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1.
J Orthop Res ; 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-35005809

RESUMO

Diabetes mellitus contributes to intervertebral disc degeneration. Nucleus pulposus cell senescence plays an important role in intervertebral disc degeneration. However, the effects of hyperglycemia on human nucleus pulposus cells and the underlying process remains poorly understood. In the current study, we evaluated the effects of high glucose levels on human nucleus pulposus cell senescence in vitro and the effects of hyperglycemia on rat nucleus pulposus aging in vivo. Human nucleus pulposus cells were cultured in high-glucose medium (200 mM glucose) for 48 h. Senescence-associated ß-galactosidase staining, western blot analysis, and enzyme-linked immunosorbent assays were performed to evaluate human nucleus pulposus cell senescence. Flow cytometry and enzyme-linked immunosorbent assays were used to evaluate reactive oxygen species and advanced glycation end-product levels. Transcriptome sequencing followed by bioinformatics analysis was used to understand the abnormal biological processes of nucleus pulposus cells cultured in high-glucose medium. Diabetes mellitus rat models were established and histopathological and immunohistochemical analysis was conducted to examine nucleus pulposus tissue senescence in vivo. Exposure to a high glucose concentration promoted human nucleus pulposus cell senescence and increased the senescence-related secretion phenotype in human nucleus pulposus cells in vitro and in rat nucleus pulposus tissue in vivo. Bioinformatics analysis showed that hub genes were involved in nucleus pulposus cell cycle activities and cell senescence. The results suggest that appropriate blood glucose control may be key to preventing intervertebral disc degeneration in diabetic patients.

3.
Zhongguo Fei Ai Za Zhi ; 25(1): 46-53, 2022 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-35078285

RESUMO

Lung cancer is one of the most prevalent malignancies with the highest morbidity and mortality rates worldwide. In recent years, with the development of immune-oncology research and several therapeutic antibodies have reach the clinic, many breakthroughs have been made in immunotherapy. The advent of immunotherapy has revolutionized the treatment of NSCLC, but the response and durable clinical benefit are only observed in a small subset of patients. Therefore, strategies to screen the potential beneficial population and improve the efficacy of immunotherapy remain an essential topic. In the current article, the author review the biomarkers that have potential to better predict responders to immunotherapy and to provide ideas for the clinical application of immunotherapy.
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4.
J Inflamm Res ; 15: 381-394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35079223

RESUMO

Purpose: We attempted to explore the prognostic value of baseline inflammatory and nutritional biomarkers at diagnosis in patients with early-stage breast cancer and develop a novel scoring system, the inflammatory-nutritional prognostic score (INPS). Patients and Methods: We collected clinicopathological and baseline laboratory data of 1259 patients with early-stage breast cancer between December 2010 and November 2012 from Sun Yat-sen University Cancer Center. Eligible patients were randomly divided into training and validation cohorts (n = 883 and 376, respectively) in a 7:3 ratio. We selected the most valuable biomarkers to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the predictive nomogram. Results: Four inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), prognostic nutritional index (PNI), and albumin-alkaline phosphatase ratio (AAPR), were selected using the LASSO Cox analysis to construct INPS, which remained an independent prognostic indicator per the multivariate Cox regression analysis. Patients were stratified into low- and high-INPS groups based on the cutoff INPS determined by the maximally selected rank statistics. The prognostic model for overall survival consisting of INPS and other independent clinicopathological indicators showed excellent discrimination with C-indexes of 0.825 (95% confidence interval [CI]: 0.786-0.864) and 0.740 (95% CI: 0.657-0.822) in the training and validation cohorts, respectively. The time-dependent ROC curves showed a higher predictive accuracy of our prognostic nomogram than that of traditional tumor-node-metastasis staging. Conclusion: Baseline INPS is an independent indicator of OS in patients with early-stage breast cancer. The INPS-based prognostic nomogram could be used as a practical tool for individualized prognostic predictions.

5.
J Orthop Surg Res ; 16(1): 711, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876214

RESUMO

OBJECTIVE: The present study aimed to determine the role of the discoidin domain receptor 2 (DDR2) in the osteonectin (ON) regulation of osteoblast mineralization through the activation of p38 mitogen-activated protein kinase (MAPK). METHODS: Four groups were established: the ON group, the inhibitor group, the Ddr2-small interfering ribonucleic acid (siRNA) group, and the control group. Osteoblasts from the parietal bones of neonatal Sprague-Dawley rats were isolated and cultured. In the ON group, 1 µg/mL ON was added to the osteoblasts. The gene expressions of collagen 1 (Col 1) and Ddr2 were detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In the inhibitor group, the osteoblasts were added to WRG-28 (a specific DDR2 inhibitor), and in the Ddr2-siRNA group, the osteoblasts were transfected with Ddr2-siRNA. The gene and protein expressions of DDR2, bone sialoprotein, osteocalcin, osteopontin, and p38 MAPK were determined using RT-qPCR and western blot analysis. Alizarin red staining and transmission electron microscopy were used to detect mineralization. RESULTS: The results showed that ON enhanced the osteoblast Col 1 and Ddr2 gene expressions, while the use of a Ddr2-siRNA/DDR2-blocker decreased the OPN, BSP, OCN, and P38 gene and protein expressions and reduced osteoblast cellular activity and mineralized nodules. CONCLUSION: The present study demonstrated that DDR2 activation of p38 MAPK is an important approach to ON-regulating osteoblast mineralization.

6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(12): 1525-1530, 2021 Dec 15.
Artigo em Chinês | MEDLINE | ID: mdl-34913307

RESUMO

Objective: To investigate the effectiveness of sliding trochanteric osteotomy (STO) in total hip arthroplasty (THA) for Crowe type Ⅳ developmental dysplasia of the hip (DDH). Methods: Between July 2016 and April 2021, 52 patients (57 hips) with Crowe type Ⅳ DDH who underwent primary THA were enrolled according to inclusion criteria. There were 5 males and 47 females with a median age of 51 years (range, 18-76 years). There were 47 cases of single hip and 5 cases of bilateral hips. The leg length discrepancy (LLD) was 50.50 (44.00, 55.00) mm, visual analogue scale (VAS) score was 8.0 (6.0, 9.0), and Harris score was 58.0±5.0 before operation. Trendelenburg sign was positive in 46 patients (46 hips). All patients underwent STO and THA using Wagner-cone stem. The operation time, intraoperative blood loss, blood transfusion volume, Trendelenburg sign, and related complications were observed. During follow-up, VAS and Harris scores were recorded to evaluate the hip pain and function. X-ray film was used to measure the LLD and observe the bone union situations. Results: The operation time was 90-125 minutes (mean, 105 minutes). Introperative blood loss was 420-800 mL (mean, 640 mL). Ten patients underwent blood transfusion and the amount of allogeneic blood transfusion was 2-4 U (mean, 3 U). All incisions healed by first intention after operation. All patients were followed up 4-60 months (median, 24 months). At last follow-up, LLD was 6.00 (4.00, 7.75) mm, showing significant difference when compared with that before operation ( Z=-6.278, P=0.000). After operation, 51 hips (89.5%) achieved bone union at the osteotomy site, 4 hips (7.0%) had fibrous union, and 2 hips (3.5%) had nonunion. The healing time of osteotomy was 3-12 months, with an average of 6 months. At last follow-up, the VAS score was 3.0 (2.0, 5.0) and the Harris score was 85.0±6.0. The differences between pre- and post-operation were significant ( Z=-6.176, P=0.000; t=-25.285, P=0.000). Trendelenburg sign remained positive in 4 patients (4 hips) at last follow-up and the difference was significant when compared with preoperative ( χ 2=67.947, P=0.000). One patient had a medial femoral cortical fracture when Wagner-cone stem was implanted during operation, and 2 patients had early symptoms of sciatic nerve palsy after operation, and no other related complications occurred. Conclusion: For Crowe type Ⅳ DDH patients, STO applied in THA can reduce the resected bone mass, provide better exposure of hip as well as improve function of hip abductor muscle. Wagner-cone stem is recommended.


Assuntos
Artroplastia de Quadril , Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Neurosci Bull ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741260

RESUMO

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.

8.
Fitoterapia ; 156: 105072, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34728327

RESUMO

Pseudostellaria heterophylla (Miq.) Pax. (Taizishen, TZS) contains a variety of natural active cyclic-peptide compounds (CP). In this article, four kinds of CP monomers were isolated by HPLC and the structures were identified by mass spectrometry. The in vivo absorption of CP was detected by UPLC-MS/MS. The interaction between CP and membrane receptor was analyzed by SPR. As a result, the relative absorption rate of CP was Pesudostellarin B > Heterophyllin B > Pesudostellarin C > Pesudostellarin E. The difference in absorption rate of CP in vivo was related to its interaction with membrane receptors. The absorption mechanism of CP might be different. This is the first report that in vivo absorption study of different CP from TZS and explore its absorption mechanism, laying a theoretical foundation for the research and development of its oral drugs, and providing new ideas for the study of the absorption mechanism of CP from traditional Chinese medicine.

9.
Ecotoxicol Environ Saf ; 228: 113017, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34823214

RESUMO

Soil alkalization severely limits plant growth and development, however, the mechanisms of alkaline response in plants remain largely unknown. In this study, we performed physiological and transcriptomic analyses using two alfalfa cultivars (Medicago sativa L.) with different sensitivities to alkaline conditions. The chlorophyll content and shoot fresh mass drastically declined in the alkaline-sensitive cultivar Algonquin (AG) following alkaline treatment (0-25 mM Na2CO3 solution), while the alkaline-tolerant cultivar Gongnong NO.1 (GN) maintained relatively stable growth and chlorophyll content. Compared with AG, GN had higher contents of Ca2+ and Mg2+; the ratios of Ca2+ and Mg2+ to Na+, proline and soluble sugar, as well as higher enzyme activities of peroxidase (POD) and catalase (CAT) under the alkaline conditions. Furthermore, transcriptomic analysis identified three categories of alkaline-responsive differentially expressed genes (DEGs) between the two cultivars: 48 genes commonly induced in both the cultivars (CAR), 574 genes from the tolerant cultivar (TAR), and 493 genes from the sensitive cultivar (SAR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that CAR genes were mostly involved in phenylpropanoid biosynthesis, lipid metabolism, and DNA replication and repair; TAR genes were significantly enriched in metabolic pathways, such as biosynthesis of amino acids and secondary metabolites including flavonoids, and the MAPK signaling pathway; SAR genes were specifically enriched in vitamin B6 metabolism. Taken together, the results identified candidate pathways associated with genetic variation in response to alkaline stress, providing novel insights into the mechanisms underlying alkaline tolerance in alfalfa.

10.
Lipids Health Dis ; 20(1): 167, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823555

RESUMO

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. METHODS: Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. RESULTS: In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. CONCLUSIONS: The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

11.
Mater Horiz ; 8(6): 1744-1755, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34846504

RESUMO

The binary Ta-N chemical system includes several compounds with notable prospects in microelectronics, solar energy harvesting, and catalysis. Among these, metallic TaN and semiconducting Ta3N5 have garnered significant interest, in part due to their synthetic accessibility. However, tantalum sesquinitride (Ta2N3) possesses an intermediate composition and largely unknown physical properties owing to its metastable nature. Herein, Ta2N3 is directly deposited by reactive magnetron sputtering and its optoelectronic properties are characterized. Combining these results with density functional theory provides insights into the critical role of oxygen in both synthesis and electronic structure. While the inclusion of oxygen in the process gas is critical to Ta2N3 formation, the resulting oxygen incorporation in structural vacancies drastically modifies the free electron concentration in the as-grown material, thus leading to a semiconducting character with a 1.9 eV bandgap. Reducing the oxygen impurity concentration via post-synthetic ammonia annealing increases the conductivity by seven orders of magnitude and yields the metallic characteristics of a degenerate semiconductor, consistent with theoretical predictions. Thus, this inverse oxygen doping approach - by which the carrier concentration is reduced by the oxygen impurity - offers a unique opportunity to tailor the optoelectronic properties of Ta2N3 for applications ranging from photochemical energy conversion to advanced photonics.

12.
Breed Sci ; 71(3): 384-389, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34776745

RESUMO

Soybean red crown rot (RCR) caused by Calonectria ilicicola is a serious soil-borne disease affecting soybean production and quality. The current visual necrosis-based method for the measurement of RCR severity is prone to subjectivity as well as time consuming and laborious as it requires digging out and washing the roots to remove adhering soil prior to the visual scoring. Using cultivar Enrei, we show that, upon C. ilicicola infection, relative fresh weights (RFW; fresh weights relative to non-inoculated control plants) showed a significant negative correlation with visual RCR severity in apical shoot (trifoliate and above, R2 = 0.96), shoot (unifoliate and above, R2 = 0.82) and roots (R2 = 0.89). Furthermore, apical shoot RFW efficiently correlated with varying levels of C. ilicicola resistance in two test sets containing 37 soybean cultivars and three wild soybean accessions, exhibiting a significant correlation with visual severity (R2 = 0.72 and 0.79, p < 0.01). Taken together, our results suggest that RFW can serve as an index of soybean RCR severity, providing a simple, rapid, consistent, and cost-effective method for evaluating C. ilicicola resistance in soybeans.

13.
Front Cell Dev Biol ; 9: 777215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805180

RESUMO

The dysregulation of iron homeostasis has been explored in malignancies. However, studies focusing on the association between the serum iron level and prognosis of patients with early-stage triple-negative breast cancer (TNBC) are scarce. Accordingly, in current study, 272 patients with early-stage TNBC treated at Sun Yat-sen University Cancer Center (SYSUCC) between September 2005 and October 2016 were included as a training cohort, another 86 patients from a previous randomized trial, SYSUCC-001, were analyzed as a validation cohort (SYSUCC-001 cohort). We retrospectively collected their clinicopathological data and tested the serum iron level using blood samples at the diagnosis. In the training cohort, patients were divided into low-iron and high-iron groups according to the serum iron level cut-off of 17.84 µmol/L determined by maximally selected rank statistics. After a median follow-up of 87.10 months, patients with a low iron had a significantly longer median disease-free survival (DFS) of 89.13 [interquartile range (IQR): 66.88-117.38] months and median overall survival (OS) of 92.85 (IQR: 68.83-117.38) months than those in the high-iron group (median DFS: 75.25, IQR: 39.76-105.70 months, P = 0.015; median OS: 77.17, IQR: 59.38-110.28 months, P = 0.015). Univariate and multivariate Cox analysis demonstrated the serum iron level to be an independent predictor for DFS and OS. Then, a prognostic nomogram incorporating the serum iron level, T stage and N stage was developed for individualized prognosis predictions. It had good discriminative ability with a C-index of DFS (0.729; 95% CI 0.666-0.792) and OS (0.739; 95% CI 0.666-0.812), respectively. Furtherly, we validated the predictive model in the SYSUCC-001 cohort, which also showed excellent predictive performance with a C-index of DFS (0.735; 95% CI 0.614-0.855) and OS (0.722; 95% CI 0.577-0.867), respectively. All these suggested that the serum iron level might be a potential prognostic biomarker for patients with early-stage TNBC, the predictive model based on it might be served as a practical tool for individualized survival predictions.

14.
Open Med (Wars) ; 16(1): 1653-1667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34761116

RESUMO

The aim of this study was to clarify the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in proliferation, migration, and invasion of malignant pleural mesothelioma (MPM) cells. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of MALAT1 in MPM cell lines. The effects of MALAT1 and miR-141-3p on the proliferation, migration, and invasion of MPM cells were studied through a series of in vitro cellular experiments. The flow cytometry was utilized to detect the cell apoptosis. The dual-luciferase reporter assay was employed to explore the binding relationship among MALAT1, miR-141-3p, and YES-associated protein 1 (YAP1). MALAT1 was overexpressed in MPM cell lines, while its knockdown significantly inhibited the cell proliferation, migration, and invasion, and increased the number of MPM cells in the G0/G1 phase. In addition, MALAT1 could directly bind to miR-141-3p and inhibit its expression. YAP1 has been identified as a downstream target of miR-141-3p, and its expression level was inhibited by miR-141-3p. MALAT1 can be used as a competitive endogenous RNA (ceRNA) to regulate the YAP1-Hippo signaling pathway through miR-141-3p, promote the proliferation, migration, and invasion of MPM cells, and provide a new target for the therapy of MPM.

15.
J Mater Chem A Mater ; 9(36): 20653-20663, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34671478

RESUMO

The (opto)electronic properties of Ta3N5 photoelectrodes are often dominated by defects, such as oxygen impurities, nitrogen vacancies, and low-valent Ta cations, impeding fundamental studies of its electronic structure, chemical stability, and photocarrier transport. Here, we explore the role of ammonia annealing following direct reactive magnetron sputtering of tantalum nitride thin films, achieving near-ideal stoichiometry, with significantly reduced native defect and oxygen impurity concentrations. By analyzing structural, optical, and photoelectrochemical properties as a function of ammonia annealing temperature, we provide new insights into the basic semiconductor properties of Ta3N5, as well as the role of defects on its optoelectronic characteristics. Both the crystallinity and material quality improve up to 940 °C, due to elimination of oxygen impurities. Even higher annealing temperatures cause material decomposition and introduce additional disorder within the Ta3N5 lattice, leading to reduced photoelectrochemical performance. Overall, the high material quality enables us to unambiguously identify the nature of the Ta3N5 bandgap as indirect, thereby resolving a long-standing controversy regarding the most fundamental characteristic of this material as a semiconductor. The compact morphology, low defect content, and high optoelectronic quality of these films provide a basis for further optimization of photoanodes and may open up further application opportunities beyond photoelectrochemical energy conversion.

16.
Langmuir ; 37(44): 12952-12960, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34714096

RESUMO

Bulk nanobubbles (BNBs) have attracted substantial interest from academia and industry owing to their peculiar properties and extensive potential applications. However, a scalable engineering method needs to be developed. Herein, we developed a nanobubble generator based on venturi-type recirculating hydrodynamic cavitation. The existence of nanobubbles produced by our generator was confirmed using physicochemical test methods, including the Tyndall effect, multiple freeze-thaw degassing experiments, and trace metal analysis. Subsequently, the effects of different operating parameters (circulation time and operating pressure) on bulk nanobubble production and properties, as well as their stability, were investigated. The results suggest that the characteristics of BNBs varied with the circulation time (5-20 min) and operating pressure (2-5 bar). However, all the particle size distribution of BNBs had a bimodal distribution with a mean diameter of 180-210 nm for the different circulation time and operating pressures. For example, by increasing the circulation time from 5 to 20 min, the peak value of size distribution decreased from 333/122 nm to 218/52 nm, and the average sample scattering signal count rate (Avg. Count Rate) increased from 133 to 303 Kcps. The evaluation of the stability of the BNBs formed for the circulation time of 15 min and the operating pressure of 3 bar showed that they could continue existence and stability in the suspension for 72 h. The study results might provide a valuable method for further investigation of industrial applications of venturi-type nanobubble generators.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34506873

RESUMO

PURPOSE: An unmet clinical need in non-small cell lung cancer (NSCLC) management is the accurate prediction of radiation response in patients receiving radical radiation therapy. We explored the intrinsic radiosensitivity of NSCLC from the proteomic profiles of NSCLC cell lines and paraffin-embedded human samples. METHODS AND MATERIALS: To uncover radiosensitivity-specific proteomic and signaling pathways, we performed quantitative proteomics by data-independent acquisition mass spectrometry assay on 29 human NSCLC cell lines and 13 paraffin-embedded human NSCLC samples. We validated closely interacting radioresistant proteins by western blotting, immunofluorescence, real-time quantitative polymerase chain reaction in NSCLC cell lines, and immunohistochemistry in paraffin-embedded human samples. We validated the functions of 3 key hub proteins by lentivirus transfection, clonogenic survival assay, and flow cytometry. RESULTS: The proteomic profiling of NSCLC showed that the intrinsic radiosensitivity of NSCLC is mainly modulated by signaling pathways of proteoglycans in cancer, focal adhesion, and regulation of the actin cytoskeleton. We identified 71 differentially expressed proteins and validated 8 closely interacting proteins as radioresistant proteins of NSCLC. Moreover, we also validated the functionality of integrin-linked protein kinase, p21-activated kinase 1, and Ras GTPase-activating-like protein IQGAP1 in the radiation response of NSCLC cell lines. Finally, with the NSCLC radiosensitivity-specific proteins, we delineated the atlas network of NSCLC radiosensitivity-related signaling pathways. CONCLUSIONS: Radiosensitivity-specific proteins could guide individualized radiation therapy in clinical practice by predicting the radiation response of patients with NSCLC. Moreover, the NSCLC radiosensitivity-related signaling pathway atlas could guide further exploration of the underlying mechanism.

18.
J Cardiol ; 78(6): 586-597, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34489160

RESUMO

BACKGROUND: Coronary artery disease (CAD) is a common heart disease with high incidence and mortality. Myocardial ischemia is the main type of CAD, which negatively affects health worldwide. The aim of the present study was to investigate the function and mechanism of myocardial infarction-associated transcript (MIAT) in myocardial ischemia. METHODS: Human cardiomyocytes (HCM) were treated with oxygen-glucose deprivation (OGD) to set the in vitro model and mouse myocardial ischemia/reperfusion (I/R) was set for in vivo model. Cell viability and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and immunofluorescence analysis. Inflammatory cytokines levels were detected by enzyme-linked immunosorbent assay. Gene and protein expressions were identified by quantitative real time-polymerase chain reaction or Western blotting. The interaction of MIAT, miR-181a-5p, and janus kinase 2 (JAK2) was identified by dual-luciferase report assay. Mouse heart tissues histopathological condition were observed by hematoxylin and eosin assays. RESULTS: Expression of MIAT and JAK2 were increased in OGD-treated HCM and mice of I/R model group, and miR-181a-5p was decreased. MIAT silencing could reverse the OGD treatment induced cell proliferation inhibition, cleaved caspase-3 and Bcl2-associated X (Bax) levels increased, while those of B-cell lymphoma-2 (Bcl-2) and mitochondria's cyt-C decreased. Besides, MIAT knockdown attenuated the OGD-induced increase of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 levels. Moreover, MIAT targeted miR-181a-5p to enhance the expression of JAK2 and signal Transducer and Activator of Transcription 3 (STAT3), and miR-181a-5p overexpression promoted proliferation, whereas it inhibited apoptosis in OGD-induced cardiomyocytes. Furthermore, the regulatory effects of MIAT knockdown in cell proliferation, apoptosis, and inflammatory injury was reversed by inhibition of miR-181a-5p or overexpression of JAK2 in OGD-treated HCM. Knockdown of MIAT reduced myocardial injury caused by I/R treatment in vivo. CONCLUSION: MIAT knockdown inhibited apoptosis and inflammation by regulating JAK2/STAT3 signaling pathway via targeting miR-181a-5p in myocardial ischemia model. MIAT can be a possible therapeutic target for controlling the progression of myocardial ischemia.

19.
Low Urin Tract Symptoms ; 13(4): 481-489, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34240558

RESUMO

OBJECTIVES: We aimed to determine the prevalence of urinary incontinence (UI) during the peri- and postpartum period in women from Nanjing, China, and estimate its risk factors. METHODS: From January to December 2018, a total of 6500 postpartum women were enrolled and asked to complete the questionnaires. Of these, 6370 (98%) women returned the questionnaires with valid responses. Additional data were collected, including age, height, weight, gestation time and parity, and neonatal weight. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was used. Surface electromyography (sEMG) and a biofeedback training system were used as a testing platform, and PESEMG values were obtained. RESULTS: The prevalence of UI during pregnancy and at 6 weeks postpartum in women was 29.76% and 12.50%, respectively. The prevalence of stress UI (SUI), urge UI (UUI), mixed UI (MUI), and other types of UI that developed during pregnancy was 25.48%, 1.66%, 1.65%, and 0.97%, respectively. The prevalence of SUI, UUI, MUI, and other types of UI at 6 weeks postpartum was 8.49%, 2.07%, 1.16%, and 0.77%, respectively. Multivariate analysis showed that advanced age, greater postpartum body mass index (BMI), macrosomia, multiparity, and vaginal delivery were risk factors of postpartum UI. Women with mild degree of UI in pregnancy, those who had undergone cesarean section, and those without UI before pregnancy were relieved from UI at 6 weeks postpartum. CONCLUSIONS: The rate of UI in peri- and postpartum women from Nanjing is consistent across China. The most common type of UI was SUI, with many risk factors affecting its occurrence. Advanced age, greater postpartum BMI, multiparity, macrosomia, and vaginal delivery might be the main risk factors of UI in postpartum women.


Assuntos
Incontinência Urinária por Estresse , Incontinência Urinária , Cesárea , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Período Pós-Parto , Gravidez , Prevalência , Fatores de Risco , Inquéritos e Questionários , Incontinência Urinária/epidemiologia , Incontinência Urinária por Estresse/epidemiologia , Incontinência Urinária de Urgência/epidemiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-34306154

RESUMO

Objective: The purpose of our research is to systematically explore the multiple mechanisms of Hemerocallis fulva Flowers (HF) on depressive disorder (DD). Methods: The components of HF were searched from the literature. The targets of components were obtained from PharmMapper. After that, Cytoscape software was used to build a component-target network. The targets of DD were collected from DisGeNET, PharmGKB, TTD, and OMIM. Protein-protein interactions (PPIs) among the DD targets were executed to screen the key targets. Afterward, the GO and KEGG pathway enrichment analysis were performed by the KOBAS database. A compound-target-KEGG pathway network was built to analyze the key compounds and targets. Finally, the potential active substances and targets were validated by molecular docking. Results: A total of 55 active compounds in HF, 646 compound-related targets, and 527 DD-related targets were identified from public databases. After treated with PPI, 219 key targets of DD were acquired. The gene enrichment analysis suggested that HF probably benefits DD patients by modulating pathways related to the nervous system, endocrine system, amino acid metabolism, and signal transduction. The network analysis showed the critical components and targets of HF on DD. Results of molecular docking increased the reliability of this study. Conclusions: It predicted and verified the pharmacological and molecular mechanism of HF against DD from a holistic perspective, which will also lay a foundation for further experimental research and rational clinical application of DD.

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