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1.
Nat Protoc ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022622

RESUMO

High-content imaging is needed to catalog the variety of cellular phenotypes and multicellular ecosystems present in metazoan tissues. We recently developed iterative bleaching extends multiplexity (IBEX), an iterative immunolabeling and chemical bleaching method that enables multiplexed imaging (>65 parameters) in diverse tissues, including human organs relevant for international consortia efforts. IBEX is compatible with >250 commercially available antibodies and 16 unique fluorophores, and can be easily adopted to different imaging platforms using slides and nonproprietary imaging chambers. The overall protocol consists of iterative cycles of antibody labeling, imaging and chemical bleaching that can be completed at relatively low cost in 2-5 d by biologists with basic laboratory skills. To support widespread adoption, we provide extensive details on tissue processing, curated lists of validated antibodies and tissue-specific panels for multiplex imaging. Furthermore, instructions are included on how to automate the method using competitively priced instruments and reagents. Finally, we present a software solution for image alignment that can be executed by individuals without programming experience using open-source software and freeware. In summary, IBEX is a noncommercial method that can be readily implemented by academic laboratories and scaled to achieve high-content mapping of diverse tissues in support of a Human Reference Atlas or other such applications.

2.
Macromol Biosci ; : e2100406, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014754

RESUMO

Bioscaffold implantation is a promising approach to facilitate the repair and regeneration of wounded neural tissue after injury to the spinal cord or peripheral nerves. However, such bioscaffold grafts currently result in only limited functional recovery. We report the generation of a neural scaffold using a combination of collagen and glutenin. We tested the conduit material and mechanical properties, as well as its effect on astrocyte behavior. After neural injuries, astrocytes move into the lesion and participate in the process of remodeling the micro-architecture of the wounded neural tissue. In this study, human astrocytes grown on glutenin-collagen scaffolds showed higher motility and a lower proliferation rate compared with those grown on collagen scaffolds. RNA sequencing revealed that astrocytes grown on the two types of scaffolds showed differentially expressed genes in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways such as actin cytoskeleton and focal adhesion that regulate astrocyte migration on scaffolds. The gene expression of aggrecan and versican, chondroitin sulfate proteoglycans that inhibit axonal growth, was down-regulated in astrocytes grown on glutenin-collagen scaffolds. These outcomes indicate that the implantation of glutenin-collagen scaffolds may promote astrocyte function in the neural regeneration process by enhanced cell migration and reduced glial scar formation. This article is protected by copyright. All rights reserved.

3.
Transplant Proc ; 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34986976

RESUMO

In Taiwan, living donor liver transplant (LDLT) has accounted for the majority of liver transplantation due to organ shortage. Dual-graft LDLT is a feasible way to resolve the insufficient graft size and remnant liver in donors. We presented a heavy-weight patient underwent dual-graft LDLT, and cystic duct was used to resolve the inadequate bile duct length and limited appropriate position in dual-graft LDLT. We harvested a right lobe graft (segment 5, 6, 7, and 8 without middle hepatic vein) and a left lobe graft (segment 1, 2, 3, and 4 without middle hepatic vein) stepwise, and placed the grafts orthotopically. For proper tension and length of biliary reconstruction, we anastomosed the right intrahepatic duct of the right lobe graft to cystic duct of the recipient. Before the biliary reconstruction, the metal probe was inserted in the lumen of cystic duct in recipient to ensure the patency and destroy the Heister valve of cystic duct, then the internal biliary stent (5 Fr pediatric feeding tube) was placed in the donor's right intrahepatic duct to recipient's cystic duct and common bile duct, which allows the endoscopic removal of the internal stent. The patient has survived more than 16 months with normal liver function.

4.
Food Chem ; 366: 130595, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34298393

RESUMO

Herein, a surface-enhanced Raman scattering (SERS)-integrated LFS platform was developed for rapid and simultaneous screening of multiple genetically modified organism (GMO) components (promoter, codon, and terminator) in soybean. Research demonstrated that, on the same test line (T line) of single LFS, three different GMP components can be well distinguished with the help of three SERS nano tags. Good linear correlations between SERS signal and concentration of each GMO component were also obtained for quantitative analysis. Of greater importance, whether these multiple analytes coexisted or not, varied in the same concentration trend or not, these multiple GMP components can be rapidly (15 min) and accurately screened with satisfied sensitivity and specificity by decoding the signals on the same T line. We envision that this decoding platform can further improve the potential of LFS and SERS for practical applications and provide a promising alternative for multiple screening of GMO identification in food.


Assuntos
Análise Espectral Raman , Organismos Geneticamente Modificados , Sensibilidade e Especificidade
5.
Bioact Mater ; 10: 295-305, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34901547

RESUMO

The overexpression of heat shock proteins (HSPs) in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments, inducing thermoresistance and thus diminishing the treatment efficacy. Here, we report a distinct "non-inhibitor involvement" strategy to address this issue through engineering a calcium-based nanocatalyst (G/A@CaCO3-PEG). The constructed nanocatalyst consists of calcium carbonate (CaCO3)-supported glucose oxidase (GOD) and 2D antimonene quantum dots (AQDs), with further surface modification by lipid bilayers and polyethylene glycol (PEG). The engineered G/A@CaCO3-PEG nanocatalyst features prolonged blood circulation, which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment, resulting in rapid release of drug cargo in the tumor microenvironment. The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate (ATP) and subsequent down-regulation of HSP expression. This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells' thermoresistance. Consequently, synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy. Systematic in vitro and in vivo evaluations have demonstrated that G/A@CaCO3-PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate (83.92%). This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply.

6.
Talanta ; 236: 122821, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635211

RESUMO

Well-defined structures and compositions of nucleic acids afford oligonucleotide probes with unique chemical properties and biological functions for various biosensing applications. Herein, a unique and special oligonucleotide probe, named multifunction-integrated linear oligonucleotide probe (MI-LOP), was facile designed and reported for label-free and turn-on fluorescent detection of the codon component of genetically modified organisms (GMOs). The MI-LOP contains four different functional regions including recognition of target, serving as polymerization template, and creating polymerization primer-linked G-quadruplex (PP-G-quadruplex). Without the aid of any other oligonucleotides, the introduction of target DNA can make each function of the MI-LOP executed one-by-one, during which the species of target DNA, target analogue, and PP-G-quadruplex can be cyclically utilized and in turn induce a multiplex signal amplification responsible for substantial collection of the G-quadruplex moieties under isothermal conditions. The stable G-quadruplexes can combine with N-methyl mesoporphyrin IX (NMM) and function as efficient fluorescence light-up probes, rapidly leading to a dramatic increase in the fluorescence intensity for the amplified detection of the target codon component. Our results strongly demonstrate that the developed MI-LOP with multiplex amplification effect confers the sensing strategy a high sensitivity and specificity for quantitative and qualitative detection of the target codon. And it has also been successfully applied for analyzing target codon in the complex extractions of soybean. The achievements highlight the significance of using oligonucleotide probes as promising analytical tools to promote the basic biochemical research and help in food and environmental analysis.


Assuntos
Quadruplex G , DNA/genética , Fluorescência , Sondas de Oligonucleotídeos/genética , Plantas Geneticamente Modificadas
7.
Behav Brain Res ; 418: 113673, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34798170

RESUMO

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases related to several types of pathophysiological signs, including ß-amyloid (Aß) plaque accumulation, neuroinflammation, and neurofibrillary tangles. Similar to one of the three subunits of α-ketoglutarate dehydrogenase complex (KGDHC), oxoglutarate dehydrogenase-like (OGDHL) appears to be downregulated in triple-transgenic Alzheimer's (3 × Tg-AD) mice. KGDHC activity is specifically reduced in the brains of people with AD. However, the underlying mechanism of OGDHL in the cause of AD is still unknown. Herein, we confirmed the low expression of OGDHL in the brain of 3 × Tg-AD based on real-time quantitative PCR, Western blot, and immunohistochemistry. We also found that the upregulation of OGDHL can reduce the memory deficits of 3 × Tg-AD mice, thereby reminding its nervous system neuroprotective effect in AD. Next, we confirmed that the increase in OGDHL could reduce neuroinflammation, amyloid plaque load, and tau phosphorylation in 3 × Tg-AD mice. Additionally, we showed that the overexpression of OGDHL could activate Wnt/ß-catenin signaling based on the expression of Wnt7B in vitro. Taken together, the results show that the rise of OGDHL reasonably improves the cognitive functions according to the activation of the Wnt/ß-catenin signaling pathway. Therefore, this enzyme may be a potential strategy for AD treatment.

8.
Echocardiography ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873746

RESUMO

Subaortic left brachiocephalic vein (LBCV) is rare in prenatal diagnosis. Reported herein is a case of subaortic a LBCV diagnosed using the HDlive flow and spatiotemporal image correlation with postnatal outcomes evaluation in our hospital.

9.
Dev Comp Immunol ; : 104328, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883109

RESUMO

N-acetylcholine receptors (AChRs) are mainly distributed in the postsynaptic membrane and have been widely studied for their control of muscle contraction by regulating neural action potentials. However, the influences of AChRs on immune responses and potential mechanisms remain unclear. Here, we used the advantages of live imaging of zebrafish to explore the regulation process of AChRs on inflammatory responses. Pharmacologically activating of the receptor, we found that the expression of pro-inflammatory cytokines il-1ß, il-6, tnf-α and il-8 was significantly up-regulated and neutrophil migration to injury sites was also significantly increased. However, these phenomena were reversed under antagonism of the receptor activity. Results showed that interfering with nAChRs functions did not significantly affect zebrafish motion behavior. Results also showed that activation and antagonism of nAChRs function could regulate the phosphorylation of ERK protein respectively. We further demonstrated that ERK participated in the regulation of AChRs in cytokines expression and neutrophils migration in zebrafish. This study preliminarily revealed the roles of AChRs in inflammatory processes and their potential mechanism, providing additional evidence of peripheral immune regulation by cholinergic receptors.

10.
Biosens Bioelectron ; 198: 113804, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34864243

RESUMO

A convenient, fast and non-invasive portable electrochemical uricometer (PUM) assisted with the uricase-packaged nanoflowers (NFs) was constructed for continually and accurately monitoring of uric acid (UA) in urine samples at random intervals in just 20 s. Only a small amount of urine (50 µL) was needed for each test. Electrochemical deposition was adopted to modify gold nanoparticles (AuNPs) on screen-printed carbon electrodes (SPCE) and uricase-inorganic hybrid NFs (UOx-NFs) induced by calcium ions (Ca2+) were introduced for UA detection with expected specificity. Cyclic voltammetry (CV) (detection limit of 8.87 µM and liner range of 0-4 mM) and amperometry (detection limit of 0.82 µM and liner range of 0-5 mM) protocols were studied for UA detection, respectively. Finally, the uric acid in urine had be successfully continually monitored from volunteers with various dietary choosing, the results of which can be adopted as the effective evidence for uric acid control.

11.
Parasit Vectors ; 14(1): 601, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895326

RESUMO

BACKGROUND: Breast cancer is the most common cause of cancer-related death among women, and prognosis is especially poor for patients with triple-negative breast cancer (TNBC); therefore, there is an urgent need for new effective therapies. Recent studies have demonstrated that the uracil auxotroph Toxoplasma gondii vaccine displays anti-tumor effects. Here, we examined the immunotherapy effects of an attenuated uracil auxotroph strain of T. gondii against 4T1 murine breast cancer. METHODS: We constructed a uracil auxotroph T. gondii RH strain via orotidine 5'-monophosphate decarboxylase gene deletion (RH-Δompdc) with CRISPR/Cas9 technology. The strain's virulence in the T. gondii-infected mice was determined in vitro and in vivo by parasite replication assay, plaque assay, parasite burden detection in mice peritoneal fluids and survival analysis. The immunomodulation ability of the strain was evaluated by cytokine detection. Its anti-tumor effect was evaluated after its in situ inoculation into 4T1 tumors in a mouse model; the tumor volume was measured, and the 4T1 lung metastasis was detected by hematoxylin and eosin and Ki67 antibody staining, and the cytokine levels were measured by an enzyme-linked immunosorbent assay. RESULTS: The RH-Δompdc strain proliferated normally when supplemented with uracil, but it was unable to propagate without the addition of uracil and in vivo, which suggested that it was avirulent to the hosts. This mutant showed vaccine characteristics that could induce intense immune responses both in vitro and in vivo by significantly boosting the expression of inflammatory cytokines. Inoculation of RH-Δompdc in situ into the 4T1 tumor inhibited tumor growth, reduced lung metastasis, promoted the survival of the tumor-bearing mice and increased the secretion of Th1 cytokines, including interleukin-12 (IL-12) and interferon-γ (INF-δ), in both the serum and tumor microenvironment (TME). CONCLUSION: Inoculation of the uracil auxotroph RH-Δompdc directly into the 4T1 tumor stimulated anti-infection and anti-tumor immunity in mice, and resulted in inhibition of tumor growth and metastasis, promotion of the survival of the tumor-bearing mice and increased secretion of IL-12 and IFN-γ in both the serum and TME. Our findings suggest that the immunomodulation caused by RH-Δompdc could be a potential anti-tumor strategy.

12.
iScience ; 24(12): 103514, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34950858

RESUMO

Toxoplasma gondii surface antigen 1 (TgSAG1) is a surface protein of tachyzoites, which plays a crucial role in toxoplasma gondii infection and host cell immune regulation. However, how TgSAG1 regulates these processes remains elucidated. We utilized the biotin ligase -TurboID fusion with TgSAG1 to identify the host proteins interacting with TgSAG1, and identified that S100A6 was co-localized with TgSAG1 when T. gondii attached to the host cell. S100A6, either knocking down or blocking its functional epitopes resulted in inhibited parasites invasion. Meanwhile, S100A6 overexpression in host cells promoted T. gondii infection. We further verified that TgSAG1 could inhibit the interaction of host cell vimentin with S100A6 for cytoskeleton organization during T. gondii invasion. As an immunogen, TgSAG1 could promote the secretion of tumor necrosis factor alpha (TNF-α) through S100A6-Vimentin/PKCθ-NF-κB signaling pathway. In summary, our findings revealed a mechanism for how TgSAG1 functioned in parasitic invasion and host immune regulation.

13.
Front Aging Neurosci ; 13: 758137, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955812

RESUMO

Subcortical ischemic vascular disease (SIVD) can cause cognitive impairment and affect the static functional connectivity of resting functional magnetic resonance imaging (fMRI). Numerous previous studies have demonstrated that functional connectivities (FCs) fluctuate dynamically over time. However, little is known about the impact of cognitive impairment on brain dynamic functional connectivity (DFC) in SIVD patients with MCI. In the present study, the DFC analysis method was applied to the resting functional magnetic resonance imaging (fMRI) data of 37 SIVD controls (SIVD-Control) without cognitive impairment, 34 SIVD patients with amnestic MCI (SIVD-aMCI) and 30 SIVD patients with nonamnestic MCI (SIVD-naMCI). The results indicated that the cognitive impairment of SIVD mainly reduced the mean dwell time of State 3 with overall strong positive connections. The reduction degree of SIVD-aMCI was larger than that of SIVD-naMCI. The memory/execution function impairment of SIVD also changed the relationship between the mean dwell time of State 3 and the behavioral performance of the memory/execution task from significant to non-significant correlation. Moreover, SIVD-aMCI showed significantly lower system segregation of FC states than SIVD-Control and SIVD-naMCI. The system segregation of State 5 with overall weak connections was significantly positive correlated with the memory performance. The results may suggest that the mean dwell time of State 3 and the system segregation of State 5 may be used as important neural measures of cognitive impairments of SIVD.

14.
J Med Internet Res ; 23(12): e27008, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34958305

RESUMO

BACKGROUND: Emergency department (ED) crowding has resulted in delayed patient treatment and has become a universal health care problem. Although a triage system, such as the 5-level emergency severity index, somewhat improves the process of ED treatment, it still heavily relies on the nurse's subjective judgment and triages too many patients to emergency severity index level 3 in current practice. Hence, a system that can help clinicians accurately triage a patient's condition is imperative. OBJECTIVE: This study aims to develop a deep learning-based triage system using patients' ED electronic medical records to predict clinical outcomes after ED treatments. METHODS: We conducted a retrospective study using data from an open data set from the National Hospital Ambulatory Medical Care Survey from 2012 to 2016 and data from a local data set from the National Taiwan University Hospital from 2009 to 2015. In this study, we transformed structured data into text form and used convolutional neural networks combined with recurrent neural networks and attention mechanisms to accomplish the classification task. We evaluated our performance using area under the receiver operating characteristic curve (AUROC). RESULTS: A total of 118,602 patients from the National Hospital Ambulatory Medical Care Survey were included in this study for predicting hospitalization, and the accuracy and AUROC were 0.83 and 0.87, respectively. On the other hand, an external experiment was to use our own data set from the National Taiwan University Hospital that included 745,441 patients, where the accuracy and AUROC were similar, that is, 0.83 and 0.88, respectively. Moreover, to effectively evaluate the prediction quality of our proposed system, we also applied the model to other clinical outcomes, including mortality and admission to the intensive care unit, and the results showed that our proposed method was approximately 3% to 5% higher in accuracy than other conventional methods. CONCLUSIONS: Our proposed method achieved better performance than the traditional method, and its implementation is relatively easy, it includes commonly used variables, and it is better suited for real-world clinical settings. It is our future work to validate our novel deep learning-based triage algorithm with prospective clinical trials, and we hope to use it to guide resource allocation in a busy ED once the validation succeeds.

15.
BMJ Open ; 11(12): e055770, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34937724

RESUMO

INTRODUCTION: Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes and is common in patients with kidney failure. However, there is no evidence on the occurrence, recurrence and treatment of HK in patients on haemodialysis (HD) in China. METHODS AND ANALYSIS: The HK Prevalence, Recurrence, and Treatment in Haemodialysis Study is a prospective, multicentre, observational, cohort study being conducted across 15-18 sites in China. Approximately 600 patients with end-stage kidney disease on HD are anticipated to be enrolled and will be followed up for 24 weeks. Patients will be in the long interdialytic interval (LIDI) at enrolment and will receive follow-up care every 4 weeks in LIDI for pre-dialysis and post-dialysis (at enrolment only) serum potassium measurements. To obtain pre-dialysis serum potassium levels in the short interdialytic interval (SIDI), a follow-up visit will be performed in the SIDI during the first week. Information on concomitant medications, blood gas analysis and biochemistry measurements will be obtained at enrolment and at each follow-up visit. The primary endpoint will be the proportion of patients experiencing HK (defined as serum potassium level >5.0 mmol/L) at the study enrolment or during the 24-week follow-up. The key secondary endpoint will be the proportion of patients experiencing HK recurrence (defined as any HK event after the first HK event) within 1-6 months (if applicable) during the 24-week follow-up, including enrolment assessment. ETHICS AND DISSEMINATION: This study has been approved by Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (2020-040). Other participating subcentres must also obtain ethics committee approval prior to the start of the study. The Good Clinical Practice regulations shall be strictly followed during the test implementation. Amendments to the protocol will be reviewed by the ethics committees. Written informed consent will be obtained from all participants before collection of any patient data and patient information. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04799067).

16.
Anal Chem ; 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963277

RESUMO

Detection of pathogenic bacteria is of vital significance for combating and preventing infectious diseases. In this work, we developed a multivalent aptamer probe (Multi-VAP)-based trigging isothermal circular amplification (TICA) for rapidly and ultrasensitively detecting Salmonella. In this sensing system, the fluorescence of Multi-VAP was strongly quenched via the dual effect of FRET. Introduction of Salmonella to the system forced the configuration change of Multi-VAP, leading to the occurrence of a TICA responsible for tuning all of the fluorescence-quenched Multi-VAP into a complete restoration state. This prominent feature allows the reasonable combination of a strong background restraint and great target signal amplification into one sensing system, which in turn benefits the improvement of the signal-to-noise ratio to ensure that the system has an ultrahigh sensitivity. Combined with the employment of an aptamer to ensure that it has excellent specificity, the Salmonella can be quantitatively and qualitatively analyzed even from human serum. The total processing merely requires sample addition and incubation. The turnaround time of the complete analysis from "sample-to-result" was within 30 min. With the method to decrease the time to detect and simplify the process to operate, the assay was successfully used as a sensing platform for specific detection of as few as 9 CFU/mL Salmonella.

17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(10): 1243-1248, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34955136

RESUMO

OBJECTIVE: To evaluate the effect of lower limb neuromuscular electrical stimulation (NMES) on mechanical ventilation patients in intensive care unit (ICU). METHODS: Databases including the Cochrane Library, PubMed, Web of Science, Embase, SinoMed, CNKI, VIP and Wanfang database were searched from inception to May 2021. Randomized controlled trails (RCT) about the influence of NMES of lower limbs in patients with mechanical ventilation in ICU were collected. Routine rehabilitation measures were implemented in the control group, while the combination of routine rehabilitation and NMES on the lower limbs was implemented in the observation group. The literature screening, data extracting, and bias risk assessment of included studies were conducted independently by two reviewers. RevMan 5.3 software was used to perform Meta-analysis. Funnel plot was used to test publication bias. RESULTS: A total of 8 RCT were eventually enrolled. The literature quality evaluation results showed that 1 study was grade A and 7 studies were grade B, suggesting that the quality of the included literature was relatively high. The Meta-analysis results showed that NMES in the lower extremities could effectively shorten the duration of mechanical ventilation in ICU patients [standardized mean difference (SMD) = -0.51, 95% confidence interval (95%CI) was -0.72 to -0.31, P < 0.000 01], increase the maximum inspiratory pressure [MIP; mean difference (MD) = 14.19, 95%CI was 9.30 to 19.09, P < 0.000 01], and improve the functional status of critically ill patients [functional status score for ICU (FSS-ICU); MD = 10.44, 95%CI was 3.12 to 17.77, P = 0.005] with statistically significances. However, there were no significant advantages in increasing the Medical Research Council (MRC) score (MD = 2.13, 95%CI was -1.38 to 5.63, P = 0.23), reducing ICU mortality [relative risk (RR) = 0.80, 95%CI was 0.51 to 1.24, P = 0.31], shortening length of ICU stay (MD = -0.54, 95%CI was -3.67 to 2.59, P = 0.74), and the combined effect was not statistically significant. Funnel plot based on the duration of mechanical ventilation showed that the distribution of included articles was basically symmetrical, and no publication bias was detected. CONCLUSIONS: NMES of the lower limbs can not only shorten the ventilation duration effectively, but also improve the MIP and functional status of mechanically ventilated patients in ICU. However, it has no significant effect on the MRC score, ICU mortality and length of ICU stay of patients with mechanical ventilation. In the future, high-quality, large sample size and multi-center RCT are needed to verify the effects of NMES.


Assuntos
Unidades de Terapia Intensiva , Respiração Artificial , Estado Terminal , Estimulação Elétrica , Humanos , Tempo de Internação , Extremidade Inferior
18.
Phytomedicine ; : 153840, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34836745

RESUMO

BACKGROUND: Pulmonary vascular remodeling is the key pathological feature of pulmonary arterial hypertension (PAH) characterized by a pattern of lipid-related insulin resistance(IR), hormonal derangements and metabolic reprogramming. Our previous studies have demonstrated osthole as natural coumarin compound derived from traditional Chinese medicine is a promising agent for the treatment of pulmonary vascular remodeling in PAH. PURPOSE: The present study sought to delineate lipid metabolic modulatory mechanism of osthole against pulmonary vascular remodeling by employing an interdisciplinary strategy. METHODS: Rat model with PAH induced with MCT and PASMCs proliferation model induced with PDGF-BB were established in this study. Serum and lung tissues were used to lipid-related IR, hormone related indexes, pulmonary vascular remodeling analysis. Then, lipid metabolic gene, key enzymes, metabolites and cell proliferation indexes were examined to investigate metabolic regulatory mechanism in vivo and vitro model of PAH. RESULTS: Osthole significantly showed improvement of lipid-related IR and hormone dysregulation in rats with PAH evidenced by elevating testosterone, androgen receptor and cyclic guanosine monophosphate (cGMP), inhibiting phosphodiesterase-5(PDE-5), modulating lipid-related IR indexes total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG)/HDL-C ratio. Additionally, osthole limited key metabolic gene and enzymes to inhibit accumulation of decadienyl-l-carnitine in lipid metabolism, thus to promote oxidative phosphorylation and ATP production through inhibition of miRNA-22-3p, fatty acid translocase (CD36), fatty acid synthase (FAS), phospholipase A2 (PLA2), carnitine palmitoyltransferase 1A (CPT1A), hexokinase 2 (HK2), activation of metabolic switch isocitrate dehydrogenase 3α (IDH3α), NADH dehydrogenase 1 (ND1). We found for the first time miRNA-22-3p modulated PASMCs proliferation and vascular remodeling by regulating lipid metabolism reprogramming. Those modifications uncovered therapeutic mechanism of osthole against pulmonary vascular remodeling. CONCLUSION: Our findings revealed the function of miRNA-22-3p in PASMCs and demonstrated a novel mechanism that miRNA-22-3p as a regulator can be targeted by osthole to greatly restore dysregulated lipid metabolism thus to alleviate pulmonary vascular remodeling in PAH, which provides novel insight into the potential therapeutic target for PAH, further highlights the development potential of osthole derived new drug against PAH.

20.
Ann Transl Med ; 9(17): 1369, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733921

RESUMO

Background: Long non-coding RNAs (lncRNAs) have recently been found to be vital regulators of various cancers, including colorectal cancer (CRC). It has been previously reported that the dysregulated expression of lncRNA Five prime to Xist (FTX) is involved in carcinogenesis. However, the role of lncRNA FTX in the progression of CRC is still unclear. Methods: Fluorescence in situ hybridization (FISH) was used to detect the expression of lncRNA FTX and miR-214-5p in CRC tissues. Cell Counting Kit-8 assay, transwell assay, wound-healing assay, and proliferation assay were used to explore the function of lncRNA FTX in CRC cells. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and luciferase reporter assay were used to confirm the relationship between lncRNA FTX and miR-214-5p-jagged canonical Notch ligand 1 (JAG1). We further explored the role of lncRNA FTX in vivo using xenograft tumor assay. Results: lncRNA FTX was found to be upregulated in CRC tissues by FISH. The downregulation of endogenous lncRNA FTX expression inhibited CRC cell proliferation, migration, and invasion. Mechanistically, lncRNA FTX sequestered miR-214-5p and thus released its repression on JAG1, driving the malignant progression of CRC. Conclusions: These findings give rise to a new perspective, the lncRNA FTX-miR-214-5p-JAG1 regulatory axis, in exploring the cancer-promoting mechanism of lncRNA FTX in CRC.

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