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1.
Bioengineered ; 13(5): 11732-11741, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35506298

RESUMO

Acute respiratory distress syndrome (ARDS) is a multifactorial inflammatory lung failure with a high incidence and a high cost burden. However, the underlying pathogenesis of ARDS is still unclear. Recently, microRNA has been shown to have critical function in regulating the pathogenesis of ARDS development and inflammation. To identify the important microRNA in the serum from patients with ARDS that may be potential biomarkers for the disease and explore the underlying disease mechanism. We found significant upregulation of miR-155-5p expression in serum samples from patients with ARDS compared with the control group (p < 0.01). The levels of interleukin receptors and inflammatory cytokines were significantly increased in blood samples from patients with ARDS (p < 0.05). In the cell model, miR-155-5p had a binding site in the 3'-UTR of the three interleukin receptors. In LPS-simulated BEAS-2B cells, transfection of miR-155-5p mimic inhibited the expression levels of these interleukin receptors, and was found to directly target the inflammatory response of leukocyte nodulin receptor through NF-kB signaling. In conclusion, miR-155-5p can alleviate LPS-simulated injury that induces the expression of IL17RB, IL18R1, and IL22RA2 by affecting the NF-kB pathway; however, it cannot change the occurrence of inflammatory storms. Collectively, this suggests that the progression of ARDS is the result of effects of the multiple regulatory pathways, providing novel evidence for the therapy of ARDS.


Assuntos
MicroRNAs , Síndrome do Desconforto Respiratório , Humanos , Lipopolissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Receptores de Interleucina/genética , Síndrome do Desconforto Respiratório/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-35564809

RESUMO

In this study, we investigate the relationship between ethical leadership (EL), work engagement (WE), well-being, and innovative work behavior (IWB). The significance of these variables has increased in the current era when the influence of technology is exponentially increasing in the education sector. We investigate the role of ethical leadership in determining innovative work behavior. Moreover, we investigate the moderating effect of WB in the relationship between EL and WE. We also examine the mediating impact of WE in the relationship between EL and IWB. We used a questionnaire survey approach to collect data. The target population of this study was the academic personnel, i.e., senior professors, lecturers, and supporting staff associated with the higher education sector located in Zhejiang Province, China. Data were collected in two phases. In the first phase, we sent 300 research questionnaires and received 251 responses. In the second phase, after a three-month interval, we sent 200 questionnaires and received 162 responses. However, over the two phases, we collected a total of 413 questionnaires; 43 were discarded. Therefore, for analysis, we used 370 questionnaires. The data were analyzed using the structural equation modeling through SmartPLS 3.2.2. First, in the direct relationship, results confirm that EL positively influences the IWB. Secondly, WB has a positive and moderating relationship between EL and IWB. Thirdly, we address the relationship between EL and WE. The outcome indicates that there is a positive and significant relationship. Fourth, the results of this study indicate that there is positive and significant relationship between WE and IWB. Finally, the outcomes imply that WE positively mediates between EL and IWB. Ethical leadership and well-being are important for innovative work behavior that supports managers in introducing a supportive workplace environment that promotes good interpersonal relationships with subordinates. Therefore, a good interpersonal relationship between managers and subordinates enhances the work quality. So, ethical leaders provide a supportive work environment to all subordinates regarding their work.

3.
Neurobiol Aging ; 116: 49-54, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35567899

RESUMO

Despite the similar clinical and pathological features between Niemann-Pick type C (NPC) disease and Alzheimer's disease (AD), few studies have investigated the role of NPC genes in AD. To elucidate the role of NPC genes in AD, we sequenced NPC1 and NPC2 in 1192 AD patients and 2412 controls. Variants were divided into common variants and rare variants according to minor allele frequency (MAF). Common variant (MAF≥0.01) based association analysis was conducted by PLINK 1.9. Gene-based aggregation testing of rare variants was performed by Sequence Kernel Association Test-Optimal (SKAT-O test), respectively. Age at onset (AAO) and mini-mental state examination (MMSE) association studies were also performed with PLINK 1.9. Six common variants were identified and exhibited no association with AD. Gene-based aggregation testing revealed that both NPC1 and NPC2 were not associated with AD risk. Additionally, AAO and MMSE association studies revealed that no common variants were linked with AD endophenotypes. Taken together, our study indicated that NPC1 and NPC2 may not be implicated in AD pathogenesis in the Chinese population.

4.
Phytomedicine ; 101: 154120, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35523117

RESUMO

BACKGROUND: Postmenopausal women have a high incidence of atherosclerosis. Phytosterols have been shown to have cholesterol-lowering properties. Alisa B 23-acetate (AB23A) is a biologically active plant sterol isolated from Chinese herbal medicine Alisma. However, the atherosclerosis effect of AB23A after menopause and its possible mechanism have not been reported yet. PURPOSE: To explore whether AB23A can prevent atherosclerosis by regulating farnesoid X receptor and subsequently increasing fecal bile acid and cholesterol excretion to reduce plasma cholesterol levels. METHODS: Aortic samples from premenopausal and postmenopausal women with ascending aortic arteriosclerosis were analyzed, and bilateral ovariectomized (OVX) female LDLR-/- mice and free fatty acid (FFA)-treated L02 cells were used to analyze the effect of AB23A supplementation therapy. RESULTS: AB23A increased fecal cholesterol and bile acids (BAs) excretion dependent on activation of hepatic farnesoid X receptor (FXR) in ovariectomized mice. AB23A inhibited hepatic cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) via inducing small heterodimer partner (SHP) expression. On the other hand, AB23A increased the level of hepatic chenodeoxycholic acid (CDCA), and activated the hepatic BSEP signaling. The activation of hepatic FXR-BSEP signaling by AB23A in ovariectomized mice was accompanied by the reduction of liver cholesterol, hepatic lipolysis, and bile acids efflux, and reduced the damage of atherosclerosis. In vitro, AB23A fixed abnormal lipid metabolism in L02 cells and increased the expression of FXR, BSEP and SHP. Moreover, the inhibition and silencing of FXR canceled the regulation of BSEP by AB23A in L02 cells. CONCLUSION: Our results shed light into the mechanisms behind the cholesterol-lowering of AB23A, and increasing FXR-BSEP signaling by AB23A may be a potential postmenopausal atherosclerosis therapy.

5.
Front Bioeng Biotechnol ; 10: 877964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547169

RESUMO

Inspired by the biological collective behaviors of nature, artificial microrobotic swarms have exhibited environmental adaptability and tasking capabilities for biomedicine and micromanipulation. Complex environments are extremely relevant to the applications of microswarms, which are expected to travel in blood vessels, reproductive and digestive tracts, and microfluidic chips. Here we present a strategy that reconfigures paramagnetic nanoparticles into a vector-controlled microswarm with 3D collective motions by programming sawtooth magnetic fields. Horizontal swarms can be manipulated to stand vertically and swim like a wheel by adjusting the direction of magnetic-field plane. Compared with horizontal swarms, vertical wheel-like swarms were evaluated to be of approximately 15-fold speed increase and enhanced maneuverability, which was exhibited by striding across complex 3D confinements. Based on analysis of collective behavior of magnetic particles in flow field using molecular dynamics methods, a rotary stepping mechanism was proposed to address the formation and locomotion mechanisms of wheel-like swarm. we present a strategy that actuates swarms to stand and hover in situ under a programming swing magnetic fields, which provides suitable solutions to travel across confined space with unexpected changes, such as stepped pipes. By biomimetic design from fin motion of fish, wheel-like swarms were endowed with multi-modal locomotion and load-carrying capabilities. This design of intelligent microswarms that adapt to complicated biological environments can promote the applications ranging from the construction of smart and multifunctional materials to biomedical engineering.

6.
J Nanobiotechnology ; 20(1): 223, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549949

RESUMO

Tumor microenvironment (TME), characterized by high glutathione (GSH), high hydrogen peroxide (H2O2) and acidic pH levels, is favorable for the growth, invasion and metastasis of cancer cells. Taking advantage of the specific characteristics of tumors, TME-responsive GCBD NPs are designed to deliver nanoscale coordination polymers (NCPs, GA-Cu) and chemotherapy drugs (doxorubicin, DOX) based on bovine serum albumin (BSA) nanocarriers into cancer cells for combined chemodynamic therapy (CDT) and chemotherapy. In an acidic environment, GCBD NPs could release approximately 90% copper ions, which can not only consume overexpressed GSH to modulate the TME but can also react with endogenous H2O2 in a Fenton-like reaction to achieve the CDT effect. Meanwhile, the released DOX could enter the nucleus of tumor cells and affect their proliferation to achieve efficient chemotherapy. Both in vitro and in vivo experiments showed that GCBD NPs had good biosafety and could effectively inhibit the growth of cancer cells. GCBD NPs are promising as a biocompatible nanoplatform to exploit TME characteristics for combined chemo and chemodynamic therapy, providing a novel strategy to eradicate tumors with high efficiency and specificity.

7.
Tree Physiol ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35532090

RESUMO

Gingko biloba is currently the only remaining gymnosperm of the Ginkgoaceae Ginkgo genus, and its history can be traced back to the Carboniferous 200 million years ago. Terpene trilactones (TTLs) are one of the main active ingredients in G. biloba, including ginkgolides and bilobalide. They have good curative effect on cardiovascular and cerebrovascular diseases because of their special antagonistic effect of platelet-activating factors. Therefore, it is necessary to deeply mine genes related to TTLs and to analyze their transcriptional regulation mechanism, which will hold vitally important scientific and practical significance for quality improvement and regulation of G. biloba. In this study, we performed RNA-Seq on the root (R), stem (S), immature leaf (IL), mature leaf (ML), microstrobilus (M), ovulate strobilus (OS), immature fruit (IF), and mature fruit (MF) of G. biloba. The TTL regulatory network of G. biloba in different organs was revealed by different transcriptomic analysis strategies. Weighted gene co-expression network analysis (WGCNA) revealed that the five modules were closely correlated with organs. The 12 transcription factors, 5 structural genes, and 24 CYP450 were identified as candidate regulators for TTL accumulation by WGCNA and cytoscape visualization. Finally, 6 AP2/ERFs, 2 CYP450s, and bHLH were inferred to regulate the metabolism of TTLs by correlation analysis. This study is the comprehensive to authenticate transcription factors, structural genes, and CYP450 involved in TTL biosynthesis, thereby providing molecular evidence for revealing the comprehensive regulatory network involved in TTL metabolism in G. biloba.

8.
J Mater Chem B ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35485772

RESUMO

Hydrogel wound dressings have attracted intense and increasing interest for their extracellular matrix like properties and bioactive material delivery ability. Various functional hydrogels loaded with metals (and their oxides), antibiotics and anti-inflammatory agents have been prepared to realize antioxidant, bactericidal and anti-inflammatory effects, accelerating wound healing. Nevertheless, it is still a big challenge to facilely fabricate hydrogel wound dressings with inherent desirable properties to promote wound healing and avoid some drawbacks such as toxicity of metals and drug resistance. Herein, we facilely prepared a series of (-)-epigallocatechin-3-O-gallate (EGCG)-crosslinked carboxymethyl chitosan-based hydrogels (EP gels) with inherent antioxidant, bactericidal and adhesive properties. Gluconate-terminated polyethylene glycol (PEG-glu) was introduced into gel networks to enhance the mechanical properties. The hydrogels are constructed via borate ester crosslinking between phenylboronic acid (PBA) groups of PBA-grafted carboxymethyl chitosan (CMCS-PBA) and diol groups of EGCG and PEG-glu. The hydrogels exhibited excellent self-healing properties, desirable mechanical and adhesive strength, free radical scavenging capability and outstanding bactericidal ability against S. aureus and E. coli. In the subsequent full-thickness skin defect model of mice, EP1 gel could promote the proliferation and remodeling process such as the regeneration of epidermis, dermis, and skin appendages, deposition of collagen, and upregulation of the VEGF level, thereby accelerating the healing of damaged skin. Overall, we facilely prepared polysaccharide-based hydrogels with inherent desirable properties as promising dressings for wound repair.

9.
Nanomedicine (Lond) ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35393861

RESUMO

Aim: The present study aimed to retrospectively compare the efficacy and safety between liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P) in neoadjuvant systemic treatment (NST) of breast cancer. Materials & methods: 235 patients who were diagnosed with invasive breast cancer and then received dose-dense NST with epirubicin and cyclophosphamide followed by paclitaxel were enrolled. Results: Nab-P has an advantage in improving the total and axillary-only pathologic complete response rate over Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In the Lps-P group, the proportion of patients with residual irreversible PSN is larger. Conclusion: Nab-P might be superior to Lps-P in NST of breast cancer.


Neoadjuvant systemic treatment (NST) is recommended for many patients with breast cancer before they undergo surgery to remove the cancer. This study retrospectively compared the efficacy and safety of two potential NST drugs, liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P). Two hundred thirty-five patients participated in the study. These patients had been diagnosed with invasive breast cancer and were recommended NST with paclitaxel before surgery. The results showed that more participants who received Nab-P had no signs of cancer in their tissue samples from their breasts and armpit lymph nodes than participants who received Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In conclusion, Nab-P might be superior to Lps-P for NST.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35383661

RESUMO

ABSTRACT: Contrast-induced acute kidney injury (CI-AKI) causes clinically acquired nephropathy in patients who undergo coronary interventions. Hypoxic injury to proximal tubular epithelial cells is a pathological mechanism of CI-AKI. Previous studies hypoxia activates HIF-1α/HE4/NF-κB to enhance renal fibrosis, and the SGLT-2 inhibitor luseogliflozin inhibits HIF-1α expression to reduce the progression of diabetic nephropathy. However, the therapeutic effects and mechanisms of SGLT-2 inhibitors on CI-AKI are unclear. We explored the role of the HIF-1α/HE4/NF-κB pathway in CI-AKI and how dapagliflozin effectively treats CI-AKI by inhibiting this pathway. In vitro, cells were divided into the control, hypoxia, hypoxia + dapagliflozin, and hypoxia+pSilencer-HIF-1α groups. Cellular hypoxia, apoptosis and related protein expression were evaluated by immunofluorescence, western blotting, and flow cytometry respectively. Dapagliflozin significantly decreased oxygen consumption, HIF-1α, HE4, NF-κB expression and apoptotic cells compared with the control (P < 0.01). In vivo, rats were divided into the control (C), diabetes (D), diabetes + contrast media (DCM), and diabetes + contrast media + dapagliflozin (DDCM) groups. Rats in the latter two groups were treated with dapagliflozin for 2 days. CI-AKI was induced by intravenously injecting indomethacin, N-nitro-L-arginine methyl ester, and iohexol. The effects of dapagliflozin on CI-AKI rats were elucidated by assessing renal function, H&E staining, and immunohistochemistry. Serum creatinine, urea nitrogen, TUNEL-positive tubular cells, HIF-1α, HE4, NF-κB expression, and histopathological scores were increased in DCM rats compared with C, D, and DDCM rats (P < 0.01). Thus, dapagliflozin may ameliorate CI-AKI via suppression of HIF-1α/HE4/NF-κB signaling in vitro and in vivo.

11.
Opt Express ; 30(9): 14723-14736, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473210

RESUMO

The foveal avascular zone (FAZ) is sensitive to retinal pathological process in the macular fovea area. For the purpose of efficient FAZ 3D quantification, we firstly propose a priors-guided convolutional neural network (CNN) to provide a tailor-made solution for 3D FAZ segmentation for optical coherence tomography angiography (OCTA) images. Location and topology priors are taken into account. The random central crop module is utilized to restrict the region to be processed, while the non-local attention gates are contained in the network to capture long-range dependency. The topological consistency constraint is calculated on maximum and mean projection maps through persistent homology to keep topological correctness of the model's prediction. Our method was evaluated on two OCTA datasets with 478 eyes and the experimental results demonstrate that our method can not only alleviate the over-segmentation prominently but also fit better on the contour of FAZ region.


Assuntos
Fóvea Central , Tomografia de Coerência Óptica , Angiofluoresceinografia/métodos , Fóvea Central/diagnóstico por imagem , Redes Neurais de Computação , Tomografia de Coerência Óptica/métodos
12.
EMBO J ; : e109324, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35471583

RESUMO

In activated B cells, activation-induced cytidine deaminase (AID) generates programmed DNA lesions required for antibody class switch recombination (CSR), which may also threaten genome integrity. AID dynamically shuttles between cytoplasm and nucleus, and the majority stays in the cytoplasm due to active nuclear export mediated by its C-terminal peptide. In immunodeficient-patient cells expressing mutant AID lacking its C-terminus, a catalytically active AID-delC protein accumulates in the nucleus but nevertheless fails to support CSR. To resolve this apparent paradox, we dissected the function of AID-delC proteins in the CSR process and found that they cannot efficiently target antibody genes. We demonstrate that AID-delC proteins form condensates both in vivo and in vitro, dependent on its N-terminus and on a surface arginine-rich patch. Co-expression of AID-delC and wild-type AID leads to an unbalanced nuclear AID-delC/AID ratio, with AID-delC proteins able to trap wild-type AID in condensates, resulting in a dominant-negative phenotype that could contribute to immunodeficiency. The co-condensation model of mutant and wild-type proteins could be an alternative explanation for the dominant-negative effect in genetic disorders.

13.
Nature ; 604(7904): 72-79, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35388196

RESUMO

Covalent organic frameworks (COFs) are distinguished from other organic polymers by their crystallinity1-3, but it remains challenging to obtain robust, highly crystalline COFs because the framework-forming reactions are poorly reversible4,5. More reversible chemistry can improve crystallinity6-9, but this typically yields COFs with poor physicochemical stability and limited application scope5. Here we report a general and scalable protocol to prepare robust, highly crystalline imine COFs, based on an unexpected framework reconstruction. In contrast to standard approaches in which monomers are initially randomly aligned, our method involves the pre-organization of monomers using a reversible and removable covalent tether, followed by confined polymerization. This reconstruction route produces reconstructed COFs with greatly enhanced crystallinity and much higher porosity by means of a simple vacuum-free synthetic procedure. The increased crystallinity in the reconstructed COFs improves charge carrier transport, leading to sacrificial photocatalytic hydrogen evolution rates of up to 27.98 mmol h-1 g-1. This nanoconfinement-assisted reconstruction strategy is a step towards programming function in organic materials through atomistic structural control.

14.
J Healthc Eng ; 2022: 5635063, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392150

RESUMO

Objective: To investigate the effect and mechanism of combined stellate ganglion block (SGB) and dexmedetomidine (Dex) in obesity-related acute lung injury. Methods: Thirty-six 4-week-old male Wistar rats were randomly divided into 6 groups, each with 6 rats: blank group (Control), high-fat diet group (HFD), high-fat + lipopolysaccharide (LPS)-induced acute lung injury group (HFD + LPS), SGB group, Dex group, and SGB + Dex group. H&E staining detected the pathological structure of rat lung tissue. TUNEL staining was used to examine cell apoptosis in lung tissue. Oxidative factors were accessed by biochemical reagents. ELISA was employed to measure the levels of TNF-α, IL-1ß, and MCP1 in rat alveolar lavage fluid. Western blot detected the protein expression of glucose-regulated Protein 78 (GRP78), C/EBP homologous protein (CHOP), protein kinase R-like endoplasmic reticulum kinase (PERK), and p-PERK in lung tissue. Results: The body weight of rats in the HFD group was higher than that in the control group. The use of SGB or Dex alone could significantly reduce the rate of pulmonary edema and lung cell apoptosis in HFD-induced obese rats and reduce MPO, TNF-α, IL-1ß, and MCP1 levels, increasing the activity of SOD and GSH-Px. In addition, using SGB or Dex alone can also significantly reduce the protein expression levels of GRP78, CHOP, and p-PERK. The combined use of SGB and Dex can enhance the above effects. Conclusion: The combined use of SGB and Dex can protect against obesity-related acute lung injury and is more effective than using SGB or Dex alone.


Assuntos
Lesão Pulmonar Aguda , Dexmedetomidina , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Dexmedetomidina/efeitos adversos , Humanos , Lipopolissacarídeos/efeitos adversos , Masculino , Obesidade/complicações , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transdução de Sinais , Gânglio Estrelado , Fator de Necrose Tumoral alfa/efeitos adversos
15.
STAR Protoc ; 3(1): 101088, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35462794

RESUMO

The repair products of double-stranded DNA breaks (DSBs) are crucial for investigating the mechanism underlying DNA damage repair as well as evaluating the safety and efficiency of gene-editing; however, a comprehensively quantitative assay remains to be established. Here, we describe the step-by-step instructions of the primer extension-mediated sequencing (PEM-seq), followed by the framework of data processing and statistical analysis. PEM-seq presents a full spectrum of repair outcomes for both genome-editing-induced and endogenous DSBs in mouse and human cells. For complete details on the use and execution of this profile, please refer to Gan et al. (2021), Yin et al. (2019), Liu et al. (2021a), and Zhang et al. (2021).


Assuntos
Quebras de DNA de Cadeia Dupla , Edição de Genes , Animais , Reparo do DNA/genética , Camundongos
16.
Genomics ; 114(3): 110374, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35489616

RESUMO

Zanthoxylum armatum DC. is an important economic tree species. Prickle is a type of trichome with special morphology, and there are a lot of prickles on the leaves of Z. armatum, which seriously restricts the development of Z. armatum industry. In this study, the leaves of Z. armatum cv. Zhuye (ZY) and its budding variety 'Rongchangwuci' (WC) (A less prickly mutant variety) at different developmental stages were used as materials, and the transcriptome sequencing data were analyzed. A total of 96,931 differentially expressed genes (DEGs) were identified among the samples, among which 1560 were candidate DEGs that might be involved in hormone metabolism. The contents of JA, auxin and CK phytohormones in ZY leaves were significantly higher than those in WC leaves. Combined with weighted gene co-expression network analysis, eight genes (MYC, IAA, ARF, CRE/AHK, PP2C, ARR-A, AOS and LOX) were identified, including 25 transcripts, which might affect the metabolism of the three hormones and indirectly participate in the formation of prickles. Combining with the proteins successfully reported in other plants to regulate trichome formation, ZaMYB86, a transcription factor of R2R3 MYB family, was identified through local Blast and phylogenetic tree analysis, which might regulate prickle formation of Z. armatum. Overexpression of ZaMYB86 in mutant A. thaliana resulted in the reduction of trichomes in A. thaliana leaves, which further verified that ZaMYB86 was involved in the formation of pickles. Yeast two-hybrid results showed that ZaMYB86 interacted with ZaMYB5. Furthermore, ZaMYB5 was highly homologous to AtMYB5, a transcription factor that regulated trichomes development, in MYB DNA binding domain. Taken together, these results indicated that ZaMYB86 and ZaMYB5 act together to regulate the formation of prickles in Z. armatum. Our findings provided a new perspective for revealing the molecular mechanism of prickly formation.

17.
Food Res Int ; 155: 111094, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35400468

RESUMO

Paeonia rockii is a promising woody oil crop because its seeds are rich in polyunsaturated fatty acids especially α-linolenic acid (ALA). ALA is an essential fatty acid that the human body cannot synthesize and is the direct synthetic precursor of eicosapentaenoic and docosahexaenoic acids, which play crucial roles in the development of the blood vessels, brain and nervous system of humans. However, the mechanisms underlying the dynamic changes in ALA during seed development are unknown. In this study, we found that the fatty acid content gradually increased with P. rockii seed development, with ALA being the main unsaturated acid component (37-44%). The content of ALA reached the peak value of 306.26 mg/g DW 20 days before the seeds had fully maturated. Seeds from three different developmental stages were selected for transcriptome and miRNA sequencing analyses to explore the molecular mechanism of ALA accumulation in P. rockii seeds. A total of 39 differentially expressed genes were screened for their involvement in ALA biosynthesis, among which FAD2/8, GPAT, PDAT, LACS, LPAAT, and KAS II might be the key structural genes of ALA accumulation. The differential expression of these genes was dependent on the regulation of five miRNAs (mdm_miR156b, novel miR_91, novel miR_133, novel miR_291, and novel miR_405) and four transcription factors (AP2, SNL2, TGA-like, and SPL). This study reveals the mechanism behind the dynamic changes of ALA contents in P. rockii during seed development, and also provides an important theoretical basis for the breeding of excellent varieties of P. rockii.


Assuntos
MicroRNAs , Paeonia , Regulação da Expressão Gênica de Plantas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Paeonia/genética , Melhoramento Vegetal , Transcriptoma , Ácido alfa-Linoleico
18.
Eur J Clin Nutr ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35411025

RESUMO

OBJECTIVES: To establish a risk prediction model for in-hospital death in acute stroke patients based on nutritional risk scores. METHODS: A retrospective analysis was performed including 268 acute stroke patients. The Nutritional Risk Screening 2002 (NRS2002) and modified Nutritional Risk in the Critically Ill (mNUTRIC) score were used to evaluate the nutritional status of patients with acute stroke after admission to the neurological intensive care unit (NICU), and laboratory parameters and clinical characteristics were collected. Multivariate logistic regression analysis was performed to screen the risk factors for in-hospital death in acute stroke patients, and a nomogram for predicting death based on the nutritional risk score was established. RESULTS: The mortality of acute stroke in the NICU was 25.8%. Multivariate logistic regression analysis showed that the mNUTRIC score, female sex, lymphocyte count, pulmonary infection and mechanical ventilation were independent risk factors for in-hospital mortality in acute stroke patients (P < 0.001 or 0.05). The above indexes were used to establish a prediction model of the in-hospital death risk for acute stroke patients. The area under the ROC curve, sensitivity, and specificity of the prediction model were 0.891 (95% CI = 0.853-0.928), 82.5%, and 81.7%, respectively. The nomogram was established and then internally validated using bootstrap repeat sampling 2000 times, the C-index was 0.880, and the predicted values of the calibration curve were in agreement with the measured values. CONCLUSION: The mNUTRIC-based nomogram model can be used as a reliable tool to predict the in-hospital mortality risk of acute stroke patients.

19.
Biomed Res Int ; 2022: 9170053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372571

RESUMO

NSCLC (non-small-cell lung cancer) is the deadliest cancer in the world. Artesunate is one of the most potent and rapidly acting antimalarial agents. Recently, emerging evidence has suggested the anticancer function of artesunate. In our work, we aimed to investigate the molecular mechanism of artesunate-induced growth inhibition in human lung adenocarcinoma cells and reported that the anticancer effects of artesunate is related to its ability in downregulating AKT/Survivin signaling in A549 cells. The effect of artesunate on the proliferation of A549 cells was determined by CCK-8 assay and colony formation assay; its effect on A549 cell apoptosis was evaluated by lactate dehydrogenase (LDH) release assay. The role of artesunate on the activation of AKT/Survivin signaling was analyzed by western blot and quantitative QPCR. Finally, we used two mouse tumor models to investigate the function of artesunate on the in vivo growth of lung cancer cells. Artesunate treatment caused significant growth inhibition and apoptosis in A549 cells. Mechanistically, artesunate downregulated the activation of AKT/Survivin signaling. In agreement, hyperactivation of AKT signaling restored artesunate-induced growth inhibition in A549 cells. In mouse lung cancer models, artesunate administration significantly reduced the growth of A549 cells and LLC cells in nude mice and immunocompetent mice, respectively. Our findings suggest that artesunate serves as a potential tumor suppressor in lung cancer and hopefully can provide new insight into the development of therapeutic strategies in the clinical lung cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células A549 , Animais , Apoptose , Artesunato/farmacologia , Artesunato/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Survivina/metabolismo
20.
Bioengineered ; 13(4): 11061-11071, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35475466

RESUMO

Numerous studies have suggested that the phenotypic transformation of microglia plays a role in the pathogenesis of Parkinson's disease (PD). Translocator protein (TSPO) is an 18 kDa translocator membrane protein that acts as a marker of neuroinflammation and suppresses neuroinflammation; however, its underlying mechanism remains unclear. Although TSPO ligands were found to be protective in several neurodegenerative paradigms, few studies have evaluated their effects on microglial polarization, and underlying mechanisms need to be explored. In the present study, we examined the effects of TSPO and PK11195, a TSPO ligand, on lipopolysaccharide (LPS)+interferon (IFN)-γ-induced inflammatory factors and oxidative stress in microglia using enzyme-linked immunosorbent assay. The effect of TSPO and PK11195 on LPS+IFN-γ-induced microglial cell apoptosis was examined using immunofluorescence (IF), flow cytometry, and western blotting. The interaction between TSPO and P47 was investigated using IF and co-immunoprecipitation analysis. In vivo experiments confirmed the influence of TSPO and its ligand on motility, a-Syn, and dopaminergic neuronal damage. Our findings indicate that TSPO may regulate the microglial phenotype in PD via P47, suggesting a potential role in anti-PD therapy.


Assuntos
Microglia , Doença de Parkinson , Proteínas Adaptadoras de Transdução de Sinal , Humanos , Ligantes , Lipopolissacarídeos/metabolismo , Microglia/metabolismo , Microglia/patologia , Doença de Parkinson/metabolismo , Fenótipo , Receptores de GABA/genética , Receptores de GABA/metabolismo
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