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1.
J Genet Genomics ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34757038

RESUMO

Melastomataceae have abundant morphological diversity with high economic and ornamental merit in Myrtales. The phylogenetic position of Myrtales is still contested. Here, we report the first chromosome-level genome assembly of Melastoma dodecandrum in Melastomataceae. The assembled genome size was 299.81 Mb with a contig N50 value of 3.00 Mb. Genome evolution analysis indicated that M. dodecandrum, Eucalyptus grandis and Punica granatum were clustered into a clade of Myrtales and formed a sister group with the ancestor of fabids and malvids. We found that M. dodecandrum experienced four whole-genome polyploidization events: the ancient event was shared with most eudicots, one event was shared with Myrtales, and the other two events were unique to M. dodecandrum. Moreover, we identified MADS-box genes and found that the AP1-like genes expanded, and AP3-like genes might have undergone subfunctionalization. We found that the SUAR63-like genes and AG-like genes showed different expression patterns in stamens, which may be associated with heteranthery. In addition, we found that LAZY1-like genes were involved in the negative regulation of stem branching development, which may be related to its creeping features. Our study sheds new light on the evolution of Melastomataceae and Myrtales, which provides a comprehensive genetic resource for future research.

2.
Front Immunol ; 12: 769775, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804060

RESUMO

The crosstalk between the immune system and microbiota drives an amazingly complex mutualistic symbiosis. In mammals, the upper respiratory tract acts as a gateway for pathogen invasion, and the dynamic interaction between microbiota and mucosal immunity on its surface can effectively prevent disease development. However, the relationship between virus-mediated mucosal immune responses and microbes in lower vertebrates remains uncharacterized. In this study, we successfully constructed an infection model by intraperitoneally injecting common carp (Cyprinus carpio) with spring viremia of carp virus (SVCV). In addition to the detection of the SVCV in the nose and pharynx of common carp, we also identified obvious histopathological changes following viral infection. Moreover, numerous immune-related genes were significantly upregulated in the nose and pharynx at the peak of SVCV infection, after which the expression levels decreased to levels similar to those of the control group. Transcriptome sequencing results revealed that pathways associated with bacterial infection in the Toll-like receptor pathway and the Nod-like receptor pathway were activated in addition to the virus-related Rig-I-like receptor pathway after SVCV infection, suggesting that viral infection may be followed by opportunistic bacterial infection in these mucosal tissues. Using 16S rRNA gene sequencing, we further identified an upward trend in pathogenic bacteria on the mucosal surface of the nose and pharynx 4 days after SVCV infection, after which these tissues eventually reached new homeostasis. Taken together, our results suggest that the dynamic interaction between mucosal immunity and microbiota promotes the host to a new ecological state.

3.
Toxicol Lett ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838997

RESUMO

Liver fibrosis is a reversible wound healing reaction characterized by abnormal accumulation of extracellular matrix (ECM) in response to liver injury. Recent studies have shown that it can be epigenetically regulated, especially by microRNAs (miRNAs). It has been acknowledged that activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Notably, our results showed that miR-195-3p was increased in HSCs isolated from CCl4-treated mice and that the increase was more pronounced as the degree of liver fibrosis increased. Moreover, treatment of LX-2 cells, a human immortalized hepatic stellate cell line, with TGF-ß1 resulted remarkable upregulation of miR-195-3p. Gain-of-function and loss-of-function experiments have suggested that the increased levels of miR-195-3p inhibit the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN), a negative regulator of the PI3K/Akt/mTOR signaling pathway in liver fibrosis, thereby contributing to HSC activation and proliferation and promoting the expression of profibrotic genes, such as α-SMA and collagen I, in LX-2 cells, which accelerates the accumulation of fibrous extracellular matrix deposition in the liver, while knockdown of miR-195-3p induced the opposite effect. Taken together, these results provide evidence for the harmful role of miR-195-3p in CCl4-treated mouse liver fibrosis.

4.
Biotechnol Adv ; 53: 107865, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763051

RESUMO

Fucoxanthin, the most abundant but nearly untapped carotenoid resource, is in the spotlight in the last decade from various perspectives due to a wide range of bioactivities and healthy benefits. The exploitation of fucoxanthin for nutraceutical and pharmaceutical purposes encompasses enormous scientific and economic potentials. Traditional production of fucoxanthin from brown algae (macroalgae) is constrained by limited yield and prohibitively high cost. Microalgae, as the most diverse photoautotrophs, hold the promises as sustainable sources and ideal cell factories for commercial fucoxanthin production, owing to their rich fucoxanthin content and excellent biomass productivity. In this work, the recent progress in upstream (microalgae selection, optimization of culture conditions, trophic modes, cultivation strategies and biosynthesis pathway) as well as downstream processes (extraction) of fucoxanthin production has been comprehensively and critically reviewed. The major bottlenecks, such as screening of fucoxanthin-producers, conflict between biomass and fucoxanthin accumulation under high light condition, unclear steps in biosynthesis pathway and limited evaluation of outdoor scale-up cultivation and extraction, have been pinpointed. Most importantly, the applications of emerging and conventional techniques facilitating commercialization of microalgal fucoxanthin are highlighted. The reviewed and evaluated include breeding and high-throughput screening methods of elite strains; flashing light effect inducing concurrent biomass and fucoxanthin accumulation; fucoxanthin biosynthesis and the regulatory mechanisms associating with its accumulation elucidated with the development of genetic engineering and omics techniques; and photobioreactors, harvesting and extraction techniques suitable for scaling up fucoxanthin production. In conclusion, the prospects of microalgal fucoxanthin commercialization can be expected with the joint development of fundamental phycology and biotechnology.

5.
Bioresour Technol ; : 126364, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34838634

RESUMO

The rapid start-up and stable operation of the single-stage partial nitritation-anammox (PNA) process remains a challenge in practical applications. An integrated investigation of nitrogen removal performance, sludge characteristics, activity and abundance, and microbial dynamics was implemented for 360 days via an airlift internal circulation reactor. During long-term operation, the reactor realized a stable dissolved oxygen (DO) partition and cultivated granular sludge. The nitrogen removal rate increased from 0.15 kg-N/m3/d to 1.24 kg-N/m3/d, and a high nitrogen removal efficiency of 82.6% was obtained. A stable DO partition further accelerated the bioreaction rates and enhanced the activity of functional microbes. The activities of ammonia oxidation and anammox reached 1.21 g-N/g-VSS/d and 1.43 g-N/g-VSS/d, respectively. Sludge granulation efficiently enriched the abundances of Candidatus Brocadia (7.4%) and Nitrosomonas (5.2%). These results demonstrated that efficient DO partition and stable culture of granular sludge could enhance the synergy of functional microbes for autotrophic nitrogen removal.

6.
Front Immunol ; 12: 731842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630412

RESUMO

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N 6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

7.
J Leukoc Biol ; 110(6): 1023-1031, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34643294

RESUMO

The 78-kDa glucose-regulated protein (GRP78) has extracellular, anti-inflammatory properties that can aid resolving inflammation. It has been established previously that GRP78 induced myeloid CD11c+ cell differentiation into distinct tolerogenic cells. This tolerance induction makes GRP78 a potential therapeutic agent for transplanted allogeneic grafts and autoimmune diseases, such as type 1 diabetes. In this research, it is revealed that rmGRP78-treated NOD mice bone marrow-derived CD11c+ cells (GRP78-DCs) highly expressed B7-H4 but down-regulated CD86 and CD40, and retained a tolerogenic signature even after stimulation by LPS. In the assessment of in vivo therapeutic efficacy after the adoptive transfer of GRP78-DCs into NOD mice, fluorescent imaging analyses revealed that the transfer specifically homed in inflamed pancreases, promoting ß-cell survival and alleviating insulitis in NOD mice. The adoptive transfer of GRP78-DCs also helped reduce Th1, Th17, and CTL, suppressing inflammatory cytokine production in vivo. The findings suggest that adoptive GRP78-DC transfer is critical to resolving inflammation in NOD mice and may have relevance in a clinical setting.

8.
Eur J Pharmacol ; 911: 174462, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536366

RESUMO

Liver fibrosis is a persistent pathological repair of chronic liver injury, which is characterized by excessive deposition of collagen-dominated extracellular matrix (ECM). It is well known that hepatic fibrosis can be reversed in the absence of etiology. Studies have shown that long non-coding RNA (Lnc RNA) maternally expressed gene3 (MEG3) has strong effects on the activation of hepatic stellata cells (HSCs). However, the function of MEG3 in the reversal of liver fibrosis has not been studied. In this experiment, we studied the content expression, function, and part of the potential mechanism of MEG3 in reversing liver fibrosis. In in vivo and in vitro models, we found that MEG3 was down-regulated during the formation of liver fibrosis, while it was up-regulated during the reversal of liver fibrosis. Then, it was found that the silencing of MEG3 could gradually restore the activity of the inactivated LX-2 cells, Overexpression of MEG3 can inhibit the activation of LX-2 cells, accelerate the reversal of liver fibrosis. Through catRAPID analysis, it was found that NLR family CARD domain containing 5 (NLRC5) may be a target of MEG3. We found that, after MEG3 silencing, NLRC5 expression was upregulated in LX-2 cells in the reverse phase, while, after MEG3 overexpression, NLRC5 expression was decreased. Further, we verified that MEG3 can target NLRC5 through RNA pull down experiment. Therefore, MEG3 may inhibit the activation of hepatic stellate cells by targeting NLRC5, thus accelerating the reversal of hepatic fibrosis.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34367306

RESUMO

Background: Q-1 is a novel compound extracted from the Miao medicine Tiekuaizi. Although Q-1 is known to be a coumarin derivative, its structure has not been deposited in the ACX library. Our previous study showed that Q-1 inhibits the activity of inflammatory cells. This study explores the efficacy of Q-1 in regulating rheumatoid arthritis (RA). The findings show that Q-1 acts through the NF-κB signaling pathway. Methods: The effects of Q-1 were explored using a bovine type II collagen-induced arthritis (CIA) rat model. The CIA rats were intragastrically administered with high (30 mg·kg-1) or low (15 mg·kg-1) doses of Q-1. The control group was administered with an equal volume of drinking water, while the positive control group was administered with Tripterygium glycoside (9.45 mg·kg-1) for 28 consecutive days. The arthritis indices and ankle joint swelling rates were determined. The levels of IL-1ß, IL-6, monocyte chemoattractant protein-1 (MCP-1) in serum and sialic acid (SA) in liver homogenate were determined by enzyme-linked immunosorbent assay (ELISA). The pathological features of the ankle joint were analyzed by hematoxylin and eosin (HE) staining. The IκB, P-IκB, P65, and P-P65 protein levels in synovial tissue were assayed by western blotting. Results: The arthritis index, ankle joint swelling rate, IL-1ß, IL-6, and MCP-1 levels in serum, SA level in liver tissue, and IκB, P-IκB, P65, and P-P65 protein levels in synovial tissues were significantly higher (P < 0.01) in the CIA model compared to the control group. RA was successfully replicated by the CIA model, as shown by the joint swelling results and histopathological sections of the ankle. Notably, all the above indicators decreased significantly (P < 0.01) after treatment with Q-1 compared to the model. In addition, animals treated with Q-1 showed lower inflammation in the ankle joints than the model rats. Conclusion: The findings indicate that Q-1 effectively inhibited RA in rats by downregulating IκB, P-IκB, P65, and P-P65, inhibiting the excessive release of inflammatory factors, and inhibiting the overactivation of the NF-κB signaling pathway.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1334-1339, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362526

RESUMO

OBJECTIVE: To explore the relationship between plasma sST2/Reg3α levels and acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 29 pediatric patients received allo-HSCT treatment in Department of Hematology and Oncology of Wuhan Children's Hospital from January 2019 to January 2020 were collected. Peripheral blood samples were collected at 14 and 28 day after allo-HSCT. The plasma concentrations of sST2 and Reg3α were detected by Luminex assay. RESULTS: Among 29 patients there were 15 males and 14 females with a median age of 53 (29-117) months. After allo-HSCT, 18 patients developed grade 0-I aGVHD; while 11 patients developed grade II-IV aGVHD. These included skin aGVHD in 6 cases, gastrointestinal aGVHD (GI-aGVHD) in 3 cases and gastrointestinal/skin aGVHD in 5 cases. Plasma sST2 level in II-IV aGVHD group showed significantly higher than that in 0-I aGVHD group at 28 days after allo-HSCT [101.81 (73.94-150.77) ng/ml vs 48.97 (28.82-56.69) ng/ml, P=0.021]. Also, the plasma sST2 level was significantly higher in GI-aGVHD group than that in no-aGVHD group at 28 days after allo-HSCT [118.74 (87.00-243.36) ng/ml vs 48.97 (23.55-61.40) ng/ml, P=0.004]. Plasma sST2 level ≥65.34 ng/ml at 28 days after allo-HSCT showed a sensitivity of 85.7% and a specificity of 87.5% in predicting II-IV aGVHD. And the patients with a plasma sST2 level ≥65.34 ng/ml showed a significantly higher incidence of II-IV aGVHD than those with plasma sST2 level of < 65.34 ng/ml after allo-HSCT (P=0.021). There was no significant difference in plasma Reg3α level between the patients with II-IV aGVHD and the non-aGVHD ones. CONCLUSION: The increasing plasma sST2 level after allo-HSCT in children indicates the development of II-IV aGVHD, so sST2 is promising as a biomarker for predicting II-IV aGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Criança , Pré-Escolar , Feminino , Trato Gastrointestinal , Humanos , Incidência , Masculino , Plasma
11.
Front Immunol ; 12: 725330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386017

RESUMO

Gynecologic malignancies, mainly including ovarian cancer, cervical cancer and endometrial cancer, are leading causes of death among women worldwide with high incidence and mortality rate. Recently, adoptive T cell therapy (ACT) using engineered T cells redirected by genes which encode for tumor-specific T cell receptors (TCRs) or chimeric antigen receptors (CARs) has demonstrated a delightful potency in B cell lymphoma treatment. Researches impelling ACT to be applied in treating solid tumors like gynecologic tumors are ongoing. This review summarizes the preclinical research and clinical application of engineered T cells therapy for gynecologic cancer in order to arouse new thoughts for remedies of this disease.

12.
J Leukoc Biol ; 110(6): 1209-1223, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34402104

RESUMO

Stem cell-like memory T cells (Tscm), are a newly defined memory T cell subset with characteristics of long life span, consistent self-renewing, rapid differentiation into effector T cells, and apoptosis resistance. These features indicate that Tscm have great therapeutic or preventive purposes, including being applied in chimeric Ag receptor-engineered T cells, TCR gene-modified T cells, and vaccines. However, the little knowledge about Tscm development restrains their applications. Strength and duration of TCR signaling, cytokines and metabolism in the T cells during activation all influence the Tscm development via regulating transcriptional factors and cell signaling pathways. Here, we summarize the molecular and cellular pathways involving Tscm differentiation, and its clinical application for cancer immunotherapy and prevention.

13.
Front Pharmacol ; 12: 700373, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305608

RESUMO

Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and subsequent destruction of adjacent articular cartilage and bone. In our previous work we showed that phosphatase and tension homolog deleted on chromosome 10 (PTEN) contributes to the activation of fibroblast-like synoviocytes (FLS) in adjuvant-induced arthritis (AIA), but the underlying mechanism is not unknown. In this study, we show that PTEN is downregulated while DNA methyltransferase (DNMT)1 is upregulated in FLS from RA patients and a rat model of AIA. DNA methylation of PTEN was increased by administration of tumor necrosis factor (TNF)-α in FLS of RA patients, as determined by chromatin immunoprecipitation and methylation-specific PCR. Treatment with the methylation inhibitor 5-azacytidine suppressed cytokine and chemokine release and FLS activation in vitro and alleviated paw swelling in vivo. PTEN overexpression reduced inflammation and activation of FLS via protein kinase B (AKT) signaling in RA, and intra-articular injection of PTEN-expressing adenovirus into the knee of AIA rats markedly reduced inflammation and paw swelling. Thus, PTEN methylation promotes the inflammation and activation of FLS in the pathogenesis of RA. These findings provide insight into the molecular basis of articular cartilage destruction in RA, and indicate that therapeutic strategies that prevent PTEN methylation may an effective treatment.

14.
Sci Total Environ ; 784: 147221, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34088078

RESUMO

Semiconductor nanomaterials not only bring great convenience to peoples lives but also become a potential hazard to human health. The purpose of this study was to evaluate the toxicity of CuS/CdS nanocomposites in hepatocytes and mice liver. The CuS/CdS semiconductor nanocomposites were synthesized by a biomimetic synthesis - ion exchange strategy. Nanosize was confirmed by high-resolution transmission electron microscopy and dynamic light scattering. The composition and physical properties were measured by powder X-ray diffraction, Fourier transform infrared spectra, atomic absorption spectroscopy, thermogravimetry-differential scanning calorimetry and zeta potential analysis. The results revealed that CuS/CdS nanocomposites had 8.7 nm diameter and negative potential. Ion exchange time could adjust the ratio of CuS and CdS in nanocomposites. The toxicological study revealed that CuS/CdS nanocomposites could be internalized into liver cells, inhibited endogenous defense system (e.g. GSH and SOD), induced the accumulation of oxidation products (e.g. ROS, GSSG and MDA), and caused hepatocyte apoptosis. The in vivo experiments in Balb/c mice showed that the experimental dose (4 mg/kg) didn't cause observable changes in mice behavior, physical activity and pathological characteristics, but the continuous accumulation of Cd2+ in the liver and kidney might be responsible for its long-term toxicity.


Assuntos
Nanocompostos , Animais , Cobre , Hepatócitos , Fígado , Camundongos , Nanocompostos/toxicidade , Semicondutores , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
15.
FASEB J ; 35(6): e21622, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33982351

RESUMO

Abundant regulatory genes and complex circuits involving non-coding RNAs (ncRNAs) monitor the formation and development of hepatic fibrosis (HF). Circular RNAs (circRNAs) are a class of RNAs generated from protein coding genes by back-splicing, playing crucial roles in various pathological processes, including HF. However, little is known about mechanisms of action of circRNAs, let alone in HF. In this study, we found circUbe2k enhanced in CCl4 -induced HF mice and LX-2 cells stimulated with TGF-ß1, regulating the development of HF. Restraining the expression of circUbe2k inhibited α-SMA and Col1α1 expression in CCl4 -induced HF mice and in LX-2 cells stimulated with TGF-ß1. Furthermore, inhibiting circUbe2k expression reduced hepatic stellate cells (HSCs) activation and proliferation in vivo and in vitro. Mechanistically, we demonstrated a direct interaction between circUbe2k and miR-149-5p, which results in the modulation of TGF-ß2 expressions. Together, circUbe2k may act as a "catalyst" of HSCs activation and HF through the circUbe2k/miR-149-5p/TGF-ß2 axis. Our results provide unprecedented evidence for a significant role for circUbe2k to serve as a potential biomarker for HF therapy.


Assuntos
Regulação da Expressão Gênica , Cirrose Hepática/patologia , MicroRNAs/genética , RNA Circular/genética , Fator de Crescimento Transformador beta2/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Animais , Tetracloreto de Carbono , Proliferação de Células , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Fator de Crescimento Transformador beta2/genética
16.
Orthop Surg ; 13(4): 1309-1318, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955185

RESUMO

To find out which structure is crucial for the formation of shoulder impingement syndrome with the purpose of directing surgical procedures of subacromial decompression and discussing whether it is necessary to manage acromioclavicular joint during operation and how to do it properly. METHODS: This was a retrospective study. Clinical data and preoperative computed tomography (CT) images were collected from patients who were diagnosed with rotator cuff tears between January 2017 and August 2019 (sample size: 46) and those who were diagnosed without rotator cuff tears between March 2018 and August 2019 (sample size: 44) in our institution, respectively. Three-dimensional models of shoulders were established by multiplanar reconstruction of CT scans and measurements were performed on these models. The parameters such as the acromial length and width, the axial tilt, and the distance from acromial margin to glenoid plane were measured in an adjusted axial plane, and the critical shoulder angle and the spatial volume under acromioclavicular joint were measured in an adjusted coronal plane. The demographic characteristics, the acromial morphology and the spatial volume under acromioclavicular joint were compared to find significant differences between the two groups. The association between the axial tilt and the distance from acromial margin to glenoid plane was evaluated by an ordinary least squares linear regression. RESULTS: The patients with rotator cuff tears consisted of 16 males and 30 females, among which 30 right shoulders and 16 left shoulders were included. The patients without rotator cuff tears consisted of 28 males and 16 females, among which 15 right shoulders and 29 left shoulders were involved. Significant differences between the groups were found in the acromial width (3.332 cm vs 3.111 cm), the axial tilt (33.765° vs 23.829°), the critical shoulder angle (32.630° vs 30.363°), the distance from anterior 3 cm of lateral acromial margin (range, 2.476 cm-3.302 cm vs 1.993 cm-3.089 cm), and anterior 0.9 cm of medial acromial margin (range, 0.967 cm-2.369 cm vs 0.668 cm-1.993 cm) to glenoid plane, and the spatial volume under acromioclavicular joint (1.089 cm vs 1.446 cm) in the two groups. No significant differences were found in the age (60.0 years vs 58.3 years) or the acromial length (4.187 cm vs 4.184 cm). Significant association was revealed by linear regression analysis between the axial tilt and the distance from anterior two-thirds of lateral acromial margin to glenoid plane, and similar association was also found in the anterior half of medial margin. CONCLUSION: Anterior two-thirds of lateral acromial margin, anterior half of medial acromial margin, and inferior aspect of acromioclavicular joint are crucial structures and need to be fully decompressed when treating patients with rotator cuff tears.


Assuntos
Articulação Acromioclavicular/anatomia & histologia , Articulação Acromioclavicular/diagnóstico por imagem , Acrômio/anatomia & histologia , Acrômio/diagnóstico por imagem , Imageamento Tridimensional , Síndrome de Colisão do Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Articulação Acromioclavicular/cirurgia , Acrômio/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Síndrome de Colisão do Ombro/cirurgia
17.
Bioengineered ; 12(1): 1642-1662, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33955826

RESUMO

This study aims to originate agenomic instability-derived risk index (GIRI) for prognostic analysis of clear cell renal cell carcinoma (ccRCC) and explore the mutation characteristics, immune characteristics, and immunotherapy response defined by GIRI. Differentially expressed genome instability-associated genes were obtained from the genomic unstable (GU) group and the genomic stable (GS) group. Rigorous screening conditions were assigned to the screening of hub genes, which were then used to generate the GIRI through multivariate Cox regression analysis. The selected samples were assigned to the high-risk group or the low-risk group based on the median GIRI. Possible reasons for the prognostic differences in risk subgroups were explored from the aspects of mutation profiles, immune profiles, immunomodulators, and biological pathway activities. The possibility of immunotherapy response was predicted by Tumor Immune Dysfunction and Exclusion analysis results. The prediction of drugs that might reverse the expression profiles of the risk subgroups was discovered through theonnectivity Map (CMap). High-risk populations manifested poor overall survival than low-risk populations and were characterized by elevated cumulative mutation counts and tumor mutation burden. Also, high-risk populations had higher immune scores, immunomodulator (PD-1, CTLA4, LAG3, and TIGIT) expression, and genomic instability-related pathway activities, and were more likely to reap benefits from immunotherapy. Besides, we predicted several drugs (PI3K inhibitor, ATPase inhibitor, and phenylalanyl tRNA synthetase inhibitor) targeting risk subgroups. The well established GIRI was an effective cancer biomarker for predicting ccRCC prognosis and provided apotential reference value for identifying immunotherapy response.


Assuntos
Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Instabilidade Genômica , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Carcinoma de Células Renais/genética , Humanos , Imunoterapia , Neoplasias Renais/genética , Análise Multivariada , Mutação/genética , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
18.
Chemosphere ; 278: 130436, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33839386

RESUMO

To solve the bottleneck of the unstable accumulation of nitrite in the partial nitrification (PN)-anammox (AMX) in municipal wastewater treatment, a novel process called partial denitrification (PD)-AMX has been developed. PD-AMX, which is known for cost-efficiency and environmental friendliness, has currently exhibited a promising potential for the removal of biological nitrogen from municipal wastewater and has attracted much research interest regarding its process mechanisms, as well as its practical applications. Here, we review the recent advances in the PD process and its coupling to the anammox process, including the development, basic principles, main characteristics, and critical process parameters of the stable operation of the PD-AMX process. We also explore the microbial community and its characteristics in the system and summarize the knowledge of the dominant bacteria to clarify the key factors affecting PD-AMX. Then, we introduce the engineering feasibility and economic feasibility as well as the potential challenges of the process. The induction and implementation of partial denitrification and maintenance of mainstream anammox are critical issues to be urgently solved. Meanwhile, the implementation of a full mainstream anammox application remains burdensome, while the mechanism of partial denitrification coupled to anammox needs to be further studied. Additionally, stable operation performance and process control1 methods need to be optimized or developed for the PD-AMX system for better engineering practice. This review can help to accelerate the research and application of the PD-AMX process for municipal wastewater treatment.


Assuntos
Compostos de Amônio , Purificação da Água , Anaerobiose , Reatores Biológicos , Desnitrificação , Nitrogênio , Oxirredução , Esgotos , Águas Residuárias
19.
Int J Mol Sci ; 22(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33921035

RESUMO

Acquired treatment resistance is an important cause of death in prostate cancer, and this study aimed to explore the mechanisms of chemotherapy resistance in prostate cancer. We employed castration-resistant prostate cancer (CRPC), neuroendocrine prostate cancer (NEPC), and chemotherapy-resistant prostate cancer datasets to screen for potential target genes. The Cancer Genome Atlas (TCGA) was used to detect the correlation between the target genes and prognosis and clinical characteristics. Nei endonuclease VIII-like 3 (NEIL3) knockdown cell lines were constructed with RNA interference. Prostate cancer cells were treated with enzalutamide for the androgen deprivation therapy (ADT) model, and with docetaxel and cisplatin for the chemotherapy model. Apoptosis and the cell cycle were examined using flow cytometry. RNA sequencing and western blotting were performed in the knockdown Duke University 145 (DU145) cell line to explore the possible mechanisms. The TCGA dataset demonstrated that high NEIL3 was associated with a high T stage and Gleason score, and indicated a possibility of lymph node metastasis, but a good prognosis. The cell therapy models showed that the loss of NEIL3 could promote the chemotherapy resistance (but not ADT resistance) of prostate cancer (PCa). Flow cytometry revealed that the loss of NEIL3 in PCa could inhibit cell apoptosis and cell cycle arrest under cisplatin treatment. RNA sequencing showed that the knockdown of NEIL3 changes the expression of neuroendocrine-related genes. Further western blotting revealed that the loss of NEIL3 could significantly promote the phosphorylation of ATR serine/threonine kinase (ATR) and ATM serine/threonine kinase (ATM) under chemotherapy, thus initiating downstream pathways related to DNA repair. In summary, the loss of NEIL3 promotes chemotherapy resistance in prostate cancer, and NEIL3 may serve as a diagnostic marker for chemotherapy-resistant patients.


Assuntos
Resistencia a Medicamentos Antineoplásicos , N-Glicosil Hidrolases/deficiência , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , N-Glicosil Hidrolases/genética , N-Glicosil Hidrolases/metabolismo , Invasividade Neoplásica , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fase S/efeitos dos fármacos
20.
Front Immunol ; 12: 654758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897703

RESUMO

The mucosa of vertebrates is a particularly complex but dynamic environment in which the host constantly interacts with trillions of commensal microorganisms and pathogens. Although the internal and external mucosal microbiomes with immune defense of mammals have been well investigated, the relationship between mucosal microbes and their host's immune responses has not been systematically understood in the early vertebrates. In this study, we compared the composition and distribution of mucosal microbiota in common carp (Cyprinus carpio), and found that there were significant differences of microbiota between in the internal (gut) and external mucosal (buccal mucosa, gills and skin) tissues. Next, we successfully constructed an infection model with spring viremia of carp virus (SVCV). Specifically, following viral infection, the immune and antiviral related genes showed different up-regulation in all selected mucosal tissues while significant morphological changes were only found in external tissues including buccal mucosa, gills and skin. Using 16S rRNA gene sequence, we revealed that the abundance of Proteobacteria in mucosal tissues including buccal mucosa, gills and gut showed increased trend after viral infection, whereas the abundance of Fusobacteria significantly decreased in gut. In addition, the loss of dominant commensal microorganisms and increased colonization of opportunistic bacteria were discovered in the mucosal surfaces indicating that a secondary bacterial infection might occur in these mucosal tissues after viral infection. Overall, our results firstly point out the distribution of internal and external mucosal microbiota and analyze the changes of mucosal microbiota in common carp after SVCV infection, which may indicated that the potential role of mucosal microbiota in the antiviral process in early vertebrates.


Assuntos
Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade nas Mucosas , Microbiota , Rhabdoviridae/imunologia , Animais , Biomarcadores , Biologia Computacional/métodos , Disbiose , Doenças dos Peixes/patologia , Expressão Gênica , Imuno-Histoquímica , Metagenoma , Metagenômica/métodos , Membrana Mucosa/imunologia , Membrana Mucosa/microbiologia
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