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1.
Mod Rheumatol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850093

RESUMO

OBJECTIVES: Present study aimed to illustrate the role of miR-144-3p in RA. METHODS: N1511 chondrocytes were stimulated by IL-1ß to mimic RA injury model in vitro. Rats were subjected to injection of type II collagen to establish an in vivo RA model and the arthritis index score was calculated. Cell viability was determined by CCK-8. The expression of cartilage extracellular matrix proteins (Collagen II and Aggrecan) and matrix metalloproteinases protein (MMP-13) were determined by qRT-PCR and western blots. Cell apoptosis was measured by Flow cytometry. ELISA was applied to test the secretion of pro-inflammatory cytokines (IL-1ß and TNF-α). Tissue injury and apoptosis were detected by HE staining and TUNEL staining. Interaction of miR-144-3p and BMP2 was verified by dual luciferase assay. RESULTS: MiR-144-3p was dramatically increased in IL-1ß induced N1511 cells. MiR-144-3p depletion elevated cell viability, suppressed apoptosis, pro-inflammatory cytokine releasing, and extracellular matrix loss in IL-1ß induced N1511 cells. Moreover, miR-144-3p targeted BMP2 to modulate its expression negatively. Activation of PI3K/Akt signaling compromised inhibition of BMP2 induced aggravated N1511 cell injury with IL-1ß stimulation. Inhibition of miR-144-3p alleviated cartilage injury and inflammatory in RA rats. CONCLUSION: Collectively, miR-144-3p could aggravate chondrocytes injury inflammatory response in RA via BMP2/PI3K/Akt axis.

2.
Plant Cell ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34850198

RESUMO

Phosphatidic acid (PA) is an important lipid essential for several aspects of plant development and biotic and abiotic stress responses. We previously suggested that submergence induces PA accumulation in Arabidopsis thaliana; however, the molecular mechanism underlying PA-mediated regulation of submergence-induced hypoxia signaling remains unknown. Here, we showed that in Arabidopsis, loss of the phospholipase D (PLD) proteins PLDα1 and PLDδ leads to hypersensitivity to hypoxia, but increased tolerance to submergence. This enhanced tolerance is likely due to improvement of PA-mediated membrane integrity. PA bound to the Mitogen-Activated Protein Kinases MPK3 and MPK6 in vitro and contributed to hypoxia-induced phosphorylation of MPK3 and MPK6 in vivo. Moreover, mpk3 and mpk6 mutants were more sensitive to hypoxia and submergence stress compared with wild type, and fully suppressed the submergence-tolerant phenotypes of pldα1 and pldδ mutants. MPK3 and MPK6 interacted with and phosphorylated RELATED TO AP2.12 (RAP2.12), a master transcription factor in the hypoxia signaling pathway, and modulated its activity. In addition, MPK3 and MPK6 formed a regulatory feedback loop with PLDα1 and/or PLDδ to regulate PLD stability and submergence-induced PA production. Thus, our findings demonstrate that PA modulates plant tolerance to submergence via both membrane integrity and MPK3/6-mediated hypoxia signaling in Arabidopsis.

3.
Autoimmunity ; : 1-11, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730058

RESUMO

Rheumatoid arthritis (RA) often leads to functional disabilities and deformities. MiRNA plays a vital role in cell pyroptosis. Nevertheless, the function and underlying mechanism of miR-144-3p in pyroptosis during the progression of RA remains unclear. In this study, N1511 cells were stimulated with IL-1ß to construct a RA model. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to assess the cell viability. Cell pyroptosis was detected by flow cytometry. The levels of inflammatory cytokines (TNF-α, IL-6, and IL-18) were assessed by enzyme-linked immunosorbent assay (ELISA). The relationship among specific protein 1 (SP1), microRNA-144-3p (miR-144-3p), and phosphatase and tensin homolog (PTEN) was explored by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP), respectively. The level of miR-144-3p in N1511 cells was upregulated by IL-1ß. MiR-144-3p knockdown inhibited IL-1ß-induced pyroptosis in N1511 cells, and the expressions of NOD-like receptor family pyrin domain containing 3 (NLRP3), Cleaved caspase-1, Gasdermin D (GSDMD), and Cleaved caspase-3 in IL-1ß-stimulated N1511 cells were increased. The levels of inflammatory cytokines in N1511 cells were increased by IL-1ß, which were restored by miR-144-3p knockdown. MiR-144-3p knockdown abolished IL-1ß-induced inactivation of putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin-protein (Parkin) signalling. Moreover, transcription factor SP1 could upregulate miR-144-3p expression and miR-144-3p negatively regulated PTEN expression. In summary, MiR-144-3p induced by SP1 could promote IL-1ß-induced chondrocyte pyroptosis via inhibiting PTEN expression and suppressing the activation of PINK1/Parkin signalling, which provided a new strategy against RA.

4.
Exp Biol Med (Maywood) ; : 15353702211049149, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743578

RESUMO

In our studies, cyclin B1 (CCNB1) mRNA and protein were overexpressed in hepatocellular carcinoma (HCC) tissues compared with non-HCC tissues. Moreover, CCNB1 was overexpressed in the serum of HCC patients. The expression of CCNB1 was associated with several crucial clinicopathologic characteristics, and the HCC patients with overexpressed CCNB1 had worse overall survival outcomes. In the screening of interactional genes, a total of 266 upregulated co-expression genes, which were positively associated with CCNB1, were selected from the datasets, and 67 downregulated co-expression genes, which were negatively associated with CCNB1, were identified. The key genes might be functionally enriched in DNA replication and the cell cycle pathways. CDC20, CCNA2, PLK1, and FTCD were selected for further research because they were highly connected in the protein-protein interaction networks. Upregulated CDC20, CCNA2, and PLK1 and downregulated FTCD might result in undesirable overall survival outcomes for HCC patients. The univariate Cox analysis results showed that CDC20 and PLK1 might be two independent risk factors, while FTCD might be protective in HCC. Therefore, CCNB1 may participate in the cell cycle of HCC by regulating DNA replication, and CCNB1 may provide a direction for the diagnosis of early-stage HCC and targeted HCC therapy.

5.
Pediatr Rheumatol Online J ; 19(1): 157, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749768

RESUMO

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis that predominantly affects medium-sized arteries. In addition to well-known coronary artery aneurysms (CAAs), peripheral systemic artery aneurysms (SAAs) have also been sporadically reported. In the literatures, SAAs occurred mainly in untreated, intravenous immunoglobin (IVIG)-resistant, or severe refractory KD, and thrombotic events in SAAs were rarely reported. CASE PRESENTATION: A 10-month-old boy with a history of KD was referred to our hospital for suspected pseudoaneurysm of the axillary arteries. Four months prior to presentation, he had persistent fever, conjunctival congestion, and rash. On the 10th day of fever echocardiogram showed biliteral CAAs. He was then diagnosed with KD and given IVIG 2 g/kg and aspirin at a local hospital. His fever and symptoms soon subsided and he was discharged with low dose aspirin and dipyridamole. One month prior to presentation, his parents incidentally palpated swellings in his bilateral axillae. On admission, physical examination revealed a pulsatile swelling in his right axilla and a non-pulsatile swelling in the left with impalpable left brachial and radial pulses, cooler and less active left upper limb than the right one. While the pulses of other three limbs were normal. Ultrasound examination revealed giant bilateral axillary artery aneurysms (AAAs) with massive thrombus in the left. Angiography confirmed giant bilateral AAAs with left AAAs completely occluded and fine collateral vessels connecting to the distal brachial artery, in addition to giant bilateral multiple CAAs without stenoses. The patient was given intravenous prostaglandin for 10 days to allow for formation of collateral circulation, as well as aspirin, low molecular weight heparin (which was switched to warfarin before discharge) and metoprolol. At discharge, the temperature and movement of his left upper limb improved significantly. On follow-up at 7 months, his left upper limb further improved and was similar to the right with no occurrence of cardiovascular events. The images of CAAs and AAAs on echocardiogram and computerized tomography remained the same. CONCLUSIONS: This case highlights the importance of evaluating peripheral SAAs in KD patients with CAAs, even if their course of treatment appears smooth. For both large non-aortic SAAs and CAAs in KD patients, antithrombotic therapy is of utmost importance.

6.
Macromol Biosci ; : e2100318, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773451

RESUMO

Cellulose nanocrystal (CNC) is the rod-like nano-object derived from natural cellulose with the features of low toxicity and good biocompatibility, widely used as the functional additive and nanomaterial in the biomedicine. Two negatively charged cellulose nanocrystals, CNC and TO-CNC (surface oxidized CNC), are prepared by the sulfuric acid hydrolysis and further surface oxidization. Based on electrostatic adsorption, five trace metal elements (TMEs) including cobalt (Co), nickel (Ni), manganese (Mn), lead (Pb), and cadmium (Cd) are loaded on the surface of two nanocrystals as the biocompatible nanocarriers. The adsorbed contents of TMEs on two nanocrystals are affected by their surface charge densities and the complexes can keep stability under three varied pH conditions. Two cell lines, viz. human nasopharyngeal cancer cell and normal human bronchial epithelial cell, are selected for the investigation of cytotoxity of these TME-loaded nanocrystals at the concentration range of 0.1-500 µg mL-1 . The high concentrations of TME-loaded nanocrystals will induce the inhibition of cells activity and proliferation, particularly for Pb2+ - and Cd2+ -loaded nanocrystals. The cancer cell generally exhibits more sensitivity of cytotoxity to these metal elements than the normal cell, which may be potentially used as the activity inhibitor for specific cells in the future study.

7.
BMC Musculoskelet Disord ; 22(1): 985, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823533

RESUMO

BACKGROUND: Although open reduction and internal fixation (ORIF) is recommended for lateral condylar humerus fractures (LCHFs) displaced by > 4 mm, several studies have reported the use of closed reduction and percutaneous pinning (CRPP) to treat LCHFs with significant displacement. However, little is known about the clinical differences between these two surgical techniques. This study aimed to compare the therapeutic effects of CRPP and ORIF in treating LCHFs displaced by > 4 mm. METHODS: We retrospectively reviewed pediatric LCHFs displaced by > 4 mm treated with either CRPP or ORIF at our center from June 2019 to October 2020. Song and Milch fracture classifications were used. Variables such as age at injury, sex, side injured, fracture displacement, fracture type, operating time, postoperative treatment, and complications were compared between the two techniques. RESULTS: One hundred twenty LCHFs met inclusion criteria. There were 36 Milch type I and 84 type II LCHFs, and 69 Song stage 4 and 51 stage 5 LCHFs. CRPP was performed in 45 cases and ORIF in 75 cases. No differences were found in age, sex, side injured, preoperative displacement, postoperative displacement, and length of immobilization between the CRPP and ORIF groups. There was a difference between operation time and pin duration. The CRPP group had shorter operation times and pin duration, and required no additional operations to remove internal pins. The average follow-up duration was 13.9 months. All patients achieved fracture union, and no complications such as infection, nonunion, delayed union, osteonecrosis, fishtail deformity, cubitus varus or valgus, or pain were recorded during follow-up. Bone spurs, lateral prominences, and decreased carrying angle were common complications in all groups. No obvious cubitus varus was observed. Unaesthetic scars were only observed in the ORIF groups. No differences in range of motion or elbow function was found among the different therapies. CONCLUSIONS: Both CRPP and ORIF can achieve satisfactory clinical outcomes in treating LCHFs displaced by > 4 mm. No differences were found in complications or prognoses between the two groups. However, CRPP shows some advantages over ORIF, like less invasive surgery, no obvious scarring, and no need for secondary surgery with anesthesia for pin removal.


Assuntos
Fraturas do Úmero , Estudos Transversais , Humanos , Fraturas do Úmero/diagnóstico por imagem , Fraturas do Úmero/cirurgia , Úmero , Estudos Retrospectivos , Resultado do Tratamento
8.
BMC Gastroenterol ; 21(1): 437, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809574

RESUMO

BACKGROUND: Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis. METHODS: We searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0. RESULTS: After inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients. CONCLUSIONS: Our meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Biomarcadores Tumorais , Proteínas de Choque Térmico HSP70 , Humanos , Prognóstico
10.
Int J Ophthalmol ; 14(11): 1653-1659, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804853

RESUMO

AIM: To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane (rhNGF-AM) on corneal epithelial and nerve regeneration in rabbit model. METHODS: Freshly prepared human amniotic membrane (AM) were immersed into PBS buffer containing 100 or 500 µg/mL rhNGF for 15, 30, and 60min at 4°C. The in vitro release kinetics of rhNGF was measured with ELISA. For in vivo evaluation, the AM were immersed with 500 µg/mL rhNGF for 30min. Fifty-seven rabbits were selected to establish corneal epithelial defect model. In addition to the 19 rabbits in control group, 38 rabbits received AM transplantation with or without rhNGF after the removal of central epithelium. Corneal epithelial defect area, sub-epithelial nerve fiber density, corneal sensitivity, rhNGF contents in resident AM and corneas were measured after the surgery. RESULTS: rhNGF was sustained release from the AM within 14d in vitro, with the positive correlation with initial immersion concentration. The immersion of AM in 500 µg/mL rhNGF for 30min achieved the most stable release within 14d. After transplantation in rabbit cornea, a high concentration of rhNGF in resident rhNGF-AM and cornea was maintained within 8d. Corneal epithelial healing, nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rhNGF-AM transplantation when compared to simple AM transplantation (all P<0.05). CONCLUSION: Simple immersion of AM achieves the sustained release of rhNGF, and promotes corneal epithelial wound healing and nerve regeneration, as well as the recovery of corneal sensitivity in rabbit.

11.
Int J Ophthalmol ; 14(11): 1690-1699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804858

RESUMO

AIM: To evaluate the midterm outcomes of penetrating keratoplasty (PK) following allogeneic cultivated limbal epithelial transplantation (CLET) for bilateral total limbal stem cell deficiency (LSCD). METHODS: Ten patients (10 eyes) with bilateral LSCD were enrolled in this prospective noncomparative case series study. Each participant underwent PK approximately 6mo after a CLET. Topical tacrolimus, topical and systemic steroids, and oral ciclosporin were administered postoperatively. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular surface grading scores (OSS), corneal graft epithelial rehabilitation, persistent epithelial defect (PED), immunological rejection, and graft survival rate were assessed. RESULTS: The time interval between PK and allogeneic CLET was 6.90±1.29 (6-10)mo. BCVA improved from 2.46±0.32 logMAR preoperatively to 0.77±0.55 logMAR post-PK (P<0.001). Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100% at 12 and 24mo and 80.0% at 36mo. PEDs appeared in 5 eyes at different periods post-PK, and graft rejection occurred in 4 eyes. The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK. CONCLUSION: A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate.

12.
Int J Biol Sci ; 17(15): 4493-4513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803512

RESUMO

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabolism and ferroptosis in cancer. In this review, we mainly summarized the mechanism by which lncRNAs regulate aberrant lipid metabolism in cancer, illustrated that lipid metabolism can also influence the expression of lncRNAs, and discussed the mechanism by which lncRNAs affect ferroptosis. A comprehensive understanding of the interactions between lncRNAs, lipid metabolism and ferroptosis could help us to develop novel strategies for precise cancer treatment in the future.

13.
Nat Commun ; 12(1): 6799, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815384

RESUMO

Microbial communities often perform important functions that depend on inter-species interactions. To improve community function via artificial selection, one can repeatedly grow many communities to allow mutations to arise, and "reproduce" the highest-functioning communities by partitioning each into multiple offspring communities for the next cycle. Since improvement is often unimpressive in experiments, we study how to design effective selection strategies in silico. Specifically, we simulate community selection to improve a function that requires two species. With a "community function landscape", we visualize how community function depends on species and genotype compositions. Due to ecological interactions that promote species coexistence, the evolutionary trajectory of communities is restricted to a path on the landscape. This restriction can generate counter-intuitive evolutionary dynamics, prevent the attainment of maximal function, and importantly, hinder selection by trapping communities in locations of low community function heritability. We devise experimentally-implementable manipulations to shift the path to higher heritability, which speeds up community function improvement even when landscapes are high dimensional or unknown. Video walkthroughs: https://go.nature.com/3GWwS6j ; https://online.kitp.ucsb.edu/online/ecoevo21/shou2/ .

14.
Sci Total Environ ; : 151965, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838920

RESUMO

Wnt5a is a key mediator of non-canonical Wnt signaling, and an early indicator of epithelial injury and lung dysfunction. Polycyclic aromatic hydrocarbons (PAHs) could induce acute pulmonary pathogenesis, of which the underlying mechanism remains unclear. To elucidate the potential role of Wnt5a-mediated non-canonical Wnt-YAP/TAZ signaling in the lung injury induced by short-term exposure of benzo(a)pyrene (BaP, a representative PAHs), intratracheally instilled mouse model was used and further interfered with its Wnt5a level by small molecule antagonists and agonists. Our data revealed that BaP exposure induced the lung inflammatory response and reduced the expression of Clara cell secretory protein (CC16) in a dose-dependent manner. More importantly, the activation of Wnt5a and downstream YAP/TAZ were accompanied with the enhanced release of epithelial-derived thymic stromal lymphopoietin and interleukin-33, which acted as pro-inflammatory cytokines. Functionally, inhibition of Wnt5a attenuated the BaP-induced inflammation and recuperated CC16 expression, as well as suppressed the epithelial cytokines release. Whereas promoting Wnt5a expression affected the toxic effects of BaP oppositely. Our findings together suggest that Wnt5a is a potential endogenous regulator in lung inflammation and airway epithelial injury, and Wnt5a-YAP/TAZ signaling contributes to lung dysfunction in acute exposure to BaP.

15.
Arch Iran Med ; 24(11): 845-851, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34841830

RESUMO

BACKGROUND: Comb homolog enhancer 1 (EPC1) gene is one of the important members of epigenetic inhibitor PCG family. It shows carcinogenic potential in a variety of malignant tumors, but the expression and role of EPC1 in nasopharyngeal carcinoma are unclear. The aim of this study was to explore the expression and function of enhancer of polycomb homolog 1 (EPC1) in nasopharyngeal carcinoma (NPC). METHODS: The differential expression of EPC1 in the cancer tissues and cell lines of NPC was examined by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). EPC1 expression, cell proliferation, and apoptosis were detected in NPC cell lines after EPC1 silencing, and the levels of the epithelial-mesenchymal transition (EMT)-related proteins E-cadherin and vimentin were detected in NPC cells after EPC1 silencing. The study was performed at Fujian Provincial Hospital, Fujian, China, from 2018 to 2019. RESULTS: We found that EPC1 was significantly upregulated in the cancer tissues and cell lines of NPC (P<0.001). Furthermore, knockdown of EPC1 inhibited the growth and metastasis of NPC cells. E-cadherin and vimentin were detected in NPC cells after EPC1 was knocked out. It was confirmed that inhibition of EPC1 resulted in increased E-cadherin expression (P<0.001) and decreased vimentin expression (P<0.001), suggesting that inhibition of EPC1 could inhibit the EMT in NPC cells. CONCLUSION: EPC1 expression was upregulated in NPC tissues and cell lines. Knockout of EPC1 effectively inhibited the growth of NPC cells, induced apoptosis, and inhibited invasion and metastasis. Inhibition of EPC1 could inhibit the EMT in NPC cells. All of the above findings support the viewpoint that EPC1 plays a pro-cancer role in NPC.

16.
Future Oncol ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842456

RESUMO

Aim: This study aimed to access the efficacy of plasma small nucleolar RNAs in early diagnosis of non-small-cell lung cancer (NSCLC). Methods: SNORD83A was selected based on databases and further verified in 48 paired formalin-fixed, paraffin-embedded tissues, as well as in plasma from 150 NSCLC patients and 150 healthy donors. The diagnostic efficiency of plasma SNORD83A, as well as in combination with carcinoembryonic antigen, was determined by receiver operating characteristic analysis. Results: SNORD83A was significantly increased not only in tissues but also in plasma from NSCLC patients compared with those from healthy donors. Plasma SNORD83A was able to act as a diagnostic biomarker for NSCLC. The diagnostic efficiency of carcinoembryonic antigen was also significantly elevated for early-stage NSCLC when combined with SNORD83A. Conclusion: SNORD83A can serve as a diagnostic biomarker for NSCLC.

17.
Technol Cancer Res Treat ; 20: 15330338211060202, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34825846

RESUMO

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer affecting humans. However, appropriate biomarkers for diagnosis and prognosis have not yet been established. Here, we evaluated the gene expression profiles of patients with NSCLC to identify novel biomarkers. Methods: Three datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes were analyzed. Venn diagram software was applied to screen differentially expressed genes, and gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Cytoscape was used to analyze protein-protein interactions (PPI) and Kaplan-Meier Plotter was used to evaluate the survival rates. Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), and The Human Protein Atlas (THPA) were used to analyze protein expression. Quantitative real-time polymerase (qPCR) chain reaction was used to verify gene expression. Results: We identified 595 differentially expressed genes shared by the three datasets. The PPI network of these differentially expressed genes had 202 nodes and 743 edges. Survival analysis identified 10 hub genes with the highest connectivity, 9 of which (CDC20, CCNB2, BUB1, CCNB1, CCNA2, KIF11, TOP2A, NDC80, and ASPM) were related to poor overall survival in patients with NSCLC. In cell experiments, CCNB1, CCNB2, CCNA2, and TOP2A expression levels were upregulated, and among different types of NSCLC, these four genes showed highest expression in large cell lung cancer. The highest prognostic value was detected for patients who had successfully undergone surgery and for those who had not received chemotherapy. Notably, CCNB1 and CCNA2 showed good prognostic value for patients who had not received radiotherapy. Conclusion: CCNB1, CCNB2, CCNA2, and TOP2A expression levels were upregulated in patients with NSCLC. These genes may be meaningful diagnostic biomarkers and could facilitate the development of targeted therapies.

18.
World J Gastrointest Oncol ; 13(10): 1506-1517, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34721781

RESUMO

BACKGROUND: Tubular adenocarcinoma of the colon, which originates from the epithelium of the glands, is a major health concern worldwide. However, it is difficult to detect at an early stage. The lack of biomarkers is a main barrier to the diagnosis and treatment of tubular adenocarcinoma. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted protein that induces the expression of matrix metalloproteinase-9 (MMP-9) and is involved in various tumors. NGAL and MMP-9 have been reported to be associated with tumorigenesis and development. They may have potential as biomarkers for diagnosis of tubular adenocarcinoma of the colon. AIM: To determine whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon. METHODS: Samples were collected from surgically excised tissue from various patients. The content of pro-gastrin-releasing peptide (pro-GRP) in the serum was measured by an electrochemiluminescence immunoassay. The expression patterns of NGAL and MMP-9 and the relationship between NGAL and MMP-9 were examined by quantitative real-time PCR, Western blotting and immunohistochemical analysis. RESULTS: In this study, we found that NGAL and MMP-9 can be used as biomarkers for the detection of tubular adenocarcinoma of the colon and that their combination improved diagnostic accuracy. By analyzing the expression of NGAL in tubular adenocarcinoma at different levels, we found that NGAL expression was significantly upregulated in primary tubular adenocarcinoma tissues compared with normal tissues. The upregulation of NGAL expression was strongly correlated with both the degree of differentiation and the disease stage (I-III), indicating that NGAL could serve as a diagnostic biomarker for tubular adenocarcinoma. When using NGAL as a biomarker for diagnosis, the accuracy was similar to that achieved with the widely used biomarker pro-GRP, suggesting that NGAL is reliable. Moreover, the expression of MMP-9 was also strongly correlated with the differentiation stage, demonstrating that MMP-9 could be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon. More importantly, the combination of NGAL and MMP-9 produced a more accurate diagnosis of tubular adenocarcinoma, and these results were further confirmed by immunohistochemical analysis of tissue sections. CONCLUSION: Our study demonstrated that both NGAL and MMP-9 can be used as biomarkers for the diagnosis of colon tubular adenocarcinoma and that the results could be further improved by combining them.

19.
World J Clin Cases ; 9(29): 8710-8717, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34734049

RESUMO

BACKGROUND: Desmoid fibroma is a rare soft tissue tumor originating from the aponeurosis, fascia, and muscle, and it is also known as aponeurotic fibroma, invasive fibroma, or ligamentous fibroma. AIM: To investigate the clinical and imaging features of desmoid tumors of the extremities. METHODS: Thirteen patients with desmoid fibroma of the extremities admitted to our hospital from October 2016 to March 2021 were included. All patients underwent computed tomography (CT), magnetic resonance imaging (MRI), and pathological examination of the lesion. Data on the diameter and distribution of the lesion, the relationship between the lesion morphology and surrounding structures, MRI and CT findings, and pathological features were statistically analyzed. RESULTS: The lesion diameter ranged from 1.7 to 8.9 cm, with an average of 5.35 ± 2.39 cm. All lesions were located in the deep muscular space, with the left and right forearm each accounting for 23.08% of cases. Among the 13 patients with desmoid fibroma of the extremities, the lesions were "patchy" in 1 case, irregular in 10, and quasi-round in 2. The boundary between the lesion and surrounding soft tissue was blurred in 10 cases, and the focus infiltrated along the tissue space and invaded the adjacent structures. Furthermore, the edge of the lesion showed "beard-like" infiltration in 2 cases; bone resorption and damage were found in 8, and bending of the bone was present in 2; the boundary of the focus was clear in 1. According to the MRI examination, the lesions were larger than 5 cm (61.54%), round or fusiform in shape (84.62%), had an unclear boundary (76.92%), showed uniform signal (69.23%), inhomogeneous enhancement (84.62%), and "root" or "claw" infiltration (69.23%). Neurovascular tract invasion was present in 30.77% of cases. CT examination showed that the desmoid tumors had slightly a lower density (69.23%), higher enhancement (61.54%), and unclear boundary (84.62%); a CT value < 50 Hu was present in 53.85% of lesions, and the enhancement was uneven in 53.85% of cases. Microscopically, fibroblasts and myofibroblasts were arranged in strands and bundles, without obvious atypia but with occasional karyotyping; cells were surrounded by collagen tissue. There were disparities in the proportion of collagen tissue in different regions, with abundant collagen tissue and few tumor cells in some areas, similar to the structure of aponeuroses or ligaments, and tumor cells invading the surrounding tissues. CONCLUSION: Desmoid tumors of the extremities have certain imaging features on CT and MRI. The two imaging techniques can be combined to improve the diagnostic accuracy, achieve a comprehensive diagnosis of the disease in the clinical practice, and reduce the risk of missed diagnosis or misdiagnosis. In addition, their use can ensure timely diagnosis and treatment.

20.
Front Cell Infect Microbiol ; 11: 717636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760714

RESUMO

The acute radiation-induced intestinal injury (RIII) has raised much concerns and is influenced by non-cytocidal radiation effects including the perturbations in gut microbiota. Although a number of studies have reported alteration in gut microbiota following radiation, little is known about its dynamic variation in the progression of acute RIII. In this study, mouse model were treated with total body irradiation (TBI) of 0, 4, 8 and 12 Gy, and the intestinal tissues and fecal samples were collected at 6 h, 3.5 d and 7 d post radiation. We found that the intestinal injuries were manifested in a radiation dose-dependent manner. Results from 16S rRNA gene sequencing demonstrated that the diversity of gut microbiota was not significantly affected at the prodromal stage of acute RIII, after 6 h of radiation. At the critical stage of acute RIII, after 3.5 d of radiation, the composition of gut microbiota was correlated with the radiation dose. The Pearson's correlation analysis showed that the relative abundances of phylum Proteobacteria, genera Escherichia-Shigella and Eubacterium xylanophilum_group, and species Lactobacillus murinus exhibited linear correlations with radiation dose. At the recovery stage of acute RIII, after 7 d of radiation, the diversity of gut microbiota decreased as a whole, among which the relative abundance of phyla Proteobacteria and Bacteroides increased, while that of phylum Tenericutes and genus Roseburia decreased. The intra-gastric administration of compound probiotics for 14 days improved the survival duration of mice exposed to 9 Gy TBI, alleviated the intestinal epithelial injury and partially restored the diversity of gut microbiota. Our findings suggest that acute RIII is accompanied by the dysbiosis of gut microbiota, including its decreased diversity, reduced abundance of beneficial bacteria and increased abundance of pathogens. The gut microbiota cannot be used as sensitive biomarkers at the prodromal stage in acute RIII, but are potential biomarkers at the critical stage of acute RIII. The dysbiosis is persistent until the recovery stage of acute RIII, and interventions are needed to restore it. The administration of probiotics is an effective strategy to protect against acute RIII and subsequent dysbiosis.


Assuntos
Microbioma Gastrointestinal , Probióticos , Animais , Disbiose , Eubacterium , Fezes , Lactobacillus , Camundongos , RNA Ribossômico 16S/genética
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