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1.
Ann Med ; 56(1): 2307504, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38465636

RESUMO

BACKGROUND: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. METHODS: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. RESULTS: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. CONCLUSIONS: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , Vacinação , Vacinas de Produtos Inativados
2.
J Gene Med ; 25(9): e3534, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37259225

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is a highly aggressive cancer in advanced stages and has the highest cancer-related death across the world. Anoikis has emerged as a specific form of apoptotic cell death that may play a vital role in the formation and development of tumors. METHODS: Based on The Cancer Genome Atlas dataset, we developed a novel anoikis-related genes (ARGs) signature in LUAD and evaluated the differences between low and high-risk groups in clinical characteristics, expression patterns, immune cell infiltration, and drug sensitivity, etc. According to multivariate Cox regression analysis, the risk score was identified as a significant independent prognostic factor. The possible biological pathways of ARGs' were assessed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The immune infiltration landscape and risk score of ARGs were analyzed by ESTIMATE and CIBERSORT analysis. A nomogram grounded on six key ARGs and clinicopathological features was provided. Moreover, experiment validation of the expression patterns of six hub ARGs in lung cancer cell lines was conducted. RESULTS: We identified 53 survival-related LUAD anoikis-related differentially expressed genes and finally six hub anoikis genes (LDHA, SLC2A1, SERPINB5, ITGB4, BRCA2, and PIK3R1) were selected to construct an ARG model. The risk model could efficiently cluster the patients into low- and high-risk groups which could accurately predict clinical outcomes for LUAD patients. There is evidence that the prognostic risk score is a remarkable prognostic factor in determining overall survival. Different immune statuses and drug sensitivity between low- and high-risk groups were explored according to functional analysis. On the basis of risk scores and LUAD clinicopathological features, a novel nomogram was developed. Ultimately, all six key genes except for PIK3R1 were proved to be upregulated in LUAD tissues and cell lines by bioinformatics analysis and experimental validation. CONCLUSIONS: The result of the present study suggest that ARGs could be carcinogenic to LUAD and could be used as an effective stratification factor to customize therapies and forecast the survival rate in LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Prognóstico , Anoikis/genética , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição
3.
Immunobiology ; 228(3): 152363, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36870142

RESUMO

Natural killer cell-based immunotherapy has become a leading-edge tool against cancer, but still faces a variety of challenges, such as phenotype shift and dysfunction of NK cells in tumor microenvironment. Thus, finding potent agents that could inhibit the phenotype shift and incapacity of NK cells in the tumor microenvironment is essential for improving antitumor effects. dl-tetrahydropalmatine (dl-THP), one of the active alkaloids of Chinese herb Corydalis Rhizoma, has been proven to possess antitumor activity. However, whether dl-THP acts on NK cells to enhance antitumor activity remains unknown. In this study, we found that the proportion of blood CD56dimCD16+ NK cells was decreased while the proportion of CD56brightCD16- NK cells was increased when the cells were cultured in conditional medium (CM, medium from the human choriocarcinoma cell lines JEG-3). dl-THP could alter the varied proportion of CD56dimCD16+ NK cells and CD56brightCD16- NK cells in CM respectively. Importantly, the expression level of NKp44 on CD56dimCD16+ NK cells was dramatically reduced when the cells were cultured in CM, which could also be reversed by dl-THP. Furthermore, dl-THP increased the decreased NK-cell cytotoxicity when cells were cultured in CM. In summary, our study demonstrated that dl-THP could recover the decreased NKp44 expression level on CD56dimCD16+ NK cells and restore the cytotoxicity of NK cells in tumor microenvironment.


Assuntos
Alcaloides de Berberina , Células Matadoras Naturais , Humanos , Linhagem Celular Tumoral , Antígeno CD56/metabolismo , Células Matadoras Naturais/metabolismo , Receptores de IgG/metabolismo
4.
Sci Total Environ ; 873: 162329, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36805068

RESUMO

A green approach of copper (Cu) contaminated pig manure composting by earthworm Eisenia fetida was optimized. This work aims to assess the relationship between the bio-fertility properties and bioaccumulation of Cu during vermicomposting with five different doses of Cu. The optimal concentration of copper largely promoted the enrichment of nitrogen, phosphorus, and potassium, but the biological activities of earthworms could be inhibited once the Cu concentration exceed the threshold. When the Cu doses at 300 mg kg-1, the nutrient recovery rate (Irecovery) of available nitrogen, phosphorus and potassium reached their highest value, concomitant with largest C/N ratio reduced at 46.01 %. Moreover, nutrients recovery mechanism of total phosphorus increased up to 0.11 % h-1 and higher bioaccumulations in faces and intestine were detected by 1.79 and 0.99, respectively, during vermicomposting. The maximal enzyme activity rates (kmax) indicate that the enzyme activities, such as ROS and SOD, are sensitive bioindicators, which can be used to estimate the stress response of earthworms and Cu biotoxicity. The maximum specific growth rate (µmax) of the actinomycetes (TAct) increased gradually from 0.02 to 0.04 with the increase of Cu doses, but total fungi (TF) showed different response to µmax, which decreased firstly and then increased. It was demonstrated that Cu influenced the gut microbial community to vary the bio-fertility properties and bioaccumulation of Cu in the pig manure. All the findings refer that the vermicomposting could be the sustainable agricultural practices.


Assuntos
Cobre , Oligoquetos , Suínos , Animais , Cobre/análise , Esterco/microbiologia , Agricultura , Oligoquetos/fisiologia , Nitrogênio , Fósforo , Solo
5.
J Cancer Res Clin Oncol ; 149(10): 6999-7006, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36853385

RESUMO

BACKGROUND: Observational studies showed associations between smoking, and airflow limitation, with lung squamous cell carcinoma (LUSC). However, the causal association of airflow limitation with LUSC and the modification by smoking status for the association remains unclear. METHODS: Genetic summary data were obtained from large genome-wide association studies (GWAS). One hundred two single nucleotide polymorphisms (SNPs) for airflow limitation (i.e., FEV1/FVC < 0.7) and 153 SNPs for smoking behavior were used as instrumental variables and the main MR analysis methods. The univariable and multivariable Mendelian Randomization (MR) in a two-sample setting were performed to assess the association of airflow limitation, and smoking behavior with LUSC. RESULTS: In the univariable MR analysis, genetic predisposition towards airflow limitation [Inverse Variance-Weighted (IVW) method Odds Ratio (OR) = 4.83, 95% Confidence Interval (CI) 1.55 to 15.06, P = 0.006], age of smoking initiation (IVW method OR = 0.10, 95%CI 0.02 to 0.36, P < 0.001), cigarettes smoked per day (IVW method OR = 3.10, 95%CI 2.07 to 4.63, P < 0.001), ex-smoking (IVW method OR = 0.47, 95%CI 0.31 to 0.69, P < 0.001), current smoking status (IVW method OR = 13.08, 95%CI 2.53 to 67.84, P = 0.002), pack-years of smoking (Weighted median method OR = 11.49, 95%CI 3.71 to 35.63, P < 0.001) were associated with LUSC. In the multivariable MR analysis, the causal effect of airflow limitation was still observed on LUSC (IVW method OR = 2.97, 95% CI 1.09 to 8.04, P = 0.032 adjusted for age of smoking initiation and cigarettes smoked per day; IVW method OR = 3.24, 95% CI 1.09 to 9.58, P = 0.033 adjusted for ex-smoking, current smoking status, and pack years of smoking; IVW method OR = 2.91, 95% CI 1.01 to 8.41, P = 0.049 adjusted for 5 smoking behaviors mentioned above). CONCLUSIONS: Our MR analysis demonstrated that airflow limitation is likely to be an independent predictor of LUSC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Carcinoma de Células Escamosas/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Pulmonares/genética , Pulmão
6.
Animals (Basel) ; 13(4)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36830335

RESUMO

Three ruminal cannulated Simmental crossbreed bulls (approximately 3 years of age and with 380 ± 20 kg live weight at initiation of the experiment) were used in a 3 × 3 Latin square experiment in order to determine the effects of the treatments on ruminal pH and degradability of nutrients, as well as the rumen fungal community. The experimental periods were 21 d, with 18 d of adjustment to the respective dietary treatments and 3 d of sample collection. Treatments consisted of a basal diet containing a 47.11% composition of two sources of forage as follows: (1) 100% millet straw (MILLSTR), (2) 50:50 millet straw and corn straw (COMB), and (3) 100% corn straw (CORNSTR). Dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) were tested for ruminal degradability using the nylon bag method, which was incubated for 6, 12, 24, 36, 48, and 72 h, and rumen fungal community in rumen fluid was determined by high-throughput gene sequencing technology. Ruminal pH was not affected by treatments. At 72 h, compared to MILLSTR, DM degradability of CORNSTR was 4.8% greater (p < 0.05), but when corn was combined with millet straw, the difference in DM degradability was 9.4%. During the first 24 h, degradability of CP was lower for CORNSTR, intermediate for MILLSTR, and higher for COMB. However, at 72 h, MILLSTR and COMB had a similar CP degradability value, staying greater than the CP degradability value of the CORNSTR treatment. Compared to MILLSTR, the rumen degradability of NDF was greater for CORNSTR and intermediate for the COMB. There was a greater degradability for ADF in CORNSTR, intermediate for COMB, and lower for MILLSTR. In all treatments, Ascomycota and Basidiomycota were dominant flora. Abundance of Basidiomycota in the group COMB was higher (p < 0.05) than that in the group CORNSTR at 12 h. Relative to the fungal genus level, the Thelebolus, Cladosporium, and Meyerozyma were the dominant fungus, and the abundance of Meyerozyma in COMB and CORNSTR were greater (p < 0.05) than MILLSTR at 12, 24, and 36 h of incubation. In conclusion, it is suggested to feed beef cattle with different proportions of millet straw and corn straw combinations.

7.
Heart Lung ; 58: 39-46, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36375396

RESUMO

BACKGROUND: The globally low access to pulmonary rehabilitation can be attributed to the shortage of competent professionals. Setting up specific-duty-post nurses in pulmonary rehabilitation is a novel attempt to solve it. However, their work experience in this position has not been examined. OBJECTIVES: To describe the working experience of special-duty-post pulmonary rehabilitation nurses to improve the efficiency of this mode and provide guidance for management hospitals contemplating setting up and optimizing this position. METHODS: A descriptive phenomenology qualitative approach with semi-structured in-depth interviews was adopted. RESULTS: Fourteen special-duty-post pulmonary rehabilitation nurses were recruited by purposive and snowball sampling from May to July 2021. Four main themes emerged: finding the way in the dark, meeting qualifications and requirements, seeking independence, and anticipating better development. The lack of relevant standards, inadequate support, and variation in chronic respiratory diseases had made them felt like they were finding their way in the dark. As a result of meeting new requirements and qualifications, they experienced role transition shock. Moreover, they were seeking a clear role boundary and independence to foster their sense of belonging. They suggested ways that future management and policies could nurture them to invest more in pulmonary rehabilitation development. CONCLUSION: Developing detailed working standards before work begins and providing adequate support, especially from pulmonologists was key. Compared to a clinical position, this position requires a high level of specialty knowledge, communication skills, self-learning, innovative ability, decision-making, and resilience. Special-duty-post pulmonary rehabilitation nurses suggested ways that tailored management based on the identified factors could counteract their transition shock. A clear role boundary and independence help foster belongingness. To maximize effectiveness and overcome challenges requires identifying obstacles to success, initiating strategies to overcome these and ongoing efforts to promote interdisciplinary support of the role.


Assuntos
Hospitais , Papel do Profissional de Enfermagem , Humanos , Pesquisa Qualitativa
8.
J Environ Manage ; 324: 116280, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36183526

RESUMO

Vermicomposting is a resource technology for managing animal excreta, whereas the internal relationships of the process are vital for its wide applications. The present study examined how macronutrient and micronutrient concentrations, microbial communities, and enzymatic activity of pig manure (PM) changed during the composting and vermicomposting processes and their internal interactions. The vermicomposting process increased macronutrients more significantly than composting (32.40% of total available nitrogen, 21.70% of total available phosphorous, and 12.70% of total available potassium). The vermicomposting reduced total organic carbon (7.91%), C/N ratio (61.35%), and humification index (56.47%) more than composting due to the quick decomposition of PM. After continual fertility optimization, the total microbial population, with the exception of total fungi, rose significantly to accelerate organics mineralization and improve macronutrients in vermicomposting compared to composting. Moreover, earthworm addition favored the stabilization of the PM containing higher concentrations of micronutrients after being catalyzed by the enhanced catalase activity and reduced sucrase activity after 90 days of vermicomposting. Principal component analysis and chord plots found that the generated vermicomposting products had higher fertility properties and biological activities induced by the synergistic effect of microorganisms and earthworms. These findings highlight vermicomposting is an eco-friendly management technology for processing PM and can be scaled up for agricultural applications.


Assuntos
Compostagem , Oligoquetos , Suínos , Animais , Esterco/análise , Nitrogênio/análise , Fósforo , Solo
9.
Acta Biomater ; 129: 220-234, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34082106

RESUMO

The shallow penetration depth of photothermal agents in the first near-infrared (NIR-I) window significantly limits their therapeutic efficiency. Multifunctional nanotheranostic agents in the second near-infrared (NIR-II) window have drawn extensive attention for their combined treatment of tumors. Here, for the first time, we created oxygen-deficient black SnO2-x with strong NIR (700-1200 nm) light absorption with NaBH4 reduction from white SnO2. Hyaluronic acid (HA) could selectively target cancer cells overexpressed CD44 protein. After modification with HA, the obtained nanotheranostic SnO2-x@SiO2-HA showed high dispersity in aqueous solution and good biocompatibility. SnO2-x@SiO2-HA was confirmed to simultaneously generate enough hyperthermia and reactive oxygen species with single NIR-II (1064 nm) light irradiation. Because HA is highly affined to CD44 protein, SnO2-x@SiO2-HA has specific uptake by overexpressed CD44 cells and can be accurately transferred to the tumor site. Furthermore, tumor growth was significantly inhibited following synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) with targeted specificity under the guidance of photoacoustic (PA) imaging using 1064 nm laser irradiation in vivo. Moreover, SnO2-x@SiO2-HA accelerated wound healing. This work prominently extends the therapeutic utilization of semiconductor nanomaterials by changing their nanostructures and demonstrates for the first time that SnO2-x based therapeutic agents can accelerate wound healing. STATEMENT OF SIGNIFICANCE: The phototherapeutic efficacy of nanotheranostics by NIR-I lightirradiation was restricted owing to the limitation of tissue penetration and maximum permissible exposure. To overcome these limitations, we hereby fabricated a NIR-IIlight-mediated multifunctional nanotheranostic based on SnO2-x. The introduction of oxygen vacancy strategy was employed to construct full spectrum responsive oxygen-deficient SnO2-x, endowing outstanding photothermal conversion, and remarkable production activity of reactive oxygen species under NIR-II light activation. Tumor growth was significantly inhibited following synergistic PDT/PTT with targeted specificity under the guidance of photoacoustic imaging using 1064 nm laser irradiation in vivo. Our strategy not only expands the biomedical application of SnO2, but also providea method to develop other inorganic metal oxide-based nanosystems for NIR-II light-activated phototheranostic of cancers.


Assuntos
Hipertermia Induzida , Fotoquimioterapia , Negro ou Afro-Americano , Linhagem Celular Tumoral , Humanos , Fototerapia , Dióxido de Silício , Nanomedicina Teranóstica
10.
J Med Virol ; 93(2): 1057-1069, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32761898

RESUMO

To provide a comprehensive and systematic analysis of demographic characteristics, clinical symptoms, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in pediatric patients. A meta-analysis was carried out to identify studies on COVID-19 from 25 December 2019 to 30 April 2020. A total of 48 studies with 5829 pediatric patients were included. Children of all ages were at risk for COVID-19. The main illness classification ranged as: 20% (95% confidence interval [CI]: 14%-26%; I2 = 91.4%) asymptomatic, 33% (95% CI: 23%-43%; I2 = 95.6%) mild and 51% (95% CI: 42%-61%; I2 = 93.4%) moderate. The typical clinical manifestations were fever 51% (95% CI: 45%-57%; I2 = 78.9%) and cough 41% (95% CI: 35%-47%, I2 = 81.0%). The common laboratory findings were normal white blood cell 69% (95% CI: 64%-75%; I2 = 58.5%), lymphopenia 16% (95% CI: 11%-21%; I2 = 76.9%) and elevated creatine-kinase MB 37% (95% CI: 25%-48%; I2 = 59.0%). The frequent imaging features were normal images 41% (95% CI: 30%-52%; I2 = 93.4%) and ground-glass opacity 36% (95% CI: 25%-47%; I2 = 92.9%). Among children under 1 year old, critical cases account for 14% (95% CI: 13%-34%; I2 = 37.3%) that should be of concern. In addition, vomiting occurred in 33% (95% CI: 18%-67%; I2 = 0.0%) cases that may also need attention. Pediatric patients with COVID-19 may experience milder illness with atypical clinical manifestations and rare lymphopenia. High incidence of critical illness and vomiting symptoms reward attention in children under 1 year old.


Assuntos
COVID-19/fisiopatologia , Adolescente , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Criança , Pré-Escolar , Tosse/virologia , Feminino , Febre/virologia , Humanos , Lactente , Recém-Nascido , Masculino
11.
Clin Gastroenterol Hepatol ; 17(8): 1597-1606.e5, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30391434

RESUMO

BACKGROUND & AIMS: Rectal indomethacin and spraying of the duodenal papilla with epinephrine might reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). We performed a randomized trial to compare the effects of the combination of indomethacin and epinephrine (IE) vs indomethacin plus saline (IS) in prophylaxis of post-ERCP pancreatitis (PEP). METHODS: We performed a double-blind trial at 10 centers in China, from February 2017 to October 2017, of 1158 patients with native papilla undergoing ERCP. The patients were assigned randomly to groups given IE (n = 576) or IS (n = 582). All patients received a single dose of rectal indomethacin within 30 minutes before ERCP; 20 mL of dilute epinephrine (IE group) or saline (IS group) then was sprayed on the duodenal papilla at the end of ERCP. The primary outcome was the incidence of overall PEP. Data were analyzed on an intention-to-treat principle. RESULTS: The study was terminated at the interim analysis for safety concerns and futility. The groups had similar baseline characteristics. PEP developed in 49 patients in the IE group (8.5%) and in 31 patients in the IS group (5.3%) (relative risk, 1.60, 95% CI, 1.03-2.47; P = .033). There were no significant differences between groups in proportions of patients with postsphincterotomy bleeding (2.1% in the IE group and 1.5% in the IS group) and biliary infection (1.2% in the IE group and 2.2% in the IS group). CONCLUSIONS: In a randomized trial, we found the combination of rectal indomethacin with papillary epinephrine spraying increased the risk of PEP compared with indomethacin alone. Spray epinephrine should not be used with rectal indomethacin for prevention of post-ERCP pancreatitis. ClincialTrials.gov no: NCT03057769.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Epinefrina/administração & dosagem , Indometacina/administração & dosagem , Pancreatite/etiologia , Medição de Risco/métodos , Administração Retal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática , China/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Epinefrina/efeitos adversos , Feminino , Seguimentos , Humanos , Incidência , Indometacina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Irrigação Terapêutica/efeitos adversos , Adulto Jovem
12.
Cell Immunol ; 331: 78-84, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29887420

RESUMO

Macrophages are key cell types of innate immunity and play a central role in inflammation and host defense. Leukocyte-associated Ig-like receptor-1 (LAIR-1) is highly expressed on macrophages and regulates macrophage functions in several conditions. However, whether LAIR-1 is involved in governing macrophage polarization is still not clear. Here, we investigated the effect of LAIR-1 on macrophage polarization using human macrophage polarization model with THP-1 cells. It was found that LAIR-1 was highly expressed in THP-1 macrophages. IFN-γ reduced LAIR-1 expression in THP-1 macrophages. However, IL-4 did not have an effect on the expression of LAIR-1. Moreover, activation of LAIR-1 significantly inhibited the proinflammatory M1-like macrophage differentiation and promoted alternative activation of macrophages. Therefore, LAIR-1 may play critical roles in macrophage polarization. This study provides a rationale for macrophage polarization and sheds light on homeostatic mechanism in which LAIR-1 activation can terminate inflammation which may be impaired in patients with autoimmune disease.


Assuntos
Diferenciação Celular/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Receptores Imunológicos/imunologia , Diferenciação Celular/genética , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Humanos , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/genética , Macrófagos/citologia , Macrófagos/metabolismo , Fenótipo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Células THP-1 , Células U937
13.
Front Immunol ; 8: 741, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28702027

RESUMO

Human leukocyte antigen (HLA)-G plays a crucial role in conferring fetal-maternal tolerance and ensuring a successful pregnancy. CD56bright natural killer (NK) cells accumulate at the maternal decidua in large numbers during pregnancy and are found in direct contact with fetal trophoblasts. There are increasing evidences that decidual NK (dNK) cells are crucial for pregnancy. However, the regulation of dNK cells is mostly unknown. Here, we provide evidences that the secretion function of dNK cells in recurrent spontaneous abortion was impaired, which led to the impairment of the proinvasion and proangiogenesis functions of dNK cells. Decreased HLA-G expression induced by the transfection of miR-133a mimics in HTR-8/SVneo affected the secretory functions of dNK cells. Thus, our data revealed that the functions of dNK cells could be suppressed by the decreased expression of HLA-G and suggest a possible mechanism of recurrent miscarriage.

14.
Oncol Rep ; 38(1): 343-351, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28586038

RESUMO

Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR­1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis in vitro, and suppressed the growth of transplanted tumors in vivo. Wnt3 was found to be a potential target of miR-1247-5p and overexpression of miR-1247-5p was able to significantly downregulate the expression of Wnt3 by directly targeting the 3'UTR of this gene, which was verified by luciferase reporter assay and western blotting. Furthermore, we found that the miR-1247-5p gene was hypermethylated in HepG2 cells, and the transcript of miR-1247-5p was increased significantly after treatment with the demethylation drug 5-azacytidine. These findings demonstrated that miR-1247-5p functions as a tumor suppressor in human HCC by targeting Wnt3 and that the expression of miR-1247-5p can be regulated by DNA methylation, which indicates that miR-1247-5p has the potential to be a therapeutic target as well as a diagnostic marker of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proteína Wnt3/antagonistas & inibidores , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Estudos de Casos e Controles , Ciclo Celular , Movimento Celular , Proliferação de Células , Metilação de DNA , Progressão da Doença , Genes Supressores de Tumor , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Proteína Wnt3/genética , Proteína Wnt3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Int J Mol Sci ; 17(12)2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-27918446

RESUMO

Osteoporosis is a progressive skeletal disorder characterized by low bone mass and increased risk of fracture in later life. The incidence and costs associated with treating osteoporosis cause heavy socio-economic burden. Currently, the diagnosis of osteoporosis mainly depends on bone mineral density and bone turnover markers. However, these indexes are not sensitive and accurate enough to reflect the osteoporosis progression. Metabolomics offers the potential for a holistic approach for clinical diagnoses and treatment, as well as understanding of the pathological mechanism of osteoporosis. In this review, we firstly describe the study subjects of osteoporosis and bio-sample preparation procedures for different analytic purposes, followed by illustrating the biomarkers with potentially predictive, diagnosis and pharmaceutical values when applied in osteoporosis research. Then, we summarize the published metabolic pathways related to osteoporosis. Furthermore, we discuss the importance of chronological data and combination of multi-omics in fully understanding osteoporosis. The application of metabolomics in osteoporosis could provide researchers the opportunity to gain new insight into the metabolic profiling and pathophysiological mechanisms. However, there is still much to be done to validate the potential biomarkers responsible for the progression of osteoporosis and there are still many details needed to be further elucidated.


Assuntos
Biomarcadores/metabolismo , Pesquisa Biomédica , Metabolômica/métodos , Osteoporose/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Osteoporose/tratamento farmacológico
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 32(3): 369-72, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26927558

RESUMO

OBJECTIVE: To investigate the expression levels of adhesion molecule CD49b and negative regulation molecule LAG-3 (CD223) on peripheral blood CD14(+) cells in patients with recurrent spontaneous abortion (RSA). METHODS: Peripheral blood samples were collected from 7 normal female individuals and 12 patients with RSA, and then peripheral blood mononuclear cells (PBMCs) and plasma were separated from the peripheral blood via centrifugation. The expression levels of CD49b and LAG-3 on CD14(+) cells in PBMCs were detected by flow cytometry and the levels of interleukin 10 (IL-10) and transforming growth factor ß (TGF-ß) in plasma were detected by ELISA. RESULTS: In the RSA patient group, there was no significant difference in the percentage of monocytes compared with that of the normal female group. The numbers of CD14(+) CD49b(+), CD14(+) LAG-3(+) and CD14(+) CD49b(+) LAG-3(+) cells in the RSA patient group were lower than those of the normal female group. The plasma level of TGF-ß in the RSA patient group was lower than that of the normal female group. However, there was no significant difference in the plasma level of IL-10 between the two groups. CONCLUSION: In RSA patients, the expression levels of CD49b and LAG-3 on CD14(+) monocytes and the plasma level of TGF-ß decreased obviously compared with that of the normal females.


Assuntos
Aborto Habitual/sangue , Antígenos CD/sangue , Integrina alfa2/sangue , Leucócitos Mononucleares/metabolismo , Receptores de Lipopolissacarídeos/sangue , Adulto , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interleucina-10/sangue , Fator de Crescimento Transformador beta/sangue , Proteína do Gene 3 de Ativação de Linfócitos
17.
Life Sci ; 151: 174-181, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26968781

RESUMO

AIMS: Natural killer (NK) cells play critical roles in antitumor immunity. Our previous study showed that over-expression of miR-30c-1* enhanced NKL cell cytotoxicity through up-regulation of tumor necrosis factor-α via directly targeting transcription factor homeobox containing 1. MiR-30c, the complimentary microRNA of miR-30c-1*, has been found to exert regulatory effect on T cell function. However, the effect of miR-30c on NK cells is unknown. Therefore, this study aimed to investigate whether miR-30c could play a role to enhance NK cell activation and cytotoxicity. MAIN METHODS: Chemosynthesis exogenous miR-30c mimics and miR-30c inhibitor were transfected into NKL cells and isolated human peripheral blood NK cells, respectively. The expression levels of NK group 2, member D (NKG2D), CD107a and FasL on cell surface and cytotoxic ability of miRNAs transfected NKL cells against SMMC-7721 cells were evaluated. KEY FINDINGS: MiR-30c could increase the expression of NKG2D and CD107a on NKL cells, and enhance cytotoxic ability of NKL cells to kill SMMC-7721 cells. Moreover, miR-30c could up-regulate the expression of FasL on both NKL cells and human peripheral blood NK cells. However, the peripheral blood NK cells from only four in ten healthy donors appeared high expression levels of NKG2D and CD107a after miR-30c transfection. SIGNIFICANCE: MiR-30c could promote the cytotoxicity of NKL cells in vitro by up-regulating the expression levels of NKG2D, CD107a and FasL. However, the effect of miR-30c on ex vivo NK cells from different human individuals is diverse, indicating that miR-30c may play complicate and fine adjustment in immune system.


Assuntos
Citotoxicidade Imunológica/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , MicroRNAs/farmacologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/biossíntese , Regulação para Cima/efeitos dos fármacos , Células Cultivadas , Proteína Ligante Fas/biossíntese , Humanos , Células Matadoras Naturais/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/biossíntese
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