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1.
Pharm Biol ; 60(1): 163-174, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35001799

RESUMO

CONTEXT: Yi Shen An (YSA) is an investigational composite of traditional Chinese medicine (Reference: 2010L000974) for the treatment of renal disease. OBJECTIVE: To investigate the protective effects of YSA against membranous glomerulonephritis (MGN). MATERIALS AND METHODS: Male Sprague-Dawley rats were injected with cationic bovine serum albumin (C-BSA) to create a model of MGN. Then, rats were orally treated with YSA at doses of 0.25, 0.5, 1 and 2 g/kg for 35 successive days; prednisone (5 mg/kg) was used as a positive control. At the end of the experimental period, we performed a series of tests, including 24 h urinary protein, and biochemical, immunological, antioxidative, coagulation indices, and histopathological examination. RESULTS: YSA-1 g/kg significantly lowered urinary protein from 68.37 to 30.74 mg (p < 0.01). Meantime, total protein (TP) and albumin (ALB) recovered from 66.26 and 20.51 g/L to 76.08 and 35.64 g/L (p < 0.01), respectively. YSA removed the deposition of immunoglobulin G (IgG) and complement 3c (C3c), prevented inter-capillary cell hyperplasia on the glomerular basement membrane (GBM), and reduced electron-dense deposits and fusion of podocytes. In addition, serum IgG and superoxide dismutase were significantly elevated. In contrast, malondialdehyde, total cholesterol, triglyceride, circulating immune complex (CIC), and immunoglobulin M decreased in the YSA-treated group. Moreover, the blood coagulation dysfunction was adjusted. DISCUSSION AND CONCLUSIONS: These findings indicate YSA may exert a therapeutic effect against MGN through the inhibition of CIC formation, and the removal of IgG and C3c deposition from the GBM, thus supporting the development of further clinical trials.

2.
Mol Med Rep ; 25(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34726255

RESUMO

Triple­negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The function of leucine­rich repeat­containing protein 15 (LRRC15), a member of the leucine­rich repeat superfamily, in TNBC has not yet been elucidated. The aim of this study was to identify the combined role of LRRC15 and Wnt/ß­catenin signalling pathway in the development of TNBC. The expression of LRRC15 in TNBC tissues was analysed using data from The Cancer Genome Atlas. Cell migration and invasion assays were conducted to study the function of LRRC15 in TNBC. The expression of Wnt/ß­catenin signalling proteins was analysed via western blotting. The effect of LRRC15 on ß­catenin nuclear localisation was measured by performing western blotting and luciferase assays. It was found that high LRRC15 expression was associated with poor prognosis in patients with TNBC. High expression of LRRC15 in cancer­associated fibroblasts (CAFs) promoted cell migration and invasion in TNBC cells. In addition, TNBC cells with LRRC15 overexpression in CAFs showed an aberrant increase in ß­catenin activity concomitant with nuclear localisation of ß­catenin, which inhibited its degradation. These results showed that LRRC15 promoted tumour migration and invasion in TNBC cells by regulating the Wnt/ß­catenin signalling pathway.

3.
J Mol Diagn ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34890778

RESUMO

Previous work indicated that the dual-target stool DNA test, iColocomf, showed potential utility for colorectal cancer (CRC) detection, but its clinical accuracy was not validated on larger groups. This study aimed to evaluate the performance of iColocomf in a multicenter clinical trial. In this double-blinded case-control study, we enrolled 1,164 participants from three independent hospitals, including 320 CRC patients, 148 adenomas, 396 interfering diseases, and 300 healthy controls. The primary indicators included sensitivity, specificity, and accuracy were estimated. Stool samples of participants were collected and tested by the assay. The test results were then verified by Sanger sequencing and retesting of resected participants. The sensitivity and specificity for CRC detection were 95.31% and 96.67%, respectively, with an accuracy of 90.29%. When combining the interfering diseases, the specificity was 88.39%. No statistically significant variations of positive detection rates were observed for the test in different patients' clinical features. For advanced adenomas (n=38) and non-advanced adenomas (n=110), the sensitivities were 63.16% and 33.64%, respectively. The average accuracy was 99.62% for the methylation status of 375 samples verified by Sanger sequencing, and 94.12% for 34 participants received the test second after surgical resection. The iColocomf test showed robust performance for the early detection of colorectal cancer and potential monitoring ability in clinical practice.

4.
Ecotoxicol Environ Saf ; 230: 113105, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34954678

RESUMO

Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.

5.
Plant Signal Behav ; : 2000808, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34839796

RESUMO

Protein tyrosine phosphatases play essential roles in plant growth and development and in plant responses to biotic or abiotic stresses. We recently demonstrated that an atypical dual-specificity protein tyrosine phosphatase in plants, AtPFA-DSP3 (DSP3), negatively regulates plant salt tolerance. Here, we report that a homolog of DSP3, AtPFA-DSP5 (DSP5), affects the response of plants to high-salt conditions. A loss-of-function mutant of DSP5 showed reduced sensitivity to salt treatment at the seed germination and vegetative stages of development while a gain-of-function mutant of DSP5 showed increased sensitivity to salt stress. The salt responses of dsp3dsp5 double-mutant plants were similar to those of dsp3 and dsp5 single-mutant plants. Gel overlay and firefly luciferase complementation assays showed that DSP5 interacts with MPK3 and MPK6 in vitro and in vivo. These results indicate that DSP5 is a novel negative regulator of salt responses in Arabidopsis that interacts directly with MPK3 and MPK6.

6.
Small ; : e2105308, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741427

RESUMO

The ever-increasing development of flexible and wearable electronics has imposed unprecedented demand on flexible batteries of high energy density and excellent mechanical stability. Rechargeable lithium (Li) metal battery shows great advantages in terms of its high theoretical energy density. However, the use of Li metal anode for flexible batteries faces huge challenges in terms of its undesirable dendrite growth, poor mechanical flexibility, and slow fabrication speed. Here, a highly scalable Li-wicking strategy is reported that allows ultrafast fabrication of mechanically flexible and electrochemically stable Li metal anodes. Through the rational design of the interface and structure of the wicking host, the mean speed of Li-wicking reaches 10 m2 min-1 , which is 1000 to 100 000 fold faster than the reported electrochemical deposition or thermal infusion methods and meets the industrial fabrication speed. Importantly, the Li-wicking process results in a unique 3D Li metal structure, which not only offers remarkable flexibility but also suppresses the dendrite formation. Paring the Li metal anode with lithium-iron phosphate or sulfur cathode yields flexible full cells that possess a high charging rate (8.0 mA cm-2 ), high energy density (300-380 Wh kg-1 ), long cycling stability (over 550 cycles), and excellent mechanical robustness (500 bending cycles).

7.
ACS Appl Mater Interfaces ; 13(48): 57214-57229, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34806874

RESUMO

Recently, photoassisted charging has been demonstrated as a green and sustainable approach to successfully enhance the capacitance of supercapacitors with low cost and good efficiency. However, their light-induced capacitance enhancement is relatively low and is lost quickly when the illumination is off. In this work, a novel active material system is developed for supercapacitors with the photoassisted charging capability by the decoration of a small amount of Bi2WO6 nanoparticles on an h-WO3 submicron rod surface in situ, which forms a typical type II band alignment heterostructure with a close contact interface through the co-sharing of W atoms between h-WO3 submicron rods and Bi2WO6 nanoparticles. The photogenerated charge carrier separation and transfer are largely enhanced in the h-WO3/Bi2WO6 submicron rod electrode, which subsequently allows more charge carriers to participate in its photoassisted charging process to largely enhance its capacitance improvement under simulated solar illumination than that of the h-WO3 submicron rod electrode. Furthermore, the h-WO3/Bi2WO6 submicron rod electrode could retain its photoinduced capacitance enhancement in the dark for an extended period of time from the photocatalytic memory effect. Thus, our work provides a solution to the two major drawbacks of reported supercapacitors with the light-induced capacitance enhancement property, and supercapacitors based on active materials with the photocatalytic memory effect could be utilized in various technical fields.

8.
Genet Mol Biol ; 44(3): e20210035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34606562

RESUMO

Superoxide dismutase proteins (SODs) are antioxidant enzymes with important roles in abiotic stress responses. The SOD gene family has been systematically analyzed in many plants; however, it is still poorly understood in maize. Here, a bioinformatics analysis of maize SOD gene family was conducted by describing gene structure, conserved motifs, phylogenetic relationships, gene duplications, promoter cis-elements and GO annotations. In total, 13 SOD genes were identified in maize and five members were involved in segmental duplication. Phylogenetic analysis indicated that SODs from maize and other plants comprised two groups, which could be further classified into different subgroups, with most members in the same subgroup having the same subcellular localization. The ZmSOD promoters contained 2-10 stress-responsive cis-elements with different distributions. Heatmap analysis indicated that ZmSODs were expressed in most of the detected tissues and organs. The expression patterns of ZmSODs were investigated under drought and salt treatments by qRT-PCR, and most members were responsive to drought or salt stress, especially some ZmSODs with significant expression changes were identified, such as ZmCSD2 and ZmMSD2, suggesting the important roles of ZmSODs in abiotic stress responses. Our results provide an important basis for further functional study of ZmSODs in future study.

9.
Res Sq ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34611654

RESUMO

What enabled SARS-CoV-2, but not other coronaviruses, to cause a global pandemic? Here we investigated key structural determinants of the pandemic. Using SARS-CoV-1 and bat RaTG13-CoV as comparisons, we identified two molecular switches that regulate the conformations of SARS-CoV-2 spike protein: (i) a furin motif loop turns SARS-CoV-2 spike from a closed conformation to a mixture of open and closed conformations, and (ii) a K417V mutation turns SARS-CoV-2 spike from mixed conformations to an open conformation. We showed that the open conformation favors viral potency by exposing the RBD for receptor binding and viral entry, while the closed conformation supports viral immune evasion by hiding the RBD from neutralizing antibodies. Hence SARS-CoV-2 spike has evolved to reach a balance between potency and immune evasiveness, which contributes to the pandemic spread of SARS-CoV-2.The dynamics between viral potency and invasiveness is likely to further evolve, providing insights into future evolution of SARS-CoV-2.

10.
BMJ Open ; 11(10): e043790, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598979

RESUMO

OBJECTIVES: As early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in evaluating the progression and prognosis of patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: Hospital-based study in China. PARTICIPANTS: Adult patients with COVID-19 from December 15, 2019 to March 15, 2020. END POINT: Disease severity and mortality. METHODS: Clinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis. RESULTS: 29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p<0.05). The multivariate logistic analysis suggested that CRP, NLR and D-dimer were independent risk factors for the disease progression of COVID-19 (all p<0.05). The model combining all of them owned the highest area under the receiver operating characteristic curve (AUC) predicting disease progression and death of COVID-19, with AUC of 0.894 (95% CI 0.857 to 0.931) and 0.918 (95% CI 0.873 to 0.962), respectively. Survival analysis suggested that the patients with a high level of CRP, NLR or D-dimer performed shorter overall survival time (all p<0.05). CONCLUSIONS: The combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.


Assuntos
COVID-19 , Laboratórios , Adulto , Progressão da Doença , Humanos , Neutrófilos , Prognóstico , Curva ROC , Estudos Retrospectivos , SARS-CoV-2
11.
Front Plant Sci ; 12: 751965, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675955

RESUMO

The wall-associated kinase (WAK) multigene family plays critical roles in various cellular processes and stress responses in plants, however, whether WAKs are involved in salt tolerance is obscure. Herein, we report the functional characterization of a rice WAK, WAK112, whose expression is suppressed by salt. Overexpression of OsWAK112 in rice and heterologous expression of OsWAK112 in Arabidopsis significantly decreased plant survival under conditions of salt stress, while knocking down the OsWAK112 in rice increased plant survival under salt stress. OsWAK112 is universally expressed in plant and associated with cell wall. Meanwhile, in vitro kinase assays and salt tolerance analyses showed that OsWAK112 possesses kinase activity and that it plays a negative role in the response of plants to salt stress. In addition, OsWAK112 interacts with S-adenosyl-L-methionine synthetase (SAMS) 1/2/3, which catalyzes SAM synthesis from ATP and L-methionine, and promotes OsSAMS1 degradation under salt stress. Furthermore, in OsWAK112-overexpressing plants, there is a decreased SAMS content and a decreased ethylene content under salt stress. These results indicate that OsWAK112 negatively regulates plant salt responses by inhibiting ethylene production, possibly via direct binding with OsSAMS1/2/3.

12.
PLoS Pathog ; 17(9): e1009897, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34492082

RESUMO

The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Imunogenicidade da Vacina , Nanopartículas/uso terapêutico , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Desenho de Fármacos , Feminino , Células HEK293 , Humanos , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos/imunologia
13.
Adv Mater ; 33(41): e2102802, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34432922

RESUMO

Because of the large abundance of sodium (Na) as a source material and the easy fabrication of Na-containing compounds, the sodium (Na) battery is a more environmentally friendly and sustainable technology than the lithium-ion battery (LIB). Na-metal batteries (SMBs) are considered promising to realize a high energy density to overtake the cost effectiveness of LIBs, which is critically important in large-scale applications such as grid energy storage. However, the cycling stability of the Na-metal anode faces significant challenges particularly under high cycling capacities, due to the complex failure models caused by the formation of Na dendrites. Here, a universal surface strategy, based on a self-regulating alloy interface of the current collector, to inhibit the formation of Na dendrites is reported. High-capacity (10 mAh cm-2 ) Na-metal anodes can achieve stable cycling for over 1000 h with a low overpotential of 35 mV. When paired with a high-capacity Na3 V2 (PO4 )2 F3 cathode (7 mAh cm-2 ), the SMB delivers an unprecedented energy density (calculated based on all the cell components) over 200 Wh kg-1 with flooded electrolyte, or over 230 Wh kg-1 with lean electrolyte. The dendrite-free SMB also shows high cycling stability with a capacity retention per cycle over 99.9% and an ultrahigh energy efficiency of 95.8%.

14.
Elife ; 102021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338634

RESUMO

Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking viral receptor angiotensin-converting enzyme 2 (ACE2). The lead drug candidate possessing an Fc tag (Nanosota-1C-Fc) bound to SARS-CoV-2 RBD ~3000 times more tightly than ACE2 did and inhibited SARS-CoV-2 pseudovirus ~160 times more efficiently than ACE2 did. Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy against live SARS-CoV-2 infection in both hamster and mouse models. Unlike conventional antibodies, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-Fc documented an excellent in vivo stability and a high tissue bioavailability. As effective and inexpensive drug candidates, Nanosota-1 may contribute to the battle against COVID-19.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Anticorpos de Domínio Único/farmacologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , COVID-19/metabolismo , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Modelos Moleculares , Pandemias , Ligação Proteica , Conformação Proteica , Receptores Virais/imunologia , Receptores Virais/metabolismo , Anticorpos de Domínio Único/química , Glicoproteína da Espícula de Coronavírus/metabolismo
15.
Front Plant Sci ; 12: 675838, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367201

RESUMO

Embryogenesis is a critical developmental process that establishes the body organization of higher plants. During this process, the biogenesis of chloroplasts from proplastids is essential. A failure in chloroplast development during embryogenesis can cause morphologically abnormal embryos or embryonic lethality. In this study, we isolated a T-DNA insertion mutant of the Arabidopsis gene EMBRYO DEFECTIVE 2726 (EMB2726). Heterozygous emb2726 seedlings produced about 25% albino seeds with embryos that displayed defects at the 32-cell stage and that arrested development at the late globular stage. EMB2726 protein was localized in chloroplasts and was expressed at all stages of development, such as embryogenesis. Moreover, the two translation elongation factor Ts domains within the protein were critical for its function. Transmission electron microscopy revealed that the cells in emb2726 embryos contained undifferentiated proplastids and that the expression of plastid genome-encoded photosynthesis-related genes was dramatically reduced. Expression studies of DR5:GFP, pDRN:DRN-GFP, and pPIN1:PIN1-GFP reporter lines indicated normal auxin biosynthesis but altered polar auxin transport. The expression of pSHR:SHR-GFP and pSCR:SCR-GFP confirmed that procambium and ground tissue precursors were lacking in emb2726 embryos. The results suggest that EMB2726 plays a critical role during Arabidopsis embryogenesis by affecting chloroplast development, possibly by affecting the translation process in plastids.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34388030

RESUMO

Background: WWP1 (WW domain-containing E3 ubiquitin protein ligase 1) is increased in several kinds of carcinomas, but the influence of WWP1 in papillary thyroid cancer (PTC) is not well understood. Materials and Methods: The expression of WWP1 in PTC tissues and cells is detected by real-time reverse transcription PCR. The biological role of WWP1 on PTC cell growth, apoptosis, migration, and invasion ability was assessed with the Cell Counting Kit-8, colony forming, flow cytometry, wound healing, and transwell assays, respectively. Results: The expression of WWP1 mRNA and protein is increased in PTC tissue samples and cells. There is closely correlation between the up expression of WWP1 and clinical parameters, such as tumor size, TNM, and distant metastasis. Knockdown of WWP1 blocks cell proliferation, migration, and invasion, causes cell cycle arrest, and induces apoptosis in PTC cells. Knockdown of WWP1 increases PTEN level and reduces p-PI3K and p-Akt level in PTC cells. Conclusions: Knockdown of WWP1 suppressed cell proliferation, migration, and invasion of PTC cell by downregulating the expression of p-PI3K and p-Akt, contributing to their understanding the pathogenesis of PTC.

17.
Biochem Biophys Res Commun ; 559: 183-190, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33945996

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the causes of cancer-related death worldwide. The abnormal proliferation ability of OSCC has become one of the major reasons for its poor prognosis. FK-506 binding protein 11 (FKBP11) is abnormally expressed in malignant tumors and affects many biological processes. The purpose of this study is to investigate the effect of FKBP11 on cell proliferation in OSCC and explore the possible regulatory mechanism. The expression of FKBP11 was detected by western blotting (WB) and/or real-time PCR in OSCC and paracancerous normal tissues in tongue squamous cell carcinoma (TSCC) cell lines, revealing high expression in OSCC and CAL-27 cells. Furthermore, FKBP11 knockdown inhibited the proliferation of CAL-27 cells by CCK-8 and colony formation assays. G2/M arrest and induction of apoptosis were observed using flow cytometry, Hoechst 33258 and Calcein-AM/PI staining, accompanied by changes in some cell cycle- and apoptosis-related proteins, including CDK1, Cyclin B1, p21, p27, p53, Bax, Bcl-2 and Caspase-3. Additionally, the expression of these proteins can be reversed by the use of pifithrin-α (PFT-α), a p53 inhibitor. An in vivo xenograft model further confirmed that FKBP11 enhanced OSCC progression. In conclusion, FKBP11 could promote cell proliferation by regulating G2/M phase and apoptosis via the p53/p21/p27 and p53/Bcl-2/Bax pathways, respectively, which suggests that it may be a new candidate target for the treatment of OSCC.


Assuntos
Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Transdução de Sinais , Proteínas de Ligação a Tacrolimo/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose/genética , Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , Proteínas de Ligação a Tacrolimo/genética
18.
Onco Targets Ther ; 14: 2463-2473, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883901

RESUMO

Objective: The purpose of this study was to investigate the function of actin-like protein 8 (ACTL8) on triple-negative breast cancer (TNBC) and its potential mechanisms. Methods: In our study, ACTL8 expression and the prognostic values of ACTL8 were evaluated via the dataset from the Cancer Genome Atlas (TCGA). At the same time, the expression of ACTL8 in TNBC cells was measured by Western blot and qRT-PCR. Then, the effects of ACTL8 on the growth and metastasis of TNBC were investigated by using 5-ethynyl-20-deoxyuridine (EdU), colony formation, flow cytometry, wound healing and transwell assays. Mechanistically, Western blot was performed to confirm the interaction between ACTL8 and phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in TNBC. Results: ACTL8 expression was upregulated in TNBC and associated with the poor prognosis of TNBC. Silencing ACTL8 suppressed the proliferation, migration and invasion, also promoted the apoptosis in MDA-MB-231 and BT-549 cells. Moreover, we found that silencing ACTL8 could inhibit the activation of PI3K/AKT/mTOR signaling pathway in MDA-MB-231 and BT-549 cells. Meanwhile, the impact of silencing ACTL8 on the proliferation, apoptosis, migration and invasion was enhanced by PI3K/AKT/mTOR pathway inhibitor (Wortmannin) and reversed by PI3K/AKT/mTOR pathway activator (740Y-P). Conclusion: Our data demonstrated that ACTL8 may facilitate the proliferation, migration and invasion, while inhibiting apoptosis through activating PI3K/Akt/mTOR signaling pathway in TNBC.

19.
Water Res ; 198: 117125, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33878660

RESUMO

Metal-free polymeric carbon nitride (C3N4) photocatalysts offer attractive technological advantages over the conventional transition metal oxides or sulfides -based photocatalysts in water disinfection, but their antimicrobial activities are limited by their rapid charge carrier recombination and low specific surface areas. By controlling photocatalytic pathways, we obtained in amino-rich holey ultrathin g-C3N4 nanosheets (AHUCN) a highly efficient inactivation rate against E-coli, which is the highest among the monolithic g-C3N4 and exceeds the antibacterial performance of the most of the previously reported g-C3N4-based photocatalysts. Both the experiments and theoretical calculations demonstrated that the high photocatalytic disinfection performance of AHUCN was derived from the synergistic advantages of their unique holey ultrathin structure and the amino - rich surface in controlling the charge separation and transfer, and most importantly in increasing the photo-production of the dominant antibacterial species, H2O2. From the analysis of the reactive oxygen species and rotating disk electrode (RDE) measurements, it was found that the presence of abundant surface amino groups enabled the switch of the oxygen-reduction pathway from the two-step single-electron indirect reduction on holey ultrathin g-C3N4 nanosheets (HUCN) to the one-step two-electron direct reduction on AHUCN. The switch of the H2O2 production pathway not only facilitated the separation of photogenerated electron-hole pairs but also promoted the generation of reactive oxygen species, greatly enhancing photocatalytic disinfection efficiency.


Assuntos
Anti-Infecciosos , Água , Antibacterianos/farmacologia , Catálise , Grafite , Peróxido de Hidrogênio , Luz , Compostos de Nitrogênio
20.
Clin Exp Rheumatol ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33886459

RESUMO

OBJECTIVES: We aimed to evaluate changes in the contrast-enhanced ultrasound (CEUS) parameters in patients with idiopathic retroperitoneal fibrosis (RPF) before and after treatment, and to analyse the value of CEUS to assess RPF activity. METHODS: We performed a prospective study that included patients with idiopathic RPF who were treated for RPF at our hospital from April 2016 to April 2019. All patients underwent CEUS examination and some of them underwent positron emission tomography/computed tomography (PET/CT) examination simultaneously. CEUS parameters included tube wall and peripheral thickness, arterial wall intensity, and lumen intensity. The changes in CEUS parameters before and after treatment were evaluated, and their correlations with the standardised uptake value (SUVmax), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed. RESULTS: Thirty-one active idiopathic RPF patients were enrolled, of whom 11 underwent PET/CT examination before treatment. Tube wall and peripheral thickness (r=0.743, p<0.01) and arterial wall intensity (r=0.702, p<0.05) both correlated significantly with SUVmax. Lumen intensity did not correlate significantly with SUVmax (r=0.544, p=0.084). The correlation coefficients between lesion thickness and ESR levels were 0.508 (p=0.037), between lesion thickness and CRP levels were 0.575 (p=0.016). Arterial wall intensity and lumen intensity were not significantly correlated with ESR or CPR levels. Tube wall and peripheral thickness, arterial wall intensity, decreased significantly after treatment (p=0.001), while the lumen intensity was not significantly changed after treatment. CONCLUSIONS: Our findings suggest that CEUS, a radiation-free and repeatable detection method, is effective for assessing idiopathic RPF disease activity.

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