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1.
PLoS One ; 16(9): e0257221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34506603

RESUMO

BACKGROUND: Bleaching is widely accepted for improving the appearance of discolored teeth; however, patient compliance is affected by bleaching-related complications, especially bleaching sensitivity. This study aimed to investigate the role of reactive oxygen species (ROS) in cytotoxicity and pain conduction activated by experimental tooth bleaching. METHODS: Dental pulp stem cells with or without N-acetyl-L-cysteine (NAC), an ROS scavenger, were cultured on the dentin side of the enamel/dentin disc. Subsequently, 15% (90 min) and 40% (30 min) bleaching gels were painted on the enamel surface. Cell viability, intracellular ROS, Ca2+, adenosine triphosphate (ATP), and extracellular ATP levels were evaluated using the Cell Counting Kit-8 assay, 2',7'-dichlorodihydrofluorescein diacetate, CellROX, fura-3AM fluorescence assay, and ATP measurement kit. The rat incisor model was used to evaluate in vivo effects after 0, 1, 3, 7, and 30 days of bleaching. Changes in gene and protein expression of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNFα), transient receptor potential ankyrin 1 (TRPA1), and Pannexin1 (PANX1) in dental pulp stem cells and pulp tissue were detected through RT-PCR, western blotting, and immunofluorescence. RESULTS: The bleaching gel suppressed dental pulp stem cell viability and extracellular ATP levels and increased intracellular ROS, Ca2+, and intracellular ATP levels. The mRNA and protein expression of IL-6, TNFα, TRPA1, and PANX1 were up-regulated in vitro and in vivo. Furthermore, the 40% gel had a stronger effect than the 15% gel, and NAC ameliorated the gel effects. CONCLUSIONS: Our findings suggest that bleaching gels induce cytotoxicity and pain conduction in dental pulp stem cells via intracellular ROS, which may provide a potential therapeutic target for alleviating tooth bleaching nociception.

2.
PLoS One ; 16(9): e0257248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507348

RESUMO

Meiosis is a complex process involving the expression and interaction of numerous genes in a series of highly orchestrated molecular events. Fam9b localized in Xp22.3 has been found to be expressed in testes. However, FAM9B expression, localization, and its role in meiosis have not been previously reported. In this study, FAM9B expression was evaluated in the human testes and ovaries by RT-PCR, qPCR, and western blotting. FAM9B was found in the nuclei of primary spermatocytes in testes and specifically localized in the synaptonemal complex (SC) region of spermatocytes. FAM9B was also evident in the follicle cell nuclei and diffusely dispersed in the granular cell cytoplasm. FAM9B was partly co-localized with SYCP3, which is essential for both formation and maintenance of lateral SC elements. In addition, FAM9B had a similar distribution pattern and co-localization as γH2AX, which is a novel biomarker for DNA double-strand breaks during meiosis. All results indicate that FAM9B is a novel meiosis-associated protein that is co-localized with SYCP3 and γH2AX and may play an important role in SC formation and DNA recombination during meiosis. These findings offer a new perspective for understanding the molecular mechanisms involved in meiosis of human gametogenesis.

3.
BMC Ophthalmol ; 21(1): 318, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470605

RESUMO

BACKGROUND: The prevalence of myopia among children in Chengdu is unknown. The aim of this study was to determine the prevalence of myopia in 3- to 14-year-old Chinese children in Chengdu. METHODS: This study was a school-based cross-sectional study in children aged 3-14 years. Visual acuity (VA), spherical equivalent error (SER) with noncycloplegic autorefraction, axial length (AL) and corneal radius (CR) were measured. RESULTS: A total of 19,455 children were recruited for this study. The prevalence of myopia was 38.1 %; the prevalence of low myopia was 26.6 %, that of moderate myopia was 9.8 %, and that of high myopia was 1.7 %. The prevalence of myopia and SER increased with age from 6 years old. The prevalence of myopia was higher, and the SER indicated more severe myopia in the girls than in the boys (40.1 % vs. 36.2 %, χ2 = 30.67, df = 1, P < 0.001; -0.93 D ± 1.75 D vs. -0.84 D ± 1.74 D, t = 3.613, df=19,453, P < 0.001). The girls had a higher prevalence of myopia and myopic SER than did the boys aged 9 years and older (P < 0.05). Among the myopic children, the rates of uncorrected, undercorrected and fully corrected myopia were 54.8 %, 31.1 and 14.1 %, respectively. AL and AL/CR increased with age from 6 years old, but CR remained stable after 4 years old. The AL was longer, and the CR was flatter in the boys than in the girls aged 3 to 14 years old (P < 0.05). CONCLUSIONS: The prevalence of myopia, AL and AL/CR increased, and the SER became more myopic with age from 6 years old. The girls had a higher prevalence of myopia and myopic SER than did the boys, but the boys had a longer AL, flatter CR and higher AL/CR ratio than did the girls. The rate of uncorrected myopia was very high in the myopic children. More actions need to be taken to decrease the prevalence of myopia, especially uncorrected myopia in children.


Assuntos
Miopia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Miopia/epidemiologia , Prevalência , Instituições Acadêmicas
4.
BMC Infect Dis ; 21(1): 913, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488670

RESUMO

BACKGROUND: While miliary tuberculosis (TB) in pregnancy is rare after in vitro fertilization and embryo transfer (IVF-ET), it poses a serious threat to the health of pregnant women and their fetuses. The present study aimed to describe the clinical features of miliary TB and pregnancy outcomes of patients after IVF-ET. METHODS: Data of infertile patients who received IVF-ET at Peking University Third Hospital between January 2012 and December 2017 were retrospectively analyzed. Patients who developed miliary TB during pregnancy were identified, and clinical characteristics of miliary TB were described. RESULTS: Out of 62,755 infertile women enrolled, 7137 (11.4 %) showed signs of prior pulmonary TB on chest X-ray (CXR). Among the 15,136 women (mean age: 33.2 ± 5.0 years) who successfully achieved clinical pregnancy, seven patients aged 28-35 years had miliary TB during pregnancy, with two patients having a complication of TB meningitis. All these patients presented with fever. Notably, old TB lesions were detected on CXR in six patients before IVF-ET; nevertheless, no anti-TB therapy was administered. Furthermore, salpingography revealed oviduct obstruction in all patients (7/7). Patients received anti-TB therapy following a diagnosis of miliary TB and were clinically cured. However, pregnancy was terminated due to spontaneous (4/7) and induced (3/7) abortion. CONCLUSIONS: TB reactivation, mostly as miliary TB and TB meningitis, is severe in pregnant women after IVF-ET and deleterious to pregnancy outcomes. Signs of prior TB on CXR may be risk factors for TB reactivation during pregnancy.

5.
BMC Cancer ; 21(1): 996, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488675

RESUMO

BACKGROUND: Esophageal cancer is a common malignant tumor and its 5-year survival rate is much lower than 30% due to its invasiveness and pronounced metastasis ability, as well as the difficulty in early diagnosis. This study aimed to elucidate the molecular mechanism of ubiquitin conjugating enzyme E2 C (UBE2C) in esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we conducted a comprehensive evaluation of the UBE2C expression in ESCC by collecting the protein and mRNA expression data (including in-house RNA-seq, in-hosue immunohistochemistry, TCGA-GTEx RNA-seq and tissue microarray) to calculate a combined standardized mean difference (SMD) and summary receiver operating characteristic curve (sROC). Kaplan-Meier (K-M) method was used for survival analysis. We also explored the mechanism of UBE2C in ESCC by combing the differentially expressed genes (DEGs) of ESCC, related-genes of UBE2C in ESCC and the putative miRNAs and lncRNAs which may regulate UBE2C. RESULTS: UBE2C protein and mRNA were highly expressed in ESCC tissues (including 772 ESCC tissue samples and 1837 non-cancerous tissue control samples). The pooled SMD of UBE2C expression values was 1.98 (95% CI: 1.51-2.45, p < 0.001), and the the area under the curve (AUC) of the sROC was 0.93 (95% CI: 0.90-0.95). The results of survival analysis suggested that UBE2C is likely to play different roles in different stages of the ESCC. Pathway anaylsis showed that UBE2C mainly influenced the biological function of esophageal cancer by synergistic effects with CDK1, PTTG1 and SKP2. We also constructed a potential UBE2C-related ceRNA network for ESCC (HCP5/has-miR-139-5p/UBE2C). CONCLUSION: UBE2C mRNA and protein level were highly expressed in ESCC and UBE2C was likely to play different roles in different stages of the ESCC.

6.
Phytother Res ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34514657

RESUMO

Overactivation of TGF-ß/ALK5/Smad signaling pathway has been observed in the advanced stage of various human malignancies. As a key component of TGF-ß/ALK5/Smad signaling pathway transduction, TGF-ß type I receptor (also known as ALK5) has emerged as a promising therapeutic target for cancer treatment. In this study, to discover a novel ALK5 inhibitor, a commercial natural products library was screened using docking-based virtual screening, followed by luciferase reporter assay. A flavonoid glycoside kaempferol 3-O-gentiobioside (KPF 3-O-G) was identified as a potent ALK5 inhibitor through directly bound to the ATP-site of ALK5, resulting in the inhibitory effects on phosphorylation and translocation of Smad2 and expression of Smad4. Additionally, we found that KPF 3-O-G reduced cell proliferation and inhibited TGF-ß-induced cell migration and invasion. Moreover, western blotting and immunofluorescent analysis showed that KPF 3-O-G significantly reversed the TGF-ß-induced EMT biomarkers, including upregulation of E-cadherin and downregulation of N-cadherin, vimentin, and snail. In vivo study showed that KPF 3-O-G administration reduced tumor growth in human ovarian cancer xenograft mouse model, without obvious toxic effect. This study provided novel insight into the anticancer effects of KPF-3-O-G and indicated that KPF-3-O-G might be developed as potential therapeutics for cancer treatment after further validation.

7.
J Healthc Eng ; 2021: 5709104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540187

RESUMO

Cytokine-induced killer (CIK) cells have been proved to be an effective method of tumor immunotherapy in numerous preclinical and clinical studies. In our previous study, a new method was developed to prime and propagate CIK cells by the combination of IL-2 and IL-15, and this kind of CIK cells had enhanced antitumor effect on lung cancer. For renal cell carcinoma (RCC), immunotherapy plays an important role because of the poor efficacy of radiotherapy and chemotherapy. In this study, we further evaluated the antitumor effects of these enhanced CIK cells against RCC. Enhanced CIK cells were generated by IL-2 combined with IL-15 and identified by flow cytometry. HEK-293 and ACHN cell lines were used to verify the efficiency of CIK cells in vitro, and then the ACHN tumor xenograft model was also employed for in vivo study. In addition, the secreted cytokines including IFN-γ, granzyme B, TNF-α, and perforin, as well as the local microstructure were also studied. Subsequently, 20 patients with RCC were enrolled into our study, and 11 patients were randomly divided into the autologous CIK treatment group for clinical research. The results showed that enhanced CIK cells exert better antitumor effects in RCC in vitro (p < 0.01 in HEK-293 and p < 0.05 in ACHN)and in vivo (p < 0.05). Patients benefit overall survival from enhanced CIK therapy in our clinical study. Our present preclinical and clinical studies for the first time elucidated that these enhanced CIK cells would be used as an effective adjuvant therapy in the treatment of RCC.

8.
J Biol Inorg Chem ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545414

RESUMO

Six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) with the formula [Ru(N^N)2bpy(4-CH3-4'-CH2OART)](PF6)2 (Ru-ART-1-3) and [Ru(N^N)2bpy(4-CH2OART-4'-CH2OART)](PF6)2 (Ru-ART-4-6) (N^N = 2,2'-bipyridine (bpy, in Ru-ART-1 and Ru-ART-4), 1,10-phenanthroline (phen, in Ru-ART-2 and Ru-ART-5) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru-ART-3 and Ru-ART-6)), were synthesized and characterized. Among them, Ru-ART-1-3 and Ru-ART-4-6 carry one and two ART moieties, respectively. Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity among six Ru(II)-ART conjugates. These two complexes can be effectively taken up by human cervical carcinoma (HeLa) cells. In addition, they selectively kill cancer cell lines while mildly affect normal cells. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy. As a result, Ru-ART-3 and Ru-ART-6 induce autophagy-dependent cell apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. In this work, six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) have been synthesized and characterized. Among them, Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy.

9.
Sci Rep ; 11(1): 17418, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465829

RESUMO

Hyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca2+, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P < 0.0001), and proliferation factors [PCNA (P < 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.

10.
Brain Topogr ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480635

RESUMO

Integrating multimodal information into a unified perception is a fundamental human capacity. McGurk effect is a remarkable multisensory illusion that demonstrates a percept different from incongruent auditory and visual syllables. However, not all listeners perceive the McGurk illusion to the same degree. The neural basis for individual differences in modulation of multisensory integration and syllabic perception remains largely unclear. To probe the possible involvement of specific neural circuits in individual differences in multisensory speech perception, we first implemented a behavioral experiment to examine the McGurk susceptibility. Then, functional magnetic resonance imaging was performed in 63 participants to measure the brain activity in response to non-McGurk audiovisual syllables. We revealed significant individual variability in McGurk illusion perception. Moreover, we found significant differential activations of the auditory and visual regions and the left Superior temporal sulcus (STS), as well as multiple motor areas between strong and weak McGurk perceivers. Importantly, the individual engagement of the STS and motor areas could specifically predict the behavioral McGurk susceptibility, contrary to the sensory regions. These findings suggest that the distinct multimodal integration in STS as well as coordinated phonemic modulatory processes in motor circuits may serve as a neural substrate for interindividual differences in multisensory speech perception.

12.
Future Microbiol ; 16: 1041-1051, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34493087

RESUMO

Aim: To screen novel biomarkers in serum of syphilis patients using a mass spectrometry-based method. Materials & methods: Sera were collected from 18 syphilis patients and divided into three groups. Every six serum samples (before and after treatment) in each group were pooled and detected by mass spectrometry. Results: Twenty-five unique peptides corresponding to 15 Treponema pallidum proteins were discovered. Among them, Tp0369 was discovered as a promising biomarker candidate in this study. Tp0524 and Tp0984 levels decreased 0.38-fold and 0.51-fold after BPG treatment, respectively, which may be related to disease outcomes of syphilis. Conclusion: These findings confirmed the presence of detectable T. pallidum protein in patients' serum, which could promote the development of syphilis diagnostics.

13.
Chemosphere ; 287(Pt 2): 132160, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34509005

RESUMO

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes long-term inflammation and ulcers in the colon and rectum. Approximately 3 million adults were diagnosed with IBD in the US in 2015, and its incidence rate is estimated to increase by 4-6 times in 2030. Industrial pollutants are largely responsible for this significant increase in UC cases. Several epidemiological and animal studies have demonstrated the correlation between pollutants and gastrointestinal diseases, but detailed molecular mechanisms responsible for adverse effects of environmental pollutants on UC are still unknown. In the present study, we used a dextran sulfate sodium (DSS)-induced colitis mouse model, comparative metabolomics analysis, and systematic bioinformatics analysis to delineate the synergistic adverse effects of bisphenol A (BPA) and its substitute fluorene-9-bisphenol (BHPF) on UC. Subsequently, a significant alteration in gut metabolites was observed by the BPA and BHPF treatments. Furthermore, the bioinformatics analysis indicated deregulation of sugar and fatty acid metabolisms in the DSS-induced colitis model by the BPA and BHPF treatments, respectively. Additionally, both the treatments induced an inflammatory response in the model. Particularly, some DSS-deregulated metabolites, which play important roles in gut inflammation, were synergistically induced or reduced by the BPA and BHPF treatments. To the best knowledge of the authors, the synergistic adverse effects of the BPA and BHPF treatments on UC were demonstrated for the first time through gut metabolism alterations. Therefore, the present study provides novel insights in the role of environmental pollutants, such as BPA and BHPF, in UC development.

14.
Clin Ther ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34482960

RESUMO

PURPOSE: Gastric emptying time is one of limiting factors that determines the pharmacokinetic properties of drugs administered by mouth. Despite the high prevalence of obesity worldwide, modifications in gastric emptying time have not been systematically addressed in this set of patients. The current analysis aims to quantitatively address obesity-related changes in gastric emptying time of solids, semisolids, and liquids compared with lean individuals, highlighting the relevant pharmacokinetic implications of oral drug absorption in patients with obesity. METHODS: We searched the Cochrane Library, PubMed, Web of Science, and Embase for all relevant articles published until November 1, 2020. Differences in gastrointestinal variables in relation to gastric emptying between obese and lean individuals were quantified by weighted mean difference (WMD) and ratio of means (RoM). Robustness of the analyses was evaluated by subgroup analysis and publication bias test. FINDINGS: A total of 17 studies with 906 participants were included. The gastric half-emptying time of solids (WMD, -10.4 minutes; P = 0.001; RoM, 0.90; P = 0.01) and liquids (WMD, -6.14 minutes; P < 0.001; RoM, 0.83, P = 0.03) was significantly shorter in individuals with obesity compared with lean individuals. These findings were confirmed by the subgroup analyses and publication bias tests. IMPLICATIONS: Our pooled analysis systemically quantifies the differences in gastric half-emptying time between individuals with obesity and lean individuals, facilitating better understanding and prediction of drug absorption in individuals with obesity through physiologically based pharmacokinetic approaches. Obesity is associated with a faster transit of both solids and liquids through the stomach.

15.
Epilepsy Behav ; 124: 108309, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536736

RESUMO

OBJECTIVE: This study investigated the long-term response and response patterns to antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy. METHODS: Patients who had been newly diagnosed with epilepsy and had at least 3-year follow-up records were enrolled. Their long-term response and response patterns to AEDs were retrospectively analyzed. Patients were divided into two groups, a controlled group and an uncontrolled group, according to whether 3-year seizure freedom (3YSF) was achieved. Multiple logistic regression analyses were used to identify risk factors associated with a poor drug response. RESULTS: Of the 472 patients with epilepsy, 180 achieved immediate seizure control, 36 achieved early seizure control, 118 achieved late seizure control, and 138 did not achieve 3YSF. Patients who achieved 3YSF (334/472, 70.8%) were categorized into the controlled group. Among them, 53.9% (180/334) achieved 3YSF immediately, 10.8% (36/334) achieved 3YSF within 6 months, and 35.3% (118/334) achieved 3YSF after 6 months. Also in this group, 228 (228/472, 48.3%), 84 (84/472, 17.8%), 15 (15/472, 3.2%), and 7 (7/472, 1.5%) patients achieved 3YSF on the first, second, third, and fourth regimen, respectively. Multivariate analyses showed that multiple seizure types (odds ratio [OR] = 3.903, 95% confidence interval [CI]: 2.098-7.264; P < 0.001] and polytherapy (OR = 5.093, 95% CI: 3.183-8.149; P < 0.001) were independent risk factors for a poor drug response. CONCLUSION: The 3YSF rate in this cohort was 70.8%. More than half of the patients achieved long-term remission immediately after treatment. The probability of attaining 3YSF decreased with the increase in number of drug regimens, especially in patients who experienced failure of two treatment regimens.

16.
Biomaterials ; 277: 121084, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34454374

RESUMO

Infection associated with multidrug-resistant (MDR) bacteria has become a serious threat to public health, and there is an urgent demand of developing new antibiotics that offer combinatorial therapy to effectively combat MDR. Herein, a multifunctional two-dimensional nanoantibiotic was facilely designed and established on the basis of the covalent conjugation of CO-releasing molecule (CORM-401) and electrostatic adsorption of hyaluronic acid (HA) onto single-layered graphene quantum dots (SGQDs) to assemble SGQDs-CORM@HA nanosheets, abbreviated as SCH. Upon the enrichment of as-prepared nanoantibiotics in the community of targeted microbe, bacterial-secreted hyaluronidase (HAase) would cleave HA on SCH, and the sharp edges as well as the reactive sites on SGQDs-CORM nanosheets were exposed for cascade activation of synergistic antibacterial effects. Specifically, ultrathin SGQDs-CORM nanosheets can penetrate into bacterial cells deemed as the unique "nanoknife" effect. Under white light irradiation, SGQDs-CORM nanosheets can act as a high-efficient photosensitizer to generate cytotoxic singlet oxygen (1O2), as a well-recognized reactive oxygen species (ROS), to produce high oxidative stress and damage bacteria. As a complementary to photodynamic therapy (PDT), the accumulation of local ROS further triggered the release of CO to hinder the bacterial growth via causing plasma membrane damage and inducing metabolic disorders. Such synergistic treatment regimen arising from cascade-activated "nanoknife" effect and photodynamic/CO gas therapy, was devoted to outstanding on-demand antibacterial performance both in vitro and in vivo. Fascinatingly, the nanoplatform showed good biocompatibility toward both normal somatic cells and non-targeted bacteria. The remarkable antibacterial capability and admirable biocompatibility endow SCH with great potential to fight against MDR pathogens for in-coming clinical translations.

17.
Cancer Biomark ; 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34366325

RESUMO

BACKGROUND: Differential diagnosis between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains a clinical challenge. OBJECTIVE: The aim of the study is to assess the efficacy of the serum and pleural fluid (PF) miRNA panels in distinguishing MPE from BPE. METHODS: Fourteen candidate miRNAs which were shown aberrant expression in lung cancer based on previous studies were tested by quantitative real-time PCR (qRT-PCR) in 20 MPE patients and 20 BPE patients. Significantly aberrantly expressed miRNAs were further assessed by qRT-PCR in all patients enrolled in this study. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to evaluated the diagnostic performance of the miRNAs. RESULTS: miR-21, miR-29c and miR-182 were found to be significantly aberrantly expressed in the serum and PF of MPE patients. The AUCs for the combination of miR-21, miR-29c and miR-182 in serum and PF were 0.832 and 0.89 respectively in distinguishing MPE from infection-associated PE including tuberculous pleurisy and parapneumonia PE, and 0.866 and 0.919 respectively for differentiating MPE from heart failure-associated PE, which were superior to AUC of each individual miRNAs. CONCLUSIONS: miR-21, miR-29c and miR-182 in serum and PF could be useful biomarkers for MPE of diagnosis.

18.
J Clin Invest ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34375315

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR)-modified T cells have emerged as a novel approach to treat malignant tumors. This strategy has also been proposed for the treatment of HIV-1 infection. We have developed a broadly neutralizing antibody (bNAb)-derived CAR-T cell therapy which can exerted specific cytotoxic activity against HIV-1-infected cells. METHODS: We conducted an open-label trial of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of bNAb-derived CAR-T cell therapy in HIV-1-infected individuals who were undergoing analytical interruption of antiretroviral therapy (ART). RESULTS: A total of 14 participants completed only a single administration of bNAb-derived CAR-T cells. CAR-T administration was safe and well tolerated. Six participants discontinued ART, and viremia rebound occurred in all of them, with a 5.3-week median time. Notably, the cell-associated viral RNA and intact proviruses decreased significantly after CAR-T treatment. Analyses of HIV-1 variants before or after CAR-T administration suggested that CAR-T cells exerted pressure on rebound viruses, resulting in a selection of viruses with less diversity and mutations against CAR-T-mediated cytotoxicity. CONCLUSIONS: No safety concerns were identified with adoptive transfer of bNAb-derived CAR-T cells. They reduced viral reservoir. All the rebounds were due to preexisting or emergence of viral escape mutations. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03240328. FUNDING: Ministry of Science and Technology of China, National Natural Science Foundation of China, and Department of Science and Technology of Guangdong Province.

19.
Bioengineered ; 12(1): 4757-4767, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34334083

RESUMO

Metformin, a common clinical drug used to treat diabetes mellitus, is found with potential antiobese actions as reported in increasing evidences. However, the detailed mechanisms of metformin-antiobesity-related hypertension remain unrevealed. We have utilized the bioinformatics strategy, including network pharmacology and molecular docking analyses, to uncover pharmacological targets and molecular pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease 2019. In this report, the in-silico approaches using network pharmacology and molecular docking was utilized to identify the core targets, pharmacological functions and mechanisms of metformin against obesity-related hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, and 21 interaction genes, 6 core genes of metformin treating obesity-related hypertension. As results, molecular docking findings indicated the binding capability of metformin with key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2) expressed in obesity- and hypertension-dependent tissues. Metformin-exerted antihypertension/obesity actions involved in metabolic regulation, inflammatory suppression. And antihypertension/obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for ameliorating microenvironmental homeostasis in targeting tissues. In conclusion, our current bioinformatics findings have uncovered all pharmacological targets, biological functions and signaling pathways of metformin treating obesity-related hypertension, thus promoting its clinical application in future.


Assuntos
Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Biologia Computacional , Humanos , Simulação de Acoplamento Molecular , Transdução de Sinais
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1019-1027, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362477

RESUMO

OBJECTIVE: To detect the expression of different transcripts of lactamase ß(LACTB) gene in leukemic cell lines. METHODS: NCBI website and DNAstar software were used to detect the Bioinformatics analysis of LACTB. The expression of different transcripts of LACTB gene in leukemic cell lines (THP-1, HL60, K562, U937, Jurkat and Raji) was detected by reverse transcription PCR (RT-PCR), DNA and clone sequencing; the expression of different transcripts of LACTB gene in leukemic cell lines was detected by Quantitative Real-time PCR. RESULTS: There were a variety of splicing isomers in LACTB, and it could produce a variety of protein isomers with conserved N-terminal and different C-terminal, moreover, there were many splice isoforms of LACTB in leukemia cell lines, and there were different expression patterns in different cell lines, including XR1, V1, V2 and V3. The expression of total LACTB showed high in HL60 cells, while low in Raji cells, and the difference was statistically significant (P<0.05). The V1 was high expression in U937 cells but low in Raji cells, and the difference was statistically significant (P<0.05). V2 was high expression in HL60 cells but lowly in Raji cells, and the difference was statistically significant (P<0.05). The expression of V3 was low in THP-1 cells, which was significantly different as compared with that in normal bone marrow (P<0.05). CONCLUSION: The reaserch found that there are many splice isomers of LACTB in leukemic cell lines, and there are different expression patterns in different cell lines.


Assuntos
Processamento Alternativo , Leucemia , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , beta-Lactamases/genética , Células HL-60 , Humanos , Leucemia/genética , Splicing de RNA , Células U937
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