that Taraxastane inhibited the proliferation of DoTc2 cervical cancer cells in a concentration-dependent manner with an IC50 of 20µM, whereas it had lesser effect on the proliferation of normal human cervical cells. The molecule was seen to increase the ROS concentration along with decreasing MMP. Flow cytometry showed that Taraxastane didn't induce cell apoptosis in DoTc2 cells and anticancer effects were mainly in the form of DoTc2 cell necrosis. This was also evident from the western blot analysis of Bax and BCl-2 proteins whose concentration remained unchanged under Taraxastane treatment. Taraxastane treatment led to cell cycle arrest at G2/M checkpoint without any effect on Cyclin D protein expression. Western blotting of JNK and p-38 proteins showed that Taraxastane blocks the JNK/MAPK signaling pathway by preventing the phosphorylation of the former in a dose-dependent manner. Finally, the wound healing and transwell assays showed that Taraxastane inhibited the migration and invasion of cervical cancer cells, which indicates the role of Taraxastane in the prevention of cancer metastasis. CONCLUSION: To conclude, Taraxastane has remarkable anti- proliferative effect on human cervical cancer cells and thus may prove as a vital lead molecule for discovery of anticancer drugs.
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Puntos de Control del Ciclo Celular/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Plantas/química , Especies Reactivas de Oxígeno/metabolismo , Triterpenos/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Invasividad Neoplásica , Transducción de Señal , Triterpenos/farmacología , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: 2019 novel coronavirus disease (COVID-19) has become a worldwide pandemic. Under such circumstance pregnant women are also affected significantly. OBJECTIVE: This study aims to observe the clinical features and outcomes of pregnant women who have been confirmed with COVID-19. METHODS: The research objects were 55 cases of suspected COVID-19 pregnant women who gave a birth from Jan 20th 2020 to Mar 5th 2020 in our hospital-a big birth center delivering about 30,000 babies in the last 3 years. These cases were subjected to pulmonary CT scan and routine blood test, manifested symptoms of fever, cough, chest tightness or gastrointestinal symptoms. They were admitted to an isolated suite, with clinical features and newborn babies being carefully observed. Among the 55 cases, 13 patients were assigned into the confirmed COVID-19 group for being tested positive sever acute respiratory syndrome coronavirus 2(SARS-CoV-2) via maternal throat swab test, and the other 42 patients were assigned into the control group for being ruled out COVID-19 pneumonia based on new coronavirus pneumonia prevention and control program(the 7th edition). RESULTS: There were 2 fever patients during the prenatal period and 8 fever patients during the postpartum period in the confirmed COVID-19 group. In contrast, there were 11 prenatal fever patients and 20 postpartum fever patients in the control group (p>0.05). Among 55 cases, only 2 case had cough in the confirmed group. The imaging of pulmonary CT scan showed ground- glass opacity (46.2%, 6/13), patch-like shadows(38.5%, 5/13), fiber shadow(23.1%, 3/13), pleural effusion (38.5%, 5/13)and pleural thickening(7.7%, 1/13), and there was no statistical difference between the confirmed COVID-19 group and the control group (p>0.05). During the prenatal and postpartum period, there was no difference in the count of WBC, Neutrophils and Lymphocyte, the radio of Neutrophils and Lymphocyte and the level of CRP between the confirmed COVID-19 group and the control group(p<0.05). 20 babies (from confirmed mother and from normal mother) were subjected to SARS-CoV-2 examination by throat swab samples in 24 h after birth and no case was tested positive. CONCLUSION: The clinical symptoms and laboratory indicators are not obvious for asymptomatic and mild COVID-19 pregnant women. Pulmonary CT scan plus blood routine examination are more suitable for finding pregnancy women with asymptomatic or mild COVID-19 infection, and can be used screening COVID-19 pregnant women in the outbreak area of COVID-19 infection.
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Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/patología , Neumonía Viral/diagnóstico , Neumonía Viral/patología , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/virología , Adulto , Betacoronavirus/aislamiento & purificación , COVID-19 , Estudios de Casos y Controles , China/epidemiología , Tos , Femenino , Fiebre , Humanos , Pulmón/diagnóstico por imagen , Recuento de Linfocitos , Pandemias , Pleura/diagnóstico por imagen , Pleura/patología , Periodo Posparto , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
Current results regarding the effect of folic acid (FA) supplement use on gestational hypertension (GH) and preeclampsia are limited and inconsistent. We aimed to investigate whether FA supplement use was associated with GH and preeclampsia. Participants from the Tongji Maternal and Child Health Cohort with information on periconceptional FA supplement use and diagnosis of GH/preeclampsia were included (n=4853). Robust Poisson regression was used to assess the association of FA supplement use and GH and preeclampsia. Among the 4853 participants in this study, 1161 (23.9%) and 161 (3.3%) women were diagnosed with GH and preeclampsia, respectively. The risk ratio of developing GH was higher in women who used ≥800 µg/d FA supplement from prepregnancy through midpregnancy than nonusers (risk ratio, 1.33 [1.08-1.65]). After adjusting for social-demographic, reproductive, lifestyle factors, family history of hypertension, other supplement use, and gestational weight gain, the adverse association remained significant (risk ratio, 1.32 [1.06-1.64]). Restricting the analysis among women with normal weight, without family history of hypertension, and without gestational diabetes mellitus, the positive FA-GH association still existed. We did not find any significant association between FA supplement use and preeclampsia regardless of adjustment. High-dose (≥800 µg/d) FA supplement use from prepregnancy through midpregnancy was associated with increased risk of GH. Attention should be given to avoid the potential risk of GH due to inappropriate FA supplement use in women who are planning or capable of pregnancy.
Asunto(s)
Ácido Fólico/efectos adversos , Hipertensión Inducida en el Embarazo/inducido químicamente , Preeclampsia/inducido químicamente , Adulto , Femenino , Ácido Fólico/administración & dosificación , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Preeclampsia/epidemiología , Embarazo , Adulto JovenRESUMEN
A good clinical guideline for integrated traditional Chinese and Western medicine (ITCWM) should be established by multi-subject specialists, including clinical expert of ITCWM, traditional Chinese medicine and Western medicine, and medical staff from different levels of health care organization, clinical and preclinical medicine researcher, statistician, clinical epidemiologist and economist, medical decision-maker and administrative expert. Establishment of guideline should be abided by the following scientific procedure: association of ITCWM (AITCWM) or the branch of AITCWM decides the subject of clinical guideline, set up a team of special subject of clinical guideline (or decided by research project), evaluate literature systematically, prepare a draft manuscript, consult and appraise it in the same occupation, announce the content in the academic circle, collect feedback opinions and proposals and then make analysis, modify the clinical guideline, publish the clinical guideline, apply the clinical guideline, collect and appraise feedback opinions and proposals, modify and consummate the clinical guideline. In order to supply and consummate original guideline, scientific and renewed evidence should be emphasized on the basis of evidence-based medicine. The author also suggested insistence on the combination of disease and syndrome, syndrome being governed by disease, standardization of syndrome type, establishment of reasonable amount of syndrome types, standard and method of modifying the treatment. The user of guideline should pay attention to both the principle and flexibility, and the author stressed that guideline was just a diagnosis and treatment reference to clinician, which should be used flexibly and not be imitated mechanically in practical application. The practicability of guideline should be pay attention to so that the clinician can apply and manipulate the guideline easily. Meanwhile, the group of guideline establishment has an obligation to train medical staff and to promote the practice of clinical guideline. Only in this way, the authority, standardization and applicability of clinical guideline on ITCWM can be ensured, and then the expected purpose of clinical guideline establishment can be attained.
Asunto(s)
Medicina Integrativa/normas , Medicina Tradicional China/normas , Guías de Práctica Clínica como Asunto/normas , Garantía de la Calidad de Atención de Salud/normas , HumanosAsunto(s)
Salud Infantil , Diabetes Gestacional , Niño , Humanos , Femenino , Embarazo , Estudios ProspectivosRESUMEN
In order to explore the effect of Yaoliuan capsule in the prevention and treatment of vaginal bleeding after drug-induced abortion and menses recovery after drug-induced abortion, 323 cases of gestation period < or = 49 days and without contraindication, were divided randomly into study group (168 cases, taking Yaoliuan capsule) and control group (155 cases, taking placebo capsule). The results showed that in the study group, there were 161 cases (95.8%) of complete abortion, 7 cases (4.2%) of incomplete abortion; In the control group, there were 146 cases (94.2%) of complete abortion, 6 cases (3.9%) of incomplete abortion, 3 cases (1.9%) of abortion failure. The vaginal bleeding time was 5-25 days (mean 10.8 days) in study group, while that was 6-62 days (mean 19.1 days) in control group. The menstrual cycle was 30.5+/-5. 2 days and 33.8 d+/-8.6 days respectively in study and control groups. The menstrual period was 6.1+/-3. 5 days and 9.9+/-5.1 days respectively in study and control groups. Yaoliuan capsule is an effective drug to prevent and treat vaginal bleeding following drug-induced abortion, promote menstruation recovery and prevent pelvic infection.
Asunto(s)
Aborto Inducido/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Menstruación/efectos de los fármacos , Fitoterapia , Hemorragia Uterina/prevención & control , Abortivos no Esteroideos/efectos adversos , Adulto , Cápsulas , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Hemorragia Uterina/etiologíaRESUMEN
BACKGROUND: Cervical cancers are ranked the second-most hazardous ailments among women worldwide. In the past two decades, microarray technologies have been applied to study genes involved in malignancy progress. However, in most of the published microarray studies, only a few genes were reported leaving rather a large amount of data unused. Also, RNA-Seq data has become more standard for transcriptome analysis and is widely applied in cancer studies. There is a growing demand for a tool to help the experimental researchers who are keen to explore cervical cancer gene therapy, but lack computer expertise to access and analyze the high throughput gene expression data. DESCRIPTION: The dbCerEx database is designed to retrieve and process gene expression data from cervical cancer samples. It includes the genome wide expression profiles of cervical cancer samples, as well as a web utility to cluster genes with similar expression patterns. This feature will help researchers conduct further research to uncover novel gene functions. CONCLUSION: The dbCerEx database is freely available for non-commercial use at http://128.135.207.10/dbCerEx/, and will be updated and integrated with more features as needed.