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1.
Foods ; 10(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808327

RESUMO

In this paper, the protein changes during aging and the differences in the myofibrillar protein fraction at 1 h postmortem of pale, soft and exudative (PSE), and red, firm and non-exudative (RFN) pork longissimus thoracis (LT) were comparatively studied. The PSE and RFN groups were screened out based on the differences in their pH and lightness (L*) at 1 h, and their purge loss at 24 h postmortem. Based on the measured MFI, desmin degradation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, PSE meat presented more significant changes in the myofibrillar protein fraction compared to RFN meat during postmortem aging. Through liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) analysis, a total of 172 differential proteins were identified, among which 151 were up-regulated and 21 were down-regulated in the PSE group. The differential proteins were muscle contraction, motor proteins, microfilaments, microtubules, glycolysis, glycogen metabolism, energy metabolism, molecular chaperones, transport, and enzyme proteins. The AMP activated protein kinase (AMPK) signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and PI3K-Akt signaling pathway were identified as the significant pathways related to meat quality. This study suggested that the different changes of the myofibrillar protein fraction were involved in the biochemical metabolism in postmortem muscle, which may contribute to the molecular understanding of PSE meat formation.

2.
Acta Pharmacol Sin ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33633363

RESUMO

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625-2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.

3.
BMC Cancer ; 21(1): 180, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607955

RESUMO

BACKGROUND: Aberrant activation of the Wnt/ß-catenin signaling pathway is one of the most frequent abnormalities in human cancer, including colorectal cancer (CRC). Previous studies revealed pivotal functions of WNT family members in colorectal cancer, as well as their prognostic values. Nevertheless, the prognostic role and mechanisms underlying WNT7b in colorectal cancer development remains unclear. METHODS: In this study, WNT7b expression was measured by immunohistochemical staining of 100 cases of surgically resected human colorectal cancerous tissues as well as matched adjacent normal tissues constructed as tissue microarrays. In vitro studies, we attempted to substantiate the WNT7b expressional pattern previously found in immunohistochemistry staining. We used the colorectal cancer cell-line HCT116 and normal colorectal cell-line FHC for immunofluorescence staining and nuclear/cytoplasmic separated western blotting. We measured epithelial-mesenchymal transition (EMT) markers and migration capacity of HCT116 in the context of WNT7b knocked-down using short interfering RNA. Finally, clinical and prognostic values of WNT7b activation levels were examined. RESULTS: WNT7b was expressed in the nucleus in adjacent normal tissues. In CRC tissues, nuclear expression of WNT7b was similar; however, membrane and cytoplasmic expression was strikingly enhanced. Consistently, in vitro analysis confirmed the same expression pattern of WNT7b. Compared with FHC cells, HCT116 cells displayed higher levels of WNT7b membrane and cytoplasmic enrichment, as well as higher migration capacity with a sensitized EMT process. Either partial knockdown of WNT7b or blockade of the Wnt/ß-catenin signaling pathway reversed EMT process and inhibited the migration of HCT116 cells. Finally, elevated secretion levels of WNT7b were significantly associated with lymphatic and remote metastasis and predicted worse prognosis in the CRC cohort. CONCLUSION: In summary, we demonstrated that the activation of WNT7b autocrine probably contributes to CRC metastasis by triggering EMT process through the Wnt/ß-catenin signaling pathway. High levels of WNT7b autocrine secretion predicts poor outcome in patients with CRC. This molecule is a promising candidate for clinical CRC treatments.

4.
Talanta ; 225: 122057, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33592778

RESUMO

Microfluidics has become a reliable platform for circulating tumor cells (CTCs) detection because of its high integration, small size, low consumption of reagents and rapid response. Here, we developed a multifunctional microfluidic device consists of three parts, including CTCs capture area, single-layer membrane valves area, and microcavity nucleic acid detection and analysis region based on digital polymerase chain reaction (dPCR), allowing CTCs capture, lysis, and genetic characterization to be performed on a single chip. The CTCs capture chip is coupled to the nucleic acid detection chip via a control valve. CTCs were firstly trapped in the CTC capture area, and then lysed using proteinase K to release nucleic acids. Subsequently CTCs lysate was transferred into nucleic acid detection area consisting of 12800 micro-cavity chambers for nucleic acids detection. To evaluate the performance of this chip, this study detected EGFR-L858R mutation in lung cancer cell lines H1975 and A549 cells, as well as leukocytes from normal donors. The results showed that positive signals were only observed in H1975 cells, and the detected value had a high linear relationship with the expected value (R2 = 0.9897). In conclusion, this multi-functional microfluidic chip that integrates CTCs capture, lysis and nucleic acid detection can successfully detect gene mutations in CTCs, providing reference for tumor-targeted drugs and precise diagnosis and treatment.

5.
Nano Lett ; 21(4): 1722-1728, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33528254

RESUMO

Gram-negative bacteria, which possess an impermeable outer membrane, are responsible for many untreatable infections. The lack of development of new relevant antibiotics for over 50 years has increased threats. Peptides are regarded as the most promising alternatives to antibiotics. However, since the activities of existing peptides are not yet comparable to those of current antibiotics, there is an urgent need to improve their antibacterial efficiencies. Herein, we conjugate peptides onto one-dimensional rod-like tobacco mosaic virus (TMV). The peptides on the obtained nanoparticles (peptide-TMV) are hundreds of times superior to free peptides in combating Gram-negative bacteria. Through morphology and gene detection of Escherichia coli, it was revealed that following peptide-TMV application, the high osmotic pressure related to membrane damage and the generated reactive oxygen species cause Escherichia coli's death. In addition, peptide-TMV causes a downregulation of biofilm-related genes, inhibiting biofilm formation. This work paves the way to combat Gram-negative bacteria-related infection.

6.
J Biol Chem ; : 100302, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33465376

RESUMO

3,4-diaminopyridine (3,4-DAP) increases transmitter release from neuromuscular junctions (NMJs), and low doses of 3,4-DAP (estimated to reach ∼1 µM in serum) are the FDA-approved treatment for neuromuscular weakness caused by Lambert-Eaton Myasthenic Syndrome (LEMS). Canonically, 3,4-DAP is thought to block voltage-gated potassium (Kv) channels, resulting in prolongation of the presynaptic action potential (AP). However, recent reports have shown that low millimolar concentrations of 3,4-DAP have an off-target agonist effect on the Cav1 subtype ("L-type") of voltage-gated calcium (Cav) channels, and have speculated that this agonist effect might contribute to 3,4-DAP effects on transmitter release at the NMJ. To address 3,4-DAP's mechanism(s) of action, we first used patch-clamp electrophysiology to characterize the concentration-dependent block of 3,4-DAP on the predominant presynaptic Kv channel subtypes found at the mammalian NMJ (Kv3.3 and Kv3.4). We identified a previously unreported high-affinity (1-10 µM) partial antagonist effect of 3,4-DAP in addition to the well-known low affinity (0.1-1mM) antagonist activity. We also showed that 1.5 µM DAP had no effects on Cav1.2 or Cav2.1 current. Next, we used voltage imaging to show that 1.5 or 100 µM 3,4-DAP broadened the AP waveform in a dose dependent manner, independent of Cav1 calcium channels. Finally, we demonstrated that 1.5 or 100 µM 3,4-DAP augmented transmitter release in a dose-dependent manner and this effect was also independent of Cav1 channels. From these results, we conclude that low micromolar concentrations of 3,4-DAP act solely on Kv channels to mediate AP broadening and enhance transmitter release at the NMJ.

7.
Dev Dyn ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33410225

RESUMO

BACKGROUND: Persistent elevated concentrations of urinary protein can destroy proximal tubule epithelial cells (PTECs) by inducing lysosomal abnormalities, thereby aggravating PTEC damage and renal fibrosis. However, the specific mechanisms of these serial biochemical events and methods for treating or preventing PTEC damage upon proteinuria need further investigation. RESULTS: In this study, electron microscopy and dual-labeled immunofluorescence analysis for identifying lysosome type revealed inadequate primary lysosome biogenesis and secondary lysosome accumulation in the PTECs of patients with minimal change nephrotic syndrome or membranous nephropathy who suffered from proteinuria. In vitro studies on HK-2 cells indicated that this abnormality was associated with decreased expression of transcription factor EB (TFEB). In contrast, TFEB overexpressing HK-2 cells under urinary protein overload exhibited significantly reduced accumulation of secondary lysosomes and increased proportion and quantity of primary lysosomes as indicated by dual-labeled immunofluorescence. Further, these cells could upregulate lysosomal degradation functions, as determined using Cathepsin L activity assays and flow cytometry for dye quenched-albumin. CONCLUSIONS: These results indicate that abnormal TFEB expression is a key mechanism of lysosomal dyshomeostasis caused by protein overload in PTECs. TFEB is thus a potential therapeutic target for the treatment of urinary protein-related kidney disease.

8.
Nat Methods ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33288960

RESUMO

Circular RNAs (circRNAs) produced from back-spliced exons are widely expressed, but individual circRNA functions remain poorly understood owing to the lack of adequate methods for distinguishing circRNAs from cognate messenger RNAs with overlapping exons. Here, we report that CRISPR-RfxCas13d can effectively discriminate circRNAs from mRNAs by using guide RNAs targeting sequences spanning back-splicing junction (BSJ) sites featured in RNA circles. Using a lentiviral library that targets sequences across BSJ sites of highly expressed human circRNAs, we show that a group of circRNAs are important for cell growth mostly in a cell-type-specific manner and that a common oncogenic circRNA, circFAM120A, promotes cell proliferation by preventing the mRNA for family with sequence similarity 120A (FAM120A) from binding the translation inhibitor IGF2BP2. Further application of RfxCas13d-BSJ-gRNA screening has uncovered circMan1a2, which has regulatory potential in mouse embryo preimplantation development. Together, these results establish CRISPR-RfxCas13d as a useful tool for the discovery and functional study of circRNAs at both individual and large-scale levels.

9.
J Nat Prod ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296199

RESUMO

Epilepsy is a chronic neurological disorder, characterized by recurrent, spontaneous, and transient seizures, and affects more than 70 million people worldwide. Although two dozen antiepileptic drugs (AEDs) are approved and available in the market, seizures remain poorly controlled in one-third of epileptic patients who are suffering from drug resistance or various adverse effects. Recently, the xanthone skeleton has been regarded as an attractive scaffold for the discovery and development of emerging anticonvulsants. We had isolated several dihydroxanthone derivatives previously, including oliganthin H, oliganthin I, and oliganthin N, whose structures were similar and delicately elucidated by spectrum analysis or X-ray crystallographic data, from extracts of leaves of Garcinia oligantha. These xanthone analogues were evaluated for anticonvulsant activity, and a novel xanthone, oliganthin H, has been identified as a sound and effective natural inhibitor of convulsions in zebrafish in vivo. A preliminary structure-activity relationship analysis on the relationship between structures of the xanthone analogues and their activities was also conducted. Oliganthin H significantly suppressed convulsant behavior and reduced to about 25% and 50% of PTZ-induced activity, in 12.5 and 25 µM treatment groups (P < 0.01 and 0.001), respectively. Meanwhile, it reduced seizure activity, velocity, seizure duration, and number of bursts in zebrafish larvae (P < 0.05). Pretreatment of oliganthin H significantly restored aberrant induction of gene expressions including npas4a, c-fos, pyya, and bdnf, as well as gabra1, gad1, glsa, and glula, upon PTZ treatment. In addition, in silico analysis revealed the stability of the oliganthin H-GABAA receptor complex and their detailed binding pattern. Therefore, direct interactions with the GABAA receptor and involvement of downstream GABA-glutamate pathways were possible mechanisms of the anticonvulsant action of oliganthin H. Our findings present the anticonvulsant activity of oliganthin H, provide a novel scaffold for further modifications, and highlight the xanthone skeleton as an attractive and reliable resource for the development of emerging AEDs.

10.
Sensors (Basel) ; 20(23)2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33266020

RESUMO

In this paper, a new approach of multi-sensor fusion algorithm based on the improved unscented particle filter (IUPF) and a new multi-sensor distributed fusion model are proposed. Additionally, we employ a novel multi-target tracking algorithm that combines the joint probabilistic data association (JPDA) algorithm and the IUPF algorithm. To improve the real-time performance of the UPF algorithm for the maneuvering target, minimum skew simplex unscented transform combined with a scaled unscented transform is utilized, which significantly reduces the calculation of UPF sample selection. Moreover, a self-adaptive gain modification coefficient is defined to solve the low accuracy problem caused by the sigma point reduction, and the problem of particle degradation is solved by modifying the weights calculation method. In addition, a new multi-sensor fusion model is proposed, which better integrates radar and infrared sensors. Simulation results show that IUPF effectively improves real-time performance while ensuring the tracking accuracy compared with other algorithms. Besides, compared with the traditional distributed fusion architecture, the proposed new architecture makes better use of the advantages of radar and an infrared sensor and improves the tracking accuracy.

11.
Food Res Int ; 137: 109410, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233097

RESUMO

Gut microbiome has been proven to be involved in the development of type 2 diabetes (T2D). Additionally, increasing evidence showed that the composition of gut microbiome is highly associated with the outcome of T2D therapy. Previously we demonstrated that feruloylated oligosaccharides (FOs) and ferulic acid (FA) alleviated diabetic syndrome in rats, but the detailed mechanism has not been explored yet. In this study we strived to characterize how FOs and FA altered the gut microbiome and related metabolome in diabetic rats by using high-throughput sequencing of 16S rRNA and gas chromatography (GC). Our results showed that FOs reduced the abundance of Lactobacillus, Ruminococcus, Oscillibacter, and Desulfovibrio, but increased the abundance of Akkermansia, Phascolarctobacterium and Turicibacter. The structure of gut microbiome in FOs treated rats was similar with healthy rats rather than diabetic rats. Likewise, FA decreased the portion of Lactobacillus, Ruminococcus, but promoted the growth of Bacteroides, Blautia, Faecalibacterium, Parabacteroides and Phascolarctobacterium. Additionally, the short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), the main bacterial lipid metabolites in gut mediating host glucose metabolism, was dramatically elevated along with FOs and FA treatment. Our findings indicated that FOs and FA attenuated diabetic syndrome in rats most likely by modulating the composition and metabolism of gut microbiome. The study gives new insight into the mechanism underlying the anti-diabetes effect of functional foods as well as facilitates the development of dietary supplements for diabetic patients.

12.
J Comp Eff Res ; 9(16): 1105-1115, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33112181

RESUMO

Aim: This real-world data study investigated the economic burden and associated factors of readmissions for cerebrospinal fluid leakage (CSFL) post-cranial, transsphenoidal, or spinal index surgeries. Methods: Costs of CSFL readmissions and index hospitalizations during 2014-2018 were collected. Readmission cost was measured as absolute cost and as percentage of index hospitalization cost. Factors associated with readmission cost were explored using generalized linear models. Results: Readmission cost averaged US$2407-6106, 35-94% of index hospitalization cost. Pharmacy costs were the leading contributor. Generalized linear models showed transsphenoidal index surgery and surgical treatment for CSFL were associated with higher readmission costs. Conclusion: CSFL readmissions are a significant economic burden in China. Factors associated with higher readmission cost should be monitored.

13.
Front Neurosci ; 14: 867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973431

RESUMO

Background: Observation of a goal-directed motor action can excite the respective mirror neurons, and this is the theoretical basis for action observation (AO) as a novel tool for functional recovery during stroke rehabilitation. To explore the therapeutic potential of AO for dysphagia, we conducted a task-based functional magnetic resonance imaging (fMRI) study to identify the brain areas activated during observation and execution of swallowing in healthy participants. Methods: Twenty-nine healthy volunteers viewed the following stimuli during fMRI scanning: an action-video of swallowing (condition 1, defined as AO), a neutral image with a Chinese word for "watching" (condition 2), and a neutral image with a Chinese word for "swallowing" (condition 3). Action execution (AE) was defined as condition 3 minus condition 2. One-sample t-tests were performed to define the brain regions activated during AO and AE. Results: Many brain regions were activated during AO, including the middle temporal gyrus, inferior frontal gyrus, pre- and postcentral gyrus, supplementary motor area, hippocampus, brainstem, and pons. AE resulted in activation of motor areas as well as other brain areas, including the inferior parietal lobule, vermis, middle frontal gyrus, and middle temporal gyrus. Two brain areas, BA6 and BA21, were activated with both AO and AE. Conclusion: The left supplementary motor area (BA6) and left middle temporal gyrus (BA21), which contains mirror neurons, were activated in both AO and AE of swallowing. In this study, AO activated mirror neurons and the swallowing network in healthy participants, supporting its potential value in the treatment of dysphagia.

14.
Biomed Opt Express ; 11(8): 4560-4570, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32923064

RESUMO

Characterizations of circulatory and metabolic function in skeletal muscle are of great importance in clinical settings. Here in this study, we investigate the utility of photoacoustic tomography (PAT) to monitor the hemodynamic changes in forearm skeletal muscle during cuff occlusion. We show high quality photoacoustic (PA) images of human forearm in comparison with ultrasound images. Besides, we track the hemodynamic changes in the forearm during cuff occlusion cross-validated with near-infrared spectroscopy. Our study suggests that PAT, as a new tool, could be applied to common diseases affecting skeletal muscle in the future.

15.
Front Microbiol ; 11: 1607, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793143

RESUMO

It is well documented that Epichloë endophytes can enhance the resistance of grasses to herbivory. However, reports on resistance to pathogenic fungi are limited, and their conclusions are variable. In this study, we chose pathogenic fungi with different trophic types, namely, the biotrophic pathogen Erysiphales species and the necrotrophic pathogen Curvularia lunata, to test the effects of Epichloë on the pathogen resistance of Achnatherum sibiricum. The results showed that, compared to Erysiphales species, C. lunata caused a higher degree of damage and lower photochemical efficiency (Fv/Fm) in endophyte-free (E-) leaves. Endophytes significantly alleviated the damage caused by these two pathogens. The leaf damaged area and Fv/Fm of endophyte-infected (E+) leaves were similar between the two pathogen treatments, indicating that the beneficial effects of endophytes were more significant when hosts were exposed to C. lunata than when they were exposed to Erysiphales species. We found that A. sibiricum initiated jasmonic acid (JA)-related pathways to resist C. lunata but salicylic acid (SA)-related pathways to resist Erysiphales species. Endophytic fungi had no effect on the content of SA but increased the content of JA and total phenolic compounds, which suggest that endophyte infection might enhance the resistance of A. sibiricum to these two different trophic types of pathogens through similar pathways.

16.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32808659

RESUMO

Endotoxemia-induced acute kidney injury (AKI) is a common clinical condition that lacks effective treatments. Elabela (ELA) is a recently discovered kidney peptide hormone, encoded by the gene apela, and has been reported to improve cardio-renal outcomes in sepsis. However, ELA is a small peptide and is largely unsuitable for clinical use because of its short in vivo half-life. In the present study, we evaluated the potential renoprotective effects of a long-acting constant fragment (Fc)-ELA fusion protein in liposaccharide (LPS)-induced AKI in mice. LPS administration in mice for 5 days greatly lowered the gene expression of apela and impaired kidney function, as evidenced by elevated serum creatinine and the ratio of urine protein to creatinine. In addition, renal inflammation and macrophage infiltration were apparent in LPS-challenged mice. Treatment with the Fc-ELA fusion protein partially restored apela expression and attenuated the kidney inflammation. Moreover, LPS treatment induced reactive oxygen species (ROS) production and apoptosis in kidney HK-2 cells as well as in the mouse kidney, which were mitigated by ELA or Fc-ELA treatment. Finally, we found that ELA promoted the survival of HK-2 cells treated with LPS, and this action was abolished by LY204002, a PI3K/Akt inhibitor. Collectively, we have demonstrated that the Fc-ELA fusion protein has significant renoprotective activities against LPS-induced AKI in mice.

17.
Sensors (Basel) ; 20(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752059

RESUMO

As one of the important facilities for marine exploration, as well as environment monitoring, access control, and security, underwater wireless sensor networks (UWSNs) are widely used in related military and civil fields, since the sensor node localization is the basis of UWSNs' application in various related fields. Therefore, the research of localization algorithms based on UWSNs has gradually become one of the research hotspots today. However, unlike terrestrial wireless sensor networks (WSNs), many terrestrial monitoring and localization technologies cannot be directly applied to the underwater environment. Moreover, due to the complexity and particularity of the underwater environment, the localization of underwater sensor nodes still faces challenges, such as the localization ratio of sensor nodes, time synchronization, localization accuracy, and the mobility of nodes. In this paper, we propose a mobility-assisted localization scheme with time synchronization-free feature (MALS-TSF) for three-dimensional (3D) large-scale UWSNs. In addition, the underwater drift of the sensor node is considered in this scheme. The localization scheme can be divided into two phases. In Phase I, anchor nodes are distributed in the monitoring area, reducing the monitoring cost. Then, we address a time-synchronization-free localization scheme, to obtain the coordinates of the unknown sensor nodes. In Phase II, we use the method of two-way TOA to locate the remaining ordinary sensor nodes. The simulation results show that MALS-TSF can achieve a relatively high localization ratio without time synchronization.

18.
Acta Pharmacol Sin ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32759963

RESUMO

Mitophagy is a selective form of autophagy involving the removal of damaged mitochondria via the autophagy-lysosome pathway. PINK1-Parkin-mediated mitophagy is one of the most important mechanisms in cardiovascular disease, cerebral ischemia-reperfusion (I/R) injury, and neurodegenerative diseases. In this study we conducted an image-based screening in YFP-Parkin HeLa cells to discover new mitophagy regulators from natural xanthone compounds. We found that garciesculenxanthone B (GeB), a new xanthone compound from Garcinia esculenta, induced the formation of YFP-Parkin puncta, a well known mitophagy marker. Furthermore, treatment with GeB dose-dependently promoted the degradation of mitochondrial proteins Tom20, Tim23, and MFN1 in YFP-Parkin HeLa cells and SH-SY5Y cells. We revealed that GeB stabilized PINK1 and triggered Parkin translocation to the impaired mitochondria to induce mitophagy, and these effects were abolished by knockdown of PINK1. Finally, in vivo experiments demonstrated that GeB partially rescued ischemia-reperfusion-induced brain injury in mice. Taken together, our findings demonstrate that the natural compound GeB can promote the PINK1-Parkin-mediated mitophagy pathway, which may be implicated in protection against I/R brain injury.

19.
Pathol Res Pract ; 216(10): 153029, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853940

RESUMO

BACKGROUND: Many recent studies have investigated the prognostic, diagnostic, and progressive features of soluble intercellular cell adhesion molecule-1 (sICAM-1) in lung cancer patients, but the results remained inconsistent. This study aimed to explore the value of serum sICAM-1 in patients with lung cancer. METHODS: A comprehensive systematic literature search in the Wanfang databases, china national knowledge infrastructure, Pubmed, and Embase was carried out update to June 15, 2019. The standard mean difference (SMD), hazard ratio (HR), and 95% confidence interval (95% CI) were applied to investigate the effect sizes. RESULTS: 23 observational studies were included. According to our results, the serum sICAM-1 concentrations in patients with lung cancer were significantly higher than that in controls (healthy controls: SMD: 4.08, 95% CI: 3.14-5.02, P < 0.001; benign lung diseases controls : SMD: 1.48, 95% CI: 0.23-2.73,P = 0.02). Fortunately, a subgroup analysis was performed by language, treatment status, and lung cancer types, and the statistical results were similar. Serum sICAM-1 levels were markedly higher in stage III/IV than stage I/II (SMD: 1.96, 95% CI: 1.08-2.84, P < 0.001), Additionally, lung cancer patients with lymph node metastasis had a higher concentrations of serum sICAM-1(SMD: 1.83, 95% CI: 0.95-2.72, P < 0.001), as well as with distant metastasis (SMD: 0.86, 95% CI: 0.47-1.25, P < 0.001). Additionally, patients with higher sICAM-1 levels were related to a significantly poorer prognosis (progression free survival: HR: 1.16, 95% CI: 1.07-1.26, P < 0.001; overall survival: HR: 1.45, 95% CI: 1.17-1.79, P = 0.001). CONCLUSIONS: Our study suggested that serum sICAM-1 levels may act as a potential marker for diagnosing lung cancer and predicting its staging, and were negatively correlated with prognosis of lung cancer.

20.
Bioact Mater ; 5(4): 808-818, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32637745

RESUMO

3-dimensional (3D) bioprinting technology provides promising strategy in the fabrication of artificial tissues and organs. As the fundamental element in bioprinting process, preparation of bioink with ideal mechanical properties without sacrifice of biocompatibility is a great challenge. In this study, a supramolecular hydrogel-based bioink is prepared by polyethylene glycol (PEG) grafted chitosan, α-cyclodextrin (α-CD) and gelatin. It has a primary crosslinking structure through the aggregation of the pseudo-polyrotaxane-like side chains, which are formed from the host-guest interactions between α-CD and PEG side chain. Apparent viscosity measurement shows the shear-shinning property of this bioink, which might be due to the reversibility of the physical crosslinking. Moreover, with ß-glycerophosphate at different concentrations as the secondary crosslinking agent, the printed constructs demonstrate different Young's modulus (p < 0.001). They could also maintain the Young's modulus in cell culture condition for at least 21 days (p < 0.05). By co-culturing each component with fibroblasts, CCK-8 assay demonstrate cellular viability is higher than 80%. After bioprinting and culturing, immunofluorescence staining with quantification indicate the expression of Ki-67, Paxillin, and N-cadherin is higher in day 14 than those in day 3 (p < 0.05). Oil red O and Nissl body specific staining reflect strength tunable bioink may have impact on the cell fate of mesenchymal stem cells (p < 0.05). This work might provide new idea for advanced bioink in the application of re-establishing complicated tissues and organs.

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