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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(1): 5-10, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36655657

RESUMO

OBJECTIVES: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. METHODS: A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome. RESULTS: Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P<0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination (P<0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group (P<0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer (P<0.05). CONCLUSIONS: Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.


Assuntos
COVID-19 , Ácidos Nucleicos , Criança , Humanos , Infecções Assintomáticas , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19 , Fibrinogênio , Interleucina-6 , Estudos Retrospectivos , SARS-CoV-2
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(1): 57-62, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36631016

RESUMO

Objective To investigate the possible off-target effects of dynamin (DNM) inhibitor Dyngo-4a in dynamin-dependent endocytic pathways. Methods Bone marrow mesenchymal stem cells (BMSCs) obtained from SD rats were isolated and cultured, and identified by flow cytometry. The cells were divided into inhibitor control group, Dyngo-4a-treated group, negative control siRNA (si-NC) transfection group, DNM2 siRNA transfection (si-DNM2) group, si-DNM2 and Dyngo-4a co-treated group. Real time quantitative PCR and Western blot analysis were used to verify the silencing efficiencies of DNM2 gene and CCK-8 assay were used to detect the cell viability after Dyngo-4a treatment. Confocal microscopy was used to detect the number and mean fluorescence intensity (MFI) of transferrin-Dylight649-positive and dextran-TMR-positive vesicles. Results The mRNA and protein expression levels of DNM2 were down-regulated using small interfering RNA. The number of transferrin-Dylight649-positive vesicles significantly decreased in si-DNM2 group compared with si-NC group. For the number and MFI of dextran-TMR-positive vesicles, no significant change was observed between the si-DNM2 group and the si-NC group, but there was a significant reduction in the si-DNM2 and Dyngo-4a co-treated group compared with the si-DNM2 group. A significant decrease was also found in the Dyngo-4a-treated group compared with the inhibitor control group. Conclusion The off-target effects of dynamin inhibitor Dyngo-4a presents in the internalization of dextran by BMSCs.


Assuntos
Dextranos , Células-Tronco Mesenquimais , Ratos , Animais , Dextranos/metabolismo , Ratos Sprague-Dawley , Dinaminas/genética , Células-Tronco Mesenquimais/metabolismo , RNA Interferente Pequeno/genética , Transferrinas , Células da Medula Óssea/metabolismo
3.
Environ Res ; 207: 112153, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619126

RESUMO

Sediments play a pivotal role in maintaining the aquatic ecological status of rivers. However, the determination of the key toxicants that consider the combined effects of all sediment-related contaminants are still challenging and necessary for an appropriate sediment risk assessment. The effects of sediments on aquatic organisms have been reported in Liaohe River, but their key toxicity factors are not well known. To determine the key toxicity factors, twenty-six surface sediment samples from Liaohe River tributaries in Northeast China were collected. Acute toxicity test of midge larvae results showed that 6 of 26 tributaries had obvious toxic effects, with survival rates of 37%-57% (p < 0.05). The masking test showed that the main pollutants in the surface sediments of T7 and T16 were metals, that of T8 was an organic pollutant, those of T19 and T26 were organic pollutants and ammonia, and those of T17 were heavy metal and ammonia. Chemical analysis showed that the relatively high concentrations of ammonia were only presented in surface sediments of T17, T19, and T26, with PTU of 1.5, 1.2 and 1.1, respectively, whereas heavy metals were markedly high in surface sediments from T7 and T16, with PTU of 0.92 and 0.61, respectively. Interestingly, the observed toxicity in surface sediments agreed with the toxicity predicted by chemical analysis Moreover, the significant correlation between the survival and volume ratio of the sediment and overlying water confirmed ammonia nitrogen was key toxicity factor in T17, T19, and T26, whereas Cu was the key toxicity factor in T7 that cause the biological toxicity. In conclusion, the major toxic factors of ammonia and copper in the sediments were identified. Moreover, our study suggested that effect guidance strategy was an effective method for sediment quality assessment.


Assuntos
Metais Pesados , Poluentes Químicos da Água , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos/análise , Metais Pesados/análise , Metais Pesados/toxicidade , Medição de Risco , Rios/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
4.
Front Neurol ; 13: 942682, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457861

RESUMO

Background: A comparison and ranking of the clinical effects of various acupuncture and acupuncture-related therapies on patients with mild cognitive impairment. Methods: Using network meta-analysis, we assessed the direct and indirect evidence from relevant research. Seven databases [PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang database] were examined to find randomized controlled trials of acupuncture-related therapies for individuals with mild cognitive impairment. Two researchers independently reviewed the literature, retrieved the data, and evaluated the risk of bias in the included studies. The data were analyzed using Stata15.0 and R3.6.1 software. Results: A total of 27 randomized controlled trials involving 2,210 patients were included. Bayesian NMA showed that manual acupuncture combined with conventional therapy, moxibustion combined with conventional therapy, manual acupuncture, and electroacupuncture were most effective in improving the MMSE score. The most effective interventions related to the MoCA score were moxibustion combined with conventional therapy, followed by manual acupuncture combined with conventional therapy, acupressure combined with conventional therapy, and manual acupuncture combined with moxibustion. Manual acupuncture combined with moxibustion was dominant in the cluster ranking. The results of the node splitting method revealed that direct and indirect evidence were consistent (P > 0.05). In addition, publication bias was detected. Conclusion: This research will add to the body of knowledge about the safety and efficacy of acupuncture-related therapies in the treatment of mild cognitive impairment. The results of this study will also assist in the choice of clinical guidelines that optimize acupuncture treatment for patients with mild cognitive impairment.

5.
Chaos ; 32(11): 111102, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36456327

RESUMO

Change point detection (CPD) for multi-agent systems helps one to evaluate the state and better control the system. Multivariate CPD methods solve the d × T time series well; however, the multi-agent systems often produce the N × d × T dimensional data, where d is the dimension of multivariate observations, T is the total observation time, and N is the number of agents. In this paper, we propose two valid approaches based on higher-order features, namely, the Betti number feature extraction and the Persistence feature extraction, to compress the d-dimensional features into one dimension so that general CPD methods can be applied to higher-dimensional data. First, a topological structure based on the Vietoris-Rips complex is constructed on each time-slice snapshot. Then, the Betti number and persistence of the topological structures are obtained to separately constitute two feature matrices for change point estimates. Higher-order features primarily describe the data distribution on each snapshot and are, therefore, independent of the node correspondence cross snapshots, which gives our methods unique advantages in processing missing data. Experiments in multi-agent systems demonstrate the significant performance of our methods. We believe that our methods not only provide a new tool for dimensionality reduction and missing data in multi-agent systems but also have the potential to be applied to a wider range of fields, such as complex networks.

6.
Ann Transl Med ; 10(22): 1227, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36544674

RESUMO

Background: Hypoxia (low-oxygen tension) and excessive osteoclast activation are common conditions in many bone loss diseases, such as osteoporosis, rheumatoid arthritis (RA), and pathologic fractures. Hypoxia-inducible factor 1 alpha (HIF1α) regulates cellular responses to hypoxic conditions. However, it is not yet known how HIF1α directly affects osteoclast differentiation and activation. This study sought to. explore the effects of HIF1α on osteoclast differentiation and it's molecular mechanisms. Methods: L-mimosine, a prolyl hydroxylase (PHDs) domain inhibitor, was used to stabilize HIF1α in normoxia. In the presence of receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL), RAW264.7 cells were cultured and stimulated by treatment with L-mimosine at several doses to maintain various levels of intracellular HIF1α. The multi-nucleated cells were assessed by a tartrate-resistant acid phosphatase (TRAP) and F-actin ring staining assays. The osteoclast-specific genes, such as Cathepsin K, ß3-Integrin, TRAP, c-Fos, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and matrix metallo-proteinase 9 (MMP9), were analyzed by real time-polymerase chain reaction (RT-PCR). The expression of relevant proteins was analyzed by Western blot. Results: L-mimosine increased the content of intracellular HIF1α in a dose-dependent manner, which in turn promoted RANKL-induced osteoclast formation and relevant protein expression by upregulating the mitogen-activated protein kinase (MAPK) pathways. Conclusions: Our findings suggest that HIF1α directly increases the osteoclast differentiation of RANKL-mediated RAW264.7 cells in vitro by upregulating the MAPK pathways.

7.
BMC Pulm Med ; 22(1): 469, 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36476351

RESUMO

OBJECTIVE: miR-125b-5p plays an important role in the development of cancer and drug resistance. However, in cisplatin resistance of non-small cell lung cancer (NSCLC), the function and potential mechanism of miR-125b-5p is still unclear. The aim of this study was to investigate the role and molecular mechanism of miR-125b-5p in cisplatin resistance of NSCLC. METHODS: A GEO dataset (GSE168707) was analyzed to find high miR-125b-5p levels were associated with DDP resistance. miR-125b-5p expression levels were detected in A549 and A549/DDP cells via real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays, western blots and mouse model xenografted were performed to identify CREB1 as a direct target gene of miR-125b-5p. Cell proliferation and apoptosis were also performed to identify whether miR-125b-5p upregulation by TRIM28 induces DDP resistance in NSCLC through CREB1 inhibition. RESULTS: In A549/DDP cells, miR-125b-5p expression was upregulated compared to A549 cells. Then miR-125b-5p was found to increase DDP resistance in NSCLC in vivo and in vitro by increasing cell proliferation and suppressing cell apoptosis. Bioinformatic analyses were used to search for gene which miR-125b-5p can target. We identified miR-125b-5p can regulate CREB1 via luciferase reporter assays, qRT-PCR and western blots. Cell proliferation and apoptosis were also performed to confirm miR-125b-5p could impact on CREB1 and induce the DDP resistance in NSCLC. Additionally, we used bioinformatic analyses to find tripartite motif-containing 28 (TRIM28) as a transcriptional enhance factor of miR-125b-5p. The expression of TRIM28 was upregulated in A549/DDP cells compared with that in A549 cells by qRT-PCR. Finally, we found TRIM28 could mediate DDP resistance through miR-125b-5p/CREB1 axis via cell proliferation, western blot and apoptosis assay. CONCLUSIONS: Overall, our findings demonstrated novel functions and mechanisms underlying DDP resistance in NSCLC through the TRIM28/miR-125b-5p/CREB1 axis. These may serve as novel therapeutic targets to improve the treatment efficacy using DDP for NSCLC in the future.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Cisplatino , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , MicroRNAs , Proteína 28 com Motivo Tripartido , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Biologia Computacional , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 28 com Motivo Tripartido/genética , Proteína 28 com Motivo Tripartido/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Conjuntos de Dados como Assunto , Humanos , Células A549 , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo
8.
World J Clin Cases ; 10(35): 13108-13114, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36569020

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a new class of antitumor drugs that have been approved to treat a variety of malignant tumors. However, the occurrence of immune related adverse events (irAEs) has become an important reason for terminating treatment. ICIs sometimes lead to diarrhea and colitis, with severe enterocolitis potentially causing the hemorrhage of the lower gastrointestinal tract and colonic perforation. ICI-associated colitis is primarily treated with glucorticosteroids and/or agents targeting tumor necrosis factor-α. Here, we describe a case of severe ICI-associated colitis due to anti-programmed cell death ligand 1 (PD-L1) (durvalumab) treatment for small cell lung cancer with liver metastasis. The patient exhibited a poor response to rescuable therapy, and eventually received a laparoscopic subtotal colectomy and ileostomy. The data presented here will contribute to optimizing current treatment strategies for patients with severe ICI-associated colitis. CASE SUMMARY: A 71-year-old man was admitted for a second course of anti-PD-L1 + IP (durvalumab + irinotecan + cisplatin) treatment to manage lung cancer with liver metastasis, diagnosed 1 mo previously. Four days after the second dose, the patient developed abdominal pain and bloody diarrhea. Due to the anti-PD-L1 medication history and colonoscopy findings of the patient, he was diagnosed with a colitis associated with ICI treatment. After treatment with sufficient glucocorticoids and two courses of infliximab, the patient developed severe lower gastrointestinal bleeding. After adequate assessment, the patient was treated by laparoscopic surgery, and was discharged in stable condition. CONCLUSION: The early screening and hierarchical management of irAEs need the joint participation of a multidisciplinary team. For ICI-related colitis with ineffective medical treatment, timely surgical intervention could prevent the death of patients.

9.
Plant Dis ; 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572971

RESUMO

Tea plants (Camellia sinensis L.) are an important cash crop and are cultivated worldwide for their commercial value (Palanisamy et al. 2014). Tea gray blight is an important tea plant disease as it can cause a decline in tea quality and reduce yields by 20-30% (Sanjay et al. 2008). In August 2018, a disease survey was conducted on 400 ha of organic tea plantations in the Pu'er area of Yunnan Province (22.48° N, 100.58° E). The survey found that widespread disease was causing damage to 40% of the tea plantations and that the most seriously affected tea variety was Yunkang No. 10, which had an average disease incidence of 30-35%. The affected leaves grew small yellow-green spots on their tips or margins in the early stage that expanded into round or irregular brown spots with distinct concentric whorls and black conidial disks arranged in whorls when the humidity was high (Fig. 1A-B), which is consistent with tea gray blight disease (Zheng et al. 2021). Twenty-four diseased leaf samples were collected from four different tea plantations and transported to the Pu-Erh Tea Research Laboratory. Leaves with disease spots were cut into 4 mm ×4 mm square pieces, surface-sterilized with 75% alcohol for 1 min, disinfected with 1% sodium hypochlorite for 3 min, and washed thrice with sterile water. The tissue pieces were placed on potato dextrose agar (PDA) plates containing 100 µg ml-1 of chloramphenicol (Wang et al. 2021). After 3 d of culturing in the dark at 28 C, twenty pure cultures with similar morphology were obtained, and two representative isolates were selected and transferred into new PDA media. After 7 d, circular fungal colonies with dense aerial mycelium produced black, wet spore masses that grew on the PDA media (Fig. 1C-D). The conidia were spindle-shaped with four septa, measuring 25.0 (21.0-26.0) × 6.0 (4.5-7.0) µm (n=15). The conidia had three median cells, two of which were dark brown in color with unclear separations, with a single basal hyaline appendage 3.8 (3.5-4.5) µm (n=30) in length and 2-3 apical hyaline appendages 31 (27-35) µm in length (n=30) (Fig. 1E), similar to the conidial characteristics of Neopestalotiopsis piceana (Maharachchikumbura et al. 2014). Two isolates were selected for DNA extraction. The internal transcribed spacer (ITS) region, partial translation elongation factor 1-alpha (tef1-α) gene, and partial ß-tubulin (tub2) gene were amplified using the ITS1F-ITS4 primer set (White et al 1990), the EF-1α-F and EF-1α-R primer sets (Li et al. 2018), and the tub1 and tub2 primers, respectively (Chauhan et al. 2007). The ITS (OP535632 to OP535632), tef1-α (OP589285,OP589287), and tub2 (OP589286,OP589288) sequences were submitted to NCBI GenBank. Basic Local Alignment Search Tool analysis demonstrated that these sequences were 100% similar to those of N. piceana isolates available in GenBank. The sequences were compared using the Mafft software package, and sequences with the same ID were concatenated using scripts. A maximum likelihood phylogenetic tree was constructed using the MEGA (ver. 5.1) software package based on the concatenated sequences (ITS, tef1-α, and tub2). Phylogenetic analysis revealed that C-5 and B-3 showed 95% bootstrap support with N. piceana isolates in references (Fig. 2). According to the morphology and molecular characterization, C-5 and B-3 were identified as N. piceana. Pathogenicity tests on these two isolates were conducted using 36 healthy tea plants. The leaves were scratched slightly with sterile toothpick tips, after which pathogen cakes (6 mm diameter) were placed on the wounds with the mycelial side facing down and covered with sterile absorbent cotton to maintain a moist environment. Control leaves were wounded and covered with sterile PDA plugs (three replicates per treatment, three plants per replicate). Seven days later, the inoculated leaves exhibited similar symptoms observed under natural conditions, whereas the control leaves exhibited no symptoms. The same isolates as the introduced strains were isolated from the diseased tea leaves, completing Koch's postulates. To our knowledge, this is the first report of N. piceana causing gray blight on tea leaves in China. These results provide valuable information for the prevention and management of gray blight on tea leaves. References: Chauhan, J. B., et al. 2007. Indian J Biotechnol. 6: 404-406 Li, D. X., et al. 2018. J. Trop. Crops. 39:1827-1833. Maharachchikumbura, S. N., et al. 2014. Stud. Mycol. 79:121-186. Palanisamy, S., et al. 2014. Appl. Biochem. Biotechnol. 172:216-223. Sanjay, R., et al. 2008. Crop Protect. 27(3-5): 689-694. Wang, Q. M., et al. 2021. Front. Microbiol. 12:774438. White, T. J., et al. 1990. Academic, San Diego. 315-322 Zheng, S., et al. 2021. Plant Dis. 105:3723-3726.

10.
Chemistry ; 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36541269

RESUMO

We previously reported that D-amino acid-containing peptides exhibited the ability to resist enzymatic hydrolysis. This study investigated the influence of mini-PEGs modification on enzymatic hydrolysis ability of D-amino acid-containing peptides. The results showed that PEGylation promoted enzymatic hydrolysis of the D-amino acid-containing peptide, especially, the cleavage rate of the D-amino acid-containing peptide 6-w with PEG3 modification at the N-ends was up to 17 times in the presence of Proteinase K comparing with those without PEG3 modification. Moreover, analysis of the enzymatic cleavage sites demonstrated a similar cleavage pattern of the PEGylated D-amino acid-containing peptide to that of the unmodified peptide. The computational simulations further showed the enhanced enzymatic hydrolysis ability can be attributed to the strong interaction between PROK and the peptide after PEG3 modification and the resulting formation of a mature catalytic triad structure.

11.
Front Endocrinol (Lausanne) ; 13: 1004112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506074

RESUMO

Background: While it is known that inaccurate evaluation for retroperitoneal laparoscopic adrenalectomy (RPLA) can affect the surgical results of patients, no stable and effective prediction model for the procedure exists. In this study, we aimed to develop a computed tomography (CT) -based radiological-clinical prediction model for evaluating the surgical difficulty of RPLA. Method: Data from 398 patients with adrenal tumors treated by RPLA in a single center from August 2014 to December 2020 were retrospectively analyzed and divided into sets. The influencing factors were selected by least absolute shrinkage and selection operator regression model (LASSO). Additionally, the nomogram was constructed. A receiver operating characteristic curve was used to analyze the prediction efficiency of the nomogram. The C-index and bootstrap self-sampling methods were used to verify the discrimination and consistency of the nomogram. Result: The following 11 independent influencing factors were selected by LASSO: body mass index, diabetes mellitus, scoliosis, hyperlipidemia, history of operation, tumor diameter, distance from adrenal tumor to upper pole of kidney, retro renal fat area, hyperaldosteronism, pheochromocytoma and paraganglioma, and myelolipoma. The area under the curve (AUC) of the training set was 0.787, and 0.844 in the internal validation set. Decision curve analyses indicated the model to be useful. An additional 117 patients were recruited for prospective validation, and AUC was 0.848. Conclusion: This study developed a radiological-clinical prediction model proposed for predicting the difficulty of RPLA procedures. This model was suitable, accessible, and helpful for individualized surgical preparation and reduced operational risk. Thus, this model could contribute to more patients' benefit in circumventing surgical difficulties because of accurate predictive abilities.


Assuntos
Neoplasias das Glândulas Suprarrenais , Modelos Estatísticos , Humanos , Estudos Retrospectivos , Prognóstico , Adrenalectomia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia
12.
Sci Rep ; 12(1): 21183, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36476762

RESUMO

L-nucleosides were the most important antiviral lead compounds because they can inhibit viral DNA polymerase and DNA synthesis of many viruses, whereas they may lead to mutations in DNA replication and cause genomic instability. In this study, we reported the replicative bypass of L-deoxynucleosides in recombinant DNA by restriction enzyme-mediated assays to examine their impact on DNA replication in vitro and in E. coli cells. The results showed that a template L-dC inhibited Taq DNA polymerase reaction, whereas it can be bypassed by Vent (exo-) DNA polymerase as well as in cell replication, inserting correct nucleotides opposite L-dC. L-dG can be bypassed by Taq DNA polymerase and in E. coli cells, maintaining insertion of correct incoming nucleotides, and L-dG induced mutagenic replication by Vent (exo-) DNA polymerase. In contrast, L-dA can induced mutagenic replication in vitro and in E. coli cells. MD simulations were performed to investigate how DNA polymerase affected replicative bypass and mutations when D-nucleosides replaced with L-nucleosides. This study will provide a basis for the ability to assess the cytotoxic and mutagenic properties of the L-nucleoside drugs.


Assuntos
Escherichia coli , Escherichia coli/genética , Taq Polimerase
13.
J Clin Med ; 11(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36556095

RESUMO

OBJECTIVE: To investigate the independent influencing factors of bone cement displacement following percutaneous vertebral augmentation (PVA) in patients with stage I and stage II Kümmell's disease. METHODS: We retrospectively reviewed the records of 824 patients with stage Ⅰ and stage Ⅱ Kümmell's disease treated with percutaneous vertebroplasty (PVP) or percutaneous vertebroplasty (PKP) from January 2016 to June 2022. Patients were divided into the postoperative bone cement displacement group (n = 150) and the bone cement non-displacement group (n = 674) according to the radiographic inspection results. The following data were collected: age, gender, body mass index (BMI), underlying disease, bone mineral density (BMD), involved vertebral segment, Kümmell's disease staging, anterior height, local Cobb angle, the integrity of anterior vertebral cortex, the integrity of endplate in surgical vertebrae, surgical method, surgical approach, the volume of cement, distribution of cement, the viscosity of cement, cement leakage, and postoperative anti-osteoporosis treatment. Binary logistic regression analysis was performed to determine the independent influencing factors of bone cement displacement. The discrimination ability was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). RESULTS: The results of logistic regression analysis revealed that thoracolumbar junction (odds ratio (OR) = 3.23, 95% confidence interval (CI) 2.12-4.50, p = 0.011), Kümmell's disease staging (OR = 2.23, 95% CI 1.81-3.41, p < 0.001), anterior cortex defect (OR = 5.34, 95% CI 3.53-7.21, p < 0.001), vertebral endplates defect (OR = 0.54, 95% CI 0.35-0.71, p < 0.001), cement distribution (OR = 2.86, 95% CI 2.03-3.52, p = 0.002), cement leakage (OR = 4.59, 95% CI 3.85-5.72, p < 0.001), restoration of local Cobb angle (OR = 3.17, 95% CI 2.40-5.73, p = 0.024), and postoperative anti-osteoporosis treatment (OR = 0.48, 95% CI 0.18-0.72, p = 0.025) were independently associated with the bone cement displacement. The results of the ROC curve analysis showed that the AUC was 0.816 (95% CI 0.747-0.885), the sensitivity was 0.717, and the specificity was 0.793. CONCLUSION: Thoracolumbar fracture, stage Ⅱ Kümmell's disease, anterior cortex defect, uneven cement distribution, cement leakage, and high restoration of the local Cobb angle were risk factors for cement displacement after PVA in Kümmell's disease, while vertebral endplates defect and postoperative anti-osteoporosis treatment are protective factors.

14.
J Chem Phys ; 157(17): 174202, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36347708

RESUMO

Conventional time-of-flight (TOF) measurements yield charge carrier mobilities in photovoltaic cells with time resolution limited by the RC time constant of the device, which is on the order of 0.1-1 µs for the systems targeted in the present work. We have recently developed an alternate TOF method, termed nonlinear photocurrent spectroscopy (NLPC), in which carrier drift velocities are determined with picosecond time resolution by applying a pair of laser pulses to a device with an experimentally controlled delay time. In this technique, carriers photoexcited by the first laser pulse are "probed" by way of recombination processes involving carriers associated with the second laser pulse. Here, we report NLPC measurements conducted with a simplified experimental apparatus in which synchronized 40 ps diode lasers enable delay times up to 100 µs at 5 kHz repetition rates. Carrier mobilities of ∼0.025 cm2/V/s are determined for MAPbI3 photovoltaic cells with active layer thicknesses of 240 and 460 nm using this instrument. Our experiments and model calculations suggest that the nonlinear response of the photocurrent weakens as the carrier densities photoexcited by the first laser pulse trap and broaden while traversing the active layer of a device. Based on this aspect of the signal generation mechanism, experiments conducted with co-propagating and counter-propagating laser beam geometries are leveraged to determine a 60 nm length scale of drift velocity dispersion in MAPbI3 films. Contributions from localized states induced by thermal fluctuations are consistent with drift velocity dispersion on this length scale.

15.
Aging (Albany NY) ; 14(21): 8839-8855, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36375472

RESUMO

BACKGROUND: lncRNA, a type of non-coding RNA, plays an important role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, lncRNA and mRNA microarrays were performed to study the change of gene expression during osteogenic differentiation of BM-MSCs. We focused on Hedgehog interacting protein (HHIP), because HHIP mRNA and lncRNA HHIP-AS1 were gradually down-regulated on days 0, 7, and 14 during osteogenic differentiation. In addition, the gene coding lncRNA HHIP-AS1 is located on the anti-sense of Hhip gene, implying the potential interaction between lncRNA HHIP-AS1 and HHIP mRNA. METHODS: BM-MSCs with over-expressed or silenced lncRNA HHIP-AS1 were constructed to explore the biological role of HHIP-AS1 in osteogenic differentiation. BM-MSCs were lysed to determine the alkaline phosphatase activity. Fluorescence in situ hybridization and immunofluorescence were performed to analyze HHIP-AS1, HHIP, RUNX2 and osteocalcin. RESULTS: Overexpression of lncRNA HHIP-AS1 increased HHIP expression, which suppressed Hedgehog signaling pathway, as indicated by the reduction of SMO, Gli1 and Gli2. The suppression of Hedgehog signal was associated with the inhibited osteogenesis. HHIP knockdown abolished the suppression of osteogenesis induced by lncRNA HHIP-AS1 overexpression. Through binding to HHIP mRNA, lncRNA HHIP-AS1 recruited ELAVL1 to HHIP mRNA, whereby increasing the mRNA stability and the protein level. CONCLUSIONS: This study revealed that down-regulation of HHIP due to lncRNA HHIP-AS1 reduction promoted the osteogenic differentiation of BM-MSCs though removing the suppression of Hedgehog signal.


Assuntos
Células-Tronco Mesenquimais , RNA Longo não Codificante , Proteínas Hedgehog/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Hibridização in Situ Fluorescente , Diferenciação Celular/genética , RNA Mensageiro , Transdução de Sinais/genética , Células Cultivadas
16.
Cells ; 11(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36359765

RESUMO

BACKGROUND: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are characterized by systemic inflammation and high mortality, but there is no effective clinical treatment. As a classic traditional Chinese medicine (TCM) formula, MaHuang-LianQiao-ChiXiaoDou decoction (MHLQD) has been used clinically for centuries to treat liver diseases. METHODS: The LPS/D-GalN-induced ALF mice model and the CCl4+LPS/D-GalN-induced ACLF mice model were used to observe the therapeutic effects of MHLQD on mice mortality, hepatocytes death, liver injury, and immune responses. RESULTS: MHLQD treatment significantly improved mice mortality. Liver injury and systemic and hepatic immune responses were also ameliorated after MHLQD treatment. Mechanistically, proteomic changes in MHLQD-treated liver tissues were analyzed and the result showed that the thrombogenic von Willebrand factor (VWF) was significantly inhibited in MHLQD-treated ALF and ACLF models. Histological staining and western blotting confirmed that VWF/RAP1B/ITGB3 signaling was suppressed in MHLQD-treated ALF and ACLF models. Furthermore, mice treated with the VWF inhibitor ADAMTS13 showed a reduced therapeutic effect from MHLQD treatment. CONCLUSIONS: Our study indicated that MHLQD is an effective herbal formula for the treatment of ALF and ACLF, which might be attributed to the protection of hepatocytes from death via VWF/RAP1B/ITGB3 signaling.


Assuntos
Insuficiência Hepática Crônica Agudizada , Medicamentos de Ervas Chinesas , Fator de von Willebrand , Animais , Camundongos , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Lipopolissacarídeos , Proteômica , Transdução de Sinais , Fator de von Willebrand/efeitos dos fármacos , Fator de von Willebrand/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
17.
Nanomaterials (Basel) ; 12(21)2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36364585

RESUMO

Sensitive detection of prostate-specific antigens (PSA) in serum is essential for the prevention and early treatment of prostate cancer. Simple and disposable electrochemical immunosensors are highly desirable for screening and mobile detection of PSAs in high-risk populations. Here, an electrochemical immunosensor was constructed based on amino-rich nanochannels array-modified patterned, inexpensive, and disposable indium tin oxide (ITO) electrodes, which can be employed for the sensitive detection of PSA. Using an amino-group-containing precursor, a vertically ordered mesoporous silica nanochannel film (VMSF) containing amino groups (NH2-VMSF) was rapidly grown on ITO. When NH2-VMSF contained template surfactant micelle (SM), the outer surface of NH2-VMSF was directionally modified by aldehyde groups, which enabled further covalent immobilization of the recognitive antibody to prepare the immuno-recognitive interface. Owing to the charge-based selective permeability, NH2-VMSF can electrostatically adsorb negatively charged redox probes in solution (Fe(CN)63-/4-). The electrochemical detection of PSA is realized based on the mechanism that the antigen-antibody complex can reduce the diffusion of redox probes in solution to the underlying electrode, leading to the decrease in electrochemical signal. The constructed immunosensor can achieve sensitive detection of PSA in the range from 10 pg/mL to 1 µg/mL with a limit of detection (LOD) of 8.1 pg/mL. Sensitive detection of PSA in human serum was also achieved. The proposed disposable immunosensor based on cheap electrode and nanochannel array is expected to provide a new idea for developing a universal immunosensing platform for sensitive detection of tumor markers.

18.
Front Bioeng Biotechnol ; 10: 1058300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440439

RESUMO

Osteoporosis is an age-related systemic skeletal disease leading to bone mass loss and microarchitectural deterioration. It affects a large number of patients, thereby economically burdening healthcare systems worldwide. The low bioavailability and complications, associated with systemic drug consumption, limit the efficacy of anti-osteoporosis drugs currently available. Thus, a combination of therapies, including local treatment and systemic intervention, may be more beneficial over a singular pharmacological treatment. Hydrogels are attractive materials as fillers for bone injuries with irregular shapes and as carriers for local therapeutic treatments. They exhibit low cytotoxicity, excellent biocompatibility, and biodegradability, and some with excellent mechanical and swelling properties, and a controlled degradation rate. This review reports the advantages of hydrogels for adjuvants loading, including nature-based, synthetic, and composite hydrogels. In addition, we discuss functional adjuvants loaded with hydrogels, primarily focusing on drugs and cells that inhibit osteoclast and promote osteoblast. Selecting appropriate hydrogels and adjuvants is the key to successful treatment. We hope this review serves as a reference for subsequent research and clinical application of hydrogel-based delivery systems in osteoporosis therapy.

19.
Front Pharmacol ; 13: 1043975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438811

RESUMO

Osteoclast is a hematopoietic precursor cell derived from the mononuclear macrophage cell line, which is the only cell with bone resorption function. Its abnormal activation can cause serious osteolysis related diseases such as rheumatoid arthritis, Paget's disease and osteoporosis. In recent years, the adverse effects caused by anabolic anti-osteolytic drugs have increased the interest of researchers in the potential therapeutic and preventive effects of natural plant derivatives and natural compounds against osteolytic diseases caused by osteoclasts. Natural plant derivatives and natural compounds have become major research hotspots for the treatment of osteolysis-related diseases due to their good safety profile and ability to improve bone. This paper provides an overview of recent advances in the molecular mechanisms of RANKL and downstream signaling pathways in osteoclast differentiation, and briefly outlines potential natural compounds with antiosteoclast activity and molecular mechanisms.

20.
Int J Med Sci ; 19(13): 1977-1988, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438917

RESUMO

Purpose: Retroperitoneal liposarcoma (RLPS) is a rare malignancy without effective treatment. Since current treatment for unresectable RLPS is unsatisfactory, immunotherapy and targeted therapy are urgently needed. Siglec-15 is a transmembrane protein highly homologous to PD-L1 and is involved in tumor immune escape. The biological function of Siglec-15 in RLPS, its prognostic relevance and its relationship with PD-L1 need to be further clarified. In this study, we aimed to explore the biological function of Siglec-15 in sarcomas through bioinformatics analysis, and we also evaluated Siglec-15 and PD-L1 expression in RLPS samples. The relationship between the expression of Siglec-15 and PD-L1 and their clinicopathological relevance and prognostic value were also investigated in clinical RLPS patients. Methods: The RNA sequencing data of 259 sarcoma cases and 48 RLPS cases from TCGA were used to analyze the Siglec-15 expression and the differentially expressed genes (DEG) related with Siglec-15 expression. In addition, DEGs were subsequently analyzed through the gene ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network. Tumor specimens were obtained from 91 RLPS patients of our sarcoma center, and Siglec-15 and PD-L1 expression were evaluated using immunohistochemistry. The correlation between the expression level of these two markers as well as their correlation with clinicopathological factors and prognosis of RLPS patients was also assessed. Results: GEPIA analysis showed that the high expression of Siglec-15 was associated with poor sarcoma OS (P=0.034). A total of 682 differential genes were identified between the high and low expression groups of Siglec-15 in RLPS. Enrichment analysis of the KEGG pathway showed that Siglec-15 was related to the Hippo signaling pathway and the neuroactive ligand-receptor interaction. GO annotation analysis showed that the expression of Siglec-15 may thus be able to affect serine hydrolase activity, alongside signal receptor activator activity. The top 5 genes with the largest number of connection points are APOA1, F2, AHSG, AMBP, SERPINC1. In subsequent studies, we used 91 liposarcoma samples from our center for verification. Siglec-15 was expressed in 84.6% of RLPS cases, whereas PD-L1 was expressed in 17.6% of RLPS cases. A negative correlation was observed between Siglec-15 and PD-L1 expression (P=0.020). In this group of RLPS patients, high Siglec-15 expression was correlated with poorer disease-free survival (DFS) (P=0.021), and it was an independent predictor of DFS (hazard ratio: 2.298; 95% confidence interval: 1.154-4.576; P=0.018). However, we did not find a correlation between PD-L1 expression and overall survival or DFS in RLPS patients. Conclusion: The DEG and signaling pathways identified in the study could provide a preliminary understanding of the underlying molecular mechanisms of Siglec-15 in the development and progression of RLPS. High expression of Siglec-15 was a negative independent predictive factor for DFS of RLPS. The negative relationship between Siglec-15 and PD-L1 expression suggested that the Siglec-15 pathway might be an important supplement to PD-L1 treatment.


Assuntos
Lipossarcoma , Sarcoma , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biologia Computacional , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico
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