RESUMO
A novel photoredox/nickel dual catalytic intermolecular alkylarylation of vinylarenes with tertiary and secondary alkyltrifluoroborates and aryl bromides is described, which affords 1,1-diarylalkane frameworks that are found in various natural products as well as functionalized molecules in good to excellent yield and regioselectivity through a radical relay process. Notably, this redox-neutral reaction could proceed efficiently with good tolerance of various substrates, including a great diversity of commercially available (hetero)aryl bromides, alkyltrifluoroborates, and vinylarenes.
RESUMO
Background: Hearing loss is a common sensorineural dysfunction with a high incidence in China. Although genetic factors are important causes of hearing loss, hearing-related gene detection has not been widely adopted in China. Objective: Establishing a rapid and efficient method to simultaneously detect hotspot hearing loss gene mutations. Methods: A reverse dot blot assay combined with a flow-through hybridization technique was developed for the simultaneous detection of 13 hotspot mutations of 4 hearing loss-related genes including GJB2, GJB3, SLC26A4, and the mitochondrial gene MT-RNR1. This method involved PCR amplification systems and a hybridization platform. Results: The technique can detect 13 hotspot mutations of 4 hearing loss-related genes. And a total of 213 blood samples were used to evaluate the availability of this method. Discussion: Our reverse dot blot assay was a simple, rapid, accurate, and cost-effective method to identify hotspot mutations of 4 hearing loss-related genes in a Chinese population.
RESUMO
Preeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.
Assuntos
Bactérias , Fezes , Microbioma Gastrointestinal , Metagenômica , Pré-Eclâmpsia , Viroma , Humanos , Feminino , Pré-Eclâmpsia/virologia , Pré-Eclâmpsia/microbiologia , Gravidez , Microbioma Gastrointestinal/genética , Viroma/genética , Adulto , Fezes/virologia , Fezes/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Vírus/genética , Vírus/classificação , Vírus/isolamento & purificação , MetagenomaRESUMO
Acute rejection is not uncommon after vascularized composite allotransplantation. We reported the effects of adjunctive topical immunosuppressant with topical tacrolimus (Protopic®) and steroid cream (Clobetasol®) in the management of acute rejection in two hand transplantation patients. Case 1 is a 45-year-old male with distal forearm deficit 4 years ago and Case 2 is a 30-year-old male with a proximal forearm deficiency 2 years ago, respectively. Both of them suffered from occupational accident and received hand allotransplantation. Induction was performed with antithymocyte globulins and methylprednisolone. Maintenance therapy consisted of tacrolimus (FK506), mycophenolate mofetil, and prednisone. Both cases experienced acute rejection, which we treated with topical tacrolimus and Clobetasol for 2 weeks, combined with systemic immunosuppressant maintenance therapy without adding pulse-steroid therapy. Clinically, both cases recovered after adjunctive treatments. The skin biopsies showed significantly decreased perivascular lymphocyte infiltration after topical treatment. Immunohistochemical staining showed that CD3+ T-cells and CD20+ B-cells were suppressed in the recovery phase. FoxP3-positive regulatory T cells were increased after treatment. Topical tacrolimus and Clobetasol as an adjunctive treatment with maintenance systemic immunosuppressives may be useful to control acute rejection, which correlated with modulation of lymphocyte activation, especially T cells. The treatment needs further investigation with gaining more comparable data.
Assuntos
Transplante de Mão , Tacrolimo , Adulto , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisona , Linfócitos TRESUMO
AIMS: To evaluate the effectiveness of a mobile health (mHealth) application, based on self-regulation theory, on patients' knowledge of wound care, skills in changing dressings and anxiety. DESIGN: A prospective randomized controlled trial. METHODS: Seventy patients (or family members) at a 1,500-bed university hospital in Taiwan were randomized into an experimental (N = 35) or control group (N = 35) from March to December 2016. The experimental group used a mHealth application for wound care; the control group received verbal instructions and a booklet. Instruments to collect data were a wound care knowledge scale, wound care skills scale, State-Trait Anxiety Inventory, and a digital heart variability device. Data were collected at baseline, after three additional demonstrations and before discharge. The generalized estimating equation was used for statistical analysis. RESULTS: The experimental group showed significantly higher levels of wound care knowledge, improved wound care skills, lower levels of state anxiety, and lower heart rate variability than the control group after baseline data collection. CONCLUSIONS: Results support hat a mHealth application may be effective in health education. Clinicians can use the results to promote patients' wound care knowledge, enhance their wound care skills, and reduce anxiety related to dressing changes. IMPACT: Lack of wound care knowledge and skills can affect the willingness and ability to perform effective wound dressing changes, producing anxiety and having an impact on a patient's self-care after hospital discharge. mHealth applications (apps) have the potential to deliver health information in targeted and tailored ways that strengthen the self-management of diseases. mHealth app can increase wound care knowledge, improve care skills, and reduce anxiety related to wound care. mHealth app effectively supports self-monitoring of the wound healing process, self-judgement of the wound condition, and self-reaction of wound care accuracy. mHealth app provides step-by-step visual tutorials on wound care that allow patients and family caregivers to take pictures of the wounds and monitor the wound healing process. mHealth app for wound care knowledge is an effective and individualized method for learning. CLINICAL TRIAL: This study was registered by U.S. National Library of Medicine, ClinicalTrials.gov (ID: NCT03683303).
Assuntos
Ansiedade , Bandagens , Conhecimentos, Atitudes e Prática em Saúde , Aplicativos Móveis , Telemedicina/métodos , Humanos , Estudos Prospectivos , TaiwanRESUMO
OBJECTIVE: To evaluate the association between the fetal fraction of cell-free DNA at the second trimester and subsequent spontaneous preterm birth. METHODS: In this retrospective cohort study, data were collected from women with singleton pregnancies who underwent noninvasive prenatal testing at 14 to 25 weeks of gestation. The eligible patients were classified into three groups according to pregnancy outcome: birth at ≥37 weeks of gestation (term group), delivery at <34 weeks of gestation (early spontaneous preterm), and delivery at 34+0 to 36+6 weeks of gestation (late spontaneous preterm). Stepwise linear regression was performed to determine the maternal characteristics associated with the fetal fraction of cell-free DNA. Logistic regression was used to determine the relationship between the fetal fraction of cell-free DNA and pregnancy outcomes by adjusting for history of preterm birth. RESULTS: A total of 8129 singleton pregnancies met the recruitment criteria. Among them, 7790 (95.83%) were in the term group, 284 (3.49%) were in the late spontaneous preterm group, and 55 (0.68%) were in the early spontaneous preterm group. The fetal fraction of cell-free DNA was negatively correlated with body mass index, maternal age, nulliparity, and history of spontaneous preterm birth; positively correlated with gestational age; and not correlated with assisted reproduction or surface antigen of hepatitis B virus (HBsAg) positivity. After adjusting for history of preterm birth, a logistic regression analysis demonstrated no statistically significant associations between the fetal fraction of cell-free DNA and spontaneous preterm birth in any of the preterm groups (<34 weeks, 34+0 to 36+6 weeks, and <37 weeks). CONCLUSION: Our preliminary study found no relationship between the fetal fraction on NIPT at the second trimester and subsequent spontaneous preterm birth.
Assuntos
Ácidos Nucleicos Livres/análise , Nascimento Prematuro/sangue , Adulto , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez/sangue , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the gut microbiota differences of obese children compared with the control healthy cohort to result in further understanding of the mechanism of obesity development. METHODS: We evaluated the 16S rRNA gene, the enterotypes, and quantity of the gut microbiota among obese children and the control cohort and learned the differences of the gut microbiota during the process of weight reduction in obese children. RESULTS: In the present study, we learned that the gut microbiota composition was significantly different between obese children and the healthy cohort. Next we found that functional changes, including the phosphotransferase system, ATP-binding cassette transporters, flagellar assembly, and bacterial chemotaxis were overrepresented, while glycan biosynthesis and metabolism were underrepresented in case samples. Moreover, we learned that the amount of Bifidobacterium and Lactobacillus increased among the obese children during the process of weight reduction. CONCLUSION: Our results might enrich the research between gut microbiota and obesity and further provide a clinical basis for therapy for obesity. We recommend that Bifidobacterium and Lactobacillus might be used as indicators of healthy conditions among obese children, as well as a kind of prebiotic and probiotic supplement in the diet to be an auxiliary treatment for obesity.
Assuntos
Microbioma Gastrointestinal/genética , Trato Gastrointestinal/microbiologia , Microbiota/genética , Obesidade/microbiologia , Adolescente , Povo Asiático , Bifidobacterium/genética , Bifidobacterium/fisiologia , Criança , Pré-Escolar , Estudos de Coortes , Dieta , Suplementos Nutricionais , Humanos , Lactobacillus/genética , Lactobacillus/fisiologia , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , RNA Ribossômico 16S/genética , Redução de Peso/fisiologiaRESUMO
OBJECTIVE: Spinal muscular atrophy (SMA) is a common and fatal autosomal recessive disorder. Approximately 94% of SMA patients are caused by homozygous deletion of SMN1 gene. SMA carrier screening is recommended considering the high carrier frequency (1 in 35-50) as well as severity of the disease. METHODS: A prospective population-based cohort study was carried out on 4719 pregnant women from Shanghai region. Copy numbers of SMN1 and SMN2 genes were effectively determined with denaturing high performance liquid chromatography (DHPLC) technique. The method has detected 94% of SMA cases with deletion or conversion of the SMN1 genes. RESULTS: Ninety SMA carriers with only one copy of the SMN1 gene were identified among the 4719 pregnant woman. The carrier rate was 1.9%. Respectively, 1.2% and 0.6% of the carriers were caused by SMN1 gene deletion and SMN1 gene conversion. CONCLUSION: Through this study, we have determined the frequency of SMA mutation carriers in a population of pregnant women. The result may provide a basis for genetic counseling in order to reduce the rate of SMA affected births.
Assuntos
Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Adulto , China , Feminino , Deleção de Genes , Testes Genéticos/métodos , Humanos , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Prospectivos , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Adulto JovemRESUMO
A series of 1,2,4-triazole derivatives containing 1,4-benzodioxan (5a-5q) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential MetAP2 inhibitors. All the synthesized compounds were first reported. Among the compounds, compound 5k showed the most potent biological activity against HEPG2 cancer cell line (IC(50)=0.81 µM for HEPG2 and IC(50)=0.93 µM for MetAP2), which was comparable to the positive control. Docking simulation by positioning compound 5k into the MetAP2 structure active site was performed to explore the possible binding model. The results of apoptosis and Western-blot assay demonstrated that compound 5k possessed good antitumor activity against HEPG2 cancer cell line. Therefore, compound 5k with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 cancer cell.
Assuntos
Aminopeptidases/antagonistas & inibidores , Antineoplásicos/síntese química , Dioxanos/síntese química , Dioxanos/farmacologia , Metaloendopeptidases/antagonistas & inibidores , Triazóis/síntese química , Triazóis/farmacologia , Animais , Antineoplásicos/farmacologia , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dioxanos/química , Células HeLa , Células Hep G2 , Humanos , Camundongos , Modelos Moleculares , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Relação Estrutura-Atividade , Triazóis/químicaRESUMO
A novel type of cinnamic acid quinazoline amide derivatives (20-42), which designed the combination between quinazoline as the backbone and various substituted cinnamic acid as the side chain, have been synthesized and their biological activities were evaluated within cytotoxicity assay firstly and then potent EGFR inhibitory activity. Compound 42 demonstrated the most potent inhibitory activity (IC(50)=0.94 µM for EGFR), which could be optimized as a potential EGFR inhibitor in the further study. Docking simulation was performed to position compound 42 into the EGFR active site to determine the probable binding model. Analysis of the binding conformation of 42 in active site displayed compound 42 was stabilized by hydrogen bonding interactions with Lys822, which was different from other derivatives. In the further study, Compounds 43 and 44 had been synthesized and their biological activities were also evaluated, which were the same as that we expected. Compound 43 has demonstrated significant EGFR (IC(50)=0.12 µM) and tumor growth inhibitory activity as a potential anticancer agent.
Assuntos
Antineoplásicos/síntese química , Cinamatos/síntese química , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/efeitos dos fármacos , Inibidores de Proteínas Quinases/síntese química , Quinazolinas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cinamatos/química , Cinamatos/farmacologia , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos , Modelos Moleculares , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Ligação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/química , Quinazolinas/farmacologiaRESUMO
OBJECTIVE: The study was to investigate the role of EFEMP1 in angiogenesis and growth of cervical carcinoma in vivo. METHODS: Effects of EFEMP1 on proliferation of Hela cells and HUVECs, invasion of Hela cells and migration of HUVECs, and adhesion of Hela cells to HUVECs were evaluated by MTT, Transwell chamber assay and adhesion assay, respectively. EFEMP1 overexpression in Hela cells was achieved by stable EFEMP1 gene transfection into Hela cells by Lipofectamin™ 2000 and the effectiveness of transfection was verified with western-blotting. The effect of EFEMP1 transfection upon the VEGF expression of Hela cells was detected with ELISA. The nude mouse models bearing cervical cancer were established with Hela cells transfected with EFEMP1 gene to observe the role of EFEMP1 in angiogenesis and growth of cervical cancer in vivo. VEGF expression and microvascular density of cervical cancer tissues were detected with immunohistochemistry and CD34 labeling respectively to elucidate the pathway by which EFEMP1 influences the growth of cervical cancer. RESULTS: Proliferation and invasion of Hela cells were promoted by the EFEMP1 protein. The EFEMP1 gene transfection into Hela cells was successful and EFEMP1 gene obtained stable high expression in Hela cells. Compared to the control, the tumors with EFEMP1 overexpression showed a faster growth rate and had a higher level of VEGF expression and microvascular density. EFEMP1 gene transfection elevated the VEGF protein level in Hela cells and EFEMP1 protein facilitated the adhesion of Hela cells to HUVECs. However, no direct effect of EFEMP1 was observed on proliferation, migration and tube formation of HUVECs. CONCLUSIONS: EFEMP1 promoted the angiogenesis and accelerated the growth of cervical carcinoma in vivo through a VEGF up-regulation pathway.