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1.
Analyst ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35551289

RESUMO

Cellular imaging using carbon dots is an important research method in several fields. Herein, green-emissive carbon quantum dots (G-CDs) with a pretty high absolute quantum yield (QY) were fabricated via a one-step solvothermal method by using m-phenylenediamine and concentrated hydrochloric acid. G-CDs displayed strong green fluorescence with excitation/emission peaks at 460/500 nm, and their absolute quantum yield was as high as 58.65%. Further experiments suggested that the G-CDs we prepared have good solubility, excellent biocompatibility, and the capacity of rapidly imaging HeLa and 4T1 cells. Over expectations, the G-CDs could penetrate cells in only 10 s and the confocal images showed that the G-CDs could target the nucleus of cells. Moreover, by using 920 nm as the excitation wavelength, two-photon imaging has been successfully applied to 4T1 cells, overcoming the inherent limitations of single-photon imaging. The extremely high absolute quantum efficiency, ultra-fast imaging speed, and two-photon imaging capability make the G-CDs have good application potential in biomedical analysis and the clinical diagnostic field.

2.
J Exp Bot ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35552690

RESUMO

In plants, xylem vessel length is important for long-distance water transport; however, the currently used methods for vessel length measurement are inconvenient and time-consuming. The semi-automated Pneumatron device is based on the pneumatic theory, is similar to the air injection method, and can rapidly estimate vessel length. Mean vessel length was compared between the newly-developed Pneumatron device and air injection method in seven species with different vessel lengths (2.3 to 78.7 cm). The results were consistent between two methods, regardless of whether the same or different samples were used. The theory underlying the gas flow in vessels was improved and expanded, and compared to that underlying the water flow to better understand the pneumatic processes within a stem sample. Moreover, a new and simple equation for gas flow in vessels was derived based on the molar gas flow (mol·s -1) rather than volume flow, because the former remains constant with distance throughout the stem axis. We strongly recommend using the Pneumatron device in future studies owing to its low cost, convenience, rapidity, and simple operation. Nonetheless, several cautions are warranted to avoid artifacts during measurements.

4.
World J Surg Oncol ; 20(1): 162, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35598017

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) causes numerous deaths worldwide. however, biomarkers for NSCLC prognosis are scarce for its heterogeneity. Proteins containing the RING finger domain RING finger protein 180 (RNF180) is a key mediator for ubiquitination, which controls cell cycle and regulates progression in certain human tumors. However, the detailed function of RNF180 in NSCLC remains unclear. In the present study, we aimed to investigate the role of RNF180 and its molecule network in NSCLC. METHODS: Quantitative real-time polymerase chain reaction and immunohistochemical staining were used to analyze RNF180 levels. RNA interference and lentiviral-mediated vector transfections were performed to silence and overexpress RNF180 in NSCLC cells. Furthermore, Cell Counting Kit-8 was used for assessing biological function of RNF180 in cell proliferation and a xenograft model for examining its function in vivo. The activity of glycolysis was determined by examining the level of the extracellular acidification rate (ECAR). RESULTS: RNF180 expression decreased in NSCLC tissues, and its expression was positively correlated with the survival rate of patients with NSCLC. Moreover, RNF180 overexpression suppressed the proliferation and glycolytic activities in NSCLC cells and restricted its tumorigenicity in vivo. Furthermore, RNF180 silencing promoted the proliferation and glycolysis metabolism of NSCLC cells, whereas C-myc inhibitor disrupted these effects. The underlying anti-oncogene of RNF180 involved in C-myc downregulation via ubiquitin-dependent degradation. CONCLUSIONS: Together, these results firstly indicated the anti-tumor properties of RNF180 and its correlation with NSCLC progression, thereby endorsing the potential role of RNF180 as an efficient prognostic biomarker for tumor recurrence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/genética
5.
J Mass Spectrom ; 57(6): e4831, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35562642

RESUMO

Frozen section examination could provide pathological diagnosis for surgery of thyroid nodules, which is time-consuming, skill- and experience-dependent. This study developed a rapid classification method for thyroid nodules and machine learning. Total 69 tissues were collected including 43 nodules and 26 nodule-adjacent tissues. Intraoperative frozen section was first performed to give accurate diagnosis, and the rest frozen specimen were pretreated for probe electrospray ionization mass measurement. By multivariate analysis of mass scan data, a series compounds were found downregulated in the extraction solution of papillary thyroid carcinoma (PTC), but some were found upregulated by mass spectrometry imaging. m/z 758.5713 ([PC[34:2] + H]+ ), m/z 772.5845 ([PC[32:0] + K]+ ), and m/z 786.6037 ([PC[36:2] + H]+ ) were firstly identified as potential biomarkers for nodular goiter (NG). Machine learning was employed by means of support vector machine (SVM) and random forest (RF) algorithms. For classification of PTC from NG, SVM and RF algorithms exhibited the same performance and the concordance was 94.2% and 94.4% between prediction and pathological diagnosis with positive and negative mass dataset, respectively. For the classification of PTC from PTC adjacent tissues, SVM was better than RF and the concordance was 93.8% and 83.3% with positive and negative mass dataset, respectively. With the identified compounds as training features, the sensitivity and specificity are 87.5% and 88.9% for the test set. The developed method could also correctly predict the malignancy of one medullary thyroid carcinoma and one adenomatous goiter (benign). The diagnosis time is about 10 min for one specimen, and it is very promising for the intraoperative diagnosis of papillary thyroid carcinoma.

6.
BMC Surg ; 22(1): 183, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568851

RESUMO

BACKGROUND: Previous studies reported that transnasal ileus tube was a new and useful method for rapid relief of small intestinal obstruction. However, no study reported the impacts of the transnasal ileus tube for Crohn's disease combined with intestinal obstruction. We aimed to describe the strategy to the small intestine obstruction caused by Crohn's disease on the basis of transnasal ileus tube insertion. METHODS: From November 2019 to November 2021, the data of 6 hospitalized patients with CD, diagnosed and conservatively treated in The Second Hospital of Nanjing, were not relived and retrospectively collected. After the insertion of transnasal ileus tube, demographic information, clinical features and treatment data were extracted from medical records. RESULTS: Six Crohn's disease patients with intestinal obstruction were included. Half of them were male. The patients aged from 29 to 70 years. Five patients had chronic intestinal obstruction more than one year. Three patients had intestinal surgery history. One patient had colonic abdominal fistula and anastomotic fistula, when she took intermittent usage of sulfsalazine and steroid. On admission, all the patients had abdominal pain, distention and mass. Five patients had anemia, low albumin and cholinesterase. All CDAI scores were more than 400. Compared to 19 patients with incomplete intestinal obstruction improved by nasogastric decompression tube, 6 patients with intestinal obstruction catheter had significant difference in time for relieving abdominal pain and distension (p = 0.003), time for alleviating abnormal mass (p ≤ 0.01), drainage volume (p = 0.004), and preoperative CDAI score (p = 0.001). Compared with X-ray image before insertion, complete remission of obstruction of 5 patients were observed in intestinal cavity after insertion. After 1-2 months nutrition, all the patients had small intestine resection and ileostomy, half of them underwent colectomy and fistula repair, and 4 patients were performed enterolysis at the same time, the residual small intestine length ranging from 250 to 400 cm. 1 patient had permanent ileostomy;1 patient had abdominal infection after operation. The typical manifestations of acute and chronic inflammation, transmural inflammation, pseudopolyps and serous fiber hyperplasia could be seen in pathological findings of patients 1 to 5. All the patients continued enteral nutrition after surgery. Four patients were treated with infliximab or vedolizumab. CONCLUSION: The current intestinal obstruction catheter which is used to treat patients with Crohn's combined obstruction can afford quick clinical remission, longer nutrition time, and suitable preoperative CDAI score for operation, which is worthy of wildly being used.

7.
Mol Biotechnol ; 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35435590

RESUMO

The MADS-box gene family has multiple molecular and biological functions in plants. Here, the LiSEP3 gene of the MADS-box gene family of' 'Sorbonne' was obtained by homologous cloning using the petals of the flowering stage of Lilium Oriental Hybrid 'Sorbonne.' The ORF full-length sequence is 729 bp, encoding 242 amino acids. Bioinformatics analysis showed that the relative molecular weight of the LiSEP3 protein is 27.67 kD and the isoelectric point (pI) is 9.16. The prediction result of the gene positioning is transcription in its nucleus. Homologous alignment of amino acid sequences showed that the protein not only had typical MADS-box and K-box domains, but also contained two short and relatively conservative SEP motifs. The phylogenetic tree showed that the amino acid sequence encoded by the LiSEP3 gene had the closest relationship with SEP3 in monocotyledon plants such as Apostasia odorata. The results of real-time PCR showed that LiSEP3 gene was mainly expressed in petal. During flower development, the expression level of the LiSEP3 gene showed an overall trend of initially increasing and then decreasing. The flowering time of LiSEP3 transgenic Arabidopsis thaliana L. plants was earlier than that of wild-type Arabidopsis thaliana L. plants, compared with wild type, the number of rosette leaves is less. In the transgenic plants, the expression of flowering-associated AtSPL5 and AtGI genes was up-regulated, while the expression of AtSVP and AtFRI genes that inhibit flowering was down-regulated, which was consistent with the statistical results of the flowering time of LiSEP3 transgenic plants. Our results illustrate that the heterologous expression of SEP3 functional genes in the MADS-box family promoted the flowering period of transgenic plants of this hybrid. This research provides a theoretical basis for improving the flowering period of ornamental plants through plant genetic engineering technology and enhancing their economic and social values.

8.
ACS Appl Mater Interfaces ; 14(15): 17249-17258, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35403425

RESUMO

Developing high-performance non-noble metal bifunctional oxygen reduction and evolution reaction electrocatalysts is a critical factor for the commercialization of rechargeable Zn-air batteries. Herein, Co/Co-N/Co-O rooted on reduced graphene oxide (rGO) hybrid boron and nitrogen codoped carbon (BCN) nanotube arrays (BCN/rGO-Co) is prepared by facile low-temperature precross-linking and high-temperature pyrolysis treatment. Benefit from the synergistic effect of its B/N codoping, Co/Co-N/Co-O bifunctional active sites, 3D hybrid porous structure of BCN nanotubes, and highly conductive rGO sheets. The obtained BCN/rGO-Co exhibits superior bifunctional oxygen catalytic activity with a positive ORR half-wave potential (0.85 V) and a low OER potential (1.61 V) at 10 mA cm-2. Additionally, the BCN/rGO-Co-based liquid Zn-air batteries displays a large peak power density of 157 mW cm-2, and a long charge/discharge cycle stability of 200 h, outdoing the commercial Pt/C+Ru/C catalyst.

9.
J Immunol ; 208(9): 2109-2121, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35418470

RESUMO

CD1d, a lipid Ag-presenting molecule for invariant NKT (iNKT) cells, is abundantly expressed on adipocytes and regulates adipose homeostasis through iNKT cells. CD1d gene expression was restored in visceral adipose tissue adipocytes of CD1d knockout (KO) mice to investigate the interactions between adipocytes and immune cells within adipose tissue. We developed an adipocyte-specific targeting recombinant adeno-associated viral vector, with minimal off-target transgene expression in the liver, to rescue CD1d gene expression in visceral adipose tissue adipocytes of CD1d KO mice, followed by assessment of immune cell alternations in adipose tissue and elucidation of the underlying mechanisms of alteration. We report that adeno-associated virus-mediated gene transfer of CD1d to adipocytes in CD1d KO mice fails to rescue iNKT cells but leads to massive and selective expansion of T cells within adipose tissue, particularly CD8+ T effector cells, that is associated with adipocyte NLRP3 inflammasome activation, dysregulation of adipocyte functional genes, and upregulation of apoptotic pathway proteins. An NLRP3 inhibitor has no effect on T cell phenotypes whereas depletion of CD8+ T cells significantly attenuates inflammasome activation and abolishes the dysregulation of adipocyte functional genes induced by adipocyte CD1d. In contrast, adipocyte overexpression of CD1d fails to induce T cell activation in wild-type mice or in invariant TCR α-chain Jα18 KO mice that have a normal lymphocyte repertoire except for iNKT cells. Our studies uncover an adipocyte CD1d → CD8+ T cell → adipocyte inflammasome cascade, in which CD8+ T cells function as a key mediator of adipocyte inflammation likely induced by an allogeneic response against the CD1d molecule.


Assuntos
Linfócitos T CD8-Positivos , Inflamassomos , Adipócitos , Animais , Antígenos CD1d , Linfócitos T CD8-Positivos/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
10.
Front Neurol ; 13: 847418, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35481274

RESUMO

Object: Although revision surgery for recurrent craniopharyngiomas is more challenging than primary surgery and often accompanies a higher risk of death and complications, endoscopic endonasal transsphenoidal surgery (EETS) is sometimes still an effective and reliable treatment option. In this study, we introduced the surgical outcomes of EETS for recurrent craniopharyngiomas and summarized the surgical experiences. Methods: Between 2014 and 2018, 28 patients with recurrent craniopharyngiomas underwent 29 EETS in our department. We regarded the patient undergoing two EETS as two independent patients in statistical analysis. Of the 29 patients, 16 had undergone 1 previous surgery, 10 had undergone 2 previous surgeries, and the remaining 3 patients had undergone 3 surgeries. The extent of resection, visual and endocrine outcomes, and complications of all the patients were collected and analyzed. Results: Gross total resection was accomplished in 16 patients (55.17%), subtotal resection in 11 patients (37.93%), and partial resection in 2 patients (6.9%). Among the 22 patients with preoperative visual acuity and visual field impairment, some degree of vision improvement was observed in 18 patients, 3 patients were without visual change, and perpetual deterioration of vision occurred in one patient. The remaining six patients had normal vision before and after surgery. Postoperative endocrine tests showed that, among five patients with normal preoperative pituitary hormone function, only one patient still had normal pituitary hormone function and the other four patients had one or more hypothalamic-pituitary axes involved. None of the patients with preoperative endocrine dysfunction had endocrine function improved. Diabetes insipidus was observed in six new cases postoperatively. Cerebrospinal fluid (CSF) leakage occurred in 1 patient. One patient had bacterial meningitis, which was cured with antibiotics and a lumbar drain. No serious morbidity and mortality occurred in all patients. Conclusions: For recurrent craniopharyngiomas, a personalized treatment plan should be developed according to the tumor characteristics and the patient's situation. There is no omnipotent method to be used for all patients. The EETS still is a safe and effective way to treat recurrent craniopharyngiomas in appropriate patients.

12.
Ther Adv Chronic Dis ; 13: 20406223221076894, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465053

RESUMO

Background: To assess the effectiveness of metformin treatment on long-term outcomes in first-ever stroke patients with type 2 diabetes mellitus (T2DM) in China. Methods: From August to September 2019, all patients with first-ever stroke and T2DM from 232 hospitals in China Mainland were included. The enrolled patients were divided into two groups: the metformin treatment (MT) and the no-metformin treatment (No-MT) groups. All discharged patients would receive a telephone follow-up at 12-month after admission. Results: In total, 7587 first-ever stroke patients with T2DM [age: median (IQR) = 66 (57-73) years; 57.35% male] were recruited. Out of those 7587 included patients, 3593 (47.36%) received MT. The in-hospital case fatality rate was lower in the MT group than the No-MT group [MT group versus No-MT group: 1.09% versus 2.30%; absolute difference = -1.75% (95% CI = -2.15 to -1.17%); OR = 0.63 (95% CI = 0.47 to 0.84)]. The 12-month case fatality rate was lower in the MT group than the No-MT group [4.72% versus 8.05%; absolute difference = -4.05% (95% CI = -5.58 to -2.41); OR = 0.69 (95% CI = 0.50 to 0.88)]. The 12-month disability rate was also lower in the MT group than the No-MT group [14.74% versus 19.41%; absolute difference = -5.70% (95% CI = -7.25 to -3.22); OR = 0.83 (95% CI = 0.70 to 0.95)]. Furthermore, the recurrence rate did not differ significantly between the MT and No-MT groups (p = 0.29). Conclusion: The study reveals that metformin use in stroke patients with T2DM results in a less severe stroke and lower fatality and disability rates.

14.
Nanomaterials (Basel) ; 12(7)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35407340

RESUMO

In this work, low-temperature Schottky source/drain (S/D) MOSFETs are investigated as the top-tier devices for 3D sequential integration. Complementary Schottky S/D FinFETs are successfully fabricated with a maximum processing temperature of 500 °C. Through source/drain extension (SDE) engineering, competitive driving capability and switching properties are achieved in comparison to the conventional devices fabricated with a standard high-temperature (≥1000 °C) process flow. Schottky S/D PMOS exhibits an ON-state current (ION) of 76.07 µA/µm and ON-state to OFF-state current ratio (ION/IOFF) of 7 × 105, and those for NMOS are 48.57 µA/µm and 1 × 106. The CMOS inverter shows a voltage gain of 18V/V, a noise margin for high (NMH) of 0.17 V and for low (NML) of 0.43 V, with power consumption less than 0.9 µW at VDD of 0.8 V. Full functionality of CMOS ring oscillators (RO) are further demonstrated.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35389034

RESUMO

BACKGROUND: Androgenetic alopecia is considered to be an independent predictor of mortality from diabetes mellitus and heart disease. However, whether androgenetic alopecia causes changes in microcirculation is unknown. OBJECTIVE: The objective of the study was to investigate whether alterations in nailfold capillaries occur in androgenetic alopecia patients. METHODS: The nailfold capillaroscopy images of androgenetic alopecia patients and matched controls were collected and analyzed. RESULTS: The frequencies of avascular areas, dilated, bushy and bizarre capillaries and capillary disorganization, nailfold capillaroscopy scores of 2 or scores both 2 and 3 were significantly higher in the androgenetic alopecia group than in the healthy controls (9.0% vs. 0%, 57.7% vs. 19.2%, 3.8% vs. 0%, 2.8% vs. 1.3%, 3.8% vs. 0%, 38.5% vs. 12.8% and 39.7% vs. 12.8%, respectively). LIMITATIONS: The results of this study may be biased on account of the limited sample size or the presence of an undiagnosed disease in participants which could alter the nailfold capillaries. CONCLUSION: Bushy, bizarre and dilated capillaries, capillary disorganization, avascular areas and nailfold capillaroscopy scores of 2 or 2 and 3 were more common in androgenetic alopecia patients than in healthy controls. These findings indicate that abnormalities in microcirculation may be involved in androgenetic alopecia.

16.
Curr Med Imaging ; 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410618

RESUMO

OBJECTIVE: To analyze the clinical and imaging features of desmoplastic fibroma of bone (DFB) for correct diagnosis. MATERIALS AND METHODS: Twenty patients with DFB confirmed by pathology were enrolled, and the imaging presentations were analyzed. Among 20 patients, plain X-ray was performed in all patients, computed tomography (CT) was performed in 12, and magnetic resonance imaging (MRI) was conducted in eight. The clinical and imaging presentations were analyzed and classified to assist correct diagnosis. RESULTS: Twenty patients with DFB were retrieved including eleven males and nine females with an age range of 2-52 years (median 27). The DFB involved the femur in six patients, ilium in five, tibia in four, humerus in two, lumbar vertebra in one, radius in one, and calcaneus in the remaining one. DFB was common in the metaphysis of long bones could involve the diaphysis and epiphysis. The imaging presentations were divided into four types: the cystic expansile destruction in ten patients, osteolytic destruction in five, mixed destruction in four, and paraosseous destruction in one. CT value was 30 -60 Hu in the lesion area (6 cases CT value>45Hu). In eight patients with MRI scanning, the lesion in five patients presented with unevenly equal or low signal on T1WI and unevenly equal or high signal on T2WI, with irregular stripes or patches of low signal on both T1WI and T2WI. In the rest three patients, the lesion was evenly equal or low signal on T1WI and evenly high signal on T2WI. MRI more clearly showed a mass in the adjacent soft tissue and the range of edema in the DFB lesion. Conclusion DFB is a rare tumor with strong local aggressiveness, cystic bone destruction, formation of tumor bone trabeculae, soft tissue masses on imaging presentations, low signals on T1WI and T2WI in the lesion, but no periosteal reaction or calcification, which are helpful for diagnosis of the disease and differentiation from other ones.

17.
Gastroenterol Res Pract ; 2022: 1498293, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35419052

RESUMO

Background: Bone loss is common in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of metabolic bone disease in patients newly diagnosed with IBD and to identify the risk factors for bone loss over time. Methods: We performed a retrospective, both cross-sectional and longitudinal, study to extract the risk factors of bone loss (including osteopenia and osteoporosis) in patients newly diagnosed with IBD, using dual-energy X-ray absorptiometry (DXA). Results: A total of 639 patients newly diagnosed with IBD that had at least one DXA were included in the cross-sectional study. Osteopenia and osteoporosis were diagnosed in 24.6% and 5.4% of patients, respectively. Age at diagnosis, body mass index, and serum phosphorus were identified as independent factors associated with bone loss at baseline. A total of 380 of the 639 IBD patients (including 212 CD patients and 168 UC patients) with at least a second DXA scan were included in the longitudinal study. 42.6% of the patients presented a worsening of bone loss in the follow-up study. Menopause, albumin, and use of corticosteroids were identified as independent factors associated with worsening of bone loss. Conclusions: Metabolic bone disease is common in IBD patients, and there is a significant increase in prevalence of bone loss over time. Postmenopausal female, malnourished patients, and those requiring corticosteroid treatment are at risk for persistent bone loss. Therefore, BMD measurements and early intervention with supplementation of calcium and vitamin D are recommended in IBD patients with high-risk factors.

18.
J Mater Chem B ; 10(18): 3550-3559, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35420087

RESUMO

Herein, five aggregation-induced emission (AIE) photosensitizers (PSs) with D-π-A structures are smoothly designed and synthesized through donor and acceptor engineering. The photophysical properties and theoretical calculation results show that the synergistic effect of methoxy substituted tetraphenylethene (MTPE), 3,4-ethylenedioxythiophene can enhance the intramolecular charge transfer effect (ICT), and promote the intersystem crossing (ISC) process of the whole molecule. In these AIE-PSs, the best-performing AIE-PS (MTPE-DT-Py) has bright NIR (740 nm) emission, the highest 1O2 generation efficiency (5.9-fold that of Rose Bengal) and efficient mitochondrial targeting ability. Subsequently, PDT anti-cancer and anti-bacterial experiments indicate that MTPE-DT-Py could obviously target mitochondria and kill breast cancer cells (MCF-7), and selectively inactivate S. aureus (G(+)) under white light irradiation. This work mainly proposes a practical design strategy for high effect AIE-PSs and provides more excellent candidates for fluorescence imaging-guided photodynamic therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Luz , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Staphylococcus aureus
19.
Aging (Albany NY) ; 14(8): 3464-3483, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439731

RESUMO

BACKGROUND: As a major component of the tumor tissue, the tumor microenvironment (TME) has been proven to associate with tumor progression and immunotherapy. Ovarian cancer accounts for the highest mortality rate among gynecologic malignancies. Its clinical treatment decision is highly correlated with the prognosis, underscoring the need to evaluate the prognosis and choose the proper clinical treatment through TME information. METHOD: This study constructs a score with TME information obtained by the CIBERSORT algorithm, which classifies the patients into high and low TMEscore groups with quantified TME infiltration patterns through the PCA algorithm. TMEscore was constructed by TCGA cohort and validated in GEO cohort. Univariate and multivariate Cox proportional hazards model analyses were used to demonstrate prognostic value of TMEscore in overall and stratified analysis. RESULT: TMEscore is highly correlated with survival and high TMEscore group has a better prognosis. In order to improve treatment decision, the expression of immune checkpoints, immunophenoscore (IPS) and ESTIMATE score showed a high TMEscore have a better immune microenvironment and respond better to immune checkpoint inhibitors (ICIs). Meanwhile, the mutation landscape between TMEscore groups was profiled, and 13 genes were found mutated differently between the two groups. Among them, BRCA1 has more mutations in the high TMEscore group and speculated that high TMEscore patients might be a beneficiary population of PARP inhibitors combined with immunotherapy. CONCLUSION: TMEscore based on TME with prognostic value and clinical value is proposed for the identification of targets treatment and immunotherapy strategies for ovarian cancer.


Assuntos
Neoplasias Ovarianas , Microambiente Tumoral , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/terapia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Prognóstico , Microambiente Tumoral/genética
20.
Front Immunol ; 13: 854785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392086

RESUMO

Increasing evidence has demonstrated that pyroptosis, a type of inflammatory programmed cell death, plays an important role in the pathogenesis and progression of gastric cancer. However, it remains unclear whether pyroptosis-related long non-coding RNAs (lncRNAs) can be used to predict the diagnosis and prognosis of gastric adenocarcinoma. This study aimed to evaluate and test the role of the lncRNA signature associated with pyroptosis as a prognostic tool for stomach adenocarcinoma (STAD) and to ascertain their immune value. Relative RNA-sequencing data were extracted from The Cancer Genome Atlas database (TCGA), and data preprocessing was performed for STAD. Pearson correlation analysis was used to determine whether lncRNAs were significantly correlated with pyroptosis based on 23 genes related to pyroptosis. Univariate Cox regression and least absolute shrinkage and selection operator(LASSO) analyses were both adopted to select features and establish the pyroptosis-related lncRNA (PRL) prognostic signature. Kaplan-Meier(KM) survival analysis of the different risk groups was conducted according to the risk scores. We further examined the functional enrichment, tumor microenvironment, and landscape of mutation status among the different risk groups, and these analyses further explained the reasons for the differences in the prediction as well as survival value of the different risk groups. Four lncRNAs, including HAND2-AS1, LINC01354, RP11-276H19.1, and PGM5-AS1, were involved in the PRL signature and used to split STAD patients into two risk groups. Overall survival time(OS) was significantly higher in the low-risk group than in the high-risk group in both the training and validation groups. Functional enrichment analysis was further employed to analyze differentially expressed genes in high- and low-risk groups to identify potential molecular functions and pathways associated with pyroptosis in the gastric cancer microenvironment. Protein-protein interaction (PPI) and Friends analysis identified hub genes that may play a key role in differentially expressed genes in high- and low-risk groups. In addition, there were remarkable discrepancies between the different risk groups in the tumor stage (P < 0.01) and histologic grade (P < 0.05). Furthermore, drug-susceptibility testing indicated potential sensitive chemotherapeutic drugs for each risk group. This study is the first to establish and validate STAD-associated PRLs that can effectively guide the prognosis and the immune microenvironment in STAD patients and provide evidence for the development of molecularly targeted therapies related to pyroptosis.


Assuntos
Adenocarcinoma , RNA Longo não Codificante , Neoplasias Gástricas , Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Humanos , Prognóstico , Piroptose/genética , Neoplasias Gástricas/genética , Microambiente Tumoral/genética
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