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1.
Cancer Sci ; 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33931925

RESUMEN

Traditional histopathology performed by pathologists by the naked eye is insufficient for accurate and efficient diagnosis of bladder cancer (BCa). We collected 643 H&E-stained BCa images from Shanghai General Hospital and The Cancer Genome Atlas (TCGA). We constructed and cross-verified automatic diagnosis and prognosis models by performing a machine learning algorithm based on pathomics data. Our study indicated that high diagnostic efficiency of the machine learning-based diagnosis model was observed in patients with BCa, with area under the curve (AUC) values of 96.3%, 89.2%, and 94.1% in the training cohort, test cohort, and external validation cohort, respectively. Our diagnosis model also performed well in distinguishing patients with BCa from patients with glandular cystitis, with an AUC value of 93.4% in the General cohort. Significant differences were found in overall survival in TCGA cohort (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.56-2.81, P < .0001) and the General cohort (HR = 5.32, 95% CI: 2.95-9.59, P < .0001) comparing patients with BCa of high risk vs low risk stratified by risk score, which was proved to be an independent prognostic factor for BCa. The integration nomogram based on our risk score and clinicopathologic characters displayed higher prediction accuracy than current tumor stage/grade systems, with AUC values of 77.7%, 83.8%, and 81.3% for 1-, 3-, and 5-y overall survival prediction of patients with BCa. However, prospective studies are still needed for further verifications.

2.
Orthop Surg ; 2021 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-33943016

RESUMEN

OBJECTIVE: To investigate the methods and outcomes of hip arthroscopy for hip labrum calcification, and to discuss the clinical, imaging, and intraoperative findings of hip labrum calcification. METHODS: This is a therapeutic case series study. From January 2015 to June 2018, 15 patients who met the inclusion and exclusion criteria were followed up for at least 2 years for an analysis on the outcomes of arthroscopy in the treatment of hip labrum calcification and the clinical, imaging, and intraoperative findings of the patients. There were eight males and seven females, with an average age of 38.9 ± 8.8 years (range, 23-50 years). The visual analog scale (VAS), the modified Harris hip score (mHSS), and the international hip outcome tool (iHOT-12) were used to evaluate the outcomes of surgery. RESULTS: A total of 15 patients were followed up for at least 2 years (28.1 ± 2.9 months). The average calcified volume was 118.0 mm3 (range, 19.4-609.2 mm3 ) and calcified volume was related to the preoperative hip function score. Thirteen patients had pain in the groin area (86.7%). Labrum calcifications were located (according to the clock distribution) as follows: 14 patients were anterior and superior (11:00-3:00); 12 cases of femoroacetabular impingement (FAI) were observed during operation, including five cases of pincer type, two cases of cam type, and five cases of mixed type. VAS pain score means were 7.73 ± 1.28 before surgery, decreasing to 2.0 ± 0.89 and 1.73 ± 0.79 at 1 and 2 years post-surgery, respectively. mHSS scores were 57.40 ± 6.23 before surgery and 82.10 ± 4.76 and 83.18 ± 4.07, 1 and 2 years post-surgery, respectively; iHOT-12 mean score pre-surgery was 37.67 ± 4.85, increasing to 67.64 ± 5.30 and 72.18 ± 4.49, 1 and 2 years post-surgery, respectively. Compared with preoperative values, postoperative VAS, mHSS, and iHOT-12 scores were significantly improved (P < 0.01); iHOT-12 scores also significantly decreased from 1 to 2 years postoperatively (P = 0.034). No patient had complications. CONCLUSION: Hip arthroscopy is an effective method for the treatment of hip labrum calcification. The size of calcification influenced preoperative symptoms and function. Long-term irritation from FAI may be one important cause of labrum calcification.

3.
Clin Nutr ; 40(5): 2726-2733, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33933738

RESUMEN

BACKGROUND & AIMS: Mendelian randomization (MR) studies have reported the causal association between serum calcium levels and bone mineral density (BMD). The results showed that genetically increased serum calcium levels in individuals with normal calcium levels did not increase BMD and could even reduce BMD. However, whether there are differences in the association between serum calcium and BMD in different age strata remains unclear. METHODS: We selected eight serum calcium genetic variants with genome-wide significance (P < 5.00E-08) as the potential instrumental variables. We conducted an MR analysis to evaluate the impact of serum calcium levels on total body BMD in five age strata, 0-15, 15-30, 30-45, 45-60, and ≥60 years, using large-scale serum calcium (61,079 individuals) and total body BMD genome-wide association study (66,628 individuals) datasets. For pleiotropy analysis, we used a manual method and four common statistical methods, namely the MR-Egger intercept, MR-PRESSO, heterogeneity, and Steiger filtering tests. For MR analysis, we selected four MR methods, namely inverse-variance weighted, weighted median, MR-Egger, and MR-PRESSO. In addition to the univariable MR analysis, we conducted a multivariate MR analysis taking into account the effect of serum parathyroid hormone levels. RESULTS: Univariable MR analysis using the inverse-variance weighted method indicated that per 0.5-mg/dL increase (about 1 standard deviation) in serum calcium levels was statistically significantly associated with reduced total body BMD only in the ≥60 years stratum (effect estimate (beta) = -0.545, 95% confidence interval (CI): -0.892 to -0.198, P = 0.002). The weighted median regression (beta = -0.446, 95% CI: -0.821 to -0.094, P = 1.40E-02) and MR-PRESSO (beta = -0.545, 95% CI: -0.892 to -0.198, P = 0.022) MR methods further supported this suggestive association. The multivariable MR analysis also found a significant association between increased serum calcium levels and reduced total body BMD in the ≥60 years stratum (beta = -0.547, 95% CI: -0.934 to -0.16, P = 0.006). CONCLUSIONS: Our results provide genetic evidence that increased serum calcium levels did not improve BMD in the general population and that the elevated serum calcium levels in generally healthy populations, especially in adults older than 60 years, may even reduce the BMD. Our results are comparable with those of recent MR findings.

4.
Invest Ophthalmol Vis Sci ; 62(6): 4, 2021 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-33944893

RESUMEN

Purpose: Dichoptic training is becoming a popular tool in amblyopia treatment. Here we investigated the effects of dichoptic demasking training in children with amblyopia who never received patching treatment (NPT group) or were no longer responsive to patching (PT group). Methods: Fourteen NPT and thirteen PT amblyopes (6-16.5 years; 24 anisometropic, two strabismus, and one mixed) received dichoptic demasking training for 17 to 22 sessions. They used the amblyopic eye (AE) to practice contrast discrimination between a pair of Gabors that were dichoptically masked by a band-filtered noise pattern simultaneously presented in the fellow eye (FE). Dichoptic learning was quantified by the increase of maximal tolerable noise contrast (TNC) for AE contrast discrimination. Computerized visual acuities and contrast sensitivity functions for both eyes and the Randot stereoacuity were measured before and after training. Results: Training improved maximal TNC by six to eight times in both groups, along with a boost of AE acuities by 0.15 logMAR (P < 0.001) in the NPT group and 0.06 logMAR (P < 0.001) in the PT group. This visual acuity improvement was significantly dependent on the pretraining acuity. Stereoacuity was significantly improved by 41.6% (P = 0.002) in the NPT group and 64.2% (P < 0.001) in the PT group. The stereoacuity gain was correlated to the pretraining interocular acuity difference (r = -0.49, P = 0.010), but not to the interocular acuity difference change (r = -0.28, P = 0.15). Training improved AE contrast sensitivity in the NPT group (P = 0.009) but not the PT group (P = 0.76). Moreover, the learning effects in 12 retested observers were retained for 10 to 24 months. Conclusions: Dichoptic training can improve, and sometimes even restore, the stereoacuity of amblyopic children, especially those with mild amblyopia (amblyopic VA ≦0.28 logMAR). The dissociation of stereoacuity gain and the interocular acuity difference change suggests that the stereoacuity gain may not result from a reduced interocular suppression in most amblyopes. Rather, the amblyopes may have learned to attend to, or readout, the stimulus information to improve stereopsis.

5.
J Neurochem ; 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33950542

RESUMEN

The adverse side effects of opioids, especially antinociceptive tolerance, limit their clinical application. A recent study reported that platelet-derived growth factor receptor ß (PDGFRß) blockage selectively inhibited morphine tolerance. Autophagy has been reported to contribute to the cellular and behavioral responses to morphine. However, little is known about the relationship between PDGFRß and autophagy in the mechanisms of morphine tolerance. In this study, rats were intrathecally administered with morphine twice daily for 7 days to induce antinociceptive tolerance, which was evaluated using a tail-flick latency test. By administration autophagy inhibitor 3-Methyladenine, PDGFRß inhibitor imatinib, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 hydrochloride and minocycline hydrochloride, western blot, immunofluorescence, and transmission electron microscopy techniques were used to elucidate the roles of PDGFRß, autophagy, and related signaling pathways in morphine tolerance. This study demonstrated for the first time that spinal PDGFRß in microglia promotes autophagy in gamma-aminobutyric acid (GABA) interneurons through activating p38 MAPK pathway during the development of morphine tolerance, which suggest a potential strategy for preventing the development of morphine tolerance clinically, thereby improving the use of opioids in pain management.

6.
Anim Sci J ; 92(1): e13545, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33793035

RESUMEN

This study was conducted to investigate the effects of dietary supplementation xylo-oligosaccharides (XOS), coated sodium butyrate (CSB), and their combination on growth performance, immune parameters, and intestinal barrier of broilers. A total of 192 1-day-old chicks were assigned to a 2 × 2 factorial design including two dietary additives (0 and 150 mg/kg XOS and 0 and 400 mg/kg CSB). This trial lasted for 42 days. CSB supplementation increased the thymus and bursa index, blood myeloperoxidase (MPO) activity, and IgG and IgM concentrations, whereas adding XOS only improved IgM concentration (p < .05). A significant interaction was observed for MPO activity. Furthermore, broilers fed CSB and their interaction exhibited increased ileal villus height/crypt depth (VH/CD) and goblet cells numbers in the ileum, as well as decreased ileal CD (p < .05). Broilers fed XOS and CSB individually showed higher ileal VH, the number of goblet cells in the duodenum and jejunum (p < .05). Moreover, XOS and CSB individual supplementation upregulated the expression of claudin3 in the ileum (p < .05). Simultaneously, a significant interaction was found for the ileal expression of claudin3. Overall, XOS and CSB supplementation could improve the development of immune organs, the small intestine morphology, and the intestinal physical barrier of broilers. Although no clear synergy of XOS and CSB was detected, the combination had positively affect broilers intestinal barrier and immune parameters.

7.
Dalton Trans ; 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33881067

RESUMEN

Palladium (Pd) is regarded as a potential non-platinum electrocatalyst to drive oxygen reduction in fuel cells. The development of Pd-based electrocatalysts with high performances through structural engineering is still highly desirable. Herein, a facile one-pot synthesis strategy with the assistance of dual surface protecting agents was developed to fabricate carbon-supported Pd (Pd/C) nanodendrites with high mesoporosity. The mesoporous spherical Pd/C nanodendrites are built with connected nanoparticles with a small size of several nanometers and coated by simultaneously formed carbon layers. The used dual protecting agents, glycine and oleylamine, exhibit synergistic effects to engineer Pd growth to form the unique mesoporous dendritic structure. Benefiting from the mesoporous feature, small size, defect-rich surface and carbon coating, the obtained mesoporous Pd/C nanodendrites exhibit great electrocatalytic performance toward the oxygen reduction reaction (ORR).

9.
PLoS One ; 16(4): e0250380, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33886641

RESUMEN

Essential genes, which form the basis of life activities, are crucial for the survival of organisms. Essential genes tend to be located in operons, but how they are distributed in operons is still unclear for most prokaryotes. In order to clarify the general rule of position preference of essential genes in operons, an index of the average position of genes in an operon was proposed, and the distributions of essential and non-essential genes in operons in 51 bacterial genomes and two archaeal genomes were analyzed based on this new index. Consequently, essential genes were found to preferentially occupy the front positions of the operons, which tend to be expressed at higher levels.

10.
Chin J Nat Med ; 19(4): 241-254, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33875165

RESUMEN

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl4)-induced fibrosis model. Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels, inflammatory cell infiltration and collagen deposition caused by CCl4. The increased expression of liver fibrosis markers, such as collagen 1, fibronectin, α-smooth muscle actin (α-SMA) and transforming growth factor-ß (TGF-ß), and inflammatory factors, such as chemokine (C-C motif) ligand 2 (MCP-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2 (ERK1/2)-protein kinase B (AKT) signaling pathways. Collectively, these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition, decreasing inflammatory reactions and bile acid accumulation, which provides insights into the mechanisms of herb-pair in improving liver fibrosis.

11.
Artículo en Inglés | MEDLINE | ID: mdl-33876278

RESUMEN

PURPOSE: To investigate the etiologies and the clinical characteristics of angle-closure glaucoma (ACG) patients younger than 40 years old in Chinese. METHODS: Inpatients with diagnosis of ACG and diagnosed age younger than or equal to 40 years old, who were admitted in Eye, Ear, Nose, and Throat Hospital Fudan University from 2002 to 2017, were included in this retrospective non-comparative case series. The underlying causes and clinical features for all the patients were analyzed by comprehensive review of medical charts. RESULTS: A total of 298 patients (463 eyes) met the criteria, including 153 females (51.3%) and 145 males (48.7%); the mean age was 25.6 ± 13.0 years. Primary angle-closure glaucoma (PACG), uveitis, and anterior segment dysgenesis (ASD) were the top three etiologies in our patients, which accounted for 32.6%, 20.3%, and 15.1% of the total patients respectively. PACG mainly occurs after 30 years of age and ASD is the top reason of ACG in patients younger than 20 years old. Other known etiologies include iridocorneal endothelial syndrome, neovascular glaucoma, nanophthalmos, retinitis pigmentosa, spherophakia, bestrophinopathy, persistent fetal vasculature, iridociliary cysts, congenital retinoschisis, Marfan's syndrome, retinopathy of prematurity, familial exudative vitreoretinopathy, congenital retinal folds, Coat's disease, and neurofibromatosis. CONCLUSIONS: We described the uncommon presentation of ACG in Chinese young patients. Although unusual, most of the etiologies could be identified. Therefore, more careful and comprehensive examinations are needed for early detection and timely treatment for young ACG patients.

12.
Ultrasound Med Biol ; 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33858722

RESUMEN

The conventional manual approach to measurement of aortic pulse wave velocity (PWV) by Doppler ultrasonography is time consuming and operator dependent. Here we report a new semi-automated methodology for more efficient and objective measurement of aortic PWV and results of tests of its clinical feasibility and reproducibility. Carotid-femoral pulse wave velocity (cfPWV) was measured in 50 patients with suspected coronary artery disease (aged 59.2 ± 10.0 y, 36 males) by three independent observers, including two experienced sonographers and one cardiologist without ultrasonographic experience. The cfPWV measured by the semi-automatic method (cfPWVA) was compared with reference values obtained by averaging measurements by two experienced sonographers using the conventional standard manual method (cfPWVM). Measurements of cfPWVA were feasible in all 50 patients and exhibited excellent agreement with averaged cfPWVM from the two experienced sonographers, with an intraclass correlation coefficient (ICC) of 0.915 (95% confidence interval: 0.876-0.942). The inexperienced observer-measured cfPWVA did not differ from the cfPWVM measured by the two experienced sonographers (8.04 ± 1.29 vs. 8.14 ± 1.32 m/s, p > 0.05), with a high consistency by ICC of 0.877 (0.793-0.928). Bland-Altman plots further illustrated the good agreement between the two methods and good intra- and inter-observer reproducibility. Time consumption for cfPWV measurement using the new method was significantly less than that for the manual method (122 ± 35 s vs. 455 ± 105 s, p < 0.0001), saving about 73% of the time. This new semi-automatic methodology for aortic PWV measurement not only has an accuracy similar to that of the conventional standard manual method but is also highly feasible and time saving. It may provide a reliable, simple and reproducible approach to arterial stiffness evaluation in clinical settings.

13.
Front Cell Infect Microbiol ; 11: 648040, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33842394

RESUMEN

Objective: To investigate the characteristics of hosts, antimicrobial susceptibility, and molecular epidemiology of mucoid serotype 3 Streptococcus pneumoniae (S. pneumoniae) isolated from children in China. Method: S. pneumoniae isolates collected between January 2016 and December 2019 were analyzed. S. pneumoniae isolates with mucoid phenotype were selected visually, and serotype 3 isolates were confirmed by Quellung reaction. The antimicrobial susceptibility was measured by E-test. Multilocus sequence typing was used for clonal analysis. Results: Twenty (3.04%) isolates of mucoid serotype 3 S. pneumoniae were identified from 657 clinical isolates, and all of them were noninvasive strains. The mean age of the hosts was 5.69 ± 3.28 years. The isolates included: 50.0% from the dissected tonsil or adenoid tissue in children with obstructive sleep apnea-hypopnea syndrome, 45.0% from sputum or bronchial lavages in children with pneumonia, and 5.0% from vaginal secretions of one patient with vulvovaginitis. All isolates were susceptible to penicillin, cefuroxime, ceftriaxone, meropenem, vancomycin, levofloxacin, trimethoprim/sulfamethoxazole, and rifampin but resistant to erythromycin. Sequence type (ST)505 and its clonal complex (CC) were the main genotypes (95%). Antimicrobial susceptibility of ST180 and ST505 were compared, and the minimum inhibitory concentration (MIC) of ST505 isolates was significantly higher than that of ST180 for tetracycline, trimethoprim/sulfamethoxazole, and meropenem. Conclusions: Mucoid serotype 3 Streptococcus pneumoniae can be isolated from various body parts, among which the respiratory system is the most common. It can cause noninvasive infection in children, and it has high susceptibility to a variety of antibiotics, especially ß-lactams, but is resistant to macrolides. CC505 is the novel clonal complex found in China, which may be related to the worldwide mainstream clonal complex (CC180) but has its own biological characteristics.

14.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(4): 431-438, 2021 Apr 15.
Artículo en Chino | MEDLINE | ID: mdl-33855826

RESUMEN

Objective: To compare the effectiveness of posterior malleolus fractures treated by plate and screw internal fixation through posterolateral approach. Methods: The clinical data of 95 patients with posterior malleolus fractures who were admitted between January 2016 and December 2019 and met the selection criteria were retrospectively analysed. They were divided into plate group (44 cases, treated with posterolateral plate internal fixation) and screw group (51 cases, treated with posterolateral screw internal fixation) according to different treatment methods. There was no significant difference in general data between the two groups of patients such as age, gender, cause of injury, side of injury, ankle fracture or injury classification, time from injury to operation, and percentage of posterior ankle fracture area to the distal tibia articular surface ( P>0.05). The operation time, hospital stay, fracture healing time, and surgical complications were compared between the two groups. Imaging examinations (X-ray film, CT scan and reconstruction) were used to assess the reduction quality of ankle fracture, articular congruity, and re-displacement in ankle fracture. At last follow-up, the pain visual analogue scale (VAS) score was used to evaluate the patients' pain, and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was used to evaluate ankle joint function. Results: Patients in both groups were followed up 6-30 months, with an average of 18.2 months. The operation time of the plate group was significantly longer than that of the screw group ( U=-2.040, P=0.041); there was no significant difference in hospital stay between the two groups ( U=-1.068, P=0.285). Incision swelling occurred in 2 cases in the plate group, sural nerve injury in 3 cases, and traumatic arthritis in 2 cases during follow-up. In the screw group, there were 1, 2, and 2 cases, respectively. The incidence of complications in the two groups (15.9% vs. 9.8%) was not significantly different ( P=0.372). All patients who underwent tibiofibular screw fixation underwent the removal of the tibiofibular screw before taking full weight bearing at 12 weeks after operation, and there was no screw fracture and retention. During the follow-up, there was no infection, re-displacement of fracture, delayed bone union or nonunion, and there was no significant difference in fracture healing time between the two groups ( t=0.345, P=0.731). There was no significant difference between the two groups of reduction quality of ankle fracture and articular congruity evaluation results ( P>0.05). At last follow-up, there was no significant difference in VAS score, AOFAS ankle-hindfoot score and evaluation grade between the two groups ( P>0.05). Conclusion: Both the plate and screw internal fixation through posterolateral approach can achieve satisfied effectiveness in the treatment of posterior ankle fractures with maintenance of fracture reduction, and recovery of ankle joint function. The screw internal fixation has the advantages of minimal invasion and shorter operation time.


Asunto(s)
Fracturas de Tobillo , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Tornillos Óseos , Fijación Interna de Fracturas , Humanos , Estudios Retrospectivos , Tibia , Resultado del Tratamiento
15.
Vaccines (Basel) ; 9(3)2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33808531

RESUMEN

K48-linked ubiquitination determining antigen degradation and the endosomal recruitments of p97 and Sec61 plays vital roles in dendritic cell (DC) cross-presentation. Our previous studies revealed that nicotine treatment increases bone marrow-derived dendritic cell (BM-DC) cross-presentation and promotes BM-DC-based cytotoxic T lymphocyte (CTL) priming. But the effect of nicotine on K48-linked ubiquitination and the mechanism of nicotine-increased BM-DC cross-presentation are still uncertain. In this study, we first demonstrated that ex vivo nicotine administration obviously increased K48-linked ubiquitination in BM-DC. Then, we found that K48-linked ubiquitination was essential for nicotine-augmented cross-presentation, BM-DC-based CTL priming, and thereby the superior cytolytic capacity of DC-activated CTL. Importantly, K48-linked ubiquitination was verified to be necessary for nicotine-augmented endosomal recruitments of p97 and Sec61. Importantly, mannose receptor (MR), which is an important antigenic receptor for cross-presentation, was exactly catalyzed with K48-linked ubiquitination by the treatment with nicotine. Thus, these data suggested that K48-linked ubiquitination contributes to the superior adaptive immunity of nicotine-administrated BM-DC. Regulating K48-linked ubiquitination might have therapeutic potential for DC-mediated immune therapy.

16.
Anal Cell Pathol (Amst) ; 2021: 6683391, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33828938

RESUMEN

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancers in developing countries. A major contributor to the high mortality rate of OSCC is the tendency of oral cancer cells to metastasize to lymph nodes around the head and neck during the early stages of cancer development. Matrix metalloproteinase 9 (MMP-9), an endopeptidase, can degrade the extracellular matrix and basement membrane and plays a key role in tumor invasion and metastasis. In vitro, cell migration ability was conducted by scratching assays. We also investigated the interaction abilities between OSCC cells and vascular endothelial cells (ECs) by an adhesion assay and transendothelial migration assay. And we established a BALB/c nude mouse tongue-xenografted metastasis model to investigate the role of MMP-9 and explore its potential underlying mechanism in OSCC growth, lymph node metastasis, and angiogenesis in vivo. The results showed that knockdown of MMP-9 could significantly suppress OSCC cell migration, proliferation, interactions between endothelial cells, xenografted tumor growth, and angiogenesis and simultaneously markedly inhibited OSCC cell metastasis to mouse lymphonodi cervicales superficiales, axillary lymph nodes, and even distant inguinal lymph nodes. Mechanistic studies revealed that knockdown of MMP-9 also led to a decreased expression of RhoC, Src, and F-actin by RT-PCR, western blotting, and immunohistochemistry. And the bioinformatic analysis showed that MMP-9, RhoC, and Src mRNA expression was positively and linearly correlated in OSCC on TCGA database. Together, our findings indicated that MMP-9 plays a very important role in OSCC growth, migration, angiogenesis, and lymph node metastasis, and its potential mechanism may be mediated by RhoC and Src gene expression.

17.
Reprod Domest Anim ; 2021 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-33866621

RESUMEN

Cows are susceptible to pathogenic bacterial infection after pregnancy, leading to inflammation of the endometrium. Aucubin (AU) has been proven to exhibit highly effective anti-inflammatory activity, but its ability to protect against endometritis in dairy cows remains unclear. Therefore, the goal of the present study was to evaluate the protective effect of AU on the LPS-induced inflammatory response of bovine endometrial epithelial cells (BEECs). After pre-treating BEECs with AU (10, 20 and 50 µM) for 6 hr, the cells were stimulated with LPS for 3 hr. Subsequently, BEECs apoptosis was analysed by flow cytometry, the expression of pro-inflammatory cytokine mRNA was detected by qRT-PCR, and changes in NF-κB and Keap1/Nrf2 signalling were analysed by western blotting and immunofluorescence analyses. The results showed that AU can reduce TNF-α, IL-1ß, IL-6, COX-2 and iNOS mRNA expression in BEECs and reduce cell apoptosis. Furthermore, AU significantly reduced the level of NF-κB p65 and IκB phosphorylation and inhibited the nuclear translocation of NF-κB p65. AU also activated the Keap1/Nrf2 pathway, promoting the nuclear transfer of Nrf2 and increasing Keap1, Nrf2, HO-1 and NQO1 mRNA and protein levels. Taken together, these results indicate that AU ameliorates the LPS-induced inflammatory response by inhibiting NF-κB and activating the Keap1/Nrf2 signalling pathway, which has a protective effect on BEECs.

18.
Nat Commun ; 12(1): 2396, 2021 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-33888704

RESUMEN

Arrestins recognize different receptor phosphorylation patterns and convert this information to selective arrestin functions to expand the functional diversity of the G protein-coupled receptor (GPCR) superfamilies. However, the principles governing arrestin-phospho-receptor interactions, as well as the contribution of each single phospho-interaction to selective arrestin structural and functional states, are undefined. Here, we determined the crystal structures of arrestin2 in complex with four different phosphopeptides derived from the vasopressin receptor-2 (V2R) C-tail. A comparison of these four crystal structures with previously solved Arrestin2 structures demonstrated that a single phospho-interaction change results in measurable conformational changes at remote sites in the complex. This conformational bias introduced by specific phosphorylation patterns was further inspected by FRET and 1H NMR spectrum analysis facilitated via genetic code expansion. Moreover, an interdependent phospho-binding mechanism of phospho-receptor-arrestin interactions between different phospho-interaction sites was unexpectedly revealed. Taken together, our results provide evidence showing that phospho-interaction changes at different arrestin sites can elicit changes in affinity and structural states at remote sites, which correlate with selective arrestin functions.

19.
Food Funct ; 12(8): 3705-3719, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-33900354

RESUMEN

Similar to other food contaminants, dietary oxidized soybean oil (OSO) is also a toxic xenobiotic for animal and human nutrition. This research evaluated the effects of maternal OSO exposure during lactation on mammary mitochondrial injury and intestinal barrier of sucking progeny. Twenty-four female adult SD rats were fed a fresh soybean oil (FSO) homozygous diet (7%) or an OSO homozygous diet (7%) during lactation. On day 21 of lactation, upregulated mRNA expression of Sirt3 and PRDX3 and downregulated mRNA expression of Mfn2 were observed in mammary tissues in the OSO group compared to the control group (P < 0.05). Maternal OSO consumption increased the FasL transcriptional level in the mammary glands of rat dams (P < 0.05), while the mRNA expression of Bax, Bcl-2, Caspase3, and Fas was not different from that in the control group (P > 0.05). OSO enhanced the Nrf2 transcriptional level and decreased the expression of Keap1 and PPARα in mammary tissues (P < 0.05). In addition, the contents of CAT, MDA, SOD were not affected by dietary OSO (P > 0.05), while the concentration of H2O2 was significantly decreased in the OSO-treated mammary glands of rat dams (P < 0.05). Maternal OSO exposure during lactation did not affect the organ coefficients of pups (P > 0.05). However, maternal OSO consumption influenced the intestinal tight junction protein expression of progeny (P < 0.05). In summary, the present study demonstrated that dietary OSO may aggravate mammary injury and mitochondria dysfunction, but the OSO-induced damage was self-alleviating via the promotion of Sirt3 and PRDX3 expression and further scavenging of oxidative products.

20.
Theranostics ; 11(11): 5160-5173, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33859740

RESUMEN

Objectives: Disruption of anisotropic phenotypes of the meniscus would contribute to OA progression. Exploring phenotype changes of the anisotropic meniscus in joint degeneration would help understand the biologic interaction between the meniscus and OA, and further facilitate the therapeutic strategies of meniscus injury-related joint degeneration. Meanwhile, engineering biomimetic meniscal tissue mimicking the anisotropy of the healthy meniscus remains a challenge. Methods & Results: Meniscal disruption of phenotype anisotropy (PBV growth, cellular phenotype and ECM depositions) was confirmed in OA patient samples. To recapitulate healthy meniscus phenotypes, 3D-bioprinted anisotropic TCM meniscus constructs with PBV growth and regional differential cell and ECM depositions were generated. Transplanted 3D-bioprinted meniscus into rabbit knees recapitulated phenotypes of native healthy meniscus and conferred long-term protection against secondary joint degeneration. Conclusion: 3D-bioprinted TCM meniscus not only restored the anisotropy of native healthy meniscus with PBV infiltration and better shape retention, but better maintained joint function and prevented secondary joint degeneration, which provided a new strategy for the clinical treatment of meniscus injury-related joint degenerative diseases.

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