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1.
J Ethnopharmacol ; 282: 114643, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34534597

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: With the features of multiple-components and targets as well as multifunction, traditional Chinese medicine (TCM) has been widely used in the prevention and treatment of various diseases for a long time. During the application of TCM, the researches about bioavailability enhancement of the bioactive constituents in formula are flourishing. Bushen-Yizhi formula (BSYZ), a TCM prescription with osthole (OST) as one of the main bioactive ingredients, have been widely used to treat kidney deficiency, mental retardation and Alzheimer's disease. However, the underlying biological mechanism and compound-enzyme interaction mediated bioavailability enhancement of OST are still not clearly illuminated. AIM OF THE STUDY: The aim of this study is to explore the material basis and molecular mechanism from BSYZ in the bioavailability enhancement of OST. Screening the potential CYP3A4 inhibitors using theoretical prediction and then verifying them in vitro, and pharmacokinetics study of OST in rat plasma under co-administrated of screened CYP3A4 inhibitors and BSYZ were also scarcely reported. MATERIALS AND METHODS: Screening of CYP3A4 inhibitors from BSYZ was performed with molecular docking simulation from systems pharmacology database. The screened compounds were verified by using P450-Glo Screening Systems. A multiple reaction monitoring (MRM) mass spectrometry method was established for OST quantification. Male Sprague-Dawley rats divided into four groups and six rats in each group were employed in the pharmacokinetics study of OST. The administrated conditions were group I, OST (20 mg/kg); group II, BSYZ (containing OST 1 mg/mL, at the dose of 20 mg/kg OST in BSYZ); group III, co-administration of ketoconazole (Ket, 75 mg/kg) and OST (20 mg/kg); group IV, co-administration of CYP3A4 inhibitor (10 mg/kg) and OST (20 mg/kg). They were determined by using HPLC-MS/MS (MRM) and statistical analysis was performed using student's t-test with p < 0.05 as the level of significance. RESULTS: 21 potential CYP3A4 inhibitors were screened from BSYZ compounds library. From the results of verification in vitro, we found 4 compounds with better CYP3A4 inhibition efficiency including Oleic acid, 1,2,3,4,6-O-Pentagalloylglucose, Rutin, and Schisantherin B. Under further verification, Schisantherin B exhibited the best inhibitory effect on CYP3A4 (IC50 = 0.339 µM), and even better than the clinically used drug (Ket) at the concentration of 5 µM. In the study of pharmacokinetics, the area under the curve (AUC, ng/L*h) of OST after oral administration of BSYZ, Ket and Schisantherin B (2196.23 ± 581.33, 462.90 ± 92.30 and 1053.03 ± 263.62, respectively) were significantly higher than that of pure OST treatment (227.89 ± 107.90, p < 0.01). CONCLUSIONS: Schisantherin B, a profoundly effective CYP3A4 inhibitor screened from BSYZ antagonized the metabolism of CYP3A4 on OST via activity inhibition, therefore significantly enhanced the bioavailability of OST in rat plasma. The results of this study will be helpful to explain the rationality of the compatibility in TCM formula, and also to develop new TCM formula with more reasonable drug compatibility.

2.
J Hazard Mater ; 422: 126858, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34419845

RESUMO

Toxicological effects of nanoplastics have been demonstrated in a variety of organisms, yet their impacts on bacteria, especially on the antibiotic resistance evolution remain under explored. Herein, we report individual and combined effects of nano-polystyrene (nano-PS) and erythromycin (ERY) on growth and resistance mutations of Escherichia coli. The toxicity of nano-PS was dependent on size and functional modifications, with 30 nm and amino-modified PS (PS-NH2, 200 nm) showing the greatest toxicity. Adsorption of nano-PS onto bacterial surface and the subsequent increase of intracellular ROS or the probable mechanical damage were considered as the primary toxic mechanisms. Furthermore, nano-PS increased the bacterial resistance mutations, which was due to the oxidative damage to DNA and the SOS response. In addition, PS-NH2 presented synergistic effects with ERY while non-modified PS had no impact, although both of them showed adsorption capacity to ERY. This was likely because the positively charged PS-NH2 acted as a carrier of ERY and enhanced the interactions between ERY and the bacteria. Our findings raised the concerns about the risk of nanoplastics in accelerating the bacterial resistance evolution, and highlighted the necessity of including combined effects of nanoplastics and co-contaminants in risk assessment.

3.
Respir Med ; 190: 106681, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34784563

RESUMO

BACKGROUND: Small airway dysfunction (SAD) is an early lesion of chronic respiratory disease that is best detected using impulse oscillometry (IOS). Few studies have investigated risk factors for IOS-defined SAD (IOS-SAD) in a large population. We aimed to explore the clinical features of and risk factors for IOS-SAD in a community-based population. METHODS: We divided subjects into IOS-SAD and non-SAD groups based on a cutoff of >0.07 kPa/L/s in the difference between the resistance at 5 Hz versus the resistance at 20 Hz (R5-R20). All participants underwent spirometry, IOS, and completed a questionnaire; some participants underwent computed tomography (CT). We analyzed the risk factors for SAD based on binary logistic regression. RESULTS: The total cohort comprised 1327 subjects. The prevalence of IOS-SAD was 32.9% (437/1327). Compared with the non-SAD group, the IOS-SAD group was older (64.0 ± 7.8 vs. 59.6 ± 7.8 years, p < 0.001), included less never-smokers (30.2% vs. 35.8%, p < 0.001), had greater airway resistance and worse lung function, indicated by a larger R5-R20 (0.15 ± 0.08 vs. 0.03 ± 0.02 kPa/L/s, p < 0.001) and smaller forced expiratory volume in 1 s to forced vital capacity after bronchodilation (60.2 ± 14.4% vs. 72.6 ± 10.0%, p < 0.001); on CT, the IOS-SAD group had higher prevalences of emphysema and gas trapping. Risk factors for SAD were older age, high BMI, smoking, childhood cough, and asthma. CONCLUSION: Subjects with IOS-SAD had increased airway resistance and visible CT changes. Individuals with smoking exposure, advanced age, high BMI, childhood cough, and asthma were more prone to SAD. CLINICAL TRIAL REGISTRATION: ChiCTR1900024643.

4.
Sci Total Environ ; : 151636, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774633

RESUMO

BACKGROUND: The global burden of acute lower respiratory infection (ALRI) attributable to air pollution has increased in recent years, but the association between ALRI and exposure to size-specific particulate matter has not been investigated using different exposure metrics. METHODS: We obtained ALRI admission from seven cities from 2014 to 2016 in China. Different sized particles were measured using three metrics (a) daily mean, (b) hourly peak, and (c) daily excessive concentration hours (DECH). Generalized additive models were fitted for each of the seven cities, and the city-specific estimates were then pooled using random-effects meta-analysis models. Stratified analyses were conducted to examine the effect modifications of gender, age, and season. We also estimated the disease burden due to particulate matter exposures. RESULTS: There were 111,426 ALRI (79,803 pneumonia and 31,622 bronchiolitis) hospital admissions under the age of 15 between 2014 and 2016 in our study. Daily means were associated with the largest ALRI estimates (95% confidence interval [CI]): 2.43% (0.79%, 4.11%) for PM2.5, 2.25% (0.11%, 4.44%) for PMc, and 2.64% (0.73%, 4.58%) for PM10. The magnitude of effect sizes were followed by DECH: 1.94% (0.51%, 3.39%) for PM2.5, 0.88% (-0.14%, 1.92%) for PMc, 1.86% (0.50%, 2.01%) for PM10; and hourly peak: 0.70% (-0.60%, 2.01%) for PM2.5, 1.05% (-0.13%, 2.66%) for PMc, and 1.20% (-0.20%, 2.62%) for PM10 at lag03. We found significantly higher effects in cold seasons than that in warm seasons, while we did not find a significant different between gender and age groups. CONCLUSIONS: The adverse effects of exposure to particulate matter on ALRI hospitalizations are reconfirmed. DECH was a possible alternative exposure indicator for PM2.5 assessment, which may affect air quality standards in the future.

5.
Theranostics ; 11(20): 9791-9804, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815786

RESUMO

Rationale: Platelets play an essential role in atherosclerosis, but the underlying mechanisms remain to be addressed. This study is to investigate the role of platelets in d-flow induced vascular inflammation and the underlying mechanism. Methods: We established a disturbed blood flow (d-flow) model by partial carotid ligation (PCL) surgery using atherosclerosis-susceptible mice and wild-type mice to observe the d-flow induced platelet accumulation in the subendothelium or in the plaque by immunostaining or transmission electron microscopy. The mechanism of platelet subendothelial accumulation was further explored by specific gene knockout mice. Results: We observed presence of platelets in atherosclerotic plaques either in the atheroprone area of aortic arch or in carotid artery with d-flow using Ldlr-/- or ApoE-/- mice on high fat diet. Immunostaining showed the subendothelial accumulation of circulating platelets by d-flow in vivo. Transmission electron microscopy demonstrated the accumulation of platelets associated with monocytes in the subendothelial spaces. The subendothelial accumulation of platelet-monocyte/macrophage aggregates reached peak values at 2 days after PCL. In examining the molecules that may mediate the platelet entry, we found that deletion of platelet C-type lectin-like receptor 2 (CLEC-2) reduced the subendothelial accumulation of platelets and monocytes/macrophages by d-flow, and ameliorated plaque formation in Ldlr-/- mice on high fat diet. Supportively, CLEC-2 deficient platelets diminished their promoting effect on the migration of mouse monocyte/macrophage cell line RAW264.7. Moreover, monocyte podoplanin (PDPN), the only ligand of CLEC-2, was upregulated by d-flow, and the myeloid-specific PDPN deletion mitigated the subendothelial accumulation of platelets and monocytes/macrophages. Conclusions: Our results reveal a new CLEC-2-dependent platelet subendothelial accumulation in response to d-flow to regulate vascular inflammation.

6.
Front Pharmacol ; 12: 722360, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803675

RESUMO

Background: Chronic low-grade inflammation is recognized as a key pathophysiological mechanism of insulin resistance. Leukotriene B4 (LTB4), a molecule derived from arachidonic acid, is a potent neutrophil chemoattractant. The excessive amount of LTB4 that is combined with its receptor BLT1 can cause chronic low-grade inflammation, aggravating insulin resistance. Berberine (BBR) has been shown to relieve insulin resistance due to its anti-inflammatory properties. However, it is not clear whether BBR could have any effects on the LTB4-BLT1 axis. Methods: Using LTB4 to induce Raw264.7 and HepG2 cells, we investigated the effect of BBR on the LTB4-BLT1 axis in the progression of inflammation and insulin resistance. Results: Upon exposure to LTB4, intracellular insulin resistance and inflammation increased in HepG2 cells, and chemotaxis and inflammation response increased in RAW264.7 cells. Interestingly, pretreatment with BBR partially blocked these changes. Our preliminary data show that BBR might act on BLT1, modulating the LTB4-BLT1 axis to alleviate insulin resistance and inflammation. Conclusions: Our study demonstrated that BBR treatment could reduce intracellular insulin resistance and inflammation of hepatic cells, as well as chemotaxis of macrophages induced by LTB4. BBR might interact with BLT1 and alter the LTB4-BLT1 signaling pathway. This mechanism might be a novel anti-inflammatory and anti-diabetic function of BBR.

7.
Front Pharmacol ; 12: 775521, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803718

RESUMO

Objectives: Genital herpes (GH) is a common sexually transmitted disease mainly caused by herpes simplex virus 2 (HSV-2). JieZe-1 (JZ-1) is an in-hospital prescription that has been used in Tongji Hospital for many years to treat various lower female genital tract infectious diseases. Our previous study showed that JZ-1 can protect against HSV-2 infection in vitro by inducing autophagy. However, whether JZ-1 can protect against HSV-2 infection in vivo, and the underlying mechanisms involved still remain unclear. Therefore, this study was designed to address above questions. Methods: 8-week-old female balb/c mice were injected intravaginally with HSV-2 to establish GH model. The symptom score, body weight, and histological examination were recorded to assess the animal model of HSV-2 infected and the therapeutic effect of JZ-1. Inflammatory response was determined by detecting inflammatory cells infiltration and local cytokines levels. After then, under autophagy inhibitor chloroquine application, we measured the levels of cell apoptosis and autophagy and investigated the relationship between enhanced autophagy and cell apoptosis. Next, the classic PI3K/Akt/mTOR axis was examined, and in vitro experiment was carried out for further verification. Results: Our results showed that JZ-1 administration significantly reduces symptom score, increases weight gain and alleviates histological damage in HSV-2 infection-induced GH in balb/c mice. JZ-1 administration obviously ameliorates inflammatory responses with reduced T-lymphocytes, T helper cells, macrophages and neutrophils infiltration, and local IL-1ß, IL-6, TNF-α and CCL2 levels. HSV-2 infection leads to massive cell apoptosis, which was also restored by JZ-1. Meanwhile, we found that HSV-2 infection blocks autophagic flux in vivo and JZ-1 administration induces autophagy. After chloroquine application, it was observed that the inhibition of autophagy is strongly associated with increased cell apoptosis, whereas the promotion of autophagy remarkedly decreases apoptosis. These results suggested that JZ-1 inhibits cell apoptosis in GH by inducing autophagy, which was further supported in later in vitro experiment. Additionally, PI3K/Akt/mTOR signaling pathway was also downregulated by JZ-1 administration. Conclusion: Our data demonstrated that JZ-1 can alleviate HSV-2 infection-induced GH in balb/c mice by inhibiting cell apoptosis via inducing autophagy, and the underlying mechanisms may be associated with the inhibition of PI3K/Akt/mTOR pathway.

8.
Front Endocrinol (Lausanne) ; 12: 759049, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803921

RESUMO

Purpose: To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC). Methods: Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan-Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC. Results: Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS. Conclusions: Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.

9.
Comput Biol Med ; : 105037, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34809964

RESUMO

Medical imaging has been increasingly adopted in the process of medical diagnosis, especially for skin diseases, where diagnoses based on skin pathology are extremely accurate. The diagnostic reports of skin pathology images has the distinguishing features of extreme repetitiveness and rigid formatting. However, reports written by inexperienced radiologists and pathologists can have a high error rate, and even experienced clinicians can find the reporting task both tedious and time-consuming. To address this challenge, this paper studies the automatic generation of diagnostic reports based on images of skin pathologies. A novel deep learning-based image caption framework named the automatic generation network (AGNet), which is an effective network for the automatic generation of skin imaging reports, is proposed. The proposed AGNet consists of four parts: (1) the image model that extracts features and classifies images; (2) the language model that codes data and generates words using comprehensible language; (3) the attention module that connects the "tail" of the image model and the "head" of the language model, and computes the relationship between images and captions; (4) the embedding and labeling module that processes the input caption data. In case study, The AGNet is verified on a skin pathological image dataset and compared with several state-of-the-art models. The results show that the AGNet achieves the highest scores of the evaluation metrics of image caption among all comparison models, demonstrating the promising performance of the proposed method.

10.
Infect Dis Health ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34810151

RESUMO

BACKGROUND: The hospital environment is characterised by a dense network of interactions between healthcare workers (HCWs) and patients. As highlighted by the coronavirus pandemic, this represents a risk for disease transmission and a challenge for contact tracing. We aimed to develop and pilot an automated system to address this challenge and describe contacts between HCWs and patients. METHODS: We developed a bespoke Bluetooth Low Energy (BLE) system for the hospital environment with anonymous tags worn by HCWs and fixed receivers at patient room doors. Proximity between wearable tags inferred contact between HCWs. Tag-receiver interactions inferred patient room entry and exit by HCWs. We performed a pilot study in four negative pressure isolation rooms from 13 April to 18 April 2021. Nursing and medical staff who consented to participate were able to collect one of ten wearable BLE tags during their shift. RESULTS: Over the four days, when divided by shift times, 27 nursing tags and 3 medical tags were monitored. We recorded 332 nurse-nurse interactions, for a median duration of 58 s [interquartile range (IQR): 39-101]. We recorded 45 nursing patient room entries, for a median 7 min [IQR: 3-21] of patient close contact. Patient close contact was shorter in rooms on airborne precautions, compared to those not o transmission-based precautions. CONCLUSION: This pilot study supported the functionality of this approach to quantify HCW proximity networks and patient close contact. With further refinements, the system could be scaled-up to support contact tracing in high-risk environments.

11.
Dis Markers ; 2021: 6915329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790278

RESUMO

PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that play important roles in germline development and carcinogenesis. In this study, we used the deep sequencing of small RNA Transcriptome to explore the piRNA expression in six clear cell renal carcinoma (ccRCC) tissues and matched adjacent normal tissues and found that six piRNAs were upregulated and sixteen were downregulated in ccRCC tissues. Among them, piRNA-31115 (NCBI accession number: DQ571003) was the most upregulated piRNA in ccRCC tissues compared with matched adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to confirm piR-31115 expression in other ccRCC tissues (n = 40) and ccRCC cell lines. Besides, function analysis demonstrated that silencing of piR-31115 inhibited ccRCC cell proliferation, motility, and invasiveness. Mechanistic investigations showed that piRNA-31115 may activate epithelial-mesenchymal transition (EMT) via the PI3K/AKT signaling pathway. Hence, piR-31115 may represent an oncogene in the development of ccRCC.

12.
Biol Res Nurs ; : 10998004211050047, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719282

RESUMO

Background: Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in immunoregulation, but also responsible for lactation. Prolactin levels in women with chronic fatigue are higher than normal, but a chronic fatigue state inhibits postpartum lactation in humans. Objectives: This paper explored the inhibition mechanism of lactation by postpartum fatigue in rats. Methods: Postpartum fatigue models were built by forcing mother rats to stand in water and divided into 3-hour, 9-hour and 15-hour per day fatigue groups according to the underwater time. Mother rats and their offspring were reunited in a dry cage for 90 minutes every 3 hours for feeding. The expression of PRL, PRL receptor (PRLR), Janus Kinase 2 (JAK 2), and Signal transducers and activators of transcription 5 (STAT5) mRNA were analyzed and the microstructure of mammary gland were observed under light and electron microscopy. Results: The expression of pituitary PRL mRNA and its downstream signaling pathway JAK2 and STAT5 mRNA were down-regulated in the severe postpartum fatigue rats. PRL mRNA responses were dose-related to duration of fatigue. The expression of PRLR mRNA increased. Postpartum fatigue led to functional degeneration of mammary gland. The breast lobules were shrunk and the number of alveoli were decreased. Few milk protein granules and fat droplets were observed in the cytoplasm under transmission electron microscope. Conclusion: Postpartum fatigue inhibits the lactation by down-regulating the expression of PRL and PRL-dependent signaling pathway in rats.

13.
Sci Rep ; 11(1): 21743, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741082

RESUMO

There is no specific treatment for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). It is not clear when transjugular intrahepatic portosystemic shunt (TIPS) should be implemented in PA-HSOS patients. This study aimed to evaluate the timing of TIPS using total bilirubin (TBIL) as a measure, and to investigate efficacy of TIPS. We retrospectively analyzed the medical records of 10 PA-HSOS patients, among whom 4 patients had received TIPS (TIPS group), and the remaining patients were assigned to the internal medicine group. In the TIPS group, the TBIL level before TIPS was 84.4 ± 45.2 µmol/L (> 3 mg/dL), and TBIL levels were increased to different degrees after TIPS. With the extension of time, serum TBIL levels gradually decreased, and no liver failure occurred. With regards to the short-term outcomes, 3 patients recovered, 1 developed chronic illness and 0 died in the TIPS group. Moreover, 0 patients recovered, 5 developed chronic illness and 1 died in the internal medicine group. The rank sum test of group design revealed significant differences in clinical outcomes (P = 0.02). It was suggested that when the internal medicine effect of PA-HSOS patients is poor, TIPS should be considered, which is no trestricted to the limit of 3 mg/dL TBIL. It was also found TIPS effectively promote the recovery of liver function and reduce the occurrence of chronicity.

14.
Physiol Mol Biol Plants ; 27(10): 2269-2282, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34744365

RESUMO

Genetic diversity of plants is the brace of biodiversity and diversity within species, between species, and of ecosystems. SSR markers are the most preferable molecular marker tool that has been successfully used to study the genetic diversity of plant species. Development of miRNA-SSR markers has been deed in animals but is still limited in plants. In this study, 365 precursors miRNA were extracted from Melilotus albus (Ma) genome and used to design Ma miRNA-SSR primers. 137 Ma primer pairs (79 from known and 58 from novel pre-miRNAs) were obtained. 66 pairs of Ma miRNA-SSR primers were selected with polymorphisms and expected fragment size. The polymorphisms of primers were evaluated in 60 individuals of 15 Ma accessions. A total of 66 primer pairs showed high polymorphism, with average polymorphic information content of 0.49 among 15 Ma accessions and 0.63 among 18 Melilotus species, indicating that these primers have high polymorphisms. The number of alleles produced per primer ranged from 2 to 6 with an average of 3.6 alleles per locus in Ma accessions, and 2 to 10 numbers of alleles with a mean of 5.24 alleles per locus in Melilotus spp. For further studies, the genetic relationship was examined and the cluster analysis showed that 15 Ma accessions were grouped in three groups, on the other hand, 18 Melilotus species clustered into two groups. The analysis of molecular variance (AMOVA) revealed that 64.82% of the variation was found within the species and 35.18% between the species. The population structure analysis showed similar results with PCA analysis in that 18 species were grouped in two groups. In addition, 16,450 miRNA target genes were identified and used for GO and KEGG analysis. This is the first study to develop miRNA-SSR molecular markers in Melilotus spp., which has a great potential for marker-assisted, genetic improvement, genotyping applications, QTL analysis, and molecular-assisted selection studies for plant breeders and other researchers. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-01086-z.

15.
Front Psychol ; 12: 687447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603122

RESUMO

Based on the textual data of the resumes of 499 high-level talents, this study attempts to explore the factors affecting the selection and funding of high-level talents in western China. From the empirical analysis, we found that (1) the western Chinese government tends to favor the young and native talents, with a high initial academic degree (the degree obtained before working) and final academic degree (the highest degree obtained); (2) the talents with more experience, higher education, national talent titles, and participation in national projects are more likely to receive higher levels of funding; (3) it is easier for talents in universities and research institutes to be entitled as high-level talents and to gain funding than those in enterprises; and (4) talents in the fields of medicine, agronomy, and basic sciences are more likely to be entitled as high-level talents than those in other professional fields.

16.
Ann Surg Oncol ; 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34601641

RESUMO

BACKGROUND AND OBJECTIVES: Watch-and-wait is variably adopted by surgeons and the impact of this on outcomes is unknown. We compared the disease-free survival and organ preservation rates of locally advanced rectal cancer patients treated by expert colorectal surgeons at a comprehensive cancer center. METHODS: This study included retrospective data on patients diagnosed with stage II/III rectal adenocarcinoma from January 2013 to June 2017 who initiated neoadjuvant therapy (either with chemoradiation, chemotherapy, or a combination of both) and were treated by an expert colorectal surgeon. RESULTS: Overall, 444 locally advanced rectal cancer patients managed by five surgeons were included. Tumor distance from the anal verge, type of neoadjuvant therapy, and organ preservation rates varied by treating surgeon. There was no difference in disease-free survival after stratifying by the treating surgeon (p = 0.2). On multivariable analysis, neither the type of neoadjuvant therapy nor the treating surgeon was associated with disease-free survival. CONCLUSIONS: While neoadjuvant therapy type and organ preservation rates varied among surgeons, there were no meaningful differences in disease-free survival. These data suggest that among expert colorectal surgeons, differing thresholds for selecting patients for watch-and-wait do not affect survival.

17.
Front Microbiol ; 12: 729914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671330

RESUMO

Influenza neuraminidase (NA) is able to induce cross-subtype immunity and is considered as a promising target for the development of universal influenza vaccines. However, commercial influenza vaccines only induced low NA-specific immune responses due to the low amounts and the denatured conformation of NA proteins in current inactivated or split influenza vaccines. Here we investigated the protective efficacy of recombinant tetrameric and monomeric NA proteins to determine whether the conformation contributed to induce protective immunity. We found that H1N1 P R 8NA tetramer (NA tet ) could provide complete homologous protection against A/PR8 (H1N1) virus infection in mice, while the protection of H1N1 P R 8NA monomer (NA mono ) was moderate. Higher levels of NA-reactive binding and inhibition antibodies and less weight loss were observed in the H1N1 P R 8NA tet -vaccinated group. Similarly, H5N1 V N NA tet immunization exhibited a preferable heterologous protection than H5N1 V N NA mono , but neither H7N9 S H NA tet nor H7N9 S H NA mono vaccination showed heterosubtypic protection. We also compared the effect of three adjuvants, aluminum, 3'3'-cGAMP (cGAMP), and Poly(I:C), on the humoral response and protective efficacy induced by H1N1 P R 8NA tet . H1N1 P R 8NA tet protein adjuvanted with aluminum was observed to exhibited better capacity in inducing NA-specific humoral immunity and preventing weight loss than with cGAMP or Poly(I:C). In conclusion, our data demonstrate that tetrameric NA with natural conformation is required to induce protective anti-NA immunity. The NA tetramer could provide homologous protection and subtype-specific cross-protection. In addition, the aluminum adjuvant is preferable in recombinant NA protein vaccination.

18.
J Clin Lab Anal ; : e24003, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676904

RESUMO

BACKGROUND: Circular RNA (circRNA) affects the occurrence and development of human cancers, but the specific mechanism of hepatocellular carcinoma (HCC) has not yet been fully understood. METHODS: CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell viability, migration, invasion, and other indicators were used for cell function analysis. Knockdown and overexpression techniques were used to explore the mechanism of circCORO1C in the occurrence and development of HCC by RNA sequencing, qRT-PCR, western blot, and other methods. RESULTS: Among the thousands of circRNAs, 1238 circRNAs were significantly changed. As for the top 10 upregulated circRNAs, the expression of circRNAs, hsa_circ_0036412, hsa_circ_0036411, hsa_circ_0028071, hsa_circ_0036409, hsa_circ_0000437, hsa_circ_0021427, hsa_circ_0097182, hsa_circ_0028067, hsa_circ_0006852, and hsa_circ_0003620 were significantly increased. In regard to the top 10 downregulated circRNAs, the expression of hsa_circ_0123629, hsa_circ_0096121, hsa_circ_0038932, hsa-circRNA3310-44, hsa_circ_0045746, hsa_circ_0016836, hsa-circRNA10899-9, hsa_circ_0050116, hsa_circ_0035543, and hsa_circ_0092118 decreased significantly. About these circRNAs, the downregulation of hsa_circ_0006852 (circCORO1C) can inhibit the tumorigenesis of HCC cells in vivo and in vitro, and the overexpression of circCORO1C can enhance the proliferation and metastasis ability of HCC cells. Mechanistically, circCORO1C activated the NF-κB signaling pathway, increased P65 phosphorylation and upregulation of c-Myc and COX-2, leading to increased PD-L1 expression. CONCLUSION: CircCORO1C upregulates c-Myc and COX-2 through NF-κB signaling pathway, leading to the upregulation of PD-L1, which jointly promotes the development of HCC, suggesting that circCORO1C is a promising biomarker and therapeutic target for HCC.

19.
Front Endocrinol (Lausanne) ; 12: 743962, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675880

RESUMO

Aims/Hypothesis: We aimed to explore whether and to what extent overweight or obesity could increase the risk of hypertension, and further to estimate the roles of genetic and early-life familial environmental factors in their association. Methods: This prospective twin study was based on the Chinese National Twin Registry (CNTR), which collected information from self-report questionnaires. We conducted unmatched case-control analysis to examine the association between overweight or obesity and hypertension. And further to explore whether genetics and familiar environments shared within a twin pair, accounted for their association via co-twin matched case-control design. Generalized estimating equation (GEE) models and conditional logistic regressions were used in the unmatched and matched analyses, respectively. Then, we used logistic regressions to test the difference in odds ratios (ORs) between the unmatched and matched analyses. Finally, through bivariate twin model, the roles of genetic and environmental factors in the body mass index (BMI)- hypertension association were estimated. Results: Overall, we included a total of 30,617 twin individuals, of which 7533 (24.6%) twin participants were overweight or obesity and 757 (2.5%) developed hypertension during a median follow-up time of 4.4 years. In the GEE model, overweight or obesity was associated with a 94% increased risk of hypertension (OR=1.94, 95% confidence interval (CI): 1.64~2.30). In the conditional logistic regression, the multi-adjusted OR was 1.80 (95% CI: 1.18~2.74). The difference in OR between unmatched and matched analyses was significant (P=0.016). Specifically, overweight or obesity was not associated with hypertension risk in the co-twin design when we full controlled genetic and familiar environmental factors (OR=0.89, 95 CI: 0.46~1.72). After controlling for age and sex, we found the positive BMI-hypertension association was mainly explained by a genetic correlation between them (r A= 0.59, 95% CI: 0.44~1.00). Conclusions/Interpretation: Genetics and early-life environments shared by participants within a twin pair appear to account for the association between overweight or obesity and hypertension risk.

20.
Mol Ther Nucleic Acids ; 26: 637-648, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34703649

RESUMO

N6-methyladenosine (m6A) is capable of mediating circRNA generation in carcinoma biology. Nevertheless, the posttranscriptional systems of m6A and circRNA in hepatocellular carcinoma (HCC) development are still unclear. The present study identified a circRNA with m6A modification, circHPS5, which was increased in neoplasm HCC tissues and indicated poor patient survival. Silencing of circHPS5 inhibited epithelial-mesenchymal transition (EMT) and cancer stem-like cell (CSC) phenotypes. Notably, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. In addition, we demonstrated that circHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate HCC cell tumorigenesis. Accordingly, the m6A modification of circHPS5 was found to modulate cytoplasmic output and increase HMGA2 expression to facilitate HCC development. The new regulatory model of "circHPS5-HMGA2" provides a new perspective for circHPS5 as an important prognostic marker and therapeutic target in HCC and provides mechanistic insight for exploring the carcinogenic mechanism of circHPS5 in HCC.

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