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2.
Ear Nose Throat J ; : 1455613211040577, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34628970

RESUMO

A 73-year-old woman having a throat lump sensation and dysphagia for the past several months presented at our otorhinolaryngology outpatient clinic. A physical examination disclosed a protruding subepithelial mass over the right tonsil fossa. The mass was not tender and had no mucosal lesions or signs of active infection. Therefore, we arranged face and neck computed tomography scans, which reported a solitary osseous lesion over the anterior-right aspect of the C1-2 joint. Considering the rarity and unfamiliar anatomy of this disease, we built a 3D-printed model to assist with the surgical rehearsal of the procedure as well as with a preoperation discussion with the patient and her family. We arranged a combined Otolaryngology-Neurosurgery department approach after discussion with the neurosurgeon and successfully removed the lesion without sacrificing the overlying longus capitis muscle. The pathology examination revealed no evidence of malignancy. The final diagnosis was cervical spine solitary osteochondroma. The patient had a complete recovery of both oral cavity and normal swallowing function. No tumor recurred during the 3-year follow-up. On the basis of this case, in-house 3D-printing technology can offer a rapid, reliable model for an interdisciplinary team to use to enhance personalized presurgical planning, thus providing better patient engagement during hospitalization.

3.
Cancer ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623636

RESUMO

BACKGROUND: The objective of this study was to assess whether entecavir (ETV) in combination with interferon-α (IFN-α) could reduce hepatocellular cancer (HCC) and extrahepatic cancers (EHCs) in patients with chronic hepatitis B (CHB). METHODS: The cohort consisted of 4194 patients with CHB treated with ETV combined with IFN-α or ETV monotherapy at a tertiary hospital in Beijing, China, from January 2009 to December 2017. The risks, hazard ratios (HRs), and 95% confidence intervals (CIs) of HCC and EHCs were compared in the 2 groups. RESULTS: In a multivariate Cox regression analysis, a significantly lower risk of HCC (HR, 0.6; 95% CI, 0.3-0.9; P = .0310) and a marginally significantly lower risk of EHCs (HR, 0.2; 95% CI, 0.02-1.3; P = .0854) were observed in the group receiving ETV combined with IFN-α in comparison with the ETV monotherapy group. The annual virological response rates were significantly higher in the combination therapy group versus the monotherapy group (33.8% vs 21.2%; P < .0001), but the hepatitis B surface antigen (HBsAg) seroclearance rates were not (1.2% vs 0.9%; P = .8537). The HRs were consistent with propensity score-based matching, inverse probability weighting adjustments, and adjustments for virological response and HBsAg seroclearance. CONCLUSIONS: ETV combined with IFN-α therapy is superior to ETV monotherapy in reducing the risk of HCC and EHCs for patients with CHB. People who can tolerate and benefit from IFN-α therapy could consider combination therapy.

4.
Health Qual Life Outcomes ; 19(1): 244, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663349

RESUMO

BACKGROUND: Previous reports regarding health-related quality of life (HRQoL) of hypertensive individuals commonly concentrated on urban population. This study focused on rural population and aimed to explore the influencing factors of HRQoL. METHODS: Date were derived from Henan Rural Cohort study. The HRQoL of participants were assessed via European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) instrument. Tobit regression model and generalized linear model were employed to explore the influencing factors of HRQoL. Another binary logistic regression was utilized to examine the robustness of our results. RESULTS: Among 23,485 rural population, 8128 participants were identified with hypertension. The mean (SD) utility index and VAS score of non-hypertension group were 0.96 (0.09) and 79.66 (14.20), respectively, while in hypertension group were 0.94 (0.14) and 75.88 (15.50), respectively. Pain/discomfort was the most common self-reported problem (23.05%) for patients. Aging and suffering with other diseases were negatively associated with HRQoL among rural patients, while high socioeconomic status and healthy lifestyles corresponded with high HRQoL. CONCLUSIONS: Hypertension did push considerable pressures on patients' HRQoL. Maintaining healthy lifestyles and improving the socioeconomic status of patients were advisable ways to reduce this burden. Trial registration The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/showproj.aspx?proj=11375.

5.
Nanoscale ; 13(39): 16799-16808, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34605515

RESUMO

A method for the synthesis of DNA-based acrylamide hydrogel microcapsules loaded with quantum dots as a readout signal is introduced. The shell of DNA-acrylamide hydrogel microcapsules is encoded with microRNA-responsive functionalities, being capable of the detection of cancer-associated microRNA. The microRNA-141 (miR-141), a potential biomarker in prostate cancer, was employed as a model target in the microcapsular biosensor. The sensing principle of the microcapsular biosensor is based on the competitive sequence displacement of target miR-141 with the bridging DNA in the microcapsule's shell, leading to the unlocking of DNA-acrylamide hydrogel microcapsules and the release of the readout signal provided by fluorescent quantum dots. The readout signal is intensified as the concentration of miR-141 increases. While miR-141 was directly measured by DNA-acrylamide hydrogel microcapsules, the linear range for the detection of miR-141 is 2.5 to 50 µM and the limit of detection is 1.69 µM. To improve the sensitivity of the microcapsular biosensor for clinical needs, the isothermal strand displacement polymerization/nicking amplification machinery (SDP/NA) process was coupled to the DNA-acrylamide hydrogel microcapsule sensor for the microRNA detection. The linear range for the detection of miR-141 is improved to the range of 102 to 105 pM and the limit of detection is 44.9 pM. Compared to direct microcapsular biosensing, the detection limit for miR-141 by microcapsules coupled with strand-displacement amplification is enhanced by four orders of magnitude.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Pontos Quânticos , Cápsulas , Hidrogéis , Limite de Detecção , MicroRNAs/genética
6.
Schizophr Bull ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34508358

RESUMO

Schizophrenia is a complex and heterogeneous syndrome. Whether quantitative imaging biomarkers can identify discrete subgroups of patients as might be used to foster personalized medicine approaches for patient care remains unclear. Cross-sectional structural MR images of 163 never-treated first-episode schizophrenia patients (FES) and 133 chronically ill patients with midcourse schizophrenia from the Bipolar and Schizophrenia Network for Intermediate Phenotypes (B-SNIP) consortium and a total of 403 healthy controls were recruited. Morphometric measures (cortical thickness, surface area, and subcortical structures) were extracted for each subject and then the optimized subtyping results were obtained with nonsupervised cluster analysis. Three subgroups of patients defined by distinct patterns of regional cortical and subcortical morphometric features were identified in FES. A similar three subgroup pattern was identified in the independent dataset of patients from the multi-site B-SNIP consortium. Similarities of classification patterns across these two patient cohorts suggest that the 3-group typology is relatively stable over the course of illness. Cognitive functions were worse in subgroup 1 with midcourse schizophrenia than those in subgroup 3. These findings provide novel insight into distinct subgroups of patients with schizophrenia based on structural brain features. Findings of different cognitive functions among the subgroups support clinical differences in the MRI-defined illness subtypes. Regardless of clinical presentation and stage of illness, anatomic MR subgrouping biomarkers can separate neurobiologically distinct subgroups of schizophrenia patients, which represent an important and meaningful step forward in differentiating subtypes of patients for studies of illness neurobiology and potentially for clinical trials.

7.
BMC Public Health ; 21(1): 1644, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34496822

RESUMO

BACKGROUND: The study aimed to characterize the prevalence of alcohol consumption and further investigate the relationship between alcohol consumption and type 2 diabetes mellitus (T2DM). METHODS: We studied 39,259 participants aged 18 to 79 years of the Henan Rural Cohort study. The associations between alcohol consumption and T2DM were examined using the logistic regression models and restricted cubic spline. RESULTS: For men, alcohol abstinence was associated with an increased risk of T2DM (1.491(1.265, 1.758)), whereas current drinkers were not associated with T2DM (1.03(0.91, 1.15)). Further analysis of alcohol drinkers revealed that only high-risk drinkers of WHO drinking risk levels increased the risk of T2DM (1.289(1.061,1.566)) compared to never drinkers. The risk of T2DM increased as the age of starting to consume alcohol decreased and as the number of years of consuming alcohol and the alcohol intake increased only in men. We further found that the risk of T2DM decreased as the number of years of abstinence increases and no association between alcohol abstinence and T2DM was found after more than 10 years of abstinence among men. CONCLUSIONS: Our results suggested that reducing the amount of alcohol consumed and adhering to abstinence from alcohol consumption are beneficial in reducing the risk of T2DM. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375.


Assuntos
Diabetes Mellitus Tipo 2 , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , China/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Humanos , Masculino , Prevalência , Fatores de Risco , População Rural
8.
Nature ; 597(7877): 544-548, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34526724

RESUMO

Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients1. Both the number of transferred T cells and their differentiation state are critical determinants of effective responses2,3. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into effector T cells4,5 and lower therapeutic efficacy6, whereas maintenance of a more stem-cell-like state before adoptive transfer is beneficial7. Here we show that H9T, an engineered interleukin-2 partial agonist, promotes the expansion of CD8+ T cells without driving terminal differentiation. H9T led to altered STAT5 signalling and mediated distinctive downstream transcriptional, epigenetic and metabolic programs. In addition, H9T treatment sustained the expression of T cell transcription factor 1 (TCF-1) and promoted mitochondrial fitness, thereby facilitating the maintenance of a stem-cell-like state. Moreover, TCR-transgenic and chimeric antigen receptor-modified CD8+ T cells that were expanded with H9T showed robust anti-tumour activity in vivo in mouse models of melanoma and acute lymphoblastic leukaemia. Thus, engineering cytokine variants with distinctive properties is a promising strategy for creating new molecules with translational potential.

9.
Int J Clin Pract ; : e14776, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510649

RESUMO

BACKGROUND: We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. METHODS: In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. RESULTS: In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), ß-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. CONCLUSION: Patients with viral pneumonia who received α-blockers, ß-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.

10.
Chemosphere ; 287(Pt 4): 132316, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592210

RESUMO

BACKGROUND & AIMS: As both a toxic and essential trace element in humans, limited research focuses on the association between blood manganese (Mn) and nonalcoholic fatty liver disease (NAFLD). We aimed to assess blood Mn concentration and its relationship with NAFLD among adults in Northern China. METHODS: We conducted a cohort-based case-control study among 1816 patients with NAFLD (970 males and 846 females) and 1111 healthy controls (598 males and 513 females). We used the restricted cubic splines method to investigate the potential non-linear relationship and logistic regression models to analyze the association between blood Mn and NAFLD. RESULTS: The median (p25, p75) of blood Mn concentration in males was 10.08 (8.42,11.98) µg/L, higher than that in females [9.79 (8.01,12.04)] µg/L, P = 0.011. Compared with the tertile 1 group of Mn in males, the odds ratio (95 % confidence interval) of NAFLD for tertile 2 and tertile 3 group was 0.82 (0.61,1.10) and 0.64 (0.47,0.87), respectively. The reverse correlation was consistent in patients with different fibrosis severity determined by fibrosis-4 score. The protective association was more evident in those with triglycerides ≥1.7 mmol/L [odds ratio (95 % confidence interval) of tertile 3 vs. tertile 1: 0.40 (0.22,0.75)]. We found a non-significant U-shaped relationship between Mn and NAFLD in women. CONCLUSION: There may exist sex differences for the association between blood Mn and NAFLD. Higher blood Mn may be a potential protective factor for NAFLD in males. The subjects with TG ≥ 1.7 mmol/L would benefit more from higher blood Mn levels.

11.
Clin Epigenetics ; 13(1): 181, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565450

RESUMO

BACKGROUND: This study aims to investigate the independent and combined effects of progesterone and suppressor of cytokine signaling (SOCS)-3 DNA methylation on type 2 diabetes mellitus (T2DM) among men and postmenopausal women in rural China. METHODS: A case-control study with 914 participants (329 T2DM, 585 controls) was conducted. Serum progesterone was detected with liquid chromatography-tandem mass spectrometry. DNA methylation of SOCS3 was determined by MethylTarget™. Linear regression was applied to evaluate the associations of progesterone and SOCS3 methylation with marks of glucose metabolism. Logistic regression was employed to investigate the independent and combined effects of progesterone and SOCS3 methylation with T2DM in men and postmenopausal women. RESULTS: After multiple adjustment, progesterone was positively associated with T2DM in both men (odds ratio (OR) (95% confidence interval (CI)): 2.77 (1.79, 4.29)) and postmenopausal women (OR (95% CI): 1.85 (1.26, 2.72)). Methylation level of Chr17:76,356,190 or Chr17:76,356,199 (SOCS3) was negatively associated with T2DM in both men (OR (95% CI): 0.58 (0.39, 0.86) or 0.27 (0.14, 0.51)) and postmenopausal women (OR (95% CI): 0.43 (0.29, 0.65) or 0.53 (0.28, 0.99)). Subjects with high progesterone and low Chr17:76,356,190 or Chr17:76,356,199 methylation were more susceptible to have a higher prevalence of T2DM (men: OR (95% CI): 5.20 (2.49, 10.85) or 5.62 (2.74, 11.54); postmenopausal women: OR (95% CI): 3.66 (1.85, 7.26) or 3.27 (1.66, 6.45)). CONCLUSIONS: The independent and combined effects of progesterone and SOCS3 methylation on T2DM were found among men and postmenopausal women, suggesting that ensuring low levels of progesterone and high methylation of SOCS3 could reduce the prevalence of T2DM. Trial registration The Chinese Clinical Trial registration: The Henan Rural Cohort Study, ChiCTR-OOC-15006699. Registered 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375.

12.
J Int Med Res ; 49(9): 3000605211045540, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34590915

RESUMO

OBJECTIVE: Esophagectomy is a high-risk surgical procedure with significant postoperative morbidity and mortality. This study aimed to investigate the risk factors of cervical anastomotic leakage and postoperative mortality. METHODS: In this retrospective, observational study, we recruited 1010 patients with esophageal cancer. Cox regression analysis was performed to identify factors affecting anastomotic leakage and postoperative mortality. After propensity score matching, the Kaplan-Meier curve was used to evaluate the effect of leakage on postoperative mortality. RESULTS: The number of patients with cervical anastomotic leakage, in-hospital mortality, 30-day postoperative mortality, and 60-day postoperative mortality was 194 (19.2%), 13 (1.3%), 12 (1.2%), and 16 (1.6%), respectively. The total length of hospital stay and hospital stay postoperatively were 29.7 ± 21.1 and 21.3 ± 20.3 days, respectively. Diabetes, stage IV, and an upper thoracic tumor were significant risk factors for leakage. Leakage and diabetes were significant risk factors for postoperative mortality. After propensity score matching, leakage also significantly affected postoperative mortality. CONCLUSIONS: Patients with tumors in the upper thoracic segment of the esophagus may be more prone to developing anastomotic leakage compared with those with tumors in the middle or lower thoracic segment. Anastomotic leakage may prolong the length of hospital stay and increase postoperative mortality.


Assuntos
Fístula Anastomótica , Neoplasias Esofágicas , Fístula Anastomótica/etiologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Humanos , Estudos Retrospectivos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34511012

RESUMO

INTRODUCTION: The treatment evidence for entecavir-treated chronic hepatitis B (CHB) patients without maintaining of virologic response (MVR, defined as persistent HBV DNA <20 IU/mL during therapy) remains uncertain. We aimed to determine the relationship between non-MVR and hepatocellular carcinoma (HCC) risk in entecavir-treated CHB patients. METHODS: A cohort of 1447 entecavir-treated CHB patients were enrolled. Multivariate and propensity score-based inverse probability weighting (IPW) model was performed to estimate the effect of MVR on HCC. RESULTS: During a median follow-up of 5 years, 214 (14.8%) patients occurred with non-MVR. Non-MVR patients had a higher risk of HCC [the IPW model: hazard ratio (HR) = 3.59, 95% confidence interval (CI): 2.23-5.75] than MVR patients, especially in those with cirrhosis (HR = 4.60, 95% CI: 2.81-7.56) and the high HCC score by the Chinese University of Hong Kong (HR = 4.35, 95% CI: 2.58-7.32). MVR patients with transient (HR = 4.72, 95% CI: 1.98-11.24) or persistent (HR = 12.16, 95% CI: 3.58-41.31) abnormal ALT after virologic response had higher HCC hazard. CONCLUSIONS: Our study indicated an elevated HCC probability for entecavir-treated CHB patients with Non-MVR, especially for those with cirrhosis or a high predicted score at baseline. For MVR patients, the trajectories of ALT after virologic response suggested different HCC risks.

14.
Small ; : e2103700, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34546008

RESUMO

Liquid crystal elastomer (LCE) fibers are capable of large and reversible deformations, making them an ideal artificial muscle. However, limited to stimulating source and structural design, current LCE fibers have not yet achieved both large contraction ratio and fast contraction rate to perform the intense motion. In this work, electrothermal-responsive liquid metal (LM) containing LCE (LM-LCE) fibers is reported. By introducing flexible liquid metal, LM-LCE fibers retain deformability with a large contraction ratio similar to that of pure LCE fibers and are endowed with electrical responsiveness. Applying precisely controlled electrical stimulation, the contraction ratio and rate of LM-LCE fibers can be programmed by adjusting voltage value and pulse time. Under electrical stimulation at 1.25 V cm-1 , 0.1 s, LM-LCE fibers can produce over 40% contraction ratio at an ultrafast contraction rate of up to 280% s-1 . Furthermore, LM-LCE fibers mimic human triceps muscle and can conduct precise ball shooting. LM-LCE fibers with excellent contraction ratio and rate extend their functionality as artificial muscles to perform intense movements and are expected to enrich the challenging applications of soft robots.

15.
Elife ; 102021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569932

RESUMO

Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here, we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and cytoskeletal proteins were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical-sensitive channels involved in bilayer-model mechanotransduction like Piezo or TRP proteins did not repress the ultrasound-mediated neuronal activation as efficiently. The ASIC1a-mediated ultrasound effects in mouse brain such as immediate response of ERK phosphorylation and DCX marked neurogenesis were statistically significantly compromised by ASIC1a gene deletion. Collated data suggest that ASIC1a is the molecular determinant involved in the mechano-signaling of low-intensity ultrasound that modulates neural activation in mouse brain.

16.
JMIR Med Inform ; 9(8): e23230, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463639

RESUMO

BACKGROUND: The International Classification of Diseases (ICD) code is widely used as the reference in medical system and billing purposes. However, classifying diseases into ICD codes still mainly relies on humans reading a large amount of written material as the basis for coding. Coding is both laborious and time-consuming. Since the conversion of ICD-9 to ICD-10, the coding task became much more complicated, and deep learning- and natural language processing-related approaches have been studied to assist disease coders. OBJECTIVE: This paper aims at constructing a deep learning model for ICD-10 coding, where the model is meant to automatically determine the corresponding diagnosis and procedure codes based solely on free-text medical notes to improve accuracy and reduce human effort. METHODS: We used diagnosis records of the National Taiwan University Hospital as resources and apply natural language processing techniques, including global vectors, word to vectors, embeddings from language models, bidirectional encoder representations from transformers, and single head attention recurrent neural network, on the deep neural network architecture to implement ICD-10 auto-coding. Besides, we introduced the attention mechanism into the classification model to extract the keywords from diagnoses and visualize the coding reference for training freshmen in ICD-10. Sixty discharge notes were randomly selected to examine the change in the F1-score and the coding time by coders before and after using our model. RESULTS: In experiments on the medical data set of National Taiwan University Hospital, our prediction results revealed F1-scores of 0.715 and 0.618 for the ICD-10 Clinical Modification code and Procedure Coding System code, respectively, with a bidirectional encoder representations from transformers embedding approach in the Gated Recurrent Unit classification model. The well-trained models were applied on the ICD-10 web service for coding and training to ICD-10 users. With this service, coders can code with the F1-score significantly increased from a median of 0.832 to 0.922 (P<.05), but not in a reduced interval. CONCLUSIONS: The proposed model significantly improved the F1-score but did not decrease the time consumed in coding by disease coders.

17.
Amino Acids ; 53(9): 1339-1350, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34363538

RESUMO

Mounting studies have demonstrated that RAB3GAP1 expression is modified in brain diseases with multiple neurobiological functions and processes and acts as a potentially significant target. However, the cellular and molecular events arising from RAB3GAP1 dysexpression are still incompletely understood. In this work, underexpression and overexpression of RAB3GAP1 were first induced into cultured mouse cortical neurons by transfection with lentivirus plasmids. Then we globally explored the effects of RAB3GAP1 dysexpression on the proteome of the neurons through the use of isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomics with bioinformatics. A total of 364 proteins in the RAB3GAP1-underexpression group and 314 proteins in the RAB3GAP1-overexpression group were identified to be differentially expressed. Subsequent bioinformatics analysis indicated that the proteome functional expression profiles induced by RAB3GAP1 underexpression and overexpression were different, suggesting the potential differences in biological processes and cellular effects. Subsequent intergroup cross-comparison revealed some candidate target proteins regulated directly by RAB3GAP1. Further parallel reaction monitoring (PRM) analysis illustrated that Sub1, Ssrp1, and Top1 proteins might serve as new potentially important linkers in the RAB3GAP1-mediated autophagy pathway in the cortical neurons. Collectively, the current proteomics data furnished new valuable insights to better understand the regulatory molecular mechanism of neuronal RAB3GAP1.

18.
ACS Appl Mater Interfaces ; 13(34): 41012-41020, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34410119

RESUMO

Photodynamic therapy (PDT) is a potential approach to resolve antibiotic resistance, and phenylene/thiophene-ethynylene oligomers have been widely studied as effective antibacterial reagents. Oligomers with thiophene moieties usually exhibit good antibacterial activity under light irradiation and dark conditions. In the previous study, we verified that neutral oligo-p-phenylene-ethynylenes (OPEs) exhibit better antibacterial activity than the corresponding cationic ones; however, whether this regular pattern also operates in other kinds of oligomers such as oligo-thiophene-ethynylene (OTE) is unknown. Also, the antibacterial activity comparison of OTEs bearing cyclic and acyclic amino groups will offer useful information to further understand the role of amino groups in the antibacterial process and guide the antibacterial reagent design as amino groups affect the antibacterial activity a lot. We synthesized four OTEs bearing neutral or cationic, cyclic, or acyclic amino groups and studied their antibacterial activity in detail. The experimental results indicated that the OTEs exhibited better antibacterial activity than the OPEs, the neutral OTEs exhibited better antibacterial activity in most cases, and OTEs bearing cyclic amino groups exhibited better antibacterial activity than those bearing acyclic ones in most cases. This study provides useful guidelines for further antibacterial reagent design and investigations.

19.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3205-3212, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396738

RESUMO

As an effective antipyretic medicine,Indigo Naturalis has a long history of application in the field of Chinese medicine.The content of organics,mainly indigo and indirubin,is about 10%. However,the active ingredients and mechanism of its antipyretic effect have not yet been fully elucidated. In view of this,they were investigated in this study with the rectal temperature change as an indicator and 2,4-dinitrophenol-induced fever rats as subjects. The content of PGE2 and c AMP in the hypothalamus and the serum levels of TNF-α,IL-1ß and IL-6 were determined by ELISA. Moreover,the plasma samples of fever rats were analyzed by metabonomics in combination with UPLC-Q-TOF-MS for the exploration of potential biomarkers and the discussion on the antipyretic mechanism of Indigo Naturalis and its active ingredients. The results showed that the rising trend of rectal temperature in rats was suppressed 0. 5 h after the treatment with Indigo Naturalis,organic matter,indigo or indirubin as compared with the rats of model group( P < 0. 05),among which Indigo Naturalis and organic matter had better antipyretic effect. ELISA results showed that organic matter and indigo can inhibit the expression of PGE2 and c AMP( P<0. 01),while Indigo Naturalis and organic matter were effective in curbing the increase in TNF-α( P<0. 05). A total of 21 endogenous metabolites were identified from the plasma samples of the Indigo Naturalis,organic matter,indigo and indirubin groups,which were mainly involved in glycerophospholipid metabolism.


Assuntos
Antipiréticos , Medicamentos de Ervas Chinesas , Indigofera , 2,4-Dinitrofenol , Animais , Índigo Carmim , Ratos
20.
Neuroscience ; 473: 29-43, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34425157

RESUMO

Chronic stress causes the abnormality of olfactory bulb (OB) in both anxiety and depression, however, the unique and common neurobiological underpinnings are still poorly understood. Previously, we built the three groups by chronic mild stress (CMS), depression-susceptible (Dep-Sus): with depression-like behavior, anxiety-susceptible (Anx-Sus): with anxiety-like behavior and insusceptible (Insus): without depression- and anxiety-like behaviors. To continuously explore the protein expression changes in these three groups, comparative quantitative proteomics analysis was conducted on the rat OB as crucial part of the olfactory system. Next, bioinformatics analyses were implemented whereas protein expressions were independently analyzed by parallel reaction monitoring (PRM) or Western blot (WB). The OB-proteome analysis identified totally 133 differentially expressed proteins as a CMS response. These deregulated proteins were involved in multiple functions and significant pathways potentially correlated with phenotypes of maladaptive behavior of depression or anxiety as well as adaptive behavior, and hence might act as potential candidate protein targets. The subsequent PRM-based or WB-based analyses showed that changes in Nefl, Mtmr7 and Tk2; Prkaca, Coa3, Cox6c2, Lamc1 and Tubal3; and Pabpn1, Nme3, Sos1 and Lum were uniquely associated with Dep-Sus, Anx-Sus, and Insus groups, respectively. These phenotype-specific deregulated proteins were primarily involved in multiple metabolic and signaling pathways, suggesting that the identical CMS differently impacted the olfactory protein regulation system and biological processes. To sum up, our present data as a useful proteomics underpinning provided the common and distinct molecular insights into the biochemical understanding of OB dysfunction underlying susceptibility and resiliency to chronic-stress-induced anxiety or depression.


Assuntos
Depressão , Bulbo Olfatório , Animais , Ansiedade , Transtornos de Ansiedade , Modelos Animais de Doenças , Proteômica , Ratos
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