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1.
J Nanobiotechnology ; 19(1): 302, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600560

RESUMO

BACKGROUND: Hypoxia is inherent character of most solid malignancies, leading to the failure of chemotherapy, radiotherapy and immunotherapy. Atovaquone, an anti-malaria drug, can alleviate tumor hypoxia by inhibiting mitochondrial complex III activity. The present study exploits atovaquone/albumin nanoparticles to improve bioavailability and tumor targeting of atovaquone, enhancing the efficacy of anti-PD-1 therapy by normalizing tumor hypoxia. METHODS: We prepared atovaquone-loaded human serum albumin (HSA) nanoparticles stabilized by intramolecular disulfide bonds, termed HSA-ATO NPs. The average size and zeta potential of HSA-ATO NPs were measured by particle size analyzer. The morphology of HSA-ATO NPs was characterized by transmission electron microscope (TEM). The bioavailability and safety of HSA-ATO NPs were assessed by animal experiments. Flow cytometry and ELISA assays were used to evaluate tumor immune microenvironment. RESULTS: Our data first verified that atovaquone effectively alleviated tumor hypoxia by inhibiting mitochondrial activity both in vitro and in vivo, and successfully encapsulated atovaquone in vesicle with albumin, forming HSA-ATO NPs of approximately 164 nm in diameter. We then demonstrated that the HSA-ATO NPs possessed excellent bioavailability, tumor targeting and a highly favorable biosafety profile. When combined with anti-PD-1 antibody, we observed that HSA-ATO NPs strongly enhanced the response of mice bearing tumor xenografts to immunotherapy. Mechanistically, HSA-ATO NPs promoted intratumoral CD8+ T cell recruitment by alleviating tumor hypoxia microenvironment, thereby enhancing the efficacy of anti-PD-1 immunotherapy. CONCLUSIONS: Our data provide strong evidences showing that HSA-ATO NPs can serve as safe and effective nano-drugs to enhance cancer immunotherapy by alleviating hypoxic tumor microenvironment.

2.
Food Res Int ; 149: 110662, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34600664

RESUMO

The rapid increase of genetically modified organisms (GMOs) entering the food and feed markets, and the contamination of donor (micro)organisms of transgenic elements make it more challenging for the existing GMO detection. In this study, we developed a high-throughput and contamination-removal GMO detection approach named as GmoDetector. GmoDetector targeted 64 common transgenic elements and 76 GMO-specific events collected from 251 singular GM events, and combined with next generation sequencing (NGS) and target enrichment technology to detect various GMOs. As a result, GmoDetector was able to exclude the donor (micro)organism contamination, and detect the authorized and unauthorized GMOs (UGMOs) in any forms of food or feed, such as processed or unprocessed. The sensitivity of GmoDetector is as low as 0.1% (GMO content), which has met the GMO labeling threshold for all countries. Therefore, GmoDetector is a robust tool for accurate and efficient detection of the authorized and UGMOs.

3.
Nucleic Acids Res ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634795

RESUMO

Emerging infectious diseases significantly threaten global public health and socioeconomic security. The majority of emerging infectious disease outbreaks are caused by zoonotic/vector-borne viruses. Bats and rodents are the two most important reservoir hosts of many zoonotic viruses that can cross species barriers to infect humans, whereas mosquitos and ticks are well-established major vectors of many arboviral diseases. Moreover, some emerging zoonotic diseases require a vector to spread or are intrinsically vector-borne and zoonotically transmitted. In this study, we present a newly upgraded database of zoonotic and vector-borne viruses designated ZOVER (http://www.mgc.ac.cn/ZOVER). It incorporates two previously released databases, DBatVir and DRodVir, for bat- and rodent-associated viruses, respectively, and further collects up-to-date knowledge on mosquito- and tick-associated viruses to establish a comprehensive online resource for zoonotic and vector-borne viruses. Additionally, it integrates a set of online visualization tools for convenient comparative analyses to facilitate the discovery of potential patterns of virome diversity and ecological characteristics between/within different viral hosts/vectors. The ZOVER database will be a valuable resource for virologists, zoologists and epidemiologists to better understand the diversity and dynamics of zoonotic and vector-borne viruses and conduct effective surveillance to monitor potential interspecies spillover for efficient prevention and control of future emerging zoonotic diseases.

4.
J Atheroscler Thromb ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34483222

RESUMO

AIM: We used a dataset from a cross-sectional survey conducted in China to determine which of the anthropometric indices of obesity are important in terms of carotid atherosclerosis free of cardiovascular and cerebrovascular diseases. METHODS: A total of 5,245 participants who were volunteering for carotid ultrasound unit in this cross-sectional survey were included in the present analysis. All subjects were free of angina, myocardial infarction, heart failure and stroke, and cancer. A low-risk subgroup was defined as people free of hypertension, diabetes, and hyperlipidemia. All analyses based on logistic regression were gender-specific. RESULTS: The present study consisted of 2,501 males and 2,744 females, with 776 (31.03%) diagnosed as carotid artery plaque in males and 550 (20.04%) in females. Univariable analyses in unadjusted logistic model showed significant associations between disease presence and all central obesity indices. After adjusting for more variables, only a body shape index (ABSI) was associated with the presence of disease in both males and females. Moreover, stepwise regression approaches revealed that ABSI was always an independent determinant of the presence of subclinical carotid plaque. Multiple regression shows a linear and significant increase in the prevalence of atherosclerosis in males and females as ABSI decile levels increased. Similar results were obtained when the association between ABSI and carotid plaque was studied in this low-risk subgroup. CONCLUSIONS: ABSI, as a novel anthropometric indicator compared with traditional indices, was found to have a closer relationship with subclinical carotid atherosclerosis, even in populations free of hypertension, diabetes, and hyperlipidemia.

5.
J Infect Dev Ctries ; 15(8): 1074-1079, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34516413

RESUMO

INTRODUCTION: Public life in China is gradually returning to normal with strong measures in coronavirus 2019 (COVID-19) control. Because of the long-term effects of COVID-19, medical institutions had to make timely adjustments to control policies and priorities to balance between COVID-19 prevention and daily medical services. METHODOLOGY: The framework for infection prevention and control in the inpatient department was effectively organized at both hospital and department levels. A series of prevention and control strategies was implemented under this leadership: application of rigorous risk assessment and triage before admission through a query list; classifying patients into three risk levels and providing corresponding medical treatment and emergency handling; establishing new ward visiting criteria for visitors; designing procedures for PPE and stockpile management; executing specialized disinfection and medical waste policies. RESULTS: Till June 2020, the bed occupancy had recovered from 20.0% to 88.1%. In total, 13045 patients were received in our hospital, of which 54 and 127 patients were identified as high-risk and medium-risk, respectively, and 2 patients in the high-risk group were eventually laboratory-confirmed with COVID-19. No hospital-acquired infection of COVID-19 has been observed since the emergency appeared. CONCLUSIONS: The strategies ensured early detection and targeted prevention of COVID-19 following the COVID-19 pandemic, which improved the recovery of medical services after the pandemic.


Assuntos
COVID-19/prevenção & controle , Infecção Hospitalar/prevenção & controle , Hospitais/estatística & dados numéricos , Controle de Infecções/métodos , COVID-19/epidemiologia , China/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/virologia , Hospitalização/estatística & dados numéricos , Hospitais/normas , Humanos , Controle de Infecções/instrumentação , Pacientes Internados/estatística & dados numéricos , Isolamento de Pacientes/métodos , Equipamento de Proteção Individual , Medição de Risco , Triagem
6.
Cytokine ; 148: 155689, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34507247

RESUMO

BACKGROUND: Prevention of acute rejection is the key of the success of liver transplantation. However, there are no specific indicators available for prediction of acute rejection after liver transplantation. MicroRNAs (miRNAs) are highly conserved and small noncoding RNA molecules that can be detected in peripheral blood. Here, we evaluated the potential of circulating miRNAs to serve as noninvasive biomarkers for acute rejection after liver transplantation in rats. METHODS: The liver grafts retrieved from Lewis rats were orthotopically transplanted into BN rats or Lewis rats in the acute rejection and immune tolerance group respectively, and the BN rats in the immune intervention group was intraperitoneally injected with transforming growth factor-ß1 overexpressed immature dendritic cells to suppress acute rejection before orthotopically transplanted with livers from Lewis rats. MiRNAs profiling studies were used to determine the regulation of circulating miRNAs in plasma samples of rats. Candidate miRNA was verified by quantitative reverse transcriptase polymerase chain reaction. Furthermore, the relationship between candidate miRNA and acute rejection was also evaluated. RESULTS: Microarray analysis revealed that miR-199a-3p was the mostly differentially regulated miRNAs in plasma samples among the three groups. The plasmid PCDH-CMV-EGFP-hTGF-ß1 was identified by PCR and DNA sequencing, and successfully expressed in imDCs. There were differences in the expression of miR-199a-3p in the liver tissues of the AR group on the 3rd, 7th and 10th day after liver transplantation (all p < 0.01). With time, the RAI score increased gradually, and the difference of miR-199a-3p expression gradually increased (rs = 0.92, p < 0.001), suggesting that it may be related to acute rejection. The expression of miR-199a-3p in the serum of the AR and TGF-ß1-imDCs groups gradually increased, reaching a peak at day 7 and then decreasing. There was positive relationship between the expression of miR-199a-3p and RAIs within 7 days post operation. (rs = 0.942, p < 0.05). CONCLUSION: miR-199a-3p might be an early warning marker for acute rejection after liver transplantation in rats.

7.
Cereb Cortex ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379728

RESUMO

As exemplified by the Ebbinghaus illusion, the perceived size of an object can be significantly biased by its surrounding context. The phenomenon is experienced by humans as well as other species, hence likely evolutionarily adaptive. Here, we examined the heritability of the Ebbinghaus illusion using a combination of the classic twin method and multichannel functional near-infrared spectroscopy. Results show that genes account for over 50% of the variance in the strength of the experienced illusion. Interestingly, activations evoked by the Ebbinghaus stimuli in the early visual cortex are explained by genetic factors whereas those in the posterior temporal cortex are explained by environmental factors. In parallel, the feedforward functional connectivity between the occipital cortex and the temporal cortex is modulated by genetic effects whereas the feedback functional connectivity is entirely shaped by environment, despite both being significantly correlated with the strength of the experienced illusion. These findings demonstrate that genetic and environmental factors work in tandem to shape the context-dependent visual size illusion, and shed new light on the links among genes, environment, brain, and subjective experience.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34411698

RESUMO

Bisphenol B (BPB), a widely used alternative of bisphenol A (BPA), has been detected in various environmental media and foodstuffs. However, the knowledge of the health risks about BPB is still limited. In this study, the effects of BPB on thyroid hormone homeostasis and neuronal development were evaluated by exposure of embryos 2 h post-fertilization (hpf) to BPB (0, 1, 10, 100 and 1000 µg/L) until 144 hpf. The results showed that 100 and 1000 µg/L BPB exposed larvae exhibited abnormal morphologies in phenotype and brain histological patterns. Significant decline of thyroid hormone thyroxine (T4) content and elevation of 3,5,3'-triiodothyronine (T3) content, along with the up-regulated expression of tg, trhr1, dio1, dio2, thrα, thrß genes and down-regulated expression of tsh, ttr and trh genes in BPB exposed zebrafish larvae were observed. Moreover, locomotor activity of larvae was decreased, and the transcription of genes (e.g., elavl3, gap43, zn5, α-tubulin, syn2a and mbp) related to neuronal development were inhibited after exposure to BPB. The mechanism of neurotoxicity and thyroid disruption in zebrafish larvae induced by BPB were discussed.

9.
Sheng Li Xue Bao ; 73(4): 665-680, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34405222

RESUMO

Prostaglandin E2 (PGE2) is an important lipid mediator derived from arachidonic acid. It is widely distributed in various tissues and involved in numerous physiological and pathophysiological processes. Based on the inhibition of inflammatory PGE2 production, non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the most commonly used drugs to treat pain and inflammation. However, clinical trials have revealed that NSAIDs, especially cyclooxygenase-2 (COX-2) selective inhibitors, may predispose patients to a remarkably increased cardiovascular risk, including hypertension, myocardial infarction, and heart failure. This promotes scientists to develop new drugs to not only afford pain relief but also have cardiovascular efficacy. Microsomal prostaglandin E synthase-1 (mPGES-1), the key terminal enzyme catalyzing the synthesis of inflammatory PGE2, and the four PGE2 receptors (EP1-4) have gained more attention as the promising alternative drug targets for the development of novel NSAIDs. The role of mPGES-1 and EP receptors in cardiovascular diseases also has been widely studied. In this review, we highlight the most recent advances from our and other studies on the role of PGE2, particularly mPGES-1 and the four PGE2 receptors, in cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Anti-Inflamatórios não Esteroides , Doenças Cardiovasculares/tratamento farmacológico , Ciclo-Oxigenase 2 , Dinoprostona , Humanos , Prostaglandina-E Sintases , Receptores de Prostaglandina E
10.
BMC Anesthesiol ; 21(1): 194, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289814

RESUMO

BACKGROUND: The objective of this study was to compare the analgesic potency of oxycodone versus morphine after laparoscopic deep infiltrating endometriosis resection. METHODS: Fifty patients undergoing laparoscopic deep infiltrating endometriosis resection were randomized to receive oxycodone or morphine intravenous-PCA after surgery. The primary outcome was opioid consumption during the 24 h after surgery. Secondary outcomes included time to first request for analgesia, the number of bolus, pain, sedation, nausea, vomiting, respiratory depression, and bradycardia. The prominent pain that caused patients to press the analgesic device was also recorded. RESULTS: Oxycodone consumption (14.42 ± 2.83) was less than morphine consumption (20.14 ± 3.83). Compared with the morphine group, the total number of bolus (78 vs 123) was less and the average time to first request for analgesia (97.27 ± 59.79 vs 142.17 ± 51) was longer in the oxycodone group. The incidence of nausea was higher in the morphine group than in the oxycodone group at 0-2 h (45.45% vs 17.19%), 2-4 h (50% vs 17.19%),12-24 h (40.91% vs 13.04%) and 0-24 h (39.17% vs 19.13%). The overall incidence of vomiting was higher in the morphine group (27.27% vs 13.92%). There was no difference in visual analogue scale score, the incidence of respiratory depression, and bradycardia between groups. Of the three types of pain that prompted patients to request analgesia, the incidence of visceral pain was highest (59.9%, P < 0.01). CONCLUSION: Oxycodone was more potent than morphine for analgesia after laparoscopic endometriosis resection, and oxycodone has fewer side effects than morphine. Name of the registry: Chinese Clinical Trial Registry Trial registration number: ChiCTR1900021870 URL of trial registry record: http://www.chictr.org.cn/edit.aspx?pid=35799&htm=4 Date of registration: 2019/3/13 0:00:00.

11.
Biomolecules ; 11(6)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34207942

RESUMO

Blood pressure (BP) follows a circadian rhythm, it increases on waking in the morning and decreases during sleeping at night. Disruption of the circadian BP rhythm has been reported to be associated with worsened cardiovascular and renal outcomes, however the underlying molecular mechanisms are still not clear. In this review, we briefly summarized the current understanding of the circadian BP regulation and provided therapeutic overview of the relationship between circadian BP rhythm and cardiovascular and renal health and disease.


Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Ritmo Circadiano/fisiologia , Nefropatias/fisiopatologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/fisiopatologia , China , Humanos , Hipertensão/fisiopatologia , Rim/fisiopatologia , Nefropatias/metabolismo
12.
Front Immunol ; 12: 679398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177922

RESUMO

Acute rejection induced by the recognition of donor alloantigens by recipient T cells leads to graft failure in liver transplant recipients. The role of high mobility group box 1 (HMGB1), an inflammatory mediator, in the acute allograft rejection of liver transplants is unknown. Here, rat orthotopic liver transplantation was successfully established to analyze the expression pattern of HMGB1 in liver allografts and its potential role in promoting the maturation of dendritic cells (DCs) to promote T cell proliferation and differentiation. Five and 10 days after transplantation, allografts showed a marked upregulation of HMGB1 expression accompanied by elevated levels of serum transaminase and CD3+ and CD86+ inflammatory cell infiltration. Furthermore, in vitro experiments showed HMGB1 increased the expressions of co-stimulatory molecules (CD80, CD83, and MHC class II) on bone marrow-derived DCs. HMGB1-pulsed DCs induced naive CD4+ T cells to differentiate to Th1 and Th17 subsets secreting IFN-γ and IL-17, respectively. Further in vivo experiments confirmed the administration of glycyrrhizic acid, a natural HMGB1 inhibitor, during donor liver preservation had therapeutic effects by reducing inflammation and hepatocyte damage reflected by a decline in serum transaminase and prolonged allograft survival time. These results suggest the involvement of HMBG1 in acute liver allograft rejection and that it might be a candidate therapeutic target to avoid acute rejection after liver transplantation.

13.
J Cell Mol Med ; 25(16): 7913-7921, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34132471

RESUMO

Irinotecan is a kind of alkaloid with antitumour activity, but its low solubility and high toxicity limit its application. Epigallocatechin-3-gallate (EGCG) is one of the main bioactive components in tea. The epidemiological investigation and animal and cell experiments show that EGCG has a preventive and therapeutic effect on many kinds of tumours. Here, colorectal cancer cells RKO and HCT116 were employed, and the CCK8 proliferation test was used to screen the appropriate concentration of EGCG and irinotecan, and the effects of single and/or combined drugs on migration, invasion, DNA damage, cell cycle and autophagy of tumour cells were investigated. The results showed that EGCG combined with irinotecan (0.5 µmol L- ) not only had a stronger inhibitory effect on tumour cells than EGCG or irinotecan alone but also prevented tumour cell migration and invasion. EGCG alone did not cause DNA damage in colorectal cancer cells, but its combination with irinotecan could induce S or G2 phase arrest by inhibiting topoisomerase I to cause more extensive DNA damage. EGCG also induced apoptosis by promoting autophagy with irinotecan synergistically. These results indicated that EGCG in combination with irinotecan could be a promising strategy for colorectal cancer.

14.
Ann Palliat Med ; 10(4): 4369-4374, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33966438

RESUMO

BACKGROUND: At present, the recommendation grade of transcatheter aortic valve implantation (TAVI) for aortic valve stenosis (AVS) has increased in many guidelines. Establishing an optimized TAVI nurse team is essential for improving surgical quality and outcomes. We compared the professional requirements for nurses in two surgical approaches for aortic stenosis and the different roles of nurses in the surgical teams, with an attempt to further improve the training programs for specialized nurses. METHODS: The required professional knowledge and the role of nursing staff during TAVI or AVR (Conventional aortic valve replacement) were analyzed. These included knowledge on the pathophysiology of aortic stenosis, advantages and disadvantages of different heart valves, extracorporeal circulation, nursing cooperation during valve replacement, conventional surgical instruments and interventional consumables, surgical complications, radiation protection, operation of pacemakers, theory and operation of electric defibrillation. And the surgical team members and their roles, and doctor-patient satisfaction were also compared. RESULTS: TAVI had higher requirements for the basic knowledge of the pathophysiology of aortic stenosis, advantages and disadvantages of different heart valves, extracorporeal circulation and theory and operation of electric defibrillation. And the clinical professional knowledge of conventional surgical instruments and interventional consumables, surgical complications, radiation protection, nursing cooperation, operation of pacemakers were also higher required in TAVI. Doctor-patient overall satisfaction were higher in TAVI than AVR (95.8% vs. 84.4%, 97.5% vs. 92.7%). CONCLUSIONS: The professional requirements for nurses differs between TAVI and AVR. Comprehensive programs should be designed to develop the basic knowledge and professional training for future cardiac operation.


Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Fatores de Risco , Resultado do Tratamento
16.
J Vis ; 21(4): 8, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33871554

RESUMO

The role of different spatial frequency bands in threat detection has been explored extensively. However, most studies use manual responses and the results are mixed. Here, we aimed to investigate the contribution of spatial frequency information to threat detection by using three response types, including manual responses, eye movements, and reaching movements, together with a priming paradigm. The results showed that both saccade and reaching responses were significantly faster to threatening stimuli than to nonthreatening stimuli when primed by low-spatial-frequency gratings rather than by high-spatial-frequency gratings. However, the manual response times to threatening stimuli were comparable to nonthreatening stimuli, irrespective of the spatial frequency content of the primes. The findings provide clear evidence that low-spatial-frequency information can facilitate threat detection in a response-specific manner, possibly through the subcortical magnocellular pathway dedicated to processing threat-related signals, which is automatically prioritized in the oculomotor system and biases behavior.

17.
FASEB J ; 35(5): e21530, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33813752

RESUMO

Circadian clock is involved in regulating most renal physiological functions, including water and electrolyte balance and blood pressure homeostasis, however, the role of circadian clock in renal pathophysiology remains largely unknown. Here we aimed to investigate the role of Bmal1, a core clock component, in the development of renal fibrosis, the hallmark of pathological features in many renal diseases. The inducible Bmal1 knockout mice (iKO) whose gene deletion occurred in adulthood were used in the study. Analysis of the urinary water, sodium and potassium excretion showed that the iKO mice exhibit abolished diurnal variations. In the model of renal fibrosis induced by unilateral ureteral obstruction, the iKO mice displayed significantly decreased tubulointerstitial fibrosis reflected by attenuated collagen deposition and mitigated expression of fibrotic markers α-SMA and fibronectin. The hedgehog pathway transcriptional effectors Gli1 and Gli2, which have been reported to be involved in the pathogenesis of renal fibrosis, were significantly decreased in the iKO mice. Mechanistically, ChIP assay and luciferase reporter assay revealed that BMAL1 bound to the promoter of and activate the transcription of Gli2, but not Gli1, suggesting that the involvement of Bmal1 in renal fibrosis was possibly mediated via Gli2-dependent mechanisms. Furthermore, treatment with TGF-ß increased Bmal1 in cultured murine proximal tubular cells. Knockdown of Bmal1 abolished, while overexpression of Bmal1 increased, Gli2 and the expression of fibrosis-related genes. Collectively, these results revealed a prominent role of the core clock gene Bmal1 in tubulointerstitial fibrosis. Moreover, we identified Gli2 as a novel target of Bmal1, which may mediate the adverse effect of Bmal1 in obstructive nephropathy.


Assuntos
Fatores de Transcrição ARNTL/fisiologia , Fibrose/prevenção & controle , Regulação da Expressão Gênica , Nefropatias/prevenção & controle , Proteínas Circadianas Period/fisiologia , Proteína Gli2 com Dedos de Zinco/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo
18.
PLoS One ; 16(3): e0245714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33720962

RESUMO

The small (18S) and large (28S) nuclear ribosomal DNA (rDNA) introns have been researched and sequenced in a variety of ectomycorrhizal fungal taxa in this study, it is found that both 18S and 28S rDNA would contain introns and display some degree variation in size, nucleotide sequences and insertion positions within the same fungi species (Meliniomyces). Under investigations among the tested isolates, 18S rDNA has four sites for intron insertions, 28S rDNA has two sites for intron insertions. Both 18S and 28S rDNA introns among the tested isolates belong to group I introns with a set of secondary structure elements designated P1-P10 helics and loops. We found a 12 nt nucleotide sequences TACCACAGGGAT at site 2 in the 3'-end of 28S rDNA, site 2 introns just insert the upstream or the downstream of the12 nt nucleotide sequences. Afters sequence analysis of all 18S and 28S rDNA introns from tested isolates, three high conserved regions around 30 nt nucleotides (conserved 1, conserved 2, conserved 3) and identical nucleotides can be found. Conserved 1, conserved 2 and conserved 3 regions have high GC content, GC percentage is almost more than 60%. From our results, it seems that the more convenient host sites, intron sequences and secondary structures, or isolates for 18S and 28S rDNA intron insertion and deletion, the more popular they are. No matter 18S rDNA introns or 18S rDNA introns among tested isolates, complementary base pairing at the splicing sites in P1-IGS-P10 tertiary helix around 5'-end introns and exons were weak.


Assuntos
Íntrons/genética , Micorrizas/genética , RNA Ribossômico 18S/genética , RNA Ribossômico 28S/genética , Sequência de Bases , Sequência Conservada
19.
Cancer Res ; 81(14): 3905-3915, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33687951

RESUMO

The p53 tumor suppressor is frequently inactivated by mutations in cancer. Most p53 mutations are located in the DNA-binding domain, causing local disruption of DNA-binding surface or global misfolding. Rescuing the structural defect of mutant p53 is an attractive therapeutic strategy, but its potential remains unproven due to a lack of drugs capable of efficiently rescuing misfolded p53. Although mutant p53 in tumors is inactive at 37°C, approximately 15% are temperature sensitive (ts) and regain DNA-binding activity at 32°C to 34°C (ts mutants). This temperature is achievable using a therapeutic hypothermia procedure established for resuscitated cardiac arrest patients. To test whether hypothermia can be used to target tumors with ts p53 mutations, the core temperature of tumor-bearing mice was lowered to 32°C using the adenosine A1 receptor agonist N6-cyclohexyladenoxine that suppresses brain-regulated thermogenesis. Hypothermia treatment (32 hours at 32°C × 5 cycles) activated endogenous ts mutant p53 in xenograft tumors and inhibited tumor growth in a p53-dependent fashion. Tumor regression and durable remission in a ts p53 lymphoma model was achieved by combining hypothermia with chemotherapy. The results raise the possibility of treating tumors expressing ts p53 mutations with hypothermia. SIGNIFICANCE: Pharmacologic inhibition of brain-regulated thermogenesis and induction of 32°C whole-body hypothermia specifically targets tumors with temperature-sensitive p53 mutations, rescuing p53 transcriptional activity and inducing tumor regression.See related commentary by Hu and Feng, p. 3762.

20.
Front Endocrinol (Lausanne) ; 12: 598470, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767667

RESUMO

Background: Polysomnography (PSG) is the gold standard for diagnosis of sleep-disordered breathing (SDB). But it is impractical to perform PSG in all patients with diabetes. The objective was to develop a clinically easy-to-use prediction model to diagnosis SDB in patients with diabetes. Methods: A total of 440 patients with diabetes were recruited and underwent overnight PSG at West China Hospital. Prediction algorithms were based on oxygen desaturation index (ODI) and other variables, including sex, age, body mass index, Epworth score, mean oxygen saturation, and total sleep time. Two phase approach was employed to derivate and validate the models. Results: ODI was strongly correlated with apnea-hypopnea index (AHI) (rs = 0.941). In the derivation phase, the single cutoff model with ODI was selected, with area under the receiver operating characteristic curve (AUC) of 0.956 (95%CI 0.917-0.994), 0.962 (95%CI 0.943-0.981), and 0.976 (95%CI 0.956-0.996) for predicting AHI ≥5/h, ≥15/h, and ≥30/h, respectively. We identified the cutoff of ODI 5/h, 15/h, and 25/h, as having important predictive value for AHI ≥5/h, ≥15/h, and ≥30/h, respectively. In the validation phase, the AUC of ODI was 0.941 (95%CI 0.904-0.978), 0.969 (95%CI 0.969-0.991), and 0.949 (95%CI 0.915-0.983) for predicting AHI ≥5/h, ≥15/h, and ≥30/h, respectively. The sensitivity of ODI ≥5/h, ≥15/h, and ≥25/h was 92%, 90%, and 93%, respectively, while the specificity was 73%, 89%, and 85%, respectively. Conclusions: ODI is a sensitive and specific tool to predict SDB in patients with diabetes.

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