RESUMO
BACKGROUND: The purpose of this study is to explore the effects of CB2 on bone regulation during orthodontic tooth movement. METHODS: Thirty male mice were allocated into 2 groups (n = 15 in each group): wild type (WT) group and CB2 knockout (CB2-/-) group. Orthodontic tooth movement (OTM) was induced by applying a nickel-titanium coil spring between the maxillary first molar and the central incisors. There are three subgroups within the WT groups (0, 7 and 14 days) and the CB2-/- groups (0, 7 and 14 days). 0-day groups without force application. Tooth displacement, alveolar bone mass and alveolar bone volume were assessed by micro-CT on 0, 7 and 14 days, and the number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the expression levels of RANKL and OPG in the compression area were measured histomorphometrically. RESULTS: The WT group exhibited the typical pattern of OTM, characterized by narrowed periodontal space and bone resorption on the compression area. In contrast, the accelerated tooth displacement, increased osteoclast number (P < 0.0001) and bone resorption on the compression area in CB2-/- group. Additionally, the expression of RANKL was significantly upregulated, while OPG showed low levels in the compression area of the CB2 - / - group (P < 0.0001). CONCLUSIONS: CB2 modulated OTM and bone remodeling through regulating osteoclast activity and RANKL/OPG balance.
Assuntos
Remodelação Óssea , Reabsorção Óssea , Receptor CB2 de Canabinoide , Técnicas de Movimentação Dentária , Animais , Masculino , Camundongos , Remodelação Óssea/fisiologia , Osteoclastos , Receptor CB2 de Canabinoide/genéticaRESUMO
In infants with severe bronchopulmonary dysplasia (sBPD), severe pulmonary lobar emphysema may occur as a complication, contributing to significant impairment in ventilation. Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation. However, prior to the lobectomy, it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively. In addition, preoperative planning and perioperative management are also quite challenging in these patients. This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema. Since infants with sBPD already have poor lung development and significant lung injury, lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution. Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema. However, given the technical difficulty, successful application of this technique requires close collaboration of an experienced interdisciplinary team.
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Displasia Broncopulmonar , Recém-Nascido Prematuro , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/cirurgia , Displasia Broncopulmonar/etiologia , Recém-Nascido , Brônquios , Masculino , Pneumonectomia , FemininoRESUMO
OBJECTIVES: To investigate whether evidence-based standardized nutrition protocol can facilitate the establishment of full enteral nutrition and its effect on short-term clinical outcomes in very preterm/very low birth weight infants. METHODS: A retrospective analysis was performed on the medical data of 312 preterm infants with a gestational age of ≤32 weeks or a birth weight of <1 500 g. The standardized nutrition protocol for preterm infants was implemented in May 2020; 160 infants who were treated from May 1, 2019 to April 30, 2020 were enrolled as the control group, and 152 infants who were treated from June 1, 2020 to May 31, 2021 were enrolled as the test group. The two groups were compared in terms of the time to full enteral feeding, the time to the start of enteral feeding, duration of parenteral nutrition, the time to recovery to birth weight, the duration of central venous catheterization, and the incidence rates of common complications in preterm infants. RESULTS: Compared with the control group, the test group had significantly shorter time to full enteral feeding, time to the start of enteral feeding, duration of parenteral nutrition, and duration of central venous catheterization and a significantly lower incidence rate of catheter-related bloodstream infection (P<0.05). There were no significant differences between the two groups in the mortality rate and the incidence rate of common complications in preterm infants including grade II-III necrotizing enterocolitis (P>0.05). CONCLUSIONS: Implementation of the standardized nutrition protocol can facilitate the establishment of full enteral feeding, shorten the duration of parenteral nutrition, and reduce catheter-related bloodstream infection in very preterm/very low birth weight infants, without increasing the risk of necrotizing enterocolitis.
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Enterocolite Necrosante , Sepse , Peso ao Nascer , Nutrição Enteral/métodos , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/etiologia , Enterocolite Necrosante/prevenção & controle , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Estudos Retrospectivos , Sepse/epidemiologiaRESUMO
BACKGROUND: Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China. METHODS: Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects of Se-lentinan was evaluated by cell viability, cell cycle, migration, and transwell assays and animal xenograft models. The effects of Se-lentinan on the expression levels of epithelial-mesenchymal transition (EMT) markers were determined through immunofluorescence, Western blot, and immunohistochemistry analyses. RESULTS: Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8 cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor growth and metastasis of the transplanted melanoma and colon cancer cells and showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the accumulation of selenium in the liver and kidney tissues of mice and exhibited low organ toxicity. CONCLUSION: The antitumor activity of selenium was enhanced greatly, and its side effects were reduced with the use of lentinan as drug carrier.
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Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Lentinano/farmacologia , Selênio/farmacologia , Células A549 , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Células HEK293 , Humanos , Células MCF-7 , Melanoma Experimental/tratamento farmacológico , Camundongos , Células NIH 3T3 , Metástase Neoplásica/tratamento farmacológico , Polissacarídeos/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Parthenolide (PTL) is a natural molecule isolated from Tanacetum parthenium that exhibits excellent anti-inflammatory and antitumor activities. Pulmonary fibrosis (PF), especially idiopathic pulmonary fibrosis (IPF), is a chronic lung disease that lacks a proven effective therapy. The present study evaluated the therapeutic effect of PTL on PF. METHODS: Serum-starved primary lung fibroblasts and HFL1 cells were treated with different doses of PTL, and cell viability and the migration rate were measured. Western blot analysis and a dual-luciferase assay were used to analyze the epithelial-mesenchymal transition (EMT)-related transcription factors influenced by PTL treatment in A549 cells and primary lung epithelial cells. Mice with bleomycin (BLM)-induced pulmonary fibrosis were treated with different doses of intragastric PTL, and pathological changes were evaluated using Hematoxylin-eosin (H&E) staining and immunohistochemical analysis. RESULTS: Our results demonstrated that PTL reduced the cell viability and migration rate of lung fibroblasts and inhibited the expression of EMT-related transcription factors in lung epithelial cells. In vivo studies demonstrated that PTL attenuated BLM-induced pulmonary fibrosis and improved the body weight and pathological changes of BLM-treated mice. We further demonstrated that PTL attenuated BLM-induced PF primarily via inhibition of the NF-κB/Snail signaling pathway. CONCLUSION: These findings suggest that PTL inhibits EMT and attenuates BLM-induced PF via the NF-κB/Snail signaling pathway. PTL is a worthwhile candidate compound for pulmonary fibrosis therapy.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Bleomicina/toxicidade , NF-kappa B/antagonistas & inibidores , Fibrose Pulmonar/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Fatores de Transcrição da Família Snail/antagonistas & inibidores , Células A549 , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fatores de Transcrição da Família Snail/metabolismoRESUMO
According to the characteristics of gout's clinical symptoms, the common gout animal models were analyzed, and the anastomosis and application prospect of the existing gout animal models with the clinical symptoms were discussed. At present, there are three models of gout: hyperuricemia model, gouty arthritis model and gouty nephropathy model. There are many methods of gout modeling, but there is a lack of animal model replication that could reflect the characteristics of gout's clinical symptoms and reflect the etiology of gout, and there is still a gap between the clinical symptoms and the clinical symptoms. In this paper, the characteristics and modeling methods of the three animal models were summarized, and compared with the clinical symptoms and standards, the anastomosis between the existing animal models and the clinical symptoms were analyzed and discussed, and the evaluation and improvement methods of the corresponding animal models were put forward. It provides a reliable experimental method for the treatment of gout by traditional Chinese medicine.
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Gota , Hiperuricemia , Animais , Modelos Animais de DoençasRESUMO
The flavonoid quercetin exhibits significant anticancer activities with few side effects. In the current study, we characterized TL-2-8, a quercetin derivative, as a novel anticancer agent in vitro and in vivo. Cell proliferation and viability were assessed using Cell Counting Kit-8 and CellTiter-Blue assay, respectively. Cell death was examined using PI staining or a TUNEL assay. Mitophagy was determined by measuring autophagic flux and by confocal imaging. Protein expression was examined by Western blotting. We found that TL-2-8 selectively inhibited the proliferation and decreased the viability of various cancer cells (the anti-proliferation IC50 values in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells at 72 h were 8.28, 8.56, and 9.58 µmol/L, respectively), and it displayed only slight cytotoxicity against normal MCF-10A and HEK-293 cells. In MDA-MB-231 and MDA-MB-468 breast cancer cells, TL-2-8 treatment induced the degradation of multiple Hsp90 client proteins without inducing Hsp70. TL-2-8 (3, 6, 12 µmol/L) dose-dependently inhibited the expression of AHA1, an activator of Hsp90 ATPase, and decreased Hsp90-AHA1 complex formation, leading to decreased Hsp90 chaperone function and reduced polo-like kinase 1 (PLK1) signaling. Consequently, impaired mitophagy was induced via the downregulation of lysosomal-associated membrane protein 2 (LAMP2). The in vivo anticancer effects of TL-2-8 were evaluated in an MDA-MB-231 breast cancer xenograft model, which was treated with TL-2-8 (25, 50, 100 mg·kg-1·d-1, po). Administration of TL-2-8 resulted in tumor growth inhibition rates of 37.9%, 58.9% and 70.9%, respectively, whereas quercetin treatment (100 mg·kg-1·d-1, po) produced only a lower tumor growth inhibition rate (49.5%). Furthermore, TL-2-8 treatment significantly extended the lifespan of mice bearing MDA-MB-231 breast cancer cell xenografts. Our results demonstrate that TL-2-8 induces significant cell death and immature mitophagy in breast cancer cells in vitro and in vivo via AHA1 abrogation.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Flavonoides/farmacologia , Animais , Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Células HEK293 , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Concentração Inibidora 50 , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitofagia/efeitos dos fármacos , Chaperonas Moleculares/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The growing world population and shrinkage of arable land demand yield improvement of rice, one of the most important staple crops. To elucidate the genetic basis of yield and uncover its associated loci in rice, we resequenced the core recombinant inbred lines of Liang-You-Pei-Jiu, the widely cultivated super hybrid rice, and constructed a high-resolution linkage map. We detected 43 yield-associated quantitative trait loci, of which 20 are unique. Based on the high-density physical map, the genome sequences of paternal variety 93-11 and maternal cultivar PA64s of Liang-You-Pei-Jiu were significantly improved. The large recombinant inbred line population combined with plentiful high-quality single nucleotide polymorphisms and insertions/deletions between parental genomes allowed us to fine-map two quantitative trait loci, qSN8 and qSPB1, and to identify days to heading8 and lax panicle1 as candidate genes, respectively. The quantitative trait locus qSN8 was further confirmed to be days to heading8 by a complementation test. Our study provided an ideal platform for molecular breeding by targeting and dissecting yield-associated loci in rice.
Assuntos
Genoma de Planta , Hibridização Genética , Oryza/genética , Recombinação Genética , Ligação Genética , Locos de Características QuantitativasRESUMO
OBJECTIVE: To isolate, culture, and identify bone marrow mesenchymal stem cells (BMSCs) from enhanced green fluorescent protein (EGFP)-transgenic rats in vitro. METHODS: Bone marrows were isolated from tibia and femur of healthy EGFP-transgenic rats of specific pathogen free (SPF) grade. Then,the whole bone marrow adherent method was used for isolation,culture,and purification of BMSCs. The morphological change was noted by continuous observation under inverted fluorescence microscope. The growth curve of cells was drawn through the method of CCK-8 and the proliferation compared with wild type BMSCs. The surface markers of BMSCs were detected by flow cytometry. The BMSCs were induced to differentiate into osteoblasts, adipocytes, and chondrocytes lineages. The EGFP-BMSCs were transplanted into the rats intravenously, and the expression of GFP was detected. RESULTS: BMSCs stably expressing EGFP gene were obtained successfully, with the fusiform-shaped appearance and the forming of circinate cell colonies. The growth curve of EGFP-MSCs showed the characteristic of active proliferation, showing no significant difference compared with the wild-type BMSCs. The expression rates of the surface markers of BMSCs CD29, CD90, CD34, CD49d, and CD45 were 99.4%, 96.4%, 0.171%, 0.049%, and 0.038%. The GFP were detected in lung 3 days after transplantation. After osteogenic, adipogenic, and chondrogenic induction, oil red-O and alizarin red positive signals and toluidine blue positive cells were detected. CONCLUSIONS: High-purity BMSCs stably expressing green fluorescent protein gene can be cultured using the whole bone marrow adherent method. EGFP does not affect the stem cell properties and expresses stably after transplantation. The cells can be used as seed cells for subsequent research.
Assuntos
Células da Medula Óssea , Células-Tronco Mesenquimais , Adipócitos , Animais , Células Cultivadas , Condrócitos , Citometria de Fluxo , Proteínas de Fluorescência Verde , Células-Tronco Hematopoéticas , Osteoblastos , Ratos , Ratos TransgênicosRESUMO
Partial agonists of peroxisome proliferator-activated receptor γ (PPARγ) reportedly reverse insulin resistance in patients with type 2 diabetes mellitus. In this work, a novel non-thiazolidinedione-partial PPARγ ligand, MDCCCL1636 [N-(4-hydroxyphenethyl)-3-mercapto-2-methylpropanamide], was investigated. The compound displayed partial agonist activity in biochemical and cell-based transactivation assays and reversed insulin resistance. MDCCCL1636 showed a potential antidiabetic effect on an insulin-resistance model of human hepatocarcinoma cells (HepG2). High-fat diet-fed streptozotocin-induced diabetic rats treated with MDCCCL1636 for 56 days displayed reduced fasting serum glucose and reversed dyslipidemia and pancreatic damage without significant weight gain. Furthermore, MDCCCL1636 had lower toxicity in vivo and in vitro than pioglitazone. MDCCCL1636 also potentiated glucose consumption and inhibited the impairment in insulin signaling targets, such as AKT, glycogen synthase kinase 3ß, and glycogen synthase, in HepG2 human hepatoma cells. Overall, our results suggest that MDCCCL1636 is a promising candidate for the prevention and treatment of type 2 diabetes mellitus.
Assuntos
Ácido 3-Mercaptopropiônico/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , PPAR gama/agonistas , Fenóis/farmacologia , Ácido 3-Mercaptopropiônico/farmacologia , Animais , Glicemia/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/etiologia , Humanos , Hipoglicemiantes/toxicidade , Pâncreas/patologia , Pioglitazona , Ratos , Ratos Wistar , Tiazolidinedionas/uso terapêutico , Ativação Transcricional/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , Peixe-ZebraRESUMO
Neurotensin receptor-1 (NTR1), which can stimulate the intracellular cascade signal pathway, belongs to the large superfamily of G-protein coupled receptors. NTR1 is related to the occurrence and development of several kinds of diseases. In order to screen the inhibitors for the cancers associated with NTR1 protein, we established a CHO (Chinese hamster ovary) cell line in which human neurotensin receptor-1 was highly expressed. The method is to construct the recombinant plasmid which was lysed with the hNTR1 gene and transfect it into CHO cells. After selected with G418, the cell line was evaluated by Western blotting analysis and calcium flux assays. Through the calcium flux assays on FlexStation 3, we got the EC50 value of neurotensin peptide which is the natural NTR1 agonist, and the IC 50 value of SR48692 which is the known NTR1 antagonist. The established human CHO/NTR1 cell line can be used to study the profile of NTR1 biological activity and further screen of NTR1 antagonists and agonists.
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Sinalização do Cálcio , Receptores de Neurotensina/metabolismo , Animais , Células CHO , Cricetinae , Cricetulus , Humanos , Pirazóis/farmacologia , Quinolinas/farmacologia , Receptores de Neurotensina/antagonistas & inibidores , Receptores de Neurotensina/genética , TransfecçãoRESUMO
BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.
Assuntos
Microbioma Gastrointestinal , Hepatite B , Lacticaseibacillus paracasei , Humanos , Cirrose Hepática/diagnósticoRESUMO
BACKGROUND: Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants. METHODS: This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg). RESULTS: Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: ß = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: ß = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (ß=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (ß=-0.15, 95%CI -0.30, 0.00 and ß=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings. CONCLUSIONS: The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.
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Aleitamento Materno , Humanos , Aleitamento Materno/estatística & dados numéricos , Estudos Transversais , Feminino , Masculino , Recém-Nascido , Lactente , China/epidemiologia , Idade Gestacional , Fenômenos Fisiológicos da Nutrição do Lactente , Nascimento a Termo , Estudos Retrospectivos , Adulto , Estado NutricionalRESUMO
Benign familial infantile seizure (BFIS) is an autosomal dominant infantile-onset epilepsy syndrome with a typically benign prognosis. It is commonly associated with heterozygous mutations of the PRRT2 gene located on chromosome 16p11.2. The frameshift heterozygous mutation (c.649dupC, p.Arg217Profs∗8) in PRRT2 is responsible for the majority of BFIS cases. In this report, we present a rare case of a girl with a confirmed clinical and genetic diagnosis of BFIS due to a frameshift heterozygous mutation in PRRT2 (c.649dupC). She exhibited typical neurodevelopment until 15 months of age, followed by an unexpected severe autistic regression. In addition to BFIS, PRRT2 mutations are also associated with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions and paroxysmal choreoathetosis (ICCA), indicating a complex genotype-phenotype heterogeneity in PRRT2 mutations. This clinical observation highlights the possibility that BFIS patients with PRRT2 mutations may not always have a benign neurodevelopmental prognosis, emphasizing the need for long-term clinical follow-up.
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The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax ) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax , 98.7% for AUC0ât , 98.8% for AUC0â∞ ) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356).
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Equivalência Terapêutica , Metformina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum , Comprimidos , ChinaRESUMO
The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.
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OBJECTIVE: To investigate Chinese medical features of acquired immunodeficiency syndrome (AIDS) patients with pulmonary infection. METHODS: Using cluster analysis method, Chinese medical syndromes of 196 AIDS patients with pulmonary infection were analyzed. The distribution features of each syndrome type were analyzed according to the severity and CD4+ numerical analysis. RESULTS: Basic Chinese medical syndrome types could be summed up as three kinds: exterior invasion of wind heat and phlegm heat obstructing Fei syndrome (61 cases, 31.1%), Fei-Pi deficiency and Fei stagnation of phlegm syndrome (64 cases, 32.7%), Fei-Shen deficiency and yin deficiency induced inner heat syndrome (71 cases, 36.2%). There was statistical difference in the severity degree and the distribution of CD4 among the three syndrome types (P < 0.05). CONCLUSIONS: AIDS patients with pulmonary infection involve Fei, Shen, and Pi. The pathogenic factors were related to "wind", "heat", "phlegm", and "xu". The Chinese medical syndrome distribution was closely correlated with patients' immunity.
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Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Síndrome da Imunodeficiência Adquirida/diagnóstico , Adolescente , Adulto , Idoso , Análise por Conglomerados , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Infecções Respiratórias/diagnóstico , Deficiência da Energia Yang/diagnóstico , Deficiência da Energia Yin/diagnóstico , Adulto JovemRESUMO
OBJECTIVES: Body composition is an integral part of the nutritional assessment during infancy as it is closely related to future health. The three-dimensional photonic body surface scanning (3-DPS) method is a promising new technique for measuring body composition in children because of its advantages of easy operation, low cost, and no exposure to radiation. Using 3-DPS, this study aimed to illustrate the growth trajectories of body composition indicators during infancy according to sex and age. METHODS: This was a multicenter cross-sectional study. The body compositions of 9644 singleton term infants from four centers in Shandong Province, China, were assessed using 3-DPS. The data of 8769 healthy infants (52.0% boys), whose z scores of weight-for-length, length-for-age, and weight-for-age, according to World Health Organization standards, were in the range of -2 to 2, -3 to 3, and -3 to 3, respectively, were sampled to construct percentile curves of fat mass (FM), fat-free mass (FFM), FM percentage (FM%), FM index (FMI), and FFM index (FFMI) with the generalized additive model for location, scale, and shape method. RESULTS: Percentile charts for FM, FFM, FM%, FMI, and FFMI were developed based on age and sex. FM and FFM presented consistent trajectories with that of weight, with the fastest growth occurring at 1 to 3 mo of age. FM%, FMI, and FFMI increased with age, peaked at 6 mo, and gradually declined, which was consistent with the body mass index trend. All indicators, except for FFMI, were always significantly higher in boys than in girls ages 1 to 12 mo, indicating that sex differences in body composition existed mainly in FM rather than in lean body mass. CONCLUSIONS: The body composition of healthy singleton term infants during infancy varies with age; boys may have more FM accumulation than girls.