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1.
Molecules ; 26(23)2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34885803

RESUMO

Fungal pathogens have evolved combinations of plant cell-wall-degrading enzymes (PCWDEs) to deconstruct host plant cell walls (PCWs). An understanding of this process is hoped to create a basis for improving plant biomass conversion efficiency into sustainable biofuels and bioproducts. Here, an approach integrating enzyme activity assay, biomass pretreatment, field emission scanning electron microscopy (FESEM), and genomic analysis of PCWDEs were applied to examine digestibility or degradability of selected woody and herbaceous biomass by pathogenic fungi. Preferred hydrolysis of apple tree branch, rapeseed straw, or wheat straw were observed by the apple-tree-specific pathogen Valsa mali, the rapeseed pathogen Sclerotinia sclerotiorum, and the wheat pathogen Rhizoctonia cerealis, respectively. Delignification by peracetic acid (PAA) pretreatment increased PCW digestibility, and the increase was generally more profound with non-host than host PCW substrates. Hemicellulase pretreatment slightly reduced or had no effect on hemicellulose content in the PCW substrates tested; however, the pretreatment significantly changed hydrolytic preferences of the selected pathogens, indicating a role of hemicellulose branching in PCW digestibility. Cellulose organization appears to also impact digestibility of host PCWs, as reflected by differences in cellulose microfibril organization in woody and herbaceous PCWs and variation in cellulose-binding domain organization in cellulases of pathogenic fungi, which is known to influence enzyme access to cellulose. Taken together, this study highlighted the importance of chemical structure of both hemicelluloses and cellulose in host PCW digestibility by fungal pathogens.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34748028

RESUMO

PURPOSE: As a novel antiangiogenic multi-target tyrosine kinase inhibitor recently approved in China, anlotinib has exhibited promising anticancer efficacy and acceptable safety profile in the salvage treatment of small cell lung cancer (SCLC) in clinical trials. Here we retrospectively investigated the efficacy and safety of anlotinib as third- or further-line treatment in patients with refractory SCLC. PATIENTS AND METHODS: A total of 40 patients with refractory SCLC treated with anlotinib monotherapy were included in this study. The clinicopathological data, treatment information, survival data and safety data were retrospectively collected. Survival curves were constructed using the Kaplan-Meier method. Univariate analysis was performed by log-rank testing. RESULTS: Altogether, 40 patients of extensive-stage SCLC or progressive limited-stage SCLC received anlotinib monotherapy as third- or further-line treatment from July 2018 to June 2020. Four patients achieved partial response (PR), 14 patients achieved stable disease (SD), no complete response (CR) was recorded, and 22 patients experienced progressive disease (PD). The disease control rate (DCR) was 45.0%. The median progression-free survival (PFS) was 3.0 months (95% CI 2.241-3.759), and the median overall survival (OS) was 7.8 months (95% CI 3.190-12.410). The common adverse effects (AEs) included hypertension, fatigue, anorexia, cough, rash and nausea. Grade 3 treatment-related AEs occurred in 3 (7.5%) patients. One patient interrupted anlotinib treatment due to repeated grade 1 epistaxis. Univariate analysis revealed that patients without liver metastases, previously treated with radiotherapy or with Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1 had longer OS with anlotinib treatment. Cox regression analysis demonstrated that patients without liver metastases and patients with ECOG score ≤ 1 had longer PFS, while patients without liver metastases had longer OS. CONCLUSION: Anlotinib is beneficial to refractory SCLC as third- or further-line treatment, especially in patients without liver metastasis and with better physical status. Related adverse effects are tolerable and manageable.

3.
Front Oncol ; 11: 734323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745955

RESUMO

Background: Although various third-line treatments of advanced gastric cancer (AGC) significantly improved the overall survival, the optimal regimen has not been determined by now. This study aims to evaluate the efficacy and safety of multiple third-line treatments of AGC via integrated analysis and network meta-analysis (NMA) to provide valuable evidence for the optimal third-line systemic therapy for AGC. Methods: By searching the databases of PubMed, Embase and the Cochrane Central Register of Controlled Trials from Jan 01, 2005 to Dec 31, 2020, we included phase II/III randomized clinical trials (RCTs) of the third-line treatments for AGC to perform NMA. The main outcomes for NMA were median overall survival (mOS), median progression-free survival (mPFS), disease control rate (DCR) and adverse events (AEs). We also included phase IB/II non-RCTs and II/III RCTs of the third-line immune checkpoint inhibitors (ICIs) for integrated analysis for pooled mOS (POS), pooled mPFS (PPFS) and other outcomes. Results: Eight phase II/III RCTs and 2 ICIs-related phase IB/II non-RCTs were included for analysis, involving 9 treatment regimens and 3012 AGC patients. In terms of mOS, apatinib (hazard ratio [HR] 0.61, 95% credible interval [CrI] 0.48-0.78) and nivolumab (HR 0.62, 95% CrI 0.51-0.76) were the most effective treatments compared with placebo. Apatinib also significantly improved mPFS versus placebo (HR 0.38, 95% CrI 0.29-0.49). Nivolumab ranked first among all regimens for 1-year OS rate and achieved the best OS in patients with HER-2 positive tumor, patients with gastroesophageal junction (GEJ) cancer and patients without gastrectomy history. TAS-102 (OR 7.46, 95% CrI 4.61-12.51) was the most toxic treatment in terms of AEs of grade 3 and higher (≥3 AEs). Pembrolizumab was more likely to cause immune related adverse event. Finally, the POS, pooled 1-year OS rate, pooled ORR and PPFS of AGC patients treated with third-line ICIs were 5.1 months, 25%, 10% and 1.71 months respectively. Conclusions: Apatinib and nivolumab are the most effective treatments for the third-line treatment of AGC in contrast to the third-line chemotherapy. For AGC patients with HER-2 positive tumor, patients with GEJ cancer and patients without gastrectomy history, ICIs could be the optimal third-line treatment choice.

4.
Front Immunol ; 12: 762598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675941

RESUMO

Background: SMARCA4, the essential ATPase subunit of SWI/SNF chromatin remodeling complex, regulates transcription through the control of chromatin structure and is increasingly thought to play significant roles in human cancers. This study aims to explore the potential role of SMARCA4 with a view to providing insights on pathologic mechanisms implicated here. Methods: The potential roles of SMARCA4 in different tumors were explored based on The Cancer Genome Atlas (TCGA), Genotype-tissue expression (GTEx), Tumor Immune Estimation Resource (TIMER), and Gene Set Enrichment Analysis (GSEA) datasets. The expression difference, mutation and phosphorylation status, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), tumor microenvironment (TME), and immune cell infiltration related to SMARCA4 were analyzed. Results: High expression levels of SMARCA4 were observed in most cancer types. SMARCA4 expression in tumor samples correlates with poor overall survival in several cancers. Lung adenocarcinoma cases with altered SMARCA4 showed a poorer prognosis. Enhanced phosphorylation levels of S613, S695, S699, and S1417 were observed in several tumors, including breast cancer. SMARCA4 correlated with tumor immunity and associated with different immune cells and genes in different cancer types. TMB, MSI, MMR, and DNA methylation correlated with SMARCA4 dysregulation in cancers. SMARCA4 expression was negatively associated with CD8+ T-cell infiltration in several tumors. Furthermore, the SWI/SNF superfamily-type complex and ATPase complex may be involved in the functional mechanisms of SMARCA4, albeit these data require further confirmation. Conclusions: Our study offers a comprehensive understanding of the oncogenic roles of SMARCA4 across different tumors. SMARCA4 may correlate with tumor immunity.

5.
Stem Cell Res ; 57: 102581, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34688993

RESUMO

Serine hydroxymethyltransferase 2 (SHMT2), a catalytic enzyme playing an important role in aerobic cellular respiration and mitochondrial metabolism, might be pivotal in self-renewal and differentiation of human pluripotent stem cells. Herein, we used the CRISPR/Cas9 editing system to construct a homozygous SHMT2 knockout (SHMT2-KO) human embryonic stem cell (hESC) line, exhibiting a normal karyotype, colony morphology, and high expression levels of pluripotent proteins. Furthermore, SHMT2 knockout did not impact the self-renewal ability or differentiation potential into three germ layers of hESCs. Accordingly, this cell line provides a valuable model for further assessing SHMT2 functions in human embryonic development.

6.
Cancer Manag Res ; 13: 7165-7174, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34548820

RESUMO

Background: As a novel irreversible pan-ErbB inhibitor recently approved in China, pyrotinib has exhibited promising anticancer efficacy and acceptable safety profile in HER2-positive metastatic breast cancer (mBC). The aim of this retrospective study was to estimate the efficacy and safety of pyrotinib treatment in Chinese mBC patients. Methods: We retrospectively reviewed the real-world clinicopathological and treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China. Results: A total of 64 patients treated with pyrotinib were included for analysis, and the median follow-up duration was 260 days (interquartile range, 199.0 to 339.0 days). Fifty-nine (92.2%) patients had been previously treated with trastuzumab and/or T-DM1, while 11 (17.2%) patients had been exposed to lapatinib. The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Patients with exposure to lapatinib responded well to pyrotinib-based treatment, although the ORR was significantly lower compared with that of patients without exposure to lapatinib (44.1% vs 77.5%, p=0.037). Previous lapatinib exposure was negatively associated with the objective response of pyrotinib treatment (odds ratio [OR]=0.248, 95% confidence interval [CI] 0.063-0.970, p=0.045). The median progression-free survival (mPFS) for patients with previous lapatinib exposure and patients with visceral metastasis was 299 days (95% CI 240.1-357.9 days) and 359 days (95% CI 258.3-459.7 days), respectively. But the mPFS of the whole cohort has not been reached until the cut-off date. Cox multivariate analysis revealed that only visceral metastasis was an independent predictor of significantly shorter PFS (p=0.041) but not previous exposure to lapatinib (p=0.092). Diarrhea (28.1%), hand-foot syndrome (17.2%), and neutropenia (9.4%) were the most common grade 3 adverse events associated with pyrotinib treatment. Conclusion: Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure. Pyrotinib is a feasible replacement of lapatinib in combination with chemotherapeutic drugs or as a monotherapy. Adverse effects are tolerable and easily manageable.

7.
Front Plant Sci ; 12: 707184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527008

RESUMO

The critical node (CN, 85% germination) of seed viability is an important threshold for seed regeneration decisions after long-term conservation. Dependent on the germplasm, the storage period until CN is reached varies and information on the divergence of the proteomic profiles is limited. Therefore, the study aims to identify key proteins and mechanisms relevant for a long plateau phase and a late CN during artificial seed aging of wheat. Seeds of the storage-tolerant genotype (ST) TRI 23248, and the storage-sensitive genotype (SS) TRI 10230 were exposed to artificial ageing (AA) and extracted embryos of imbibed seeds were analyzed using an iTRAQ-based proteomic technique. ST and SS required AA for 24 and 18 days to reach the CN, respectively. Fifty-seven and 165 differentially abundant proteins (DAPs) were observed in the control and aged groups, respectively. Interestingly, a higher activity in metabolic processes, protein synthesis, transcription, cell growth/division, and signal transduction were already found in imbibed embryos of control ST seeds. After AA, 132 and 64 DAPs were accumulated in imbibed embryos of both aged ST and SS seeds, respectively, which were mainly associated with cell defense, rescue, and metabolism. Moreover, 78 DAPs of ST appeared before CN and were mainly enriched in biological pathways related to the maintenance of redox and carbon homeostasis and they presented a stronger protein translation ability. In contrast, in SS, only 3 DAPs appeared before CN and were enriched only in the structural constituents of the cytoskeleton. In conclusion, a longer span of plateau phase might be obtained in seeds when proteins indicate an intense stress response before CN and include the effective maintenance of cellular homeostasis, and avoidance of excess accumulation of cytotoxic compounds. Although key proteins, inherent factors and the precise regulatory mechanisms need to be further investigated, the found proteins may also have functional potential roles during long-term seed conservation.

8.
J Cancer Res Ther ; 17(3): 630-637, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269292

RESUMO

Background: Small-cell carcinoma is a relatively infrequent pathological variety of esophageal cancer. In this study, a novel nomogram model was developed to evaluate the cancer-specific survival (CSS) and overall survival (OS) of patients with primary esophageal small-cell carcinoma (ESmCC). Materials and Methods: In total, 502 patients with primary ESmCC were identified based on data from 1973 to 2015 retrieved from the surveillance, epidemiology, and end results database. Clinical characteristics such as age at diagnosis, gender, race, site, tumor stage, surgery, radiotherapy, and chemotherapy were included for multivariate logistic analyses to predict CSS and OS. Nomogram models for the prediction of CSS and OS in ESmCC patients were tested with the concordance index (C-index) method and calibration curves. Results: From our multivariate analyses, race, stage, chemotherapy, and radiotherapy, but not surgery, were significantly associated with the CSS of ESmCC patients, while age at diagnosis, stage, chemotherapy, and radiotherapy were significantly associated with their OS. Nomograms were developed using age at diagnosis, race, gender, stage, surgery, radiotherapy, and chemotherapy to predict the two survival measures; these nomograms were verified as accurate in predicting OS and CSS in ESmCC patients, with C-index values of 0.736 and 0.731, respectively. Conclusions: By utilizing easily accessible clinicopathological information, we established a simple but useful tool for predicting the CSS and OS of ESmCC patients that could help to make personalized clinical decisions for patients with this rare malignancy. Cancer-specific survival, esophageal small-cell carcinoma, nomogram, overall survival, surveillance, epidemiology, and end results.

9.
Mol Plant ; 14(11): 1814-1830, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242849

RESUMO

Post-translational modifications (PTMs), including phosphorylation and persulfidation, regulate the activity of SNF1-RELATED PROTEIN KINASE2.6 (SnRK2.6). Here, we report how persulfidations and phosphorylations of SnRK2.6 influence each other. The persulfidation of cysteine C131/C137 alters SnRK2.6 structure and brings the serine S175 residue closer to the aspartic acid D140 that acts as ATP-γ-phosphate proton acceptor, thereby improving the transfer efficiency of phosphate groups to S175 to enhance the phosphorylation level of S175. Interestingly, we predicted that S267 and C137 were predicted to lie in close proximity on the protein surface and found that the phosphorylation status of S267 positively regulates the persulfidation level at C137. Analyses of the responses of dephosphorylated and depersulfidated mutants to abscisic acid and the H2S-donor NaHS during stomatal closure, water loss, gas exchange, Ca2+ influx, and drought stress revealed that S175/S267-associated phosphorylation and C131/137-associated persulfidation are essential for SnRK2.6 function in vivo. In light of these findings, we propose a mechanistic model in which certain phosphorylations facilitate persulfidation, thereby changing the structure of SnRK2.6 and increasing its activity.

10.
Stem Cell Res ; 53: 102253, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33770698

RESUMO

It has been reported that mutations in CDH1 gene are associated with genetic susceptibility to colon, stomach, breast and prostate cancers. Here, an induced pluripotent stem cell (iPSC) line from a patient with double primary gastric and colon carcinoma carrying germline mutation (c. 1679C > G) in CDH1 gene was generated. The iPSC line had normal karyotype, expressed pluripotent markers and had ability to generate three germ layers.


Assuntos
Carcinoma , Células-Tronco Pluripotentes Induzidas , Colo , Humanos , Masculino , Mutação , Estômago
11.
J Healthc Eng ; 2021: 6611196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628402

RESUMO

The development of virtual reality technology is expected to solve traditional surgical training. The lack of methods has brought revolutionary advances in technology. The virtual surgery system based on collision detection and force feedback can enable the operator to have stronger interaction, which is an exploration of the feature of touch in virtual reality technology. Reality is an important indicator of the virtual surgical system. This article improves the realism of the system from the visual and tactile senses and uses the surrounding ball collision detection and force feedback algorithms to build a realistic surgical platform. In the virtual surgery training system, the introduction of force feedback greatly improves the sense of presence during virtual surgery interaction. The operator can feel the softness and hardness of different tissues and organs through the force feedback device. Virtual reality is an interdisciplinary comprehensive technology that has been widely used in military, film, medical, and gaming fields. Virtual reality can simulate the objective world and display it visually, making people feel immersive. Virtual surgery provides surgeons with a recyclable surgical practice platform and can help doctors perform preoperative rehearsals and predict the results of surgery. The design of collision detection and force feedback algorithms is a prerequisite to ensure the immersion and transparency of the virtual surgical training system. This article mainly introduces the collision detection and force feedback algorithm research in virtual surgery, with the intention of providing some ideas and directions for the development of virtual surgery. This paper proposes two collision detection algorithms, space decomposition method and hierarchical bounding box method, and three force feedback algorithms including spring mass point algorithm, Runge-Kutta method, and Euler method to construct virtual surgery collision detection and force feedback. Experiment with the Overall System Architecture. This paper proves through experimental results that the average collision detection time after the application of the improved collision detection and force feedback algorithm in the virtual surgery system is more than 80.7% less than the traditional method, which greatly improves the detection speed.


Assuntos
Retroalimentação , Cirurgiões , Realidade Virtual , Algoritmos , Simulação por Computador , Humanos , Interface Usuário-Computador
12.
Ecotoxicol Environ Saf ; 207: 111550, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254408

RESUMO

Cadmium (Cd) is harmful to plant growth and can be easily transferred from soil to plants. Plant cell wall plays important role in preventing Cd from entering cells. Salicylic acid (SA) mediated defense response increases plant resistance to heavy metals. In this study, all tomato seedlings were pre-treated with 100 µM SA for 3 d, then seedlings were used to analyze the role of SA in regulating plant cell wall resistance to Cd stress. The results showed that exogenous SA significantly reduced Cd accumulation in tomato plants and changed Cd distribution. By analyzing the cell wall composition, it was found cellulose, hemicellulose, pectin, and lignin were induced by SA. Interestingly, the content of Cd in pectin decreased by SA pretreatment, however it was increased in cellulose. Gene expression analysis showed SA up-regulated the expression level of lignin and cellulose synthase genes, but down-regulated the expression of pectin methylesterase related genes. In addition, SA down-regulated the activity of pectin methylesterase. These results indicated that SA pretreatment up-regulated cell wall polysaccharide synthesis and related gene expression to thicken the cell wall and block Cd from passing through. Furthermore, SA decreased pectin methylesterase activity and content to reduce cell wall Cd accumulation and change the Cd partition ratio.


Assuntos
Cádmio/metabolismo , Lycopersicon esculentum/metabolismo , Substâncias Protetoras/farmacologia , Ácido Salicílico/farmacologia , Metabolismo dos Carboidratos , Parede Celular/metabolismo , Metilação , Pectinas/metabolismo , Raízes de Plantas/metabolismo , Polissacarídeos/metabolismo , Plântula/metabolismo
13.
Front Oncol ; 10: 594125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282742

RESUMO

Background: Microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. However, a recent Japanese trial showed that regorafenib plus nivolumab had encouraging anti-cancer activity in MSS or pMMR mCRCs. Materials and Methods: We retrospectively reviewed the efficacy and safety data of combination therapy with regorafenib plus anti-PD-1 antibody in patients with refractory MSS or pMMR mCRC in the medical centers of Shandong Province in China. Results: Twenty-three patients with MSS or pMMR mCRC received regorafenib plus anti-PD-1 antibody. Eighteen (78.3%) patients experienced stable disease as best response, five (21.7%) patients had progressive disease, and no partial response was observed. The disease control rate (DCR) was 78.3% (18/23), and the median progression-free survival (PFS) was 3.1 months (95% CI, 2.32-3.89). Four of five (80.0%) patients with progressive disease had baseline liver metastasis, while nine of 18 (50.0%) patients with stable disease displayed no liver metastasis. One patient receiving radiofrequency ablation treatment for liver and abdominal wall metastases prior to combination treatment experienced a remarkably prolonged PFS of 9.2 months with SD. Neither liver metastasis status nor previous exposure to regorafenib was associated with treatment outcome. Treatment-related grade 3 toxicities were observed in 5/23 (21.7%) patients. Conclusion: No objective response was observed with the combination of regorafenib plus anti-PD-1 antibody, suggesting its little clinical activity in unselected Chinese patients with pMMR/MSS mCRC. Meanwhile, it exhibited some potential benefit in this cohort in terms of DCR and PFS. Adverse events were generally tolerable and manageable. Prospective studies with large sample sizes are needed to verify the findings. This combination strategy plus local ablative therapy might be worthy of further exploration.

14.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(10): 1298-1304, 2020 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-33063497

RESUMO

Objective: To explore the effect and potential mechanism of glycyrrhizin (GL) by inhibiting high mobility group box 1 (HMGB1) on glial scar formation after spinal cord injury (SCI) in rats. Methods: Seventy-two female Sprague Dawley rats were randomly divided into sham group ( n=12), SCI model group (SCI group, n=36), GL intervention group (SCI+GL group, n=12), and nuclear factor κB (NF-κB) inhibitor [pynolidine dithiocarbamate (PDTC)] intervention group (SCI+PDTC group, n=12). The SCI models of SCI group, SCI+GL group, and SCI+PDTC group were made by modified Allen's method, the sham group was only exposed the spinal cord without any injury. First of all, Basso-Beattie-Bresnahan (BBB) score of hind limbs and slope test were performed in SCI group at 1, 2, and 3 weeks after operation; Western blot was used to detect the expressions of glial fibrillary acidic protein (GFAP) and HMGB1 proteins. Compared with the sham group, the most significant time point in the SCI group was selected for subsequent experiment, in which the most significant glial scar was formed. Then, behavioral tests (BBB score of hind limbs and slope test), histological observation of spinal cord tissue structure, Western blot detection of HMGB1, GFAP, and NF-κB proteins, and immunohistochemical staining observation of GFAP and chondroitin sulfate proteoglycan (CSPG) were used to explore the effect of GL on the formation of glial scar after SCI and its potential mechanism. Results: The BBB score and slope angle of the SCI group increased gradually with time, which were significantly lower than those of the sham group at each time point ( P<0.05). Western blot detection showed that the relative expressions of HMGB1 and GFAP proteins in the SCI group at 1, 2, and 3 weeks after operation were significantly higher than those in sham group ( P<0.05). The change was most obvious at 3 weeks after SCI, therefore the spinal cord tissue was selected for subsequent experiments at this time point. At 3 weeks after operation, compared with the SCI group, BBB score and slope angle of SCI+GL group significantly increased ( P<0.05); the relative expressions of HMGB1, GFAP, and NF-κB proteins detected by Western blot and the expressions of GFAP and CSPG proteins detected by immunohistochemical staining significantly decreased ( P<0.05); the disorder of spinal cord tissue by HE staining improved, inflammatory cell infiltration reduced, and glial scar formation decreased. At 3 weeks after operation, the expressions of NF-κB, GFAP, and CSPG proteins of the SCI+PDTC group significantly reduced when compared with the SCI group ( P<0.05); and the expression of NF-κB protein significantly decreased and the expressions of GFAP and CSPG proteins significantly increased when compared with the SCI+GL group ( P<0.05). Conclusion: After SCI in rats, the application of GL to inhibit the expression of HMGB1 can reduce the expression of GFAP and CSPG in the injured spinal cord, then reduce the formation of glial scars and promote the recovery of motor function of the hind limbs, and GL may play a role in inhibiting glial scar through HMGB1/NF-κB pathway.


Assuntos
Ácido Glicirrízico , Traumatismos da Medula Espinal , Animais , Cicatriz/etiologia , Cicatriz/prevenção & controle , Feminino , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , Neuroglia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico
15.
PLoS One ; 15(10): e0240421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031477

RESUMO

OBJECTIVE: To evaluate the microbial loading in aerosols produced after air-puff by non-contact tonometer (NCT) as well as the effect of alcohol disinfection on the inhibition of microbes and thus to provide suggestions for the prevention and control of COVID-19 in ophthalmic departments of hospitals or clinics during the great pandemics. METHODS: A cross-sectional study was carried out in this study. A NIDEK NCT was used for intraocular pressure (IOP) measurement for patients who visited Department of Ophthalmology in Qilu Hospital of Shandong University during March 18-25 2020. After ultra-violate (UV) light disinfection, the room air was sampled for 5 minutes. Before and after alcohol disinfection, the air samples and nozzle surface samples were respectively collected by plate exposure method and sterile moist cotton swab technique after predetermined times of NCT air-puff. Microbial colony counts were calculated after incubation for 48 hours. Finally, mass spectrometry was performed for the accurate identification of microbial species. RESULTS: Increased microbial colonies were detected from air samples close to NCT nozzle after air-puff compared with air samples at a distance of 1 meter from the nozzle (p = 0.001). Interestingly, none microbes were detected on the surface of NCT nozzle. Importantly, after 75% alcohol disinfection less microbes were detected in the air beside the nozzle (p = 0.003). Microbial species identification showed more than ten strains of microbes, all of which were non-pathogenic. CONCLUSION: Aerosols containing microbes were produced by NCT air-puff in the ophthalmic consultation room, which may be a possible virus transmission route in the department of ophthalmology during the COVID-19 pandemic. Alcohol disinfection for the nozzle and the surrounding air was efficient at decreasing the microbes contained in the aerosols and theoretically this prevention measure could also inhibit the virus. This will give guidance for the prevention of virus transmission and protection of hospital staff and patients.


Assuntos
Microbiologia do Ar , Álcoois/química , Infecções por Coronavirus/prevenção & controle , Desinfetantes/química , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Tonometria Ocular/métodos , Aerossóis/química , Betacoronavirus/fisiologia , COVID-19 , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Hospitais , Humanos , Oftalmologia/métodos , Pneumonia Viral/epidemiologia , SARS-CoV-2
16.
JTO Clin Res Rep ; 1(3): 100053, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32929416

RESUMO

Introduction: The coronavirus disease 2019 (COVID-19) outbreak throughout the world has affected millions of people in many ways, putting a huge burden on the health care system. The ongoing outbreak of this respiratory disease has posed critical challenges to public health, research, and medical communities around the world. This study aimed at evaluating the impact of COVID-19 pandemic on patients with lung cancer in the People's Republic of China. Methods: We collected data on 397 inpatients from a single center during 4 weeks of the pandemic (2020 group) and that of 2504 inpatients during the same period (4 wk) in the past 5 years (2015-2019 group). A questionnaire was used to investigate the medical demands of 803 patients with lung cancer at 65 hospitals in 20 provinces in the People's Republic of China during the pandemic. We evaluated the incidence data of COVID-19 in Guangdong to analyze the tendency of the pandemic and compared it with inpatient data. Results: The number of hospitalizations and lung cancer-related operations had steadily increased from 2015 to 2019 but reduced by an average of 26.72% (133.8) and 57.18% (45.4) in 2020. The hospital capacity decreased by 28.00% (35 inpatient beds) during the pandemic period of infection with severe acute respiratory syndrome coronavirus 2. The pandemic caused a greater impact on medical work related to lung cancer after the Chinese New Year holiday. Patients were most concerned about long waiting times for outpatient services, inpatient beds, physical examinations, or operations (406; 50.56%); the possibility of infection with the novel coronavirus (359; 44.71%); and the difficulties in getting to a hospital owing to transportation outages (279; 34.74%). Patients in stage I and II revealed having less fear about disease progression (14 [18.18%] and four [14.81%], respectively), had lower proportions of delayed medical arrangement (15 [19.48%] and six [22.22%], respectively), and complained less about complex treatment procedures (12 [15.58%] and five [18.52%], respectively). Patients in the high-infected area (345, 56.74%) complained more frequently about longer booking periods than those in the low-infected area (61, 31.28%). Conclusions: The treatment of patients with lung cancer has been affected by the pandemic to some extent. We provide suggestions on both clinical diagnosis and treatment strategies for lung cancer to optimize the process, given the urgency of the current circumstances. The demand for medical support among patients with lung cancer or other life-threatening diseases should be given sufficient attention, especially during the current COVID-19 outbreak.

17.
Plant Physiol Biochem ; 156: 257-266, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32979798

RESUMO

Hydrogen sulfide (H2S), a small gaseous signaling molecule, regulates antioxidase activity and improves plant tolerance to oxidative stress. The phytotoxic effect of Copper Oxide (II) nanoparticles (CuO NPs) is due to oxidative stress. Here, we show that H2S-mediated persulfidation of antioxidase is essential for an effective stress response of tomato exposed to CuO NPs. The CuO NP-induced increase in hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels was significantly reduced by treatment with the H2S donor NaHS. In vivo, NaHS increased superoxide dismutase (SOD), ascorbate peroxidase (APX) and peroxidase (POD) activities under CuO NP stress. In vitro, NaHS increased APX and POD activities but decreased catalase (CAT) activity. Persulfidation existed in recombinant SlCAT1, SlcAPX1 and SlPOD5 proteins. The persulfidatied cysteine (Cys) residues were verified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), revealing their position on the protein surface. Cys234 of SlCAT1 is located in the immune-responsive domain and close to the enzyme activity domain. Cys234 of SlcAPX1 and Cys 61 SlPOD5 are located in the enzyme activity domain. Persulfidation increased SlcAPX1 and SlPOD5 activities but decreased SlCAT1 activity. These data indicate that H2S-mediated persulfidation posttranslationally regulates the activities of CAT, APX and POD, thereby enhancing the plant's response to oxidative stress. Additionally, this work provides an experimental approach for the study of persulfidation in plants.


Assuntos
Antioxidantes/metabolismo , Cobre/efeitos adversos , Sulfeto de Hidrogênio/farmacologia , Lycopersicon esculentum/enzimologia , Estresse Oxidativo , Cromatografia Líquida , Peróxido de Hidrogênio/metabolismo , Lycopersicon esculentum/efeitos dos fármacos , Malondialdeído/metabolismo , Nanopartículas , Plântula/metabolismo , Superóxido Dismutase/metabolismo , Espectrometria de Massas em Tandem
18.
Plant Signal Behav ; 15(11): 1805228, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32772870

RESUMO

Hydrogen sulfide (H2S) is an important gas signal molecule, but little is known about its signal mechanism. Ca2+ is an important second messenger in plant cells, and its fluctuation in the cytoplasm causes downstream physiological responses. Our previous study found that H2S can induce the accumulation of hydrogen peroxide (H2O2). We also found that reactive oxygen species (ROS) can further induce the Ca2+ influx in guard cells by noninvasive micro-teat technology (NMT). This study confirmed that the accumulation of reactive oxygen species to induce Ca2+ signal in guard cells, resulting in stomatal closure. Thus, revealing a novel mechanism of H2S promoting stomatal closure.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sinalização do Cálcio/fisiologia , Peróxido de Hidrogênio/metabolismo , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/metabolismo
19.
Plant Physiol Biochem ; 155: 605-612, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32846396

RESUMO

Hydrogen sulfide (H2S), a small gaseous signalling molecule, plays a pivotal role in the plant response to heavy metal stress. Here, we revealed a novel mechanism of Isatis indigotica resistance to cadmium (Cd) stress, in which H2S promotes Cd accumulation in the root and decreases the long-distance transport of Cd from the root to shoot. Cd significantly inhibited Isatis indigotica growth and induced the endogenous H2S level. Application of NaHS (a H2S donor) alleviated the effects of Cd. NaHS restriction of the translocation factor of Cd, elevated the Cd content in roots and depressed the Cd content in shoots. Cd stress decreased the cellulose and pectin contents in the cell wall, but NaHS restored the effect of Cd on the cell wall components. The Cd2+ fluxes were detected by noninvasive microtest technology (NMT). The data showed that NaHS pretreatment decreased the Cd2+ influx and proportion of the Cd content in organelles. We analyzed the effect of NaHS on the metallothionein and phytochelatin (PC) contents in roots and found that the PC and metallothionein1A (MT1A) contents were induced by NaHS. Additionally, the chemical forms of Cd2+ were changed by NaHS. Thus, H2S alters the content of cell wall component, improves Cd accumulation in the cell wall, depresses Cd2+ transmembrane movement, induces the synthesis of metallothioneins and decreases the toxicity of intracellular Cd. Our finding has great value to reduce the loss of Isatis indigotica resulted by heavy metals stress.


Assuntos
Cádmio/metabolismo , Parede Celular/metabolismo , Sulfeto de Hidrogênio/metabolismo , Isatis/metabolismo , Raízes de Plantas/metabolismo , Brotos de Planta/metabolismo , Gasotransmissores/metabolismo
20.
J Exp Bot ; 71(19): 5852-5864, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32640016

RESUMO

Hydrogen sulfide (H2S) is known to have positive physiological functions in plant growth, but limited data are available on its influence on cell walls. Here, we demonstrate a novel mechanism by which H2S regulates the biosynthesis and deposition of cell wall cellulose in alfalfa (Medicago sativa). Treatment with NaHS was found to increase the length of epidermal cells in the hypocotyl, and transcriptome analysis indicated that it caused the differential expression of numerous of cell wall-related genes. These differentially expressed genes were directly associated with the biosynthesis of cellulose and hemicellulose, and with the degradation of pectin. Analysis of cell wall composition showed that NaHS treatment increased the contents of cellulose and hemicellulose, but decreased the pectin content. Atomic force microscopy revealed that treatment with NaHS decreased the diameter of cellulose fibrils, altered the arrangement of the fibrillar bundles, and increased the spacing between the bundles. The dynamics of cellulose synthase complexes (CSCs) were closely related to cellulose synthesis, and NaHS increased the rate of mobility of the particles. Overall, our results suggest that the H2S signal enhances the plasticity of the cell wall by regulating the deposition of cellulose fibrils and by decreasing the pectin content. The resulting increases in cellulose and hemicellulose contents lead to cell wall expansion and cell elongation.


Assuntos
Sulfeto de Hidrogênio , Medicago sativa , Parede Celular , Celulose , Hipocótilo , Medicago sativa/genética
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