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1.
J Agric Food Chem ; 70(46): 14732-14743, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36351282

RESUMO

The sugar moieties of natural flavonoids determine their absorption, bioavailability, and bioactivity in humans. To explore structure-dependent bioactivities of quercetin, isoquercetin, and rutin, which have the same basic skeleton linking different sugar moieties, we systemically investigated the ameliorative effects of dietary these flavonoids on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) of mice. Our results revealed that isoquercetin exhibits the strongest capability in improving NAFLD phenotypes of mice, including body and liver weight gain, glucose intolerance, and systemic inflammation in comparison with quercetin and rutin. At the molecular level, dietary isoquercetin markedly ameliorated liver dysfunction and host metabolic disorders in mice with NAFLD. At the microbial level, the three flavonoids compounds, especially isoquercetin, can effectively regulate the gut microbiota composition, such as genera Akkermansia, Bifidobacterium, and Lactobacillus, which were significantly disrupted in NAFLD mice. These comparative findings offer new insights into the structure-dependent activities of natural flavonoids for NAFLD treatment.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Quercetina/farmacologia , Glicosídeos/farmacologia , Camundongos Endogâmicos C57BL , Rutina , Flavonoides/farmacologia , Açúcares
2.
Discov Oncol ; 13(1): 128, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36409444

RESUMO

BACKGROUND: Esophagogastric junction adenocarcinoma (EJA) lacks serum biomarkers to assist in diagnosis and prognosis. Here, we aimed to evaluate the diagnostic and prognostic value of serum insulin-like growth factor binding protein 3 (IGFBP3) in EJA patients. METHODS: 320 participants were recruited from November 2016 to January 2020, who were randomly divided into a training cohort (112 normal controls and 102 EJA patients including 24 early-stage patients) and a validation cohort (56 normal controls and 50 EJA patients including 12 early-stage patients). We used receiver operating characteristics curve (ROC) to evaluate diagnostic value. The predictive performance of the nomogram was evaluated by the concordance index (C-index). RESULTS: Serum IGFBP3 levels were significantly lower in early-stage EJA or EJA patients than those in controls (P < 0.01). Measurement of serum IGFBP3 demonstrated an area under curve of 0.819, specificity 90.18% and sensitivity 43.14% in training cohort. Similar results were observed in validation cohort (0.804, 87.50%, 42.00%). Importantly, serum IGFBP3 had a satisfactory diagnostic value for early-stage EJA (0.822, 90.18%, 45.83% and 0.811, 84.48%, 50.00% in training and validation cohorts, respectively). Furthermore, survival analysis demonstrated that lower serum IGFBP3 level was related to poor prognosis (P < 0.05). Cox multivariate analysis revealed that serum IGFBP3 was an independent prognostic factor (HR = 0.468, P = 0.005). Compared with TNM stage, a nomogram based on serum IGFBP3, tumor size and TNM stage indicated an improved C-index in prognostic prediction (0.625 vs. 0.735, P = 0.001). CONCLUSIONS: We found that serum IGFBP3 was a potential diagnostic and prognostic marker of EJA. Meanwhile, the nomogram might predict the prognosis of EJA more accurately and efficiently.

3.
Iran J Public Health ; 51(10): 2298-2307, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36415798

RESUMO

Background: We aimed to explore the ole and mechanism of lactate receptor (HCAR1) in the angiogenesis of leptomeningeal fibroblast-like cells. Methods: Human brain fibroblast-like cells were selected and some cells were deactivated, analyzed and compared with HCAR1 mRNA and protein expressions in deactivated/normal cells. HCAR1-/- mice and wild type (WT) mice were selected and divided into WT, WT exercise, HCAE1 KO and HCAE1 KO exercise groups, with 10 mice for each group. HCAR1mRNA and expression levels of proteins in fibroblast-like cells, mRNA and expression levels of proteins in Collagen IV, phosphatidylinositol trihydroxykinase (PI3K), serine threonine kinase (AKT) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) in hippocampus were compared, and the microvessel density (MVD) and diameter were calculated. Results: mRNA and expression levels of proteins in Collagen IV, PI3K, AKT, ERK1/2 and MVD in hippocampus were significantly higher in the WT exercise group than those in the WT group, microvessel diameter was significantly lower than that in the WT group (P<0.05). mRNA and expression levels of proteins in Collagen IV, PI3K, AKT, ERK1/2 and MVD in hippocampus in the HCAR1 KO and HCAR1 KO exercise groups were significantly lower than those in the WT group, microvessel diameter was higher than that in the WT group (P<0.05). Compared with the HCAR1 KO exercise group, the changes of mRNA in Collagen IV, PI3K, AKT, ERK1/2 and microvascular were not significant. Conclusion: Exercise can promote cerebral angiogenesis through the activation of the lactate receptor HCAR1 and the ERK1/2-PI3K/Akt signaling pathways.

4.
Scand J Trauma Resusc Emerg Med ; 30(1): 60, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411460

RESUMO

BACKGROUND: Maxillofacial fractures can lead to massive oronasal bleeding; however, surgical hemostasis and packing procedures can be challenging owing to complex facial anatomy. Only a few studies investigated maxillofacial fractures with massive oronasal hemorrhage. However, thus far, no studies have reported a protocolized management approach for maxillofacial trauma from a single center. This study aimed to evaluate the effectiveness of protocolized management for maxillofacial fractures with oronasal bleeding. METHODS: Patients were identified from the National Cheng University Hospital trauma registry from 2010 to 2020. We included patients with a face Abbreviated Injury Scale (AIS) score of > 3 and active oronasal bleeding. Patients' characteristics were compared between the angiography and non-angiography groups and between survivors and nonsurvivors. RESULTS: Forty-nine patients were included. Among them, 34 (69%) underwent angiography, of whom 21 received arterial embolization. Forty-seven patients (96%) successfully achieved hemostasis by adhering to the treatment protocol at our institution. Compared with the non-angiography group, the angiography group had significantly more patients requiring oral intubation (97% vs. 53%, P < 0.001), Glasgow Coma Scale < 9 (GCS; 79% vs. 27%, P < 0.001), head AIS > 3 (65% vs. 13%, P = 0.001), higher Injury Severity Score (ISS; 43 [33-50] vs. 22 [18-27], P < 0.001), higher incidence of cardiopulmonary resuscitation (CPR; 41% vs. 0%, P = 0.002), higher mortality rate (35% vs. 7%, P = 0.043), and more units of packed red blood cells (PRBC) transfused within 24 h (12 [6-20] vs. 2 [0-4], P < 0.001). The nonsurvivor group had significantly more patients with hypotension (62% vs. 8%; P < 0.001), higher need for CPR (85% vs. 8%; P < 0.001), head AIS > 3 (92% vs. 33%; P < 0.001), skull base fracture (100% vs. 64%; P = 0.011), GCS score < 9 (100% vs. 50%; P = 0.003), higher ISS (50 [43-57] vs. 29 [19-48]; P < 0.001), and more units of PRBC transfused within 24 h (18 [13-22] vs. 6 [2-12]; P = 0.001) than the survivor group. More patients underwent angiography in the nonsurvivor group than in the survivor group (92% vs. 61%; P = 0.043). Among embolized vessels, the internal maxillary artery (65%) was the most common bleeding site. Hypoxic encephalopathy accounted for 92% of deaths. CONCLUSIONS: Protocol-guided management effectively optimizes outcomes in patients with maxillofacial bleeding.


Assuntos
Fraturas Ósseas , Hemorragia , Humanos , Hemorragia/etiologia , Hemorragia/terapia , Escala Resumida de Ferimentos , Escala de Gravidade do Ferimento , Escala de Coma de Glasgow
5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(9): 1281-1288, 2022.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36411713

RESUMO

Chronic stress is a serial of non-specific neuroendocrine reactions in the body when stimulated by stressors for a long time, which has been shown to have a significant effect on tumor development. Chronic stress can activate the hypothalamus-pituitary-adrenal axis and the sense-adrenal myelin system, promote catecholamine and adrenal corticosteroid secretion, regulate the downstream pathways at all levels, and modulate the secretion of immune cells and immune factors, inhibit protective immune response, and induce inflammation, thus promoting tumor cell proliferation and metastasis. Some drugs and psychotherapy can alleviate the patient's stress state, block the nerve signal transmission at all levels of access, regulate the immune system, or can become an effective means to intervene in chronic stress in tumor patients for clinical treatment to provide reference for intervention ideas. However, due to lack of relevant clinical trials, the clinical intervention effect of various drugs and psychotherapy is uncertain and needs more studies to verify the effect.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias , Humanos , Sistema Hipófise-Suprarrenal/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Neoplasias/terapia , Sistema Imunitário
6.
Front Microbiol ; 13: 1052533, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406418

RESUMO

Porcine circovirus 4 (PCV4) was identified in 2019 as a novel circovirus species and then proved to be pathogenic to piglets. However, there is a lack of its prevalence in the Southwest of China. To investigate whether PCV4 DNA existed in the Southwest of China, 374 samples were collected from diseased pigs during 2021-2022 and detected by a real-time PCR assay. The results showed that the positive rate of PCV4 was 1.34% (5/374) at sample level, and PCV4 was detected in two of 12 cities, demonstrating that PCV4 could be detected in pig farms in the Southwest of China, but its prevalence was low. Furthermore, one PCV4 strain (SC-GA2022ABTC) was sequenced in this study and shared a high identity (98.1-99.7%) with reference strains at the genome level. Combining genetic evolution analysis with amino acid sequence analysis, three genotypes PCV4a, PCV4b, and PCV4c were temporarily identified, and the SC-GA2022ABTC strain belonged to PCV4c with a specific amino acid pattern (239V for Rep protein, 27N, 28R, and 212M for Cap protein). Phylogenetic tree and amino acid alignment showed that PCV4 had an ancient ancestor with mink circovirus. In conclusion, the present study was the first to report the discovery and the evolutionary analysis of the PCV4 genome in pig herds of the Southwest of China and provide insight into the molecular epidemiology of PCV4.

7.
J Microencapsul ; : 1-12, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36369854

RESUMO

To study the effects of nanocrystallisation technology on the intestinal absorption properties and antibacterial activity of florfenicol (FF). The florfenicol nanocrystals (FF-NC) were prepared by wet grinding and spray drying. Additionally, changes in particle size, charge, morphology, and dissolution of FF-NC in the long-term stability were monitored by laser particle sizer, TEM, SEM, paddle method, and the structure of FF-NC powder was characterised by nuclear magnetic resonance (NMR) test. The antibacterial activity, intestinal absorption and intestinal histocompatibility of FF-NC were investigated by the stiletto, mini broth dilution susceptibility test, in situ single-pass intestinal perfusion (SPIP) and haematoxylin-eosin (H-E) staining. After 12 months of storage, the particle size and zeta potential of FF-NC were 280.43 ± 8.21 nm and -19.64 ± 3.45 mV, and the electron microscopy results showed that FF-NC were nearly circular with no adhesion between particles. In addition, the drug loading, encapsulation efficiency, and dissolution of FF-NC did not change significantly during storage. The inhibition zone of FF-NC against Escherichia coli and Staphylococcus aureus was 21.37 ± 1.70 mm and 25.17 ± 2.47 mm, respectively. Compared with the FF, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of FF-NC are reduced, and the absorption rate constant (Ka) and efficient permeability coefficient (Peff) of FF-NC in the three intestinal segments were increased by 1.28, 0.25, and 9.10 times and 0.59, 0.17, and 6.0 times, respectively. The results of tissue sections showed that FF-NC had little damage to the small intestinal. Nanocrystallisation technology is an effective method to increase the intestinal absorption and antibacterial activity of FF.

8.
Front Immunol ; 13: 996663, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353640

RESUMO

Activation of the cGAS-STING pathway by cytoplasmic DNA induces the production of Type-1 interferons. Recent advances in research suggest that the cGAS-STING pathway is involved in different parts of the cancer-immunity cycle (CIC) to promote or suppress antitumor immune responses. Combination therapy of STING agonists has made certain progress in preclinical as well as clinical trials, but the selection of combination therapy regimens remains a challenge. In this review, we summarize the role of the cGAS-STING in all aspects of CIC, and focus on the combination immunotherapy strategies of STING agonists and current unsolved challenges.


Assuntos
Proteínas de Membrana , Neoplasias , Humanos , DNA , Imunoterapia , Proteínas de Membrana/genética , Nucleotidiltransferases/metabolismo
9.
Taiwan J Obstet Gynecol ; 61(6): 1037-1038, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36427969

RESUMO

OBJECTIVE: We present late amniocentesis with the application of uniparental disomy (UPD) testing following successful in vitro fertilization (IVF) and transfer of three mosaic embryos in a pregnancy with a favorable outcome. CASE REPORT: A 41-year-old, gravida 2, para 0, woman underwent late amniocentesis at 28 weeks of gestation because of advanced maternal age. The pregnancy was conceived by IVF and transfer of three mosaic embryos, i.e., one embryo with mosaic trisomies 20 and 2, one embryo with mosaic partial trisomies 9 and 3 and one embryo with partial trisomies 11 and 17. First-trimester non-invasive prenatal testing (NIPT) and fetal ultrasound revealed no abnormal findings. Late amniocentesis revealed a karyotype of 46,XY. Array comparative genomic hybridization (aCGH) revealed the result of arr [GRCh37] (X,Y) × 1, (1-22) × 2. Polymorphic DNA marker analysis using the DNAs extracted from the uncultured amniocytes and parental bloods excluded UPD 20. At 38 weeks of gestation, a healthy 3010-g male baby was delivered with no phenotypic abnormalities. CONCLUSION: Prenatal diagnosis of normal karyotype following mosaic embryo transfer should include UPD testing if necessary.


Assuntos
Amniocentese , Trissomia , Gravidez , Feminino , Masculino , Humanos , Adulto , Dissomia Uniparental/diagnóstico , Dissomia Uniparental/genética , Hibridização Genômica Comparativa , Hibridização in Situ Fluorescente , Fertilização In Vitro
10.
Taiwan J Obstet Gynecol ; 61(6): 1044-1047, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36427971

RESUMO

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a de novo duplication of 2q12.2→q13 encompassing MALL, NPHP1, RGPD6 and BUB1. CASE REPORT: A 36-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX,dup(2) (q12.2q13). Simultaneous array comparative genomic hybridization (aCGH) analysis revealed a 6.1-Mb 2q12.2q13 duplication. aCGH analysis of the parental bloods did not find such a duplication. Prenatal ultrasound was unremarkable. After genetic counseling, the parents decided to terminate the pregnancy at 21 weeks of gestation, and a 420-g female fetus was delivered with no gross abnormalities. Postnatal cytogenetic analysis of the umbilical cord confirmed the prenatal diagnosis. The parental karyotypes were normal. aCGH analysis of the umbilical cord revealed the result of arr [GRCh37 (hg19)] 2q12.2q13 (107, 132, 950-113,065,779) × 3.0 with a 2q12.2→q13 duplication encompassing 20 OMIM genes including MALL, NPHP1, RGPD6 and BUB1. Polymorphic DNA marker analysis of quantitative fluorescence polymerase chain reaction (QF-PCR) on the DNAs extracted from the umbilical cord and parental bloods confirmed a maternal origin of the duplication of 2q12.2→q13. CONCLUSION: Amniocentesis may incidentally detect a de novo chromosomal segmental duplication of maternal origin in the fetus. The genetic information acquired by molecular analyses such as aCGH and QF-PCR are useful for genetic counseling under such a circumstance.


Assuntos
Amniocentese , Diagnóstico Pré-Natal , Gravidez , Feminino , Humanos , Adulto , Hibridização Genômica Comparativa , Cariotipagem , Análise Citogenética , Duplicação Cromossômica/genética , DNA , Proteínas do Citoesqueleto/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Serina-Treonina Quinases/genética
11.
Taiwan J Obstet Gynecol ; 61(6): 1039-1043, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36427970

RESUMO

OBJECTIVE: We present prenatal diagnosis and molecular cytogenetic characterization of a de novo deletion of 4q34.1→qter associated with low pregnancy associated plasma protein-A (PAPP-A) and low placental growth factor (PlGF) in the first-trimester maternal serum screening, congenital heart defect (CHD) on fetal ultrasound and a false negative non-invasive prenatal testing (NIPT) result. CASE REPORT: A 40-year-old, primigravid woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization (IVF) and embryo transfer (ET). First-trimester maternal serum screening at 12 weeks of gestation revealed low PAPP-A [0.349 multiples of the median (MoM)] and low PlGF (0.299 MoM) and showed a risk for fetal trisomy 21 and trisomy 13. However, NIPT detected no genomic imbalance and a normal result. Nevertheless, level II ultrasound revealed ventricular septal defect, single umbilical artery and a small brain midline cyst. Amniocentesis revealed a karyotype of 46,XX,del(4)(q34.1) and a 17.8-Mb deletion of 4q34.1q.35.2 on array comparative genomic hybridization (aCGH) analysis. The parental karyotypes were normal. The pregnancy was terminated at 23 weeks of gestation, and a malformed fetus was delivered with craniofacial dysmorphism. Postnatal cytogenetic analysis of the placenta confirmed the prenatal diagnosis. There was a 17.8-Mb deletion of 4q34.1q.35.2 encompassing the genes of HAND2, SORBS2 and DUX4. Polymorphic DNA marker analysis on the parental bloods and cord blood showed a paternal origin of the deletion. CONCLUSION: An abnormal first-trimester maternal serum screening result along with abnormal fetal ultrasound should alert the possibility of fetal aneuploidy, and amniocentesis is indicated even in the presence of a normal NIPT result.


Assuntos
Cardiopatias Congênitas , Proteína Plasmática A Associada à Gravidez , Gravidez , Feminino , Humanos , Adulto , Hibridização Genômica Comparativa , Fator de Crescimento Placentário , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Análise Citogenética
12.
Taiwan J Obstet Gynecol ; 61(6): 1048-1052, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36427972

RESUMO

OBJECTIVE: We present rapid confirmation of trisomy 13 of maternal origin by quantitative fluorescent polymerase chain reaction (QF-PCR) following postmortem tissue cell culture failure in a pregnancy with trisomy 13 at amniocentesis and fetal postaxial polydactyly and facial cleft. CASE REPORT: A 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+13. Prenatal ultrasound revealed postaxial polydactyly. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial cleft and postaxial polydactyly of the hand and foot. Postmortem cytogenetic analysis of the fetal tissue revealed no growth of the cells due to culture failure, but QF-PCR analysis on the DNA extracted from placenta, umbilical cord and parental bloods confirmed trisomy 13 and maternal origin of the extra chromosome 13. CONCLUSION: QF-PCR analysis is useful for rapid perinatal confirmation of trisomy 13 and the parental origin of the extra chromosome 13, especially under the circumstance of tissue cell culture failure, and the acquired information is useful for genetic counseling.


Assuntos
Amniocentese , Polidactilia , Gravidez , Feminino , Humanos , Adulto , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Trissomia/diagnóstico , Trissomia/genética , Mosaicismo , Hibridização Genômica Comparativa , Hibridização in Situ Fluorescente , Polidactilia/diagnóstico , Polidactilia/genética , Feto , Reação em Cadeia da Polimerase , Técnicas de Cultura de Células
15.
Anal Chim Acta ; 1235: 340550, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368828

RESUMO

We developed a new core-shell ratiometric fluorescent nanoprobe simply prepared by a seeded growth method. The strong luminescence arising from the shell formed by coordination self-assembly of an alkaline phosphatase (ALP) substrate, l-ascorbic acid 2-phosphate (AAP), and Tb3+, together with the weak fluorescence of the core-a metal-organic framework, UiO-66-NH2, constitutes an ideal dual-emission characteristic. Since AAP can be specifically cleaved by ALP, the well-formulated core-shell nanostructure was destroyed upon exposure to ALP. In this case, the luminescence of Tb3+ was quenched due to the inefficient antenna effect, while the fluorescence of UiO-66-NH2 was strengthened by the synergistical enhancement of dual hydrolysates to inhibit the ligand-to-metal charge transfer (LMCT) process. Using the dual signal response, this nanoprobe was employed for ratiometric fluorescence detection of ALP activity in the range of 0.05-0.6 U mL-1 with a detection limit of 0.018 U mL-1, accompanied by a discernible fluorescence color evolution from turquoise to blue. In virtue of good properties in accuracy, sensitivity, selectivity and simplicity, this assay enabled quantitative detection of ALP activity in human serum and efficient screening of ALP inhibitors. More Importantly, a smartphone-assisted paper-based sensing platform was designed for on-site visual analysis of ALP activity in human serum, which may be very promising as a facile, portable, and robust format to facilitate relevant biological and clinical applications.


Assuntos
Elementos da Série dos Lantanídeos , Ácidos Ftálicos , Humanos , Fosfatase Alcalina/química , Espectrometria de Fluorescência/métodos , Corantes Fluorescentes/química , Limite de Detecção
16.
J Agric Food Chem ; 70(47): 14831-14840, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36383360

RESUMO

Hesperetin-7-O-glucoside (Hes-7-G) is a typical flavonoid monoglucoside, which can be generated from hesperidin with the removal of rhamnose by hydrolysis. Untargeted and targeted metabolomics together with 16S rRNA gene sequencing were employed to explore the exact absorption site of Hes-7-G and its beneficial effect in mice. Intestinal 1H nuclear magnetic resonance (NMR)-based metabolomics screening showed that Hes-7-G is mainly metabolized in the small intestine of mice, especially the ileum segment. Quantification analysis of bile acids (BAs) in the liver, intestinal tract, feces, and serum of mice suggests that Hes-7-G intake accelerates the processes of biosynthesis and excretion of BAs, thus promoting digestion and lowing hepatic cholesterol and triglyceride. 16S rRNA gene sequencing reveals that Hes-7-G significantly elevates the diversity of the gut microbiota in mice, especially those bacteria associated with BA secondary metabolism. These results demonstrated that long-term dietary Hes-7-G plays beneficial roles in health by modulating the gut bacteria and BA metabolism in mice.

17.
Cell Commun Signal ; 20(1): 190, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443839

RESUMO

BACKGROUND: TGF-ß superfamily signaling is indispensable for bone homeostasis. However, the global expression profiles of all the genes that make up this signaling module in bone and bone-related diseases have not yet been well characterized. METHODS: Transcriptomic datasets from human bone marrows, bone marrow-derived mesenchymal stem cells (MSCs) and MSCs of primary osteoporotic patients were used for expression profile analyses. Protein treatments, gene quantification, reporter assay and signaling dissection in MSC lines were used to clarify the interactive regulations and feedback mechanisms between TGF-ß superfamily ligands and antagonists. Ingenuity Pathway Analysis was used for network construction. RESULTS: We identified TGFB1 in the ligand group that carries out SMAD2/3 signaling and BMP8A, BMP8B and BMP2 in the ligand group that conducts SMAD1/5/8 signaling have relatively high expression levels in normal bone marrows and MSCs. Among 16 antagonist genes, the dominantly expressed TGF-ß superfamily ligands induced only NOG, GREM1 and GREM2 via different SMAD pathways in MSCs. These induced antagonist proteins further showed distinct antagonisms to the treated ligands and thus would make up complicated negative feedback networks in bone. We further identified TGF-ß superfamily signaling is enriched in MSCs of primary osteoporosis. Enhanced expression of the genes mediating TGF-ß-mediated SMAD3 signaling and the genes encoding TGF-ß superfamily antagonists served as significant features to osteoporosis. CONCLUSION: Our data for the first time unveiled the transcription landscape of all the genes that make up TGF-ß superfamily signaling module in bone. The feedback mechanisms and regulatory network prediction of antagonists provided novel hints to treat osteoporosis. Video Abstract.


Assuntos
Osteoporose , Transcriptoma , Humanos , Retroalimentação , Ligantes , Osteoporose/genética , Osso e Ossos , Fator de Crescimento Transformador beta
18.
Front Public Health ; 10: 949622, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324459

RESUMO

The uneven distribution of medical and health resources leads to changes in the choice of patients for medical treatment, which is the key to restrict the reform of medical services in China currently. Taking service accessibility and residents' cognition as the starting point, this study utilized the data from the questionnaire and applied logistic regression and mediation test. By taking service accessibility as an explanatory variable and residents' cognition as an intermediary variable, the study examined the differences between residents' choice of medical treatment at the primary and non-primary levels. Thus, the influencing factors of residents' choice of medical treatment at the primary level were explored. The research statistics came from questionnaires of 1,589 residents in Nanjing, Jiangsu Province, China. The results showed that service accessibility and residents' cognition were significantly correlated with the residents' choice of primary medical treatment. Household registration, age, the signing situation with family doctors, hospital service fees, and distance to the hospital were positively related to residents' choice of primary medical treatment; while the reputation, scale, residents' income, and the reimbursement ratio of residents' medical insurance were negatively correlated with the choice. In addition, residents' cognition played an intermediary effect between service accessibility and the residents' choice of primary medical treatment. The signing situation with family doctors indirectly affected the choice of primary medical treatment through residents' cognition, and residents' cognition masked some negative influence of the reimbursement ratio of residents' medical insurance on the choice of primary medical treatment.


Assuntos
Características da Família , Renda , Humanos , China , Inquéritos e Questionários , Cognição
19.
EMBO J ; : e110928, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36245268

RESUMO

Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long-term self-renewal and formation of somitoids with an anterior-to-posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP-tagged endogenous HES7 protein moves along the anterior-to-posterior axis during somitoid formation. The geo-sequencing analysis further confirmed anterior-to-posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA-D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine.

20.
Front Pharmacol ; 13: 952441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249767

RESUMO

Background: Dexmedetomidine is considered an adjunct to local anaesthesia (LA) to prolong peripheral nerve block time. However, the results from a previous meta-analysis were not sufficient to support its use in paravertebral block (PVB). Therefore, we performed an updated meta-analysis to evaluate the efficacy of dexmedetomidine combined with LA in PVB. Methods: We performed an electronic database search from the date of establishment to April 2022. Randomized controlled trials (RCTs) investigating the combination of dexmedetomidine and LA compared with LA alone for PVB in adult patients were included. Postoperative pain scores, analgesic consumption, and adverse reactions were analyzed. Results: We identified 12 trials (701 patients) and found that the application of dexmedetomidine as a PVB adjunct reduced the postoperative pain severity of patients 12 and 24 h after surgery compared to a control group. Expressed as mean difference (MD) (95% CI), the results were -1.03 (-1.18, -0.88) (p < 0.00001, I2 = 79%) for 12 h and -1.08 (-1.24, -0.92) (p < 0.00001, I2 = 72%) for 24 h. Dexmedetomidine prolonged the duration of analgesia by at least 173.27 min (115.61, 230.93) (p < 0.00001, I2 = 81%) and reduced postoperative oral morphine consumption by 18.01 mg (-22.10, 13.92) (p < 0.00001, I2 = 19%). We also found no statistically significant differences in hemodynamic complications between the two groups. According to the GRADE system, we found that the level of evidence for postoperative pain scores at 12 and 24 h was rated as moderate. Conclusion: Our study shows that dexmedetomidine as an adjunct to LA improves the postoperative pain severity of patients after surgery and prolongs the duration of analgesia in PVB without increasing the incidence of adverse effects.

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