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1.
Artigo em Inglês | MEDLINE | ID: mdl-35578073

RESUMO

The construction of artificial reservoirs with various regulation types on river is currently an important form of comprehensive utilization of water energy and water resources in river basins. The type of regulation is important in controlling the residence time, which in turn affects the photosynthesis-respiration balance in the water. This process has a significant impact on carbon dioxide (CO2) emissions from reservoirs. In this study, seasonal observations were carried out from September 2020 to July 2021 at five artificial reservoirs in the Qiantang River Basin, eastern China, to reveal the characteristics of CO2 emission from the water-air interface of reservoirs with different regulating types. The results showed that the annual average CO2 emission flux of the studied reservoirs varied significantly, ranging from 4.2 to 155.3 mmol m-2 day-1 with an average of 48.4 mmol m-2 day-1, which also had a significant negative correlation with the hydraulic retention time. While downstream of the dam, the annual average CO2 emission flux was quite high with a range of 105.8 to 543.0 mmol m-2 day-1, averaging 381.6 mmol m-2 day-1. This is mainly due to the release of water with high-concentration CO2 from the bottom of the reservoir. Additionally, using related data of reservoirs around the world, a CO2 emission model with hydraulic retention time, air temperature, and reservoir age as the primary parameters was developed, which was conducive to evaluate reservoir CO2 emissions on a larger scale and provided theoretical support for effective reservoir management.

2.
Nutrients ; 14(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35565899

RESUMO

Metabolic surgery (MS) is one of the most effective therapies for treating obesity. Due to the lack of multicenter cohort research on nutritional evaluations after surgery in Chinese patients, we explored the changes in nutritional status following MS in Chinese patients. This was a retrospective study of patients (n = 903) who underwent sleeve gastrectomy (SG) (n = 640) or Roux-en-Y gastric bypass (RYGB) (n = 263) for obesity at five different hospitals in China between 17 February 2011, and 20 December 2019. Major nutrients were evaluated at baseline and 1, 3, 6, and 12 months postoperatively. Hb levels decreased, and anemia prevalence increased at 12 months after MS in the premenopausal female group. Moreover, patients with preoperative anemia had an increased risk of postoperative anemia. The ferritin levels (p < 0.001) decreased and iron deficiency increased (p < 0.001) at 12 months after MS among premenopausal females. No significant changes in folate deficiency and vitamin B12 deficiency were found throughout the study. The bone mineral density (BMD) of the femoral neck, lumbar spine, and total hip significantly decreased from baseline to 12 months after MS; however, no new patients developed osteopenia or osteoporosis after MS. Based on 12 months of follow-up, premenopausal females presented a high incidence of anemia after MS. Although we found no differences in osteopenia and osteoporosis prevalence after MS, the BMD did decrease significantly, which suggests that nutrient supplements and long-term follow-up are especially necessary postoperation.

3.
Front Genet ; 13: 872518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559030

RESUMO

Background and aims: As a major cause of liver disease worldwide, non-alcoholic fatty liver disease (NAFLD) comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high prevalence and poor prognosis of NASH, it is critical to understand its mechanisms. However, the etiology and mechanisms remain largely unknown. In addition, the gold standard for the diagnosis of NASH is liver biopsy, which is an invasive procedure. Therefore, there is a pressing need to develop noninvasive tests for NASH diagnosis. The goal of the study is to discover key genes involved in NASH development and investigate their value as noninvasive biomarkers. Methods: The Gene Expression Omnibus (GEO) database was used to obtain two datasets encompassing NASH patients and healthy controls. We used weighted gene co-expression network analysis (WGCNA) and differential expression analysis in order to investigate the association between gene sets and clinical features, as well as to discover co-expression modules. A protein-protein interaction (PPI) network was created to extract hub genes. The results were validated using another publicly available dataset and mice treated with a high-fat diet (HFD) and carbon tetrachloride (CCl4). Results: A total of 24 differentially co-expressed genes were selected by WGCNA and differential expression analysis. KEGG analysis indicated most of them were enriched in the focal adhesion pathway. GO analysis showed these genes were mainly enriched in circadian rhythm, aging, angiogenesis and response to drug (biological process), endoplasmic reticulum lumen (cellular component), and protein binding (molecular function). As a result, eight genes (JUN, SERPINE1, GINS2, TYMS, HMMR, IGFBP2, BIRC3, TNFRSF12A) were identified as hub genes. Finally, three genes were found significantly changed in both the validation dataset and the mouse model. Conclusion: Our research discovered genes that have the potential to mediate the process of NASH and might be useful diagnostic biomarkers for the disorder.

4.
BMJ Open ; 12(5): e051175, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501095

RESUMO

INTRODUCTION: The objective of the Chinese Neonatal Network (CHNN) is to provide a platform for collaborative research, outcomes evaluation and quality improvement for preterm infants with gestational age less than 32 weeks in China. The CHNN is the first national neonatal network and has the largest geographically representative cohort from neonatal intensive care units (NICUs) in China. METHODS AND ANALYSIS: Individual-level data from participating NICUs will be collected using a unique database developed by the CHNN on an ongoing basis from January 2019. Data will be prospectively collected from all infants <32 weeks gestation or <1500 g birth weight at 58 participating NICUs. Infant outcomes and inter-institutional variations in outcomes will be examined and used to inform quality improvement measures aimed at improving outcomes. Information about NICU environmental and human resource factors and processes of neonatal care will also be collected and analysed for association with outcomes. Clinical studies, including randomised controlled trials will be conducted using the CHNN data platform. ETHICS AND DISSEMINATION: This study was approved by the ethics review board of Children's Hospital of Fudan University, which was recognised by all participating hospitals. Waiver of consent were granted at all sites. Only non-identifiable patient level data will be transmitted and only aggregate data will be reported in CHNN reports and publications.


Assuntos
Saúde do Lactente , Serviços de Informação , Melhoria de Qualidade , Criança , China , Bases de Dados Factuais , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal
5.
Nat Med ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551294

RESUMO

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.

6.
Cell Death Discov ; 8(1): 227, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468881

RESUMO

Chemotherapy resistance poses an obstacle for effective treatment of uveal melanoma. In this study, we aim to investigate the effects of jumonji domain containing 2C (JMJD2C)-mediated mouse double minute-2 homolog (MDM2)/p53/interleukin 5 receptor subunit alpha (IL5RA) axis on cisplatin (CDDP) resistance in uveal melanoma. RT-qPCR and Western blot assay were performed to determine their expression patterns in uveal melanoma cell line (MUM-2B) and CDDP-resistant cell line (MUM-2B/CDDP). The enrichment of H3K9me3 in MDM2 promoter region was examined by ChIP, and the binding between p53 and ubiquitin in MUM-2B cells testified by co-IP assay. Following overexpression or silencing of JMJD2C/MDM2/p53/IL5RA, the 50% concentration of inhibition (IC50) and the biological characteristics of MUM-2B and MUM-2B/CDDP cells were examined using CCK-8 assay, SA-ß-gal staining, fluorescence-activated cell sorting analysis, and Transwell assay. Finally, the tumorigenicity of transplanted MUM-2B and MUM-2B/CDDP cells in nude mice was assessed. JMJD2C was documented to be highly expressed in uveal melanoma cells, promoting the CDDP resistance. Histone demethylase JMJD2C removed the H3K9me3 modification of MDM2 promoter, which promoted the expression of MDM2. MDM2 enhanced the IL5RA expression through stimulating the ubiquitination and degradation of p53, thus inducing CDDP resistance of uveal melanoma cells. Furthermore, the results of in vivo experiments revealed that JMJD2C mediated the MDM2/p53/IL5RA axis to expedite the growth of uveal melanoma and augment the CDDP resistance. Taken together, JMJD2C can induce histone demethylation to upregulate MDM2, thereby ubiquitinating p53 and upregulating IL5RA. As a consequence, CDDP resistance in uveal melanoma is ultimately accelerated.

7.
Urol Oncol ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35431134

RESUMO

PURPOSE: A recent study has shown that upper tract urothelial carcinoma (UTUC) patients with high-risk factors have a high local recurrence rate. The purpose of this work was to investigate the benefit of adjuvant radiotherapy (ART) for patients with high recurrence factors. METHODS: Four hundred twenty-four UTUC patients who received radical nephroureterectomy (RNU) in our hospital between 2010 and 2018 were reviewed. The significance of factors on cancer-specific survival (CSS) and recurrence-free survival (RFS) were assessed using Cox multivariate analysis. In patients with high recurrence factors, propensity score matching was used to adjust the confounding factors for ART. RESULTS: The median follow-up time was 40 (range 3-77) months. Multivariate analysis showed that multifocal tumor, G3, pT3/4 stage and positive lymph node (N+) were independent predictors for worse RFS. Multifocal tumor and pT3/4 stage were independent predictors of worse CSS in UTUC after surgery. A total of 286 patients with these high recurrence factors were identified: 192 (67.1%) patients received RNU only, and 94 (32.9%) patients received ART. Overall, ART did not improve CSS (ART 86.1% vs. RNU 78.5%.; P = 0.11). After propensity score matching, ART significantly improved the CSS of patients with high recurrence factors. The 3-year CSS was 73.1% in patients treated with RNU alone vs. 86.1% in patients treated with ART (P = 0.016). CONCLUSIONS: Results of our study demonstrated benefit of adjuvant radiotherapy in cancer specific survival in UTUC patients with high recurrence factors(multifocal tumor ,pT3/4,G3 and positive lymph node).

8.
Cell Biochem Funct ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35393670

RESUMO

Epilepsy is a nervous system disease caused by abnormal discharge of brain neurons, which is characterized by recurrent seizures. The factors that induce epilepsy include genetic and environmental factors. Genetic factors are important pathogenic factors of epilepsy, such as epilepsy caused by protocadherin-19 (PCDH-19) mutation, which is an X-linked genetic disease. It is more common in female heterozygotes, which are caused by mutations in the PCDH-19 gene. Epilepsy caused by environmental factors is mainly caused by brain injury, which is commonly caused by brain tumors, brain surgery, or trauma to the brain. In addition, the pathogenesis of epilepsy is closely related to abnormalities in some signaling pathways. The Wnt/ß-catenin signaling pathway is considered a new target for the treatment of epilepsy. This review summarizes these factors inducing epilepsy and the research hypotheses regarding the pathogenesis of epilepsy. The focus of this review centers on cadherins and the pathogenesis of epilepsy. We analyzed the pathogenesis of epilepsy induced by N-cadherin and PCDH-19 in the cadherin family members. Finally, we expect that in the future, new breakthroughs will be made in the study of the pathogenesis and mechanism of epilepsy at the cellular and molecular levels.

9.
Int J Biol Sci ; 18(6): 2292-2303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35414786

RESUMO

Ubiquitination is vital for multiple cellular processes via dynamic modulation of proteins related to cell growth, proliferation, and survival. Of the ubiquitination system components, E3 ubiquitin ligases and deubiquitinases have the most prominent roles in modulating tumor metastasis. This review will briefly summarize the observations and underlying mechanisms of multiple E3 ubiquitin ligases and deubiquitinases to regulate tumor metastasis. Further, we will discuss the relationship and importance between ubiquitination components and tumor progression.


Assuntos
Neoplasias , Ubiquitina-Proteína Ligases , Enzimas Desubiquitinantes/metabolismo , Humanos , Neoplasias/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
10.
Sci Total Environ ; 832: 154929, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35367263

RESUMO

Particulate chloride is a major component of sea salt particles and plays a key role in atmospheric chemistry. Anthropogenic pollutants over the northeastern Asia can be transported to the adjacent seas through the northwest monsoon, which profoundly influences the chloride chemistry over the seas. In this study, spatial distribution of particulate chloride and its sources over the Chinese seas were investigated based on shipboard particle samplings especially online Single Particle Aerosol Mass Spectrometer (SPAMS) over Bohai Sea, North Yellow Sea, and South Yellow Sea (SYS) during a cruise in November 2012. A strong north-to-south (N-S) gradience in marine aerosol composition was found. The Cl-/Na+ ratios in PM2.5 and single particle composition by SPAMS indicated remarkable chloride enrichment in marine aerosol in the north (Bohai Sea), while depletion in southern SYS. The results of size distribution showed that particulate chloride had higher concentration in coarse particles, while the Cl-/Na+ ratio was much higher in submicron particles. In the north (38-40°N), biomass burning, carbonaceous, and Pb-rich type particles had high fractions in all chloride-containing particles identified by SPAMS (on average 66%). Combining chemical composition with back trajectory, it was found that fine-mode chloride enrichment in the north was mainly due to anthropogenic emission especially coal combustion and biomass burning from northern China. However, the high fine-mode chloride depletion in the south (32-34°N) was probably due to acid replacement by sulfate in aged aerosol during atmospheric transport. Our new findings reveal that marine aerosol in Chinese seas would show a clear N-S pattern of more fresh and anthropogenic enriched particles in the north, but more aged aerosol in the south during the East Asia Winter Monsoon, which provides new insights for the quantitative assessment of anthropogenic impact on marine aerosol and future modeling study.

11.
Pak J Med Sci ; 38(3Part-I): 600-604, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480522

RESUMO

Objectives: To assess the association of bronchoalveolar lavage fluid (BALF) α-SMA and ß-catenin levels and the severity of pneumonia. Methods: The records of patients with severe pneumonia treated in our hospital from June 2019 to June 2020 were selected. The clinical outcome was observed within 10 days. For the purpose of analysis, patients were divided into two groups according to the outcome, 47 cases in the improvement group and 39 cases in the deterioration group. The intubation time, mechanical ventilation time and APACHE II score 10 days after admission were compared between the two groups; We assessed pulmonary infections using the clinical pulmonary infection score(CPIS). The levels of α-SMA and ß-catenin in bronchoalveolar lavage fluid at different time points were compared and analyzed, to analyze the association between the levels and the CPIS. Results: The APACHE II score in the improvement group were lower than those in the deterioration group (P<0.05). The expressions of α-SMA and ß-catenin in the BALF of patients in the improvement group were significantly lower than those of patients in the deterioration group on day 1, 3, and 7 (P<0.05); and the expressions of α-SMA and ß-catenin in the BALF of patients in the improvement group decreased with time, while those of patients in the deterioration group increased gradually with time(P<0.05). The expressions of α-SMA and ß-catenin in patients with CPIS>6 was significantly higher than those in patients with CPI≤6(P<0.05). Pearson correlation analysis showed that the levels of α-SMA and ß-catenin in BALF were positively correlated with the CPIS. Conclusion: The levels of α-SMA and ß-catenin in BALF are closely associated with the clinical condition of patients with severe pneumonia; the levels are positively associated with the severity of the disease and they increase with symptomatic worsening.

12.
Front Immunol ; 13: 812996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35296075

RESUMO

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients and also 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, namely, α/ß-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Humanos , Masculino , Metabolômica/métodos , Antígeno Prostático Específico
13.
Bone ; 159: 116378, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35257929

RESUMO

INTRODUCTION: Osteogenesis imperfecta (OI) or brittle bone disease is a genetic disorder that results in bone fragility. Bisphosphonates such as zoledronic acid (ZA) are used clinically to increase bone mass and reduce fracture risk. Human growth hormone (hGH) has been used to promote long bone growth and forestall short stature in children with OI. The potential for hGH to improve bone quality, particularly in combination with ZA has not been robustly studied. METHODS: A preclinical study was performed using n = 80 mice split evenly by genotype (WT, Col1a2+/G610C). Groups of n = 10 were treated with +/-ZA and +/-hGH in a factorial design for each genotype. Outcome measures included bone length, isolated muscle mass, bone parameters assessed by microCT analysis, dynamic histomorphometry, and biomechanical testing. RESULTS: Treatment with hGH alone led to an increase in femur length in WT but not OI mice, however bone length was increased in both genotypes with the combination of hGH/ZA. MicroCT showed that hGH/ZA treatment increased cortical BV in both WT (+15%) and OI mice (+14.3%); hGH/ZA were also found to be synergistic in promoting cortical thickness in OI bone. ZA was found to have a considerably greater positive impact on trabecular bone than hGH. ZA was found to suppress bone turnover, and this was rescued by hGH treatment in terms of cortical periosteal perimeter, but not by dynamic bone remodeling. Statistically significant improvements in long bone by microCT did not translate into improvements in mechanical strength in a 4-point bending test, nor did vertebral strength improve in L4 compression testing in WT/OI bone. DISCUSSION/CONCLUSION: These data support hGH/ZA combination as a treatment for short stature, however the improvements granted by hGH alone and in combination with ZA on bone quality are modest. Increased periosteal perimeter does show promise in improving bone strength in OI, however a longer treatment time may be required to see effects on bone strength through mechanical testing.


Assuntos
Hormônio do Crescimento Humano , Osteogênese Imperfeita , Animais , Densidade Óssea/fisiologia , Osso e Ossos , Modelos Animais de Doenças , Hormônio do Crescimento/uso terapêutico , Camundongos , Osteogênese Imperfeita/diagnóstico por imagem , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/genética , Ácido Zoledrônico/farmacologia , Ácido Zoledrônico/uso terapêutico
14.
Radiat Oncol ; 17(1): 54, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35303922

RESUMO

BACKGROUND: Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/ß ratio (about 1.5-3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/ß ratio. Therefore, this study attempted to estimate the α/ß ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. METHODS: The maximum likelihood principle in mathematical statistics was used to fit the parameters: α and ß values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification. RESULTS: Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/ß ratios were 1.78 Gy (95% CI 1.59-1.98), 3.46 Gy (95% CI 3.27-3.65), and 4.24 Gy (95% CI 4.10-4.39), respectively. Hence, the calculated α/ß ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased. CONCLUSIONS: The LQ model appeared to be inappropriate for high doses per fraction owing to α/ß ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/ß ratio should be used for calculation.


Assuntos
Modelos Lineares , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Humanos , Masculino
15.
Biomed Res Int ; 2022: 5687832, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309168

RESUMO

Met proto-oncogene (MET) amplification and tyrosine-protein kinase Met (c-Met) overexpression confer gefitinib resistance in non-small cell lung cancer (NSCLC). The natural product Licochalcone A (Lico A) exhibits a broad range of inhibitory effects against various tumors. However, the effects of Lico A on c-Met signaling and gefitinib resistance in NSCLC remain unclear. In the present study, Lico A efficiently overcame gefitinib-acquired resistance in NSCLC cells by suppressing c-Met signaling. Lico A decreased cell viability and colony formation dose-dependently and impaired in vivo tumorigenesis of gefitinib-resistant HCC827 and PC-9 cells. Furthermore, Lico A induced intrinsic apoptosis and upregulated the protein expression levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3. Lico A promoted the interaction between c-Met and E3 ligase c-Casitas B-lineage lymphoma (Cbl), which enhanced c-Cbl-mediated c-Met ubiquitination and degradation. Depletion of c-Cbl compromised Lico A-induced c-Met ubiquitination and its inhibitory efficacy in gefitinib-resistant NSCLC cells. Taken together, the results suggest that Lico A is a promising antitumor agent that might be used to overcome c-Met overexpression-mediated gefitinib resistance in NSCLC cells.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Chalconas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Ubiquitinação
16.
J Inflamm Res ; 15: 1699-1716, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282268

RESUMO

Background: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn's disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD. Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks. Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1. Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.

17.
Ther Adv Med Oncol ; 14: 17588359221076194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251314

RESUMO

Tumor-associated macrophages (TAMs), the most abundant inflammatory cell group in the tumor microenvironment, play an essential role in tumor immune regulation. The infiltration degree of TAMs in the tumor microenvironment is closely related to tumor growth and metastasis, and TAMs have become a promising target in tumor immunotherapy. Molecular imaging is a new interdisciplinary subject that combines medical imaging technology with molecular biology, nuclear medicine, radiation medicine, and computer science. The latest progress in molecular imaging allows the biological processes of cells to be visualized in vivo, which makes it possible to better understand the density and distribution of macrophages in the tumor microenvironment. This review mainly discusses the application of targeting TAM in tumor immunotherapy and the imaging characteristics and progress of targeting TAM molecular probes using various imaging techniques.

18.
Environ Sci Technol ; 56(8): 5256-5265, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35358385

RESUMO

The characteristics, sources, and atmospheric oxidation processes of marine aerosol proteinaceous matter (APM), including total proteins and free amino acids (FAAs), were investigated using a set of 1 year total suspended particulate (TSP) samples collected in the coastal area of Okinawa Island in the western North Pacific rim. The concentrations of APM at this site (total proteins: 0.16 ± 0.10 µg m-3 and total FAAs: 9.7 ± 5.6 ng m-3, annual average) are comparable to those of marine APM. The major FAA species of APM are also similar to previously reported marine APM with glycine as the dominant species (31%). Based on the different seasonal trends and weak correlations of total proteins and FAAs, we found that they were contributed by different sources, especially with the influence of long-range transport from the Asian continent of northern China and Mongolia and the oceanic area of the Bohai Sea, Yellow Sea, and East China Sea. The photochemical oxidation processes of high-molecular-weight proteins releasing FAAs (especially glycine) were also considered as an important factor influencing the characteristics of APM at this site. In addition, we propose a degradation process based on the correlation with ozone and ultraviolet radiation, emphasizing their roles in the degradation of proteins. Our findings help to deepen the understanding of atmospheric photochemical reaction processes of organic aerosols.


Assuntos
Poluentes Atmosféricos , Aerossóis/análise , Poluentes Atmosféricos/análise , Aminoácidos , China , Monitoramento Ambiental , Glicina , Japão , Material Particulado/análise , Proteínas , Estações do Ano , Raios Ultravioleta
19.
Nat Commun ; 13(1): 617, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105875

RESUMO

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis.


Assuntos
Detecção Precoce de Câncer/métodos , Lasers , Nanoestruturas/química , Neoplasias/classificação , Neoplasias/diagnóstico , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , China , Estudos de Coortes , Feminino , Humanos , Aprendizado de Máquina , Masculino , Sensibilidade e Especificidade
20.
Opt Express ; 30(1): 447-459, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35201221

RESUMO

Exploiting two interfering fields which are initially in the same temporal mode but with the spectra altered by propagating through different fibers, we characterize how the spectral profiles of temporal modes change with the fiber induced dispersion by measuring the fourth-order interference when the order number and bandwidth of temporal modes are varied. The experiment is done by launching a pulsed field in different temporal modes into an unbalanced Mach-Zehnder interferometer, in which the fiber lengths in two arms are different. The results show that the mode mismatch of two interfering fields, reflected by the visibility and pattern of interference, is not only dependent upon the amount of unbalanced dispersion but also related to the order number of temporal mode. In particular, the two interfering fields may become orthogonal under a modest amount of unbalanced dispersion when the mode number of the fields is k ≥ 2. Moreover, we discuss how to recover the spectrally distorted temporal mode by measuring and compensating the transmission induced dispersion. Our investigation paves the way for further investigating the distribution of temporally multiplexed quantum states in fiber network.

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