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1.
Acta Diabetol ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633709

RESUMO

AIMS: To explore the predictive value of ferroptosis-related (FR) biomarkers for diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This prospective observational study enrolled patients with T2DM at the Second Hospital of Jilin University between December 2021 and March 2022. DKD was measured by the urinary albumin-to-creatinine ratio. Receiver operating characteristic curve (ROC) analysis was performed to assess the predictive value of ferroptosis-related biomarkers for DKD.The risk factors for massive proteinuria were performed by multivariable logistic regression analysis. RESULTS: Finally, 118 patients (53.0 ± 12.2 years, 76 males) were enrolled, 52 of them without DKD (had normal proteinuria), while 66 with DKD. (Forty-one had microproteinuria, and 25 had massive proteinuria.) FR biomarkers, including acyl-CoA synthase long chain family member 4 (ACSL4), malondialdehyde (MDA), and reactive oxygen species (ROS), were significantly higher in the massive proteinuria group than in the other groups, while glutathione peroxidase 4 (GPX4) was significantly lower (all P < 0.05). The area under the ROC of the combination of GPX4, ACSL4, MDA, and ROS for predicting DKD was 0.804 (P < 0.001). Additionally, multivariate logistic regression analysis showed that the course of disease and ferritin levels were independent risk factors for massive proteinuria, while high serum iron, transferrin, and GPX4 levels were independent protective factors for massive proteinuria in patients with T2DM (all P < 0.05). CONCLUSIONS: The GPX4, ACSL4, MDA, and ROS combination might have a good predictive value for DKD. Additionally, the course of disease, ferritin levels, serum iron, transferrin, and GPX4 were independently associated with massive proteinuria.

2.
Dis Colon Rectum ; 66(1): e4-e9, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36515520

RESUMO

BACKGROUND: Anastomotic recurrence after bowel resection is problematic in patients with Crohn's disease. Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis is associated with a low risk of anastomotic recurrence in patients with Crohn's disease. IMPACT OF INNOVATION: Kono-S anastomosis is effective but may be time-consuming. This study aimed to describe stapled antimesenteric functional end-to-end anastomosis for patients with Crohn's disease. TECHNOLOGY MATERIALS AND METHODS: The mesentery of the affected bowel segment was divided. A 5-cm-wide stapled functional end-to-end anastomosis was performed approximately 6 cm from the affected segment. The bowel was divided transversely exactly 90° to the intestinal lumen and the mesentery, and a supporting column was then constructed. PRELIMINARY RESULTS: From January 2018 to June 2021, 17 stapled antimesenteric functional end-to-end anastomoses were performed. The mean operative time was 106 (range, 80-135) minutes, and the time to construct the stapled antimesenteric functional end-to-end anastomosis was 21 (range, 18-28) minutes. The mean follow-up time was 8.9 (range, 1-15) months. In total, 10 patients underwent surveillance endoscopy. The average Rutgeerts score was 0.8 (range, 0-4), and the incidence of endoscopic recurrence was 11.8%. No postoperative mortality or anastomotic leakage was observed. CONCLUSION: Stapled antimesenteric functional end-to-end anastomosis may be a safe and time-saving procedure for patients with Crohn's disease. FUTURE DIRECTIONS: Further prospective studies with a large sample size are warranted.


Assuntos
Doença de Crohn , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Doença de Crohn/cirurgia , Estudos Prospectivos , Anastomose Cirúrgica/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Intestinos/cirurgia , Íleo/cirurgia
3.
Talanta ; 253: 123955, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36179559

RESUMO

Circulating tumor cells (CTCs) are promising liquid biopsy biomarkers for early cancer detection and anti-cancer therapy evaluation. The ultra-low abundance of CTCs in blood samples requires highly sensitive and accurate detection ways. In this study, we propose the design of a dual-recognition electrochemical biosensor to improve both the specificity and signal response. PdPtCuRu mesoporous nanospheres (PdPtCuRu MNSs) with excellent three dimensions (3D) nanopore structures were synthesized by one-pot method and connected to mucin 1 (MUC1) aptamer to serve as signal amplification probe. Besides, superconductive carbon black, Ketjen Black (KB), and gold nanoparticles (AuNPs) modified organometallic frame (CeMOF-Au) were combined to work as signal transducer. The characteristic branching structure of KB provides abundant contact points to load CeMOF-Au to heighten the interface electron transfer rate. In addition, AuNPs were reduced on the surface of CeMOF, which could effectively bind the capture antibody and further enhance the conductivity. Under the optimized condition, the limit of detection (LOD) of the as-constructed biosensor was less than 10 cells mL-1 for model A549 cells, and showed good specificity and accuracy in spiked serum samples. We envision the as-proposed electrochemical biosensor would alternate as a useful tool for the clinical detection of CTCs for cancer diagnosis.


Assuntos
Ouro , Nanopartículas Metálicas
4.
J Environ Manage ; 328: 116670, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36521224

RESUMO

Through the case of China's Xin'an River Basin Eco-compensation Pilot (XRBEP), this study mobilizes the concept of hydrosocial territories to scrutinize how the watershed conservation behavior of stakeholders in payment for watershed services (PWS) evolves in response to eco-compensation and the coordination of interests. By drawing on the extensive literature on differential games, this study opens up our view of the complex relationship between PWS and the coordination of interests. After comparing the simulated and actual results of XRBEP, this study highlights that the coordination of interests in transboundary PWS can ultimately be socially optimal by reconciling the interests of different administrative territories. Furthermore, designing incentive-compatible coordination mechanisms of interest in transboundary PWS remains challenging, depending on the reconfiguration of PWS hydrosocial territories. Finally, the horizontal eco-compensation as a PES-like application can maximize the supply of watershed services, thus becoming a suboptimal and realistic option for realizing transboundary PWS.


Assuntos
Ecossistema , Rios , China
5.
Environ Res ; : 114987, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36462694

RESUMO

Selective separation of nitrate over chloride is crucial for eutrophication mitigation and nitrogen resource recovery but remains a challenge due to their similar ionic radius and the same valence. Herein, a polypyrrole membrane electrode (PME) was fabricated by polymerization of pyrrole (Py) and p-toluenesulfonate (pTS), which was used as a working electrode in redox transistor electrodialysis. The anions in the source solution were first incorporated into the PME at reduction potentials and then released to receiving solution at oxidation potentials. Pulse widths and potentials were optimized to maximize the ion separation performance of PME, resulting in the improvement of NO3-/Cl- separation factor up to 6.93. The ion distributions in various depths of PME indicated that both NO3- and Cl- were incorporated into PME at negative potentials. Then, NO3- was preferentially released from PME at positive potentials, but most Cl- was retained. This was ascribed to the high binding energy between Cl- and PPy/pTS structure, which was 51.4% higher than that between NO3- and PPy/pTS structure. Therefore, the higher transport rate of NO3- in comparison with Cl- was achieved, leading to a high NO3- selectivity over Cl-. This work provides a promising avenue for the selective separation of nitrate over chloride, which may contribute to nitrogen resource recycling and reuse.

6.
Front Immunol ; 13: 1061592, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466848

RESUMO

Background: Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI. Methods: We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA. Results: Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response. Conclusion: Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.


Assuntos
Aneurisma Intracraniano , MicroRNAs , Humanos , Aneurisma Intracraniano/genética , RNA Circular/genética , MicroRNAs/genética , Proteínas de Ligação a RNA , Biomarcadores , RNA Mensageiro
7.
Artigo em Inglês | MEDLINE | ID: mdl-36467550

RESUMO

Objectives: The experiment aimed to explore the effects of curcumin on motor impairment, dopamine neurons, and gut microbiota in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model. Methods: Mice were randomly assigned to six groups: normal control group, solvent control group, MPTP group, curcumin-low-dose group (40 mg/kg), curcumin-medium-dose group (80 mg/kg), and curcumin-high-dose group (160 mg/kg). After 14 days, each group of mice was subjected to the pole text, the hanging test, and the open-field test. Tyrosine hydroxylase (TH) immunohistochemistry was used to observe the survival of nigrostriatal dopamine neurons. Moreover, ultrastructural changes were observed with a transmission electron microscope in mice striatal tissue cells. Then, 16S rRNA was used to assess changes in the gut microbiota. Results: (1) Each dose of curcumin reduced pole climbing time and increased suspension score and total distance moved dose-dependently. (2) All curcumin groups improved cell wrinkling and vacuolar degeneration, increased the number of TH positives, improved cell survival, and the higher the dose of curcumin, the better the effect. (3) There were differences in microbiota composition and a relative abundance among the groups. The relative abundance of Patescibacteria, Proteobacteria, and Verrucomicrobia was higher in the MPTP group. The relative abundance of Patescibacteria, Enterobacteriaceae, Enterococcaceae all decreased in all curcumin groups. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways showed a reduction in the superpathway of N-acetylneuraminate degradation after medium- and high-dose curcumin administration. Conclusions: Curcumin regulates gut microbiota and exerts a neuroprotective effect in the MPTP mice model. This preliminary study demonstrates the therapeutic potential of curcumin for Parkinson's disease, providing clues for microbially targeted therapies for Parkinson's disease.

8.
Scand J Gastroenterol ; : 1-9, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469647

RESUMO

BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce ischemia-reperfusion injury (IRI) in many vital organs by inhibiting a systemic inflammatory response. Inflammation also plays an essential role in the pathophysiology of prolonged post-operative ileus (PPOI) in patients undergoing colorectal cancer (CRC) surgery. However, the role of RIPC is unclear in reducing the incidence of PPOI in patients undergoing CRC surgery. METHODS: This was a prospective, randomized trial of RIPC vs. placebo-controlled in patients undergoing elective laparoscopic CRC surgery. Eighty patients were randomized to either a RIPC group or a control group (40 per arm), with computer-generated randomization. The aim was to determine whether RIPC improved the recovery of gut function. The primary outcomes assessed were time to gastrointestinal tolerance and incidence of PPOI. RESULTS: Median time to stool of the RIPC group was significantly lower than that of the control group [RIPC vs. control, 4.0 (3.0, 6.0) vs. 5.0 (4.0, 7.8) days, p = 0.027]. Median time to gastrointestinal tolerance and incidence of PPOI in the RIPC group were lower than the control group; however, there were no statistical differences between the two groups [RIPC vs. control: 5.0 (3.0, 7.0) vs. 6.0 (4.0, 8.8) days, p = 0.178; 15 vs. 30%, p = 0.108]. CONCLUSION: RIPC could shorten the median time to stool in patients undergoing laparoscopic CRC surgery, but did not improve the overall recovery time of gut function or reduce the incidence of PPOI. REGISTRATION NUMBER: ChiCTR2100043313 (http://www.chictr.org.cn).Key pointsQuestion: In patients undergoing laparoscopic CRC surgery, does RIPC improve time to the overall recovery of gut function and reduce the incidence of PPOI?Findings: In this randomized clinical trial that included 80 patients undergoing elective laparoscopic CRC surgery, no significant difference was found between the RIPC group and the control group concerning median time to gastrointestinal tolerance and incidence of PPOI.Meaning: RIPC did not improve the time for overall recovery of gut function or reduce the incidence of PPOI in patients undergoing laparoscopic CRC surgery.

9.
Front Endocrinol (Lausanne) ; 13: 1074921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523590

RESUMO

Background: Steroid hormones play an essential role in many reproductive processes of vertebrates. Previous studies revealed that teleost-specific Cyp17a2 (cytochrome P450 family 17 subfamily a 2) might be required for the production of cortisol in the head-kidney and 17α,20ß-dihydroxy-4-pregnen-3-one (DHP) in ovary during oocyte maturation. However, the role of Cyp17a2 in male reproduction remains to be largely unknown. The aim of this study was to explore the essentiality of cyp17a2 gene in male steroidogenesis, spermatogenesis, and male fertility. Methods: A homozygous mutation line of cyp17a2 gene was constructed in tilapia by CRISPR/Cas9 gene editing technology. The expression level of germ cell and meiosis-related genes and steroidogenic enzymes were detected by qRT-PCR, IHC, and Western blotting. EIA and LC-MS/MS assays were used to measure the steroid production levels. And sperm quality was examined by Sperm Quality Analyzer software. Results: In this study, cyp17a2 gene mutation resulted in the significant decline of serum DHP and cortisol levels. On the contrary, significant increases in intermediate products of cortisol and DHP were found in cyp17a2-/- male fish. The deficiency of cyp17a2 led to the arrest of meiotic initiation in male fish revealing as the reduction of the expression of germ cell-related genes (vasa, piwil, oct4) and meiosis-related genes (spo11 and sycp3) by 90 dah. Afterwards, spermatogenesis was gradually recovered with the development of testis in cyp17a2-/- males, but it showed a lower sperm motility and reduced fertility compared to cyp17a2+/+ XY fish. Deletion of cyp17a2 led to the abnormal upregulation of steroidogenic enzymes for cortisol production in the head-kidney. Moreover, unaltered serum androgens and estrogens, as well as unchanged related steroidogenic enzymes were found in the testis of cyp17a2-/- male fish. Conclusion: This study proved that, for the fist time, Cyp17a2 is indispensable for cortisol and DHP production, and cyp17a2 deficiency associated curtailed meiotic initiation and subfertility suggesting the essentiality of DHP and cortisol in the male fertility of fish.


Assuntos
Ciclídeos , Animais , Feminino , Masculino , Ciclídeos/metabolismo , Cromatografia Líquida , Hidrocortisona/metabolismo , Motilidade Espermática , Sêmen , Espectrometria de Massas em Tandem , Fertilidade
10.
Metabolites ; 12(12)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36557208

RESUMO

Chrysomycin A (CA), a promising antibiotic agent, usually coexists with two analog chrysomycins B (CB) and C (CC) produced by several wild-type (WT) Streptomyces strains. With the aim to increase CA production, UV mutagenesis-based breeding had been employed on a marine-derived strain Streptomyces sp. 891 in our previous study and afforded an improved strain 891-B6 with enhanced CA yield. By comparative transcriptome analysis, significant differences in chrysomycin BGC-related gene expression between the WT strain 891 and the mutant strain 891-B6 were unveiled in the current study. Among 25 up-regulated genes in mutant 891-B6, chryA, chryB, chryC, chryF, chryG, chryK, chryP, and chryQ, responsible for the biosynthesis of benzonaphthopyranone aglycone, and chryD, chryE, and chryU in charge of production of its deoxyglycoside, were characterized. Furthermore, the expression of genes chryOII, chryOIII, and chryOIV responsible for the formation of 8-vinyl in CA from 8-ethyl in CB were greatly enhanced in strain 891-B6. These findings provide molecular mechanisms for increased yield of CA and decreased yield of CB for mutant 891-B6, which has potential application in industrial CA production.

11.
Metabolites ; 12(12)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36557235

RESUMO

Excessive fat accumulation is a common phenomenon in cultured fish, which can cause metabolic disease such as fatty liver. However, the relative regulatory approach remains to be explored. Based on this, two feeding trials were conducted. Firstly, fish were fed either a normal-fat diet (NFD) or a high-fat diet (HFD) for eight weeks and sampled at the 2nd, 4th, 6th, and 8th week after feeding (Experiment I). In the first four weeks, fish fed an HFD grew faster than those fed an NFD. Conversely, the body weight and weight gain were higher in the NFD group at the 6th and 8th weeks. Under light and transmission electron microscopes, fat accumulation of the liver was accompanied by an obvious endoplasmic reticulum (ER) swell. Accordingly, the expressions of atf-6, ire-1, perk, eif-2α, atf-4, grp78, and chop showed that ER stress was activated at the 6th and 8th weeks. In Experiment II, 50 mg/kg 4-PBA (an ERs inhibitor) was supplemented to an HFD; this was named the 4-PBA group. Then, fish was fed with an NFD, an HFD, and a 4-PBA diet for eight weeks. As the result, the excessive fat deposition caused by an HFD was reversed by 4-PBA. The expression of ER stress-related proteins CHOP and GRP78 was down-regulated by 4-PBA, and the transmission electron microscope images also showed that 4-PBA alleviated ER stress induced by the feeding of an HFD. Furthermore, 4-PBA administration down-regulated SREBP-1C/ACC/FAS, the critical pathways of fat synthesis. In conclusion, the results confirmed that ER stress plays a contributor role in the fat deposition by activating the SREBP-1C/ACC/FAS pathway. 4-PBA as an ER stress inhibitor could reduce fat deposition caused by an HFD via regulating ER stress.

12.
J Ethnopharmacol ; 304: 116028, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36529250

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Koumine, an indole alkaloid extracted from Gelsemium elegans Benth, exerts anti-inflammation and antioxidant activities. However, the effects of koumine on intestinal injury induced by H2O2 and its potential molecular mechanisms need larger studies. AIM OF THE STUDY: We established an IPEC-J2 cell damage model induced by H2O2 to explore the protective mechanism of koumine on intestinal injury. MATERIALS AND METHODS: In the experiment, cell damage models were made with hydrogen peroxide. To assess the protective effect of koumine on H2O2-induced IPEC-J2 cell injury, CCK-8, the release of LDH and ROS, transmission electron microscopy and Annexin V-FITC/PI were employed. Western Blot and Quantitative Real-time PCR were used to determine the potential alleviated mechanism of koumine on H2O2-trigged IPEC-J2 cell damage. RESULTS: The results of CCK-8 and LDH implied that koumine has a mitigative effect on H2O2-induced cell damage via upregulating cell viability and suppressing cell membrane fragmentation. Simultaneously, koumine notably inhibited the level of pro-inflammatory factors (IL-1ß, IL-6, IL-8, TNF-α and TGF-ß), the over-production of ROS along with decreasing the injury of mitochondrion, endoplasmic reticulum and lysosome induced by H2O2. Moreover, koumine dramatically attenuated H2O2-triggered IPEC-J2 cell apoptosis and autophagy. Subsequently, Western blot analysis identified NF-ΚB, PI3K and ERS as possible pathway responsible for the protective effect of koumine on H2O2-stimulated IPEC-J2 cell inflammation. CONCLUSIONS: This in vitro experimental study suggests that koumine suppresses the H2O2-induced activation of inflammatory pathways, oxidative injury, ER stress, apoptosis and autophagy, which provide a rationale for therapeutically use in major intestinal diseases.

13.
Biomater Res ; 26(1): 88, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572920

RESUMO

BACKGROUND: Transepithelial medical devices are increasing utilized in clinical practices. However, the damage of continuous natural epithelial barrier has become a major risk factor for the failure of epithelium-penetrating implants. How to increase the "epithelial barrier structures" (focal adhesions, hemidesmosomes, etc.) becomes one key research aim in overcoming this difficulty. Directly targeting the in situ "epithelial barrier structures" related proteins (such as fibronectin) absorption and functionalization can be a promising way to enhance interface-epithelial integration. METHODS: Herein, we fabricated three plasma polymerized bio-interfaces possessing controllable surface chemistry. Their capacity to adsorb and functionalize fibronectin (FN) from serum protein was compared by Liquid Chromatography-Tandem Mass Spectrometry. The underlying mechanisms were revealed by molecular dynamics simulation. The response of gingival epithelial cells regarding the formation of epithelial barrier structures was tested. RESULTS: Plasma polymerized surfaces successfully directed distinguished protein adsorption profiles from serum protein pool, in which plasma polymerized allylamine (ppAA) surface favored adsorbing adhesion related proteins and could promote FN absorption and functionalization via electrostatic interactions and hydrogen bonds, thus subsequently activating the ITG ß1-FAK-mTOR signaling and promoting gingival epithelial cells adhesion. CONCLUSION: This study offers an effective perspective to overcome the current dilemma of the inferior interface-epithelial integration by in situ protein absorption and functionalization, which may advance the development of functional transepithelial biointerfaces. Tuning the surface chemistry by plasma polymerization can control the adsorption of fibronectin and functionalize it by exposing functional protein domains. The functionalized fibronectin can bind to human gingival epithelial cell membrane integrins to activate epithelial barrier structure related signaling pathway, which eventually enhances the formation of epithelial barrier structure.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1893-1901, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36476922

RESUMO

OBJECTIVE: To evaluate the performance of a microfluidic platelet function test platform (MPFTP) previously established by our research group. METHODS: The effects of flow shear rate and storage time on platelet function test were analyzed taking the MPFTP as the object. The intra-assay variability of the MPFTP was evaluated. The function of platelet in peripheral venous blood from 24 healthy volunteers was assessed using the MPFTP and light transmission turbidity, either in the presence of 20 µmol/L acetylsalicylic acid (AS, an inhibitor of cyclooxygenase 1) or 50 µmol/L 5-phospho-2-methylthioadenosine (2-MeSAMP, a P2Y12 receptor inhibitor). The diagnostic performance of both methods in assaying platelet function inhibition by AS and 2-MeSAMP was analyzed by using receiver operating characteristic (ROC) curve. RESULTS: Under the flow shear rate of 1 500 s-1, our MPFTP could dynamically monitor platelet adhesion and aggregation, as well as quantify platelet function. Platelet aggregation increased with the increase of flow shear rate, while sample storage at room temperature for up to 5 h did not affect results of platelet function test. The intra-assay variability coefficient of variation of the MPFTP was <15%. The area under the curve of ROC showed that this platform had good diagnostic performance in the identification of platelet function inhibition by AS and 2-MeSAMP. CONCLUSION: This MPFTP shows good analytical performance for the assay of platelet function and can be developed into a new clinical platelet function test device in the future.


Assuntos
Testes de Função Plaquetária , Humanos
15.
Nutrients ; 14(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36558436

RESUMO

(1) Background: Studies have reported that COVID-19 may increase the risk of malnutrition among patients. However, the prevalence of such risk in hospitalized COVID-19 patients is uncertain due to the inconsistent use of assessment methods. (2) Methods: PubMed, Web of Science, and EMBASE were searched to identify studies on the nutritional status of hospitalized COVID-19 patients. A pooled prevalence of malnutrition risk evaluated by Nutrition Risk Score (NRS-2002) was obtained using a random effects model. Differences by study-level characteristics were examined by hospitalization setting, time of assessment, age, and country. Risk of bias was assessed using the Newcastle-Ottawa Scale. (3) Results: 53 studies from 17 countries were identified and summarized. A total of 17 studies using NRS-2002, including 3614 COVID-19 patients were included in the primary meta-analysis. The pooled prevalence of risk of malnutrition was significantly higher among ICU patients (92.2%, 95% CI: 85.9% to 96.8%) than among general ward patients (70.7%, 95% CI: 56.4% to 83.2%) (p = 0.002). No significant differences were found between age groups (≥65 vs. <65 years, p = 0.306) and countries (p = 0.893). (4) Conclusions: High risk of malnutrition is common and concerning in hospitalized patients with COVID-19, suggesting that malnutrition screening and nutritional support during hospitalization are needed.


Assuntos
COVID-19 , Desnutrição , Humanos , Avaliação Nutricional , COVID-19/epidemiologia , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Estado Nutricional , Apoio Nutricional/métodos , Hospitalização , Prevalência
16.
Chin Med ; 17(1): 128, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36352450

RESUMO

BACKGROUND: The rising global incidence of type 2 diabetes mellitus (T2DM) highlights a need for new therapies. The Zishen Pill (ZSP) is a traditional Chinese herbal decoction that has previously shown hypoglycemic effects in C57BL/KsJ-db/db mice, although the therapeutic mechanism remains unknown. This study aims to explore the underlying mechanisms of ZSP's hypoglycemic effects using db/db mice. METHODS: Db/db mice were divided into two groups: model group and ZSP group, while wt/wt mice were used as a normal control. ZSP was given to mice by gavage for 40 days. During treatment, blood glucose level and body weight were monitored continuously. Oral glucose tolerance test (OGTT) was performed at day 35. Blood and tissue samples were collected at the end of treatment for further analyses. Mice liver samples were analyzed with mRNA transcriptomics using functional annotation and pathway enrichment to identify potential mechanisms that were then explored with qPCR and Western Blot techniques. RESULTS: ZSP treatment significantly reduced weight gain and glycemic severity in db/db mice. ZSP also partially restored the glucose homeostasis in db/db mice and increased the hepatic glycogen content. Transcriptomic analyses showed ZSP increased expression of genes involved in glycolysis including Hk2, Hk3, Gck and Pfkb1, and decreased expression of G6pase. Additionally, the gene and protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and Csf1 and Flt3 mRNA expression were significantly upregulated in ZSP group. CONCLUSION: ZSP treatment reduced the severity of diabetic symptoms in db/db mice. ZSP increased expression of genes associated with glycogen synthesis and glycolysis, and decreased gluconeogenesis via the enhancement of the PI3K/AKT signaling in the liver.

17.
J Transl Med ; 20(1): 498, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324119

RESUMO

BACKGROUND: This paper aimed to examine the effects of probiotics on eight factors in the prediabetic population by meta-analysis, namely, fasting blood glucose (FBG), glycated haemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the mechanisms of action are summarized from the existing studies. METHODS: Seven databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Med) were searched until March 2022. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model to observe the efficacy of probiotic supplementation on the included indicators. RESULTS: Seven publications with a total of 460 patients were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HbA1c (WMD, -0.07; 95% CI -0.11, -0.03; P = 0.001), QUICKI (WMD, 0.01; 95% CI 0.00, 0.02; P = 0.04), TC (SMD, -0.28; 95% CI -0.53, -0.22; P = 0.03), TG (SMD, -0.26; 95% CI -0.52, -0.01; P = 0.04), and LDL-C (WMD, -8.94; 95% CI -14.91, -2.97; P = 0.003) compared to levels in the placebo group. The effects on FBG (WMD, -0.53; 95% CI -2.31, 1.25; P = 0.56), HOMA-IR (WMD, -0.21; 95% CI -0.45, 0.04; P = 0.10), and HDL-C (WMD, 2.05; 95% CI -0.28, 4.38; P = 0.08) were not different from those of the placebo group. CONCLUSION: The present study clearly indicated that probiotics may fulfil an important role in the regulation of HbA1c, QUICKI, TC, TG and LDL-C in patients with prediabetes. In addition, based on existing studies, we concluded that probiotics may regulate blood glucose homeostasis in a variety of ways. TRIAL REGISTRATION: This meta-analysis has been registered at PROSPERO with ID: CRD42022321995.


Assuntos
Estado Pré-Diabético , Probióticos , Humanos , Glicemia , HDL-Colesterol , LDL-Colesterol , Estado Pré-Diabético/tratamento farmacológico , Probióticos/farmacologia , Probióticos/uso terapêutico , Triglicerídeos
18.
N Engl J Med ; 387(20): 1855-1864, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36342163

RESUMO

BACKGROUND: Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver. METHODS: We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter. Patients were randomly assigned to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously. The primary end point was the percent change in the lipoprotein(a) concentration from baseline to week 36 (reported as the placebo-adjusted mean percent change). Safety was also assessed. RESULTS: Among the 281 enrolled patients, the median concentration of lipoprotein(a) at baseline was 260.3 nmol per liter, and the median concentration of low-density lipoprotein cholesterol was 67.5 mg per deciliter. At baseline, 88% of the patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor. At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the placebo group, whereas olpasiran therapy had significantly and substantially reduced the lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P<0.001 for all comparisons with baseline). The overall incidence of adverse events was similar across the trial groups. The most common olpasiran-related adverse events were injection-site reactions, primarily pain. CONCLUSIONS: Olpasiran therapy significantly reduced lipoprotein(a) concentrations in patients with established atherosclerotic cardiovascular disease. Longer and larger trials will be necessary to determine the effect of olpasiran therapy on cardiovascular disease. (Funded by Amgen; OCEAN[a]-DOSE ClinicalTrials.gov number, NCT04270760.).


Assuntos
Anticolesterolemiantes , Aterosclerose , Hipercolesterolemia , Lipoproteína(a) , RNA Interferente Pequeno , Humanos , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Método Duplo-Cego , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lipoproteína(a)/análise , Lipoproteína(a)/antagonistas & inibidores , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/efeitos adversos , RNA Interferente Pequeno/farmacologia , RNA Interferente Pequeno/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Inibidores de PCSK9/uso terapêutico , Ezetimiba/uso terapêutico
19.
Nucleic Acids Res ; 50(20): 11727-11737, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318259

RESUMO

CRISPR (clustered regularly interspaced short palindromic repeats) technology has achieved great breakthroughs in terms of convenience and sensitivity; it is becoming the most promising molecular tool. However, only two CRISPR activation modes (single and double stranded) are available, and they have specificity and universality bottlenecks that limit the application of CRISPR technology in high-precision molecular recognition. Herein, we proposed a novel CRISPR/Cas12a unrestricted activation mode to greatly improve its performance. The new mode totally eliminates the need for a protospacer adjacent motif and accurately activates Cas12a through toehold-mediated strand displacement and branch migration, which is highly universal and ultra-specific. With this mode, we discriminated all mismatch types and detected the EGFR T790M and L858R mutations in very low abundance. Taken together, our activation mode is deeply incorporated with DNA nanotechnology and extensively broadens the application boundaries of CRISPR technology in biomedical and molecular reaction networks.


Assuntos
Sistemas CRISPR-Cas , Neoplasias Pulmonares , Humanos , Receptores ErbB/genética , Mutação , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases
20.
Proc Natl Acad Sci U S A ; 119(49): e2214278119, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442099

RESUMO

The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models. The STING ADC further synergized with an anti-PD-L1 antibody to achieve superior antitumor efficacy. The STING ADC promoted multiple aspects of innate and adaptive antitumor immune responses, including activation of dendritic cells, T cells, natural killer cells and natural killer T cells, as well as promotion of M2 to M1 polarization of tumor-associated macrophages. These results provided the proof of concept for clinical development of the STING ADCs.


Assuntos
Imunoconjugados , Neoplasias , Animais , Camundongos , Imunoterapia , Fatores Imunológicos , Neoplasias/terapia , Macrófagos Associados a Tumor
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