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1.
Cancer Med ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723436

RESUMO

PURPOSE: Marital status has emerged as an important influence on several cancer outcomes, but its role in medullary thyroid cancer (MTC) remains unclear. This study was to explore the effects of marital status on the prognosis of MTC patients and to determine whether its effects vary by age. PATIENTS AND METHODS: We retrospectively extracted 1344 eligible patients diagnosed with MTC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the marital status, we divided those patients into married and unmarried groups. We compared the difference in overall survival (OS) and cancer-specific survival (CSS) between married and unmarried via the Kaplan-Meier analysis. Univariate and multivariate Cox proportional models were performed to identify the prognostic factors of OS and CSS. RESULTS: There were 1344 MTC eligible patients in a total of which 883 (65.7%) were married and 461 (34.3%) were unmarried. The comparison observed between married and unmarried patients was as follows: male (45.2% vs. 28.0%), age (≥52 years) (55.9% vs. 44.6%), White (86.7% vs. 78.7%), and undergo surgery (97.7% vs. 93.3%). Multivariate analysis revealed unmarried status as a risk factor independently associated with worse OS (HR: 2.15, 95% CI: 1.59-2.92) rate and CSS (HR: 1.70, 95% CI: 1.17-2.47) rate. In a further analysis stratified by age, there was no significant difference in OS and CSS between married and unmarried patients younger than 52 years. For the remaining group with 52 years old and higher, unmarried patients showed significantly higher risk of OS and CSS than married patients at all stages of the pathology except M1 stage. CONCLUSION: Married patients with MTC have a better prognosis than unmarried ones. Age can affect the association between marital status and the survival of MTC, and married elders may benefit more than youngers.

2.
Front Oncol ; 11: 705929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722250

RESUMO

Background: Alternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC). Methods: AS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established. Results: We identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC. Conclusion: Through the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.

3.
Biomed Res Int ; 2021: 8717565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778458

RESUMO

Background: Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. Methods: In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. Results: TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression (p < 0.05) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress (p < 0.05). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers (p < 0.05). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. Conclusions: Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

4.
Orthop Surg ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34747564

RESUMO

OBJECTIVE: To investigate the role of autologous platelet-rich plasma (PRP) on the repair of meniscal white-white zone injury through promoting the proliferation of canine bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: A total of 24 beagle dogs were selected to construct meniscal white-white zone injury models in both lateral knee joints. All subjects were divided into four groups: control, BMSCs, PRP, and PRP + BMSCs. Immunohistochemistry was applied in the expression detection of type I and type II collagens. HE staining and methylene blue staining were performed to observe the injury of cartilage of lateral femoral condyle in each group. ELISA was used to detect the osteopontin (OPN) content in cartilage of lateral femoral condyle. HE staining and magnetic resonance imaging (MRI) were used to observe the healing of meniscus in each group. Outcome measures include the expression of OPN in the synovial fluid of knee joint, the expression of type I collagen and type II collagen, the healing of meniscus injury, and the damage degree of lateral femoral condyle cartilage. RESULTS: Compared with the control group, the expressions of type I and type II collagens were enhanced in the PRP group and the PRP + BMSCs group. Compared with 1 week before modeling, the expression of OPN was elevated in the control group and the BMSCs group at 3 weeks after modeling. There were no significant differences in the above indicators between the PRP group and the PRP + BMSCs group. According to MRI and pathological section after HE staining, meniscal healing in the PRP group and the PRP + BMSCs group was significantly improved as compared to that of the control group and the BMSCs group (all P < 0.05), and there was no significant difference between the PRP group and the PRP + BMSCs group (P > 0.05). All subjects were divided into the non-healing group and the healing group in accordance with the HE staining results in previous experiment. The injury of cartilage of lateral femoral condyle was significantly heavier in the non-healing group than that in the healing group. CONCLUSION: The application of PRP alone or in combination with BMSCs could promote the clinical healing rate of meniscal white-white zone injury.

6.
Open Med (Wars) ; 16(1): 1653-1667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34761116

RESUMO

The aim of this study was to clarify the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in proliferation, migration, and invasion of malignant pleural mesothelioma (MPM) cells. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of MALAT1 in MPM cell lines. The effects of MALAT1 and miR-141-3p on the proliferation, migration, and invasion of MPM cells were studied through a series of in vitro cellular experiments. The flow cytometry was utilized to detect the cell apoptosis. The dual-luciferase reporter assay was employed to explore the binding relationship among MALAT1, miR-141-3p, and YES-associated protein 1 (YAP1). MALAT1 was overexpressed in MPM cell lines, while its knockdown significantly inhibited the cell proliferation, migration, and invasion, and increased the number of MPM cells in the G0/G1 phase. In addition, MALAT1 could directly bind to miR-141-3p and inhibit its expression. YAP1 has been identified as a downstream target of miR-141-3p, and its expression level was inhibited by miR-141-3p. MALAT1 can be used as a competitive endogenous RNA (ceRNA) to regulate the YAP1-Hippo signaling pathway through miR-141-3p, promote the proliferation, migration, and invasion of MPM cells, and provide a new target for the therapy of MPM.

7.
Sci Data ; 8(1): 297, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811392

RESUMO

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. As of May 23rd, 2021, over 5 million participants have collectively logged over 360 million self-assessment reports since its introduction in March 2020. The success of the Covid Symptom Study creates significant technical challenges around effective data curation. The primary issue is scale. The size of the dataset means that it can no longer be readily processed using standard Python-based data analytics software such as Pandas on commodity hardware. Alternative technologies exist but carry a higher technical complexity and are less accessible to many researchers. We present ExeTera, a Python-based open source software package designed to provide Pandas-like data analytics on datasets that approach terabyte scales. We present its design and capabilities, and show how it is a critical component of a data curation pipeline that enables reproducible research across an international research group for the Covid Symptom Study.

8.
J Am Coll Cardiol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34752902

RESUMO

BACKGROUND: Gastrointestinal bleeding is the most frequent major complication of antiplatelet therapy. In patients at low bleeding risk, however, clinically overt gastrointestinal bleeding is relatively uncommon. OBJECTIVE: We sought to assess the effects of different antiplatelet regimens on gastrointestinal mucosal injury using a novel magnetically-controlled capsule endoscopy system in patients at low bleeding risk. METHODS: Patients (n=505) undergoing percutaneous coronary intervention in whom capsule endoscopy demonstrated no ulcerations or bleeding (although erosions were permitted) after 6 months of dual antiplatelet therapy (DAPT) were randomly assigned to aspirin plus placebo (n=168), clopidogrel plus placebo (n=169), or aspirin plus clopidogrel (n=168) for an additional 6 months. The primary endpoint was the incidence of gastrointestinal mucosal injury (erosions, ulceration, or bleeding) at 6-month or 12-month capsule endoscopy. RESULTS: Gastrointestinal mucosal injury through 12 months was less with single antiplatelet therapy (SAPT) compared with DAPT (94.3% vs. 99.2%, P=0.02). Aspirin and clopidogrel monotherapy had similar effects. Among 68 patients without any gastrointestinal injury at randomization (including no erosions), SAPT compared with DAPT caused less gastrointestinal injury (68.1% vs. 95.2%, P=0.006), including fewer new ulcers (8.5% vs. 38.1%, P=0.009). Clinical gastrointestinal bleeding between 6 and 12 months was less with SAPT compared with DAPT (0.6% vs. 5.4%, P=0.001). CONCLUSIONS: Despite being at low risk of bleeding, nearly all patients receiving antiplatelet therapy developed gastrointestinal injury, although overt bleeding was infrequent. DAPT for 6 months followed by SAPT with aspirin or clopidogrel between 6 and 12 months resulted in less gastrointestinal mucosal injury and clinical bleeding compared with DAPT through 12 months.

9.
Exp Ther Med ; 22(5): 1275, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34594412

RESUMO

Oxidized low-density lipoprotein (ox-LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine-glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, respectively. The levels of TNF-α, IL-α, 4-hydroxynonenal, GPx4 and xCT expression were detected by western blot analysis. It was demonstrated that ox-LDL promoted cytokine production and reduced the proliferation, migration and angiogenesis of endothelial cells. It was also observed that ox-LDL decreased GPx4 and xCT expression and induced ferroptosis. Furthermore, the inhibition of ferroptosis by deferoxamine mesylate attenuated ox-LDL-induced endothelial cell dysfunction and restored ox-LDL-decreased GPx4 and xCT expression. Consistent with these results, GPx4 and xCT knockdown by siRNA transfection aggravated ox-LDL-induced endothelial cell dysfunction and inhibition of proliferation. To the best of our knowledge, the present study was the first to discover that fluvastatin may protect endothelial cells from ox-LDL-induced ferroptosis and dysfunction. Furthermore, knockdown of GPx4 and xCT expression blunted the protective effects of fluvastatin on ox-LDL-treated endothelial cells. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox-LDL-induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT.

10.
BMC Microbiol ; 21(1): 299, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715786

RESUMO

BACKGROUND: Peanut (Arachis hypogaea L.) is an important oil and economic crop. Calcium modulates plants in response to abiotic stresses and improves plant resistance to pathogens. Enrichment of beneficial microorganisms in the rhizosphere is associated with plant disease resistance and soil development. The purpose of this study was to analyze the differences in peanut rhizosphere microbial community structure between the calcium treatment and the control during two growth stages and to explain why calcium application could improve the resistance of peanuts to soil-borne pathogens. RESULTS: The 16S rDNA amplicon sequencing of rhizosphere microbiome showed that calcium application significantly enriched Serratia marcescens and other three dominant strains at the seedling stage. At the pod filling stage, ten dominant stains such as Sphingomonas changbaiensis and Novosphingobium panipatense were enriched by calcium. Serratia marcescens aseptic fermentation filtrate was mixed with PDA medium and inoculated with the main soil-borne pathogens in the seedling stage, which could inhibit the growth of Fusarium solani and Aspergillus flavus. The aseptic fermentation filtrate of Novosphingobium panipatense was mixed with PDA medium and inoculated with the main soil-borne pathogens in the pod filling stage, which could inhibit the growth of Sclerotium rolfsii and Leptosphaerulina arachidicola. CONCLUSIONS: Calcium application increases the resistance of peanuts to soil-borne pathogens by enriching them with specific dominant bacteria.

11.
Biomed Res Int ; 2021: 1516855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712726

RESUMO

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. The severity is classified as mild (MAP), moderately severe (MSAP), or severe (SAP). In patients with SAP, organ dysfunction can occur in the early stage of the disease course, accompanied by secondary infection, with a mortality rate of 36%-50%. In the late stage SAP, infection-related complications caused by pancreatic necrotic tissue and peripancreatic effusion are the main causes of death in patients. Dysbacteriosis of intestinal microflora, barrier dysfunction of intestinal mucosa, and translocation of enteric bacteria are considered to be the main causes of infection of pancreatic necrotic tissue and peripancreatic effusion. During the past few years, increasing attention has been paid to the metabolic activities of intestinal microflora in SAP, which plays an important role in the metabolic activities of the human body. This review is aimed at bringing together the most recent findings and advances regarding the gut microbial community and associated gut microbial community metabolites and illustrating the role of these metabolites in disease progression in severe acute pancreatitis. We hope that this review will provide new ideas and schemes for the treatment of SAP in the clinical settings.

12.
Front Plant Sci ; 12: 741463, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646290

RESUMO

Root rot, mainly caused by Fusarium oxysporum, is the most destructive disease affecting lily (Lilium spp.) production. The WRKY transcription factors (TFs) have important roles during plant immune responses. To clarify the effects of WRKY TFs on plant defense responses to pathogens, a WRKY gene (LrWRKY2) was isolated from Lilium regale Wilson, which is a wild lily species highly resistant to F. oxysporum. The expression of LrWRKY2, which encodes a nuclear protein, is induced by various hormones (methyl jasmonate, ethephon, salicylic acid, and hydrogen peroxide) and by F. oxysporum infection. In this study, LrWRKY2-overexpressing transgenic tobacco plants were more resistant to F. oxysporum than the wild-type plants. Moreover, the expression levels of jasmonic acid biosynthetic pathway-related genes (NtAOC, NtAOS, NtKAT, NtPACX, NtJMT, NtOPR, and NtLOX), pathogenesis-related genes (NtCHI, NtGlu2, and NtPR-1), and antioxidant stress-related superoxide dismutase genes (NtSOD, NtCu-ZnSOD, and MnSOD) were significantly up-regulated in LrWRKY2 transgenic tobacco lines. Additionally, the transient expression of a hairpin RNA targeting LrWRKY2 increased the susceptibility of L. regale scales to F. oxysporum. Furthermore, an F. oxysporum resistance gene (LrCHI2) encoding a chitinase was isolated from L. regale. An electrophoretic mobility shift assay demonstrated that LrWRKY2 can bind to the LrCHI2 promoter containing the W-box element. Yeast one-hybrid assay results suggested that LrWRKY2 can activate LrCHI2 transcription. An examination of transgenic tobacco transformed with LrWRKY2 and the LrCHI2 promoter revealed that LrWRKY2 activates the LrCHI2 promoter. Therefore, in L. regale, LrWRKY2 is an important positive regulator that contributes to plant defense responses to F. oxysporum by modulating LrCHI2 expression.

13.
J Inflamm Res ; 14: 5337-5347, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703272

RESUMO

Purpose: Clinically, it is challenging to manage diabetic patients with periodontitis. Biochemically, both involve a wide range of inflammatory/collagenolytic conditions which exacerbate each other in a "bi-directional manner." However, standard treatments for this type of periodontitis rely on reducing the bacterial burden and less on controlling hyper-inflammation/excessive-collagenolysis. Thus, there is a crucial need for new therapeutic strategies to modulate this excessive host response and to promote enhanced resolution of inflammation. The aim of the current study is to evaluate the impact of a novel chemically-modified curcumin 2.24 (CMC2.24) on host inflammatory response in diabetic rats. Methods: Type I diabetes was induced by streptozotocin injection; periodontal breakdown then results as a complication of uncontrolled hyperglycemia. Non-diabetic rats served as controls. CMC2.24, or the vehicle-alone, was administered by oral gavage daily for 3 weeks to the diabetics. Micro-CT was used to analyze morphometric changes and quantify bone loss. MMPs were analyzed by gelatin zymography. Cell function was examined by cell migration assay, and cytokines and resolvins were measured by ELISA. Results: In this severe inflammatory disease model, administration of the pleiotropic CMC2.24 was found to normalize the excessive accumulation and impaired chemotactic activity of macrophages in peritoneal exudates, significantly decrease MMP-9 and pro-inflammatory cytokines to near normal levels, and markedly increase resolvin D1 (RvD1) levels in the thioglycolate-elicited peritoneal exudates (tPE). Similar effects on MMPs and RvD1 were observed in the non-elicited resident peritoneal washes (rPW). Regarding clinical relevance, CMC2.24 significantly inhibited the loss of alveolar bone height, volume and mineral density (ie, diabetes-induced periodontitis and osteoporosis). Conclusion: In conclusion, treating hyperglycemic diabetic rats with CMC2.24 (a tri-ketonic phenylaminocarbonyl curcumin) promotes the resolution of local and systemic inflammation, reduces bone loss, in addition to suppressing collagenolytic MMPs and pro-inflammatory cytokines, suggesting a novel therapeutic strategy for treating periodontitis complicated by other chronic diseases.

14.
Mycoses ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34699636

RESUMO

As a frequently occurring infectious disease mainly caused by Candida albicans, vulvovaginal candidosis (VVC) affects more than 100 million women worldwide every year. Multiple factors that influence C. albicans colonization have been linked to the incidence of VVC, including high levels of circulating estrogen due to pregnancy, the use of oral contraceptives, and hormone replacement therapy. This review provides an overview of the current understanding of the mechanism(s) by which estrogen contributes to VVC, which might provide meaningful guidance to the prevention and treatment of this disease.

15.
Biochem Biophys Res Commun ; 582: 125-130, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34710827

RESUMO

CYP76AH1 is the key enzyme in the biosynthesis pathway of tanshinones in Salvia miltiorrhiza, which are famous natural products with activities against various heart diseases and others. CYP76AH1 is a membrane-associated typical plant class II cytochrome P450 enzyme and its catalytic mechanism has not to be clearly elucidated. Structural determination of eukaryotic P450 enzymes is extremely challenging. Recently, we solved the crystal structures of CYP76AH1 and CYP76AH1 in complex with its natural substrate miltiradiene. The structure of CYP76AH1 complexed with miltiradiene is the first plant cytochrome P450 structure in complex with natural substrate. The studies revealed a unique array pattern of amino acid residues, which may play an important role in orienting and stabilizing the substrate for catalysis. This work would provide structural insights into CYP76AH1 and related P450s and the basis to efficiently improve tanshinone production by synthetic biology techniques.

16.
Cell Death Dis ; 12(10): 928, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635643

RESUMO

Acute lung injury (ALI) is a complication of severe acute pancreatitis (SAP). Sitagliptin (SIT) is a DPP4 inhibitor that exerts anti-inflammatory and antioxidant effects; however, its mechanism of action in SAP-ALI remains unclear. In this study, we investigated the effects of SIT on SAP-ALI and the specific pathways involved in SAP-induced lung inflammation, including oxidative stress, autophagy, and p62-Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) signalling pathways. Nrf2 knockout (Nrf2-/-) and wild-type (WT) mice were pre-treated with SIT (100 mg/kg), followed by caerulein and lipopolysaccharide (LPS) administration to induce pancreatic and lung injury. BEAS-2B cells were transfected with siRNA-Nrf2 and treated with LPS, and the changes in inflammation, reactive oxygen species (ROS) levels, and autophagy were measured. SIT reduced histological damage, oedema, and myeloperoxidase activity in the lung, decreased the expression of pro-inflammatory cytokines, and inhibited excessive autophagy and ROS production via the activation of the p62-Keap1-Nrf2 signalling pathway and promotion of the nuclear translocation of Nrf2. In Nrf2-knockout mice, the anti-inflammatory effect of SIT was reduced, resulting in ROS accumulation and excessive autophagy. In BEAS-2B cells, LPS induced ROS production and activated autophagy, further enhanced by Nrf2 knockdown. This study demonstrates that SIT reduces SAP-ALI-associated oxidative stress and excessive autophagy through the p62-Keap1-Nrf2 signalling pathway and nuclear translocation of Nrf2, suggesting its therapeutic potential in SAP-ALI.

17.
Head Neck ; 43(12): 3720-3729, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34617646

RESUMO

BACKGROUND: Pain is an under-recognized complaint among head and neck cancer (HNC) survivors. Treatment is hindered by inadequate characterization of pain. METHODS: A secondary analysis from a prospective, longitudinal study was conducted to characterize pain prevalence, quality, and functional consequences in 77 HNC patients. Pain and pain-related outcomes were captured before treatment, at end-of-treatment, and 3, 6, 9 and 12 months post-treatment. RESULTS: Pain was most prevalent at end-of-treatment and declined over time. Chronicity of pain was established by 6 months post-treatment. Oral mucosal neuropathic pain was the most common chronic pain subtype at 12 months post-treatment. Widespread joint and muscle pain was also present at lower numbers. 40.2% of patients continued to require analgesics at 12 months. CONCLUSION: Peripheral and central pain subtypes contribute significantly to chronic pain in HNC survivors. Preventive and treatment regimens should be tailored to specific pain subtypes for optimal symptom control.


Assuntos
Neoplasias de Cabeça e Pescoço , Qualidade de Vida , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estudos Longitudinais , Dor , Estudos Prospectivos
18.
Eur J Med Chem ; 227: 113910, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34689071

RESUMO

The current COVID-19 epidemic has greatly accelerated the application of mRNA technology to our real world, and during this battle mRNA has proven it's unique advantages compared to traditional biopharmaceutical and vaccine technology. In order to overcome mRNA instability in human physiological environments, mRNA chemical modifications and nano delivery systems are two key factors for their in vivo applications. In this review, we would like to summarize the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in innovative materials and delivery strategies. The nano delivery systems include lipid delivery systems (lipid nanoparticles and liposomes), polymer complexes, micelles, cationic peptides and so on. The similarities and differences of lipid nanoparticles and liposomes are also discussed. In addition, this review also present the applications of mRNA to other areas than COVID-19 vaccine, such as infectious diseases, tumors, and cardiovascular disease, for which a variety of candidate vaccines or drugs have entered clinical trials. Furthermore, mRNA was found that it might be used to treat some genetic disease, overcome the immaturity of the immune system due to the small fetal size in utero, treat some neurological diseases that are difficult to be treated surgically, even be used in advancing the translation of iPSC technology et al. In short, mRNA has a wide range of applications, and its era has just begun.

19.
Front Pharmacol ; 12: 669516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690748

RESUMO

Alpers' syndrome is an early inceptive neurodegenerative disorder with a poor prognosis, characterized by developmental regression, intractable epilepsy, and hepatic dysfunction. Candidate genes, such as POLG, PARS2, CARS2, FARS2, NARS2, and GABRB2 are distinguished and registered following research on large cohorts that portray the clinical phenotype in such patients using expanded access to whole-exome sequencing (WES). In this study, we aimed to better understand the electroencephalogram (EEG) characteristics and clinical phenotype of different genotypes of the Alpers' syndrome, which are currently insufficiently studied. We conducted a study on seven patients with Alpers' syndrome who received treatment in Beijing Children's Hospital and had a detailed clinical EEG. Furthermore, a substantial literature search of the Chinese Biomedical Literature Database, PubMed, and Cochrane Central Register of Controlled Trials EMBASE was also conducted, which revealed a total of 22 reported cases between January 2008 to January 2021. We analyzed 29 cases of Alpers' syndrome caused by different gene variants, of which 22 cases were related to POLG gene mutation and 7 cases were related to PARS2, CARS2, FARS2, NARS2, and GABRB2 gene mutation, and found that patients with distinctive pathogenic variants exhibited comparable phenotypes and similar EEG patterns. And we defined EEG characteristics found specifically in Alpers' syndrome. Rhythmic high-amplitude delta with superimposed (poly) spikes (RHADS) is a characteristic EEG finding in the early stages of Alpers' syndrome and is a kind of epileptic phenomenon, which can provide clues for the early diagnosis of the disease.

20.
Ecotoxicol Environ Saf ; 225: 112734, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482065

RESUMO

Cadmium (Cd), a phytotoxic heavy metal accumulated in plants and fruits, has significant adverse effects on plant growth and development as well as human health. In particular, Cd pollution has become a serious agricultural issue in recent years. Apple is one of the most popular fruits consumed at the global scale. Improving apple Cd resistance via reductions in Cd absorption can benefit apple tree growth and ensure fruit safety. In this study, we determined that, under the 200 µM Cd treatment, 35S::MdIAA24 apple plants exhibited more biomass and less Cd accumulation in the tested tissues compared to wild type (WT). Furthermore, the 35S::MdIAA24 apple plants demonstrated more favorable photosynthesis characteristics, less reactive oxygen species (ROS) and a greater amount of active antioxidant enzymes under the Cd condition than WT. The expression levels of the Cd uptake genes were observed to be lower in the 35S::MdIAA24 apple plants compared with those of the WT under the Cd treatment. The results highlight the ability of the overexpression of MdIAA24 to enhance apple Cd resistance by improving antioxidant capacity and reducing Cd absorption.


Assuntos
Malus , Cádmio/toxicidade , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Humanos , Ácidos Indolacéticos , Malus/genética , Malus/metabolismo , Fotossíntese , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
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