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1.
Mol Ther ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995801

RESUMO

N6-methyladenosine (m6A) is the most prevalent RNA modification, and the effect of its dysregulation on esophageal squamous cell carcinoma (ESCC) development remains unclear. Here, by performing transcriptome-wide m6A sequencing in 16 ESCC tissue samples, we identified the key roles of m6A in TNFRSF1A (also known as TNFR1)-mediated MAPK and NF-κB activation in ESCC. Mechanistically, a functional protein involved in m6A methylation, ATXN2, is identified that augments the translation of TNFRSF1A by binding to m6A-modified TNFRSF1A mRNA. Upregulation of the TNFRSF1A protein level, a vital upstream switch for TNFRSF1A-mediated signaling events, activates the NF-κB and MAPK pathways and thus promotes ESCC development. Furthermore, TNFRSF1A m6A modifications and protein levels are upregulated in ESCC, and high levels of TNFRSF1A m6A and protein are correlated with poor ESCC patient survival. These results collectively indicate that the m6A-TNFRSF1A axis is critical for ESCC development and thus may serve as a potential druggable target.

2.
Int J Surg ; : 106184, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34861427

RESUMO

BACKGROUND: To evaluate the efficacy, safety, technical feasibility, and effect of reducing the incidence of reflux gastritis from uncut Roux-en-Y (URY) reconstruction after radical distal gastrectomy (RDG) for gastric cancer. METHODS: A literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang databases until June 30, 2020, to identify studies comparing URY reconstruction with other gastrointestinal tract reconstruction methods after RDG. The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration's risk for bias assessment tool were used to assess the risk of bias. The study was performed using review manager RevMan 5.3.0 software. RESULTS: A total of 35 original studies (six randomized clinical trials (RCTs) and 29 cohort studies) were included in this analysis with a total of 4100 patients. For reflux gastritis, URY anastomosis was significantly superior to the other four types of anastomoses (Billroth-I (odds ratio (OR) = 0.16 [0.10, 0.27], P < 0.00001); Billroth-II (OR = 0.32 [0.20, 0.51], P < 0.00001); Billroth-II with Braun (OR = 0.14 [0.007, 0.26], P < 0.00001), and Roux-en-Y (OR = 0.59 [0.38, 0.91], P = 0.02)). Furthermore, URY anastomosis was better than Billroth-II with Braun (OR = 0.07, 95%confidence interval (CI): [0.02, 0.28], P = 0.0001) and Billroth-II (OR = 0.14, 95%CI: [0.09, 0.24], P < 0.00001) anastomoses for preventing bile reflux. In addition, for anastomotic leakage, URY anastomosis was significantly superior to Roux-en-Y (OR = 0.34, 95%CI: [0.13, 0.87], P = 0.02) anastomosis, and no statistically significant difference between URY and the other three reconstruction methods was found. The postoperative hospital stay of patients receiving URY anastomosis was substantially shorter than those receiving Billroth-II with Braun (MD: 2.84, 95%CI: [-3.16, -1.80], P < 0.00001), Bollroth-II (MD: 1.23, 95%CI: [-2.10, -0.37], P = 0.005) and Roux-en-Y (MD: 1.98, 95%CI: [-2.17, -1.78], P < 0.00001) anastomoses. CONCLUSION: URY reconstruction significantly reduce the rate of reflux gastritis after RDG, and it was a more favorable reconstruction method after RDG for its operative simplicity, safety, and reduced postoperative complications especially in Roux-en-Y stasis syndrome. Large sample size cohort studies and well-designed RCTs are needed for further confirmation of our findings. OTHER: This work was supported by the National Nature Science Foundation of China (No.81871962), Industry-University-Research Innovation Fund in the Ministry of Education of the People's Republic of China (No. 2018A01013) and the Autonomous Intelligent Unmanned System (No. 62088101). This study was registered with PROSPERO (CRD42020200906).

3.
Molecules ; 26(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34885740

RESUMO

Both UV and blue light have been reported to regulate the biosynthesis of flavonoids in tea plants; however, the respective contributions of the corresponding regions of sunlight are unclear. Additionally, different tea cultivars may respond differently to altered light conditions. We investigated the responses of different cultivars ('Longjing 43', 'Zhongming 192', 'Wanghai 1', 'Jingning 1' and 'Zhonghuang 2') to the shade treatments (black and colored nets) regarding the biosynthesis of flavonoids. For all cultivars, flavonol glycosides showed higher sensitivity to light conditions compared with catechins. The levels of total flavonol glycosides in the young shoots of different tea cultivars decreased with the shade percentages of polyethylene nets increasing from 70% to 95%. Myricetin glycosides and quercetin glycosides were more sensitive to light conditions than kaempferol glycosides. The principal component analysis (PCA) result indicated that shade treatment greatly impacted the profiles of flavonoids in different tea samples based on the cultivar characteristics. UV is the crucial region of sunlight enhancing flavonol glycoside biosynthesis in tea shoots, which is also slight impacted by light quality according to the results of the weighted correlation network analysis (WGCNA). This study clarified the contributions of different wavelength regions of sunlight in a field experiment, providing a potential direction for slightly bitter and astringent tea cultivar breeding and instructive guidance for practical field production of premium teas based on light regimes.

4.
Front Cell Dev Biol ; 9: 797167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926474

RESUMO

With the development of science and technology, mankind's exploration of outer space has increased tremendously. Settling in outer space or on other planets could help solve the Earth's resource crisis, but such settlement will first face the problem of reproduction. There are considerable differences between outer space and the Earth's environment, with the effects of gravity being one of the most significant. Studying the possible effects and underlying mechanisms of microgravity on embryonic stem cell (ESC) differentiation and embryonic development could help provide solutions to healthy living and reproduction in deep space. This article summarizes recent research progress on the effects of microgravity on ESCs and early embryonic development and proposes hypotheses regarding the potential mechanisms. In addition, we discuss the controversies and key questions in the field and indicate directions for future research.

5.
Front Oncol ; 11: 733680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722278

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis.

6.
Signal Transduct Target Ther ; 6(1): 376, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34737296

RESUMO

Patients with chronic hepatitis B (CHB) undergoing interferon (IFN)-α-based therapies often exhibit a poor HBeAg serological response. Thus, there is an unmet need for new therapies aimed at CHB. This study comprised two clinical trials, including 130 CHB patients, who were treatment-naïve; in the first, 92 patients were systematically analyzed ex vivo for interleukin-2 receptor (IL-2R) expression and inhibitory molecules expression after receiving Peg-IFN-α-2b therapy. In our second clinical trial, 38 non-responder patients, in whom IFN-α therapy had failed, were treated with or without low-dose IL-2 for 24 weeks. We then examined the hepatitis B virus (HBV)-specific CD8+ T-cell response and the clinical outcome, in these patients. Although the majority of the participants undergoing Peg-IFN-α-2b therapy were non-responders, we observed a decrease in CD25 expression on their CD4+ T cells, suggesting that IFN-α therapy may provide a rationale for sequential IL-2 treatment without increasing regulatory T cells (Tregs). Following sequential therapy with IL-2, we demonstrated that the non-responders experienced a decrease in the numbers of Tregs and programmed cell death protein 1 (PD-1) expression. In addition, sequential IL-2 administration rescued effective immune function, involving signal transducer and activator of transcription 1 (STAT1) activation. Importantly, IL-2 therapy significantly increased the frequency and function of HBV-specific CD8+ T cells, which translated into improved clinical outcomes, including HBeAg seroconversion, among the non-responder CHB patients. Our findings suggest that sequential IL-2 therapy shows efficacy in rescuing immune function in non-responder patients with refractory CHB.

7.
Animals (Basel) ; 11(11)2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34827851

RESUMO

Acidification (OA), a global threat to the world's oceans, is projected to significantly grow if CO2 continues to be emitted into the atmosphere at high levels. This will result in a slight decrease in pH. Since the latter is a logarithmic scale of acidity, the higher acidic seawater is expected to have a tremendous impact on marine living resources in the long-term. An 8-week laboratory experiment was designed to assess the impact of the projected pH in 2100 and beyond on fish survival, health, growth, and fish meat quality. Two projected scenarios were simulated with the control treatment, in triplicates. The control treatment had a pH of 8.10, corresponding to a pCO2 of 321.37 ± 11.48 µatm. The two projected scenarios, named Predict_A and Predict_B, had pH values of 7.80-pCO2 = 749.12 ± 27.03 and 7.40-pCO2 = 321.37 ± 11.48 µatm, respectively. The experiment was preceded by 2 weeks of acclimation. After the acclimation, 20 juvenile black sea breams (Acanthopagrus schlegelii) of 2.72 ± 0.01 g were used per tank. This species has been selected mainly due to its very high resistance to diseases and environmental changes, assuming that a weaker fish resistance will also be susceptibly affected. In all tanks, the fish were fed with the same commercial diet. The seawater's physicochemical parameters were measured daily. Fish samples were subjected to physiological, histological, and biochemical analyses. Fish growth, feeding efficiency, protein efficiency ratio, and crude protein content were significantly decreased with a lower pH. Scanning electron microscopy revealed multiple atrophies of microvilli throughout the small intestine's brush border in samples from Predict_A and Predict_B. This significantly reduced nutrient absorption, resulting in significantly lower feed efficiency, lower fish growth, and lower meat quality. As a result of an elevated pCO2 in seawater, the fish eat more than normal but grow less than normal. Liver observation showed blood congestion, hemorrhage, necrosis, vacuolation of hepatocytes, and an increased number of Kupffer cells, which characterize liver damage. Transmission electron microscopy revealed an elongated and angular shape of the mitochondrion in the liver cell, with an abundance of peroxisomes, symptomatic of metabolic acidosis.

8.
Genome Med ; 13(1): 183, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798904

RESUMO

BACKGROUND: N6-methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on m6A modifications in linear RNA, transcriptome-wide profiling and exploration of m6A modification in circular RNAs in cancer is still lacking. METHODS: For the detection of m6A modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the m6A-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC). RESULTS: Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with m6A modifications. By using Circm6A, we identified a total of 8807 m6A-circRNAs from our m6A-seq data. The m6A-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated m6A-circRNAs were associated with a significant gain of circRNA-mRNA coexpression network, leading to the dysregulation of many important cancer-related pathways. Moreover, we found the cues that hypermethylated m6A-circRNAs may promote the circularization and translation of circRNAs. CONCLUSIONS: These comprehensive findings further bridged the knowledge gaps between m6A modification and circRNAs fields by depicting the m6A-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by m6A-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a .

9.
BMC Pregnancy Childbirth ; 21(1): 786, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34802426

RESUMO

BACKGROUND: Since the effectiveness of low-dose aspirin (LDA) in twin pregnancies is uncertain, we aimed to preliminarily assess whether LDA is beneficial in preventing preeclampsia in twin pregnancies. METHODS: This study is an observational study in two hospitals in China. Among 932 women, 277 in the First Affiliated Hospital of Chongqing Medical University were routinely treated with aspirin (100 mg daily) from 12 to 16 weeks to 35 weeks of gestational age, while 655 in Chongqing Health Center for Women and Children were not taking aspirin during pregnancy. We followed each subject and the individual details were recorded. RESULTS: LDA significantly reduced the risk of preeclampsia (RR 0.48; 95% CI 0.24-0.95) and preterm birth 34 weeks (RR 0.50; 95% CI 0.29-0.86) and showed possible benefits to lower the rate of SGA babies (RR 0.74; 95% CI 0.55-1.00). Moreover, the risk of postpartum hemorrhage was not increased by LDA (RR 0.89; 95% CI 0.35-2.26). CONCLUSIONS: Treatment with low-dose aspirin in twin pregnancies could offer some protection against adverse pregnancy outcomes in the absence of significantly increased risk of postpartum hemorrhage. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR); ChiCTR-OOC-16008203 , Retrospectively registered date: April 1st, 2016.


Assuntos
Aspirina/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Gravidez de Gêmeos/efeitos dos fármacos , Nascimento Prematuro/prevenção & controle , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Gravidez , Pontuação de Propensão
10.
Molecules ; 26(22)2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34834011

RESUMO

Chiral cholesteric molecular tweezer 7a was synthesized, and its recognition properties for Ag+, Al3+, Ca2+ etc., were investigated by UV and fluorescence spectra. The results showed that in ethanol/Tris (1/1, v/v, pH 7.0) buffer solution, the host molecular tweezer 7a had a specific recognition ability for Ag+, the detection limit was up to 1 × 10-6 mol/L, and other metal ions had little effect on Ag+ recognition. At the same time, the naked-eye detection of Ag+ was realized by the light red color of the complex solution. Furthermore, the mechanism of recognition of Ag+ by molecular tweezer 7a was studied by a nuclear magnetic titration test and computer molecular simulation, and a rapid detection method of Ag+ using host molecular tweezer 7a was established. Through the determination of Ag+ in milk powder, quinoa and other food samples, it was proved that this novel method had a good application prospect for the detection of Ag+ in food.

11.
J Clin Invest ; 131(22)2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779408

RESUMO

The tumorigenic mechanism for pancreatic ductal adenocarcinoma (PDAC) is not clear, although chronic inflammation is implicated. Here, we identified an inflammatory cytokine-regulated transfer RNA-derived (tRNA-derived) fragment, tRF-21-VBY9PYKHD (tRF-21), as a tumor suppressor in PDAC progression. We found that the biogenesis of tRF-21 could be inhibited by leukemia inhibitory factor and IL-6 via the splicing factor SRSF5. Reduced tRF-21 promoted AKT2/1-mediated heterogeneous nuclear ribonucleoprotein L (hnRNP L) phosphorylation, enhancing hnRNP L to interact with dead-box helicase 17 (DDX17) to form an alternative splicing complex. The provoked hnRNP L-DDX17 activity preferentially spliced Caspase 9 and mH2A1 pre-mRNAs to form Caspase 9b and mH2A1.2, promoting PDAC cell malignant phenotypes. The tRF-21 levels were significantly lower in PDACs than in normal tissues, and patients with low tRF-21 levels had a poor prognosis. Treatment of mouse PDAC xenografts or patient-derived xenografts (PDXs) with tRF-21 mimics repressed tumor growth and metastasis. These results demonstrate that tRF-21 has a tumor-suppressive effect and is a potential therapeutic agent for PDAC.

12.
Infect Drug Resist ; 14: 4657-4666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764660

RESUMO

Purpose: To study the in vitro and in vivo antibacterial activities of polymyxin B (PB) and other five antimicrobial agents, including imipenem (IMP), meropenem (MEM), tigecycline (TGC), sulbactam (SUL), and rifampicin (RIF), alone or in combination against carbapenem-resistant Acinetobacter baumannii (CRAB). Methods: Microbroth dilution method was used to determine the minimum inhibitory concentration (MIC) of ten strains of CRAB against six antibacterial drugs, and the checkerboard method was used to determine the fractional inhibitory concentration index (FICI). A mouse pneumonia model was established by intranasal instillation of Ab5075 to evaluate the antibacterial activity in vivo. Results: The resistance rate of ten CRAB strains to IMP, MEM, and SUL was 100%, that to PB and TGC was 0%, and that to RIF was 20%. When PB was used in combination with the other five antibiotics in vitro, it mainly showed synergistic and additive effects on CRAB. The synergistic effect of PB and RIF was maximal, followed by MEM and IMP but was weak with SUL and TGC. In vivo, compared to the model group (untreated with antibiotics), treatment group (six antibiotics alone and PB combined with the other five antibiotics) reduced the bacterial load in the lung tissue and the serum inflammatory factors (IL-1ß, IL-6, and TNF-α). The bacterial load and the inflammatory factors of the combined group decreased significantly than that of the single group (P<0.05). The IL-6 and TNF-α values of the PB combined with the RIF group were significantly lower than the two drugs used individually. Conclusion: The combination of PB and IMP, MEM, and RIF exerted robust in vitro synergistic effects on CRAB isolates. The combination of PB and the other five antimicrobial agents had a better effect in the mouse pneumonia model than single agent, while the combination of PB and RIF had the best effect.

13.
J Cosmet Dermatol ; 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34806292

RESUMO

BACKGROUND: Studies on the anti-wrinkle effects of retinol have been widely reported, but there are few reports on the infraorbital dark circles reducing effects. OBJECTIVE: To evaluate the efficiency and tolerance of one novel formulation containing supramolecular retinol plus acmella oleracea extract in Chinese urban eye skin. METHODS: Thirty-three women with dark circles and visible fine wrinkles around the eyes, aged 20-45 years, were enrolled and instructed to use the formula for 6 weeks. Instrumental measures and subject assessment were obtained at baseline and at 3-week intervals. RESULTS: After 6 weeks, Mexameter MX18 results demonstrated a statistically significant 13.8% decrease in MI (melanin index) value, and Colorimeter CL400 results demonstrated a statistically significant 0.5% increase in L* (lightness) value, which proved the efficacy of reducing dark circles. Primos-Lite data showed that the wrinkles parameters of Ra, the wrinkle area %, and number of the wrinkles under the eyes and crow's feet revealed significant reduction to varying degrees. Cutometer results showed that R2 value increased significantly by 13.0%, indicating the benefits of firmer skin. In addition, subject assessment revealed that at the end of 6 weeks, the eye skin was noticeably improved. CONCLUSIONS: By clinical evaluation and subject assessment, the novel formulation containing supramolecular retinol plus acmella oleracea extract can effectively diminish the collective signs of stressed urban eye skin for Chinese female in terms of dark circles, fine wrinkles, and sagging skin with good tolerance.

14.
Front Microbiol ; 12: 744037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712212

RESUMO

Objectives: The objective was to describe the changes of severe fever with thrombocytopenia syndrome virus (SFTSV) and antibody in the disease course and explore the relationship between antibody titers and patients' prognosis. Methods: The levels of SFTSV, virus-specific immunoglobulin M (IgM), immunoglobulin G (IgG) titers, and cytokines in 37 patients with severe fever with thrombocytopenia syndrome (SFTS) were measured dynamically by real-time PCR and ELISA during the disease course; IgG titers were followed up in 53 cases. The correlation analysis of antibody titers with individual serum cytokines was calculated using the Spearman test. Results: The average time of SFTSV duration in individual serum was 22.45 ± 7.6 days from onset. We found SFTSV turned negative within the 10th day from the onset in two patients. SFTSV-specific IgM seroconversion occurred as early as within 3 days from the onset, increased gradually within the first 2 months, decreased gradually 3 months later, and disappeared after 6 months in all the patients. The average time of SFTSV-specific IgG antibody seroconversion was at 17 days from onset in the patients; the time was later in severe cases than in mild cases (23 ± 1.4 vs. 14.3 ± 1.0 days, p < 0.0001). IgG titers were maintained at the peak levels during the periods from 6 months to 1 year and decreased from the second year gradually. Severe cases had higher IgG levels than mild cases and also had a slower decreasing trend. During follow-up, only one lost IgG antibody 7 years later; no chronic infection and sequela were found among the 53 patients. None of the patients had SFTSV reinfection even if they were bitten by ticks again. The correlation analysis showed a positive relationship between inflammatory factors and IgG antibody levels. Conclusion: IgM antibody has important value in early diagnosis of SFTS. A moderate inflammatory response is beneficial for production and duration of IgG antibodies.

15.
Front Immunol ; 12: 723609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621270

RESUMO

Radiotherapy is an effective local treatment modality of NSCLC. Its capabilities of eliminating tumor cells by inducing double strand DNA (dsDNA) damage and modulating anti-tumor immune response in irradiated and nonirradiated sites have been elucidated. The novel ICIs therapy has brought hope to patients resistant to traditional treatment methods, including radiotherapy. The integration of radiotherapy with immunotherapy has shown improved efficacy to control tumor progression and prolong survival in NSCLC. In this context, biomarkers that help choose the most effective treatment modality for individuals and avoid unnecessary toxicities caused by ineffective treatment are urgently needed. This article summarized the effects of radiation in the tumor immune microenvironment and the mechanisms involved. Outcomes of multiple clinical trials investigating immuno-radiotherapy were also discussed here. Furthermore, we outlined the emerging biomarkers for the efficacy of PD-1/PD-L1 blockades and radiation therapy and discussed their predictive value in NSCLC.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34672813

RESUMO

Background: Cell division cycle 45 (CDC45) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains unclear. Materials and Methods: The messenger RNA and protein expression levels of CDC45 in LSCC were evaluated with a t test and the standard mean difference (SMD). The ability of CDC45 expression to distinguish the LSCC was assessed through receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA), protein-protein interaction, public databases, and online tools were used to explore the potential molecular mechanism of CDC45 in LSCC. Results: A high expression of CDC45 was identified in LSCC (SMD = 2.61, 95% confidence interval [1.62-3.61]). Through ROC curves, the expression of CDC45 makes it feasible to distinguish the LSCC group from the non-LSCC counterpart. CDC45 was relevant to the progression-free interval of LSCC patients (log-rank p = 0.03). GSEAs show that CDC45 is related to the cell cycle. CDC45, CDC6, KIF2C, and AURKB were identified as hub genes of LSCC. E2F1 may be the regulatory transcription factor of CDC45. Conclusions: High expression of CDC45 likely demonstrates carcinogenic effects in LSCC, and CDC45 is a potential target in screening and treatment of LSCC.

17.
Methods Mol Biol ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34661880

RESUMO

Embryoid bodies (EBs) are aggregate of cells that contain three embryonic germ layers. They can be formed by direct differentiation from pluripotent embryonic stem cells (ESCs), which serves as a useful model for understanding early embryo development. Due to the mixture of different cell types, it is necessary to investigate EBs at the single-cell level. Here, we describe a robust and straightforward method for single-cell gene expression profiling during mouse EB differentiation from mouse ESCs (mESCs). The protocol is modified from a widely used method in the SMART-seq family, which only requires standard molecular biology techniques and lab equipment. It allows for accurate 3' counting of transcript at the single-cell level, which helps reveal cellular identities during EB formation. Combined with perturbation experiments, the method provides an opportunity for mechanistic studies of embryo development at the single-cell level.

18.
Pediatr Res ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650198

RESUMO

BACKGROUND: Propranolol, a non-selective blocker of the ß-adrenoceptor (AR), is a first-line treatment for infantile hemangioma (IH). Mast cells have been implicated in the pathophysiology of propranolol-treated hemangioma. However, the function of mast cells remains unclear. METHODS: HMC-1s (Human mast cell line) having been treated with propranolol for 24 h were centrifuged, washed with PBS twice, and maintained in cell culture medium for another 24 h. The supernatants with propranolol which were named as propranolol-treated HMC-1s supernatants were obtained. The expression of cytokines and mediators was examined among HMC-1s dealt with propranolol. HemECs (hemangioma endothelial cells) were co-cultured with propranolol-treated HMC-1s supernatants, and their proliferation and apoptosis were investigated. The autophagic-related protein was examined in HemECs using immunoblot. RESULTS: In propranolol-treated HMC-1s, the expressions of ADRB1 (ß1-AR) and ADRB2 (ß2-AR) were reduced by 70% and 60%, respectively, and that of cytokines and mediators were reduced. The proliferation was decreased, but apoptosis and autophagy were induced in HemECs treated with propranolol-treated HMC-1s supernatants. However, propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. CONCLUSIONS: Propranolol inhibit the proliferation of HemECs and promote their apoptosis and autophagy through acting on both ß1 and ß2 adrenoceptor in mast cell. IMPACT: Treated with propranolol, ß1, and ß2 adrenoceptor on human mast cell expression was reduced significantly. After hemangioma endothelial cell treated with the supernatants from propranolol-treated human mast cell, its proliferation was decreased, but apoptosis and autophagy were significantly induced. Propranolol can work well in shRNA-ADRB1 or shRNA-ADRB2 transfected HMC-1s. Mast cells may have a role in the action of propranolol in infantile hemangioma through both ß1 and ß2 adrenoceptors to inhibit the angiogenic capacity of hemangioma endothelial cells.

19.
World J Clin Cases ; 9(24): 7099-7109, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34540965

RESUMO

BACKGROUND: Colorectal liver metastases (CLM) occur in 15%-30% of patients with colorectal cancer (CRC). Advancements in next generation sequencing (NGS) can provide more precise prognoses for cancer patients and help guide clinical treatment. However, the genetic variants that predict high sensitivity to neoadjuvant chemotherapy remain unclear, especially in patients with CLM. The aim of this study was to identify the relevant genetic variants in a single CLM patient and to summarize the current evidence on mutations and single nucleotide polymorphisms (SNPs) that objectively predict sensitivity to neoadjuvant chemotherapy. CASE SUMMARY: A 76-year-old male patient, who was diagnosed as stage IV colon cancer with liver metastases, was found to have APC/TP53/KRAS mutations. He showed a good therapeutic response to 12 courses of oxaliplatin regimens combined with Bevacizumab. Genetic analysis of the patient identified 5 genes with 7 detected SNPs that may be related to a better response to chemotherapy drugs. In addition, a critical literature review was performed based on a standardized appraisal form after selecting the articles. Ultimately, 21 eligible studies were appraised to assess the association between gene mutations and good prognosis. Mutations in KRAS, TP53, SMAD4, and APC were identified as being associated with a poor response to chemotherapy drugs, whereas mutations of CREBBP and POLD1 were associated with longer overall survival. CONCLUSION: NGS can identify precise predictors of response to neoadjuvant chemotherapy, leading to improved outcomes for CRC patients.

20.
J Nat Prod ; 84(9): 2427-2436, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34469134

RESUMO

Ten new meroterpenoids, bipolaquinones A-J (1-10), and one known congener, isocochlioquinone F (11), were isolated and identified from the fermented rice cultures of a soil-derived fungus, Bipolaris zeicola. The planar structures of 1-10 were elucidated based on extensive spectroscopic analyses (including HRESIMS and 1D and 2D NMR data), and their absolute configurations were determined by single-crystal X-ray diffraction analyses, comparison of experimental electronic circular dichroism (ECD) data, ECD calculations, and hydrolysis reaction. The immunosuppressive activity assay revealed that compounds 2, 3, and 7-10 showed significant inhibitory activity against concanavalin A (ConA)-induced T lymphocyte proliferation with IC50 values ranging from 4.1 to 9.4 µM, which furnished potential lead molecules for the design and development of new immunosuppressants for treating autoimmune-associated diseases.

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