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1.
Neural Regen Res ; 19(9): 2036-2040, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38227533

ABSTRACT

JOURNAL/nrgr/04.03/01300535-202409000-00036/figure1/v/2024-01-16T170235Z/r/image-tiff Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses. Moreover, anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms. Lycium barbarum polysaccharide (LBP), derived from Goji berries, exhibits notable antioxidative and anti-inflammatory properties. In our recent double-blinded randomized placebo-controlled trial, we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression. It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines. In the double-blinded randomized controlled trial, we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group. In the LBP group, adolescents were given 300 mg/d LBP. A 6-week follow up was completed by 24 adolescents, comprising 14 adolescents from the LBP group (15.36 ± 2.06 years, 3 men and 11 women) and 10 adolescents from the placebo group (14.9 ± 1.6 years, 2 men and 8 women). Our results showed that after 6 weeks of treatment, the interleukin-17A level in the LBP group was lower than that in the placebo group. Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors, which were associated with the improvement in depressive symptoms. These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level, thereby exerting an antidepressant effect.

2.
Aging (Albany NY) ; 15(15): 7727-7740, 2023 08 04.
Article in English | MEDLINE | ID: mdl-37543429

ABSTRACT

BACKGROUND: Telomeres are considered to be a physiological marker of aging. Elucidating relationship between telomere length and sepsis is an essential step towards understanding the biological processes involved in sepsis and its salvation. Mendelian randomization studies based on SNPs have given us new insights into genetic susceptibility to disease. OBJECTIVES: To explore the causal pathway from telomere length to occurrence and 28-day mortality of sepsis. METHODS: Leveraging genetic information resource of UK Biobank, we captured three groups of large-scale GWAS data: leukocyte telomere length (LTL), sepsis and all-cause death of 28-day. Study design consisted of three parts: forward analysis, reverse analysis and one-way analysis. Genetic instrumental variables were selected for different analyses under the premise that three MR core assumptions were satisfied. Causality was determined by means of IVW. RESULTS: In forward analysis, we did not observe a significant causal pathway from sepsis to LTL under IVW model: ß (SE) was -0.0051 (0.0075) with a p-value of 0.499. In reverse analysis, based on the IVW model, the OR (95% CI) was 0.89 (0.80-0.99) and the p-values was 0.043; based on the results of leave out method and single SNP analysis, we obtained seven key SNPs. There were results of IVW model in the one-way analysis: ß (SE) was -0.0287(0.1261). CONCLUSIONS: Short LTL increases susceptibility to sepsis, but sepsis does not shorten telomere length. LTL does not affect sepsis 28-day all-cause mortality and does not serve as a causal intermediate in gene regulation during the progression of sepsis to 28-day death.


Subject(s)
Mendelian Randomization Analysis , Sepsis , Humans , Mendelian Randomization Analysis/methods , Genome-Wide Association Study , Causality , Polymorphism, Single Nucleotide , Telomere/genetics , Sepsis/genetics
3.
J Neuroinflammation ; 20(1): 161, 2023 Jul 08.
Article in English | MEDLINE | ID: mdl-37422673

ABSTRACT

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.


Subject(s)
Epilepsy, Temporal Lobe , Serpins , Animals , Mice , Astrocytes/metabolism , Epilepsy, Temporal Lobe/chemically induced , Epilepsy, Temporal Lobe/metabolism , Hippocampus/metabolism , Kainic Acid/toxicity , Neuroinflammatory Diseases , NF-kappa B/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism , Seizures/chemically induced , Seizures/metabolism , Signal Transduction , Serpins/metabolism
4.
Front Bioeng Biotechnol ; 11: 1134665, 2023.
Article in English | MEDLINE | ID: mdl-37284241

ABSTRACT

Commercial gadolinium (Gd)-based contrast agents (GBCAs) play important role in clinical diagnostic of hepatocellular carcinoma, but their diagnostic efficacy remained improved. As small molecules, the imaging contrast and window of GBCAs is limited by low liver targeting and retention. Herein, we developed a liver-targeting gadolinium (Ⅲ) chelated macromolecular MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan, namely, CS-Ga-(Gd-DTPA)n, to improve hepatocyte uptake and liver retention. Compared to Gd-DTPA and non-specific macromolecular agent CS-(Gd-DTPA)n, CS-Ga-(Gd-DTPA)n showed higher hepatocyte uptake, excellent cell and blood biocompatibility in vitro. Furthermore, CS-Ga-(Gd-DTPA)n also exhibited higher relaxivity in vitro, prolonged retention and better T1-weighted signal enhancement in liver. At 10 days post-injection of CS-Ga-(Gd-DTPA)n at a dose of 0.03 mM Gd/Kg, Gd had a little accumulation in liver with no liver function damage. The good performance of CS-Ga-(Gd-DTPA)n gives great confidence in developing liver-specifc MRI contrast agents for clinical translation.

5.
Carbohydr Polym ; 317: 121048, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37364948

ABSTRACT

Imaging and tracking biological targets or processes play an important role in revealing molecular mechanisms and disease states. Bioimaging via optical, nuclear, or magnetic resonance techniques enables high resolution, high sensitivity, and high depth imaging from the whole animal down to single cells via advanced functional nanoprobes. To overcome the limitations of single-modality imaging, multimodality nanoprobes have been engineered with a variety of imaging modalities and functionalities. Polysaccharides are sugar-containing bioactive polymers with superior biocompatibility, biodegradability, and solubility. The combination of polysaccharides with single or multiple contrast agents facilitates the development of novel nanoprobes with enhanced functions for biological imaging. Nanoprobes constructed with clinically applicable polysaccharides and contrast agents hold great potential for clinical translations. This review briefly introduces the basics of different imaging modalities and polysaccharides, then summarizes the recent progress of polysaccharide-based nanoprobes for biological imaging in various diseases, emphasizing bioimaging with optical, nuclear, and magnetic resonance techniques. The current issues and future directions regarding the development and applications of polysaccharide nanoprobes are further discussed.


Subject(s)
Contrast Media , Polymers , Animals , Magnetic Resonance Imaging , Polysaccharides , Fluorescent Dyes
6.
Curr Med Sci ; 43(3): 615-622, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37233969

ABSTRACT

OBJECTIVE: This study aimed to compare the postoperative analgesia and recovery of ultrasound-guided erector spinae plane block combined with serratus anterior plane block (ESPB combined with SAPB) versus thoracic paravertebral block (PVB) after thoracoscopic surgery. METHODS: Ninety-two patients who underwent video-assisted thoracoscopic surgery (VATS) were randomly divided into group S (n=46) and group P (n=46). After anesthesia induction, the same anesthesiologist performed ultrasound-guided ESPB at T5 and T7 levels combined with SAPB at the level of the fifth rib in the midaxillary line in group S and ultrasound-guided PVB at T5 and T7 levels in group P. Patients in both groups were given 40 mL of 0.4% ropivacaine. Eighty-six patients completed the study (group S, n=44; group P, n=42). The morphine consumption, visual analogue scale (VAS) scores at rest and coughing, and frequency of remedial analgesia were recorded at 1, 2, 4, 8, and 24 h postoperatively. Pulmonary function parameters were recorded at 1, 4, and 24 h postoperatively, and the quality of recovery (QoR)-15 score at 24 h postoperatively. The adverse effects, duration of chest tube drainage and length of stay were also recorded. RESULTS: The morphine consumption at postoperative 4 and 8 h and the incidence of ipsilateral shoulder pain (ISP) were significantly lower in group S than in group P. The QoR-15 questionnaire score at postoperative 24 h was significantly lower in group P than in group S (P<0.05). The morphine consumption was lower at 24 h postoperatively in group S than in group P, with no significant difference found yet. The morphine consumption at other observed times, VAS scores, pulmonary function parameters, frequency of remedial analgesia, duration of chest tube drainage, length of stay, and incidence of other adverse events were comparable between group S and group P. CONCLUSION: Ultrasound-guided ESPB combined with SAPB is non-inferior to PVB in terms of morphine consumption at postoperative 24 h and postoperative recovery. But, this approach can significantly reduce morphine consumption in the early postoperative period (0-8 h) after thoracoscopy with lower incidence of ISP. It is a simpler and safer operation.


Subject(s)
Analgesia , Nerve Block , Humans , Pain, Postoperative/drug therapy , Thoracic Surgery, Video-Assisted/adverse effects , Analgesia/adverse effects , Morphine Derivatives
7.
Wideochir Inne Tech Maloinwazyjne ; 18(1): 52-68, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37064553

ABSTRACT

Introduction: Nerve block is widely used for pain management after video-assisted thoracoscopic surgery (VATS). Thoracic paravertebral block (TPVB), erector spinae plane block (ESPB), serratus anterior plane block (SAPB), and intercostal nerve block (ICNB) are alternative treatments. Material and methods: Network meta-analysis based on Bayesian analyses was performed to obtain results for direct comparison, indirect comparison, and network comparison, and to make rankings based on probabilities. Covariates were adjusted to determine the effect of the covariates on results of this study. Results: The study identified 61 randomized controlled trials (RCTs) (4468 patients). There were results of probability ranking for the first ("best" treatment): 24 h morphine consumption, TPVB > ESPB > ICNB > SAPB. Covariate adjustment allowed the four treatments to change somewhat in the likelihood of the best choice. Conclusions: TPVB ranks best in our analysis. ESPB is a viable alternative. SAPB and ICNB seem to play a limited role in postoperative pain management.

8.
Oncogene ; 42(5): 351-363, 2023 01.
Article in English | MEDLINE | ID: mdl-36463370

ABSTRACT

Interferon-gamma (IFNG) has long been regarded as the flag-bearer for the anti-cancer immunosurveillance mechanisms. However, relatively recent studies have suggested a dual role of IFNG, albeit there is no direct experimental evidence for its potential pro-tumor functions. Here we provide in vivo evidence that treatment of mouse melanoma cell lines with Ifng enhances their tumorigenicity and metastasis in lung colonization allograft assays performed in immunocompetent syngeneic host mice, but not in immunocompromised host mice. We also show that this enhancement is dependent on downstream signaling via Stat1 but not Stat3, suggesting an oncogenic function of Stat1 in melanoma. The experimental results suggest that melanoma cell-specific Ifng signaling modulates the tumor microenvironment and its pro-tumorigenic effects are partially dependent on the γδ T cells, as Ifng-enhanced tumorigenesis was inhibited in the TCR-δ knockout mice. Overall, these results show that Ifng signaling may have tumor-promoting effects in melanoma by modulating the immune cell composition of the tumor microenvironment.


Subject(s)
Interferon-gamma , Melanoma , Animals , Mice , Interferon-gamma/metabolism , Melanoma/pathology , Signal Transduction , Cell Line , Carcinogenesis , Mice, Knockout , Cell Line, Tumor , Tumor Microenvironment
9.
Chinese Journal of Hepatology ; (12): 20-31, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-970940

ABSTRACT

Objective: To investigate the potential function and related mechanism of microRNA-223 (miRNA-223) in the podocyte pyroptosis of hepatitis B virus (HBV)-associated glomerulonephritis induced by HBV X protein (HBx). Methods: HBx-overexpressing lentivirus was transfected into human renal podocytes to mimic the pathogenesis of HBV-GN. Real-time fluorescence quantitative PCR and Western blotting experiments were used to detect the mRNA and protein expression of pyroptosis-related proteins [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1], and inflammatory factors (interleukin-1β and interleukin-18), respectively.TUNEL staining and flow cytometry were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression of podocytes biomarkers desmin and nephrin; Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to measure caspase-1 activity. The dual luciferase reporter gene assay was used to verify the downstream target of miRNA-223. Podocytes were divided into the following nine groups: control group (no special treatment), empty plasmid group (transfected with empty plasmid), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+miRNA-223 mimic group (transfected with HBx overexpression lentivirus and miRNA-223 mimic), HBx overexpression+miRNA-223 inhibitor group (transfected with HBx overexpression lentivirus and miRNA-223 inhibitor), HBx overexpression+miRNA-223 mimic+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 mimic+ NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 siRNA), HBx overexpression+miRNA-223 inhibitor+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 inhibitor+NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 siRNA). Results: miRNA-223 was down-regulated in HBx overexpression group compared with the control group (P < 0.05). TUNEL and immunofluorescence staining showed that NLRP3 knockdown attenuated podocyte injury and pyroptosis induced by HBx overexpression (P < 0.05). Dual luciferase reporter gene assay demonstrated that NLRP3 was one of the downstream targets of miRNA-223. Rescue experiments revealed that NLRP3 overexpression weakened the protective effect of miRNA-223 in podocyte injury (P < 0.05). The addition of miRNA-223 mimic and NLRP3 siRNA decreased the expression of NLRP3 inflammasome and cytokines, and reduced the number of pyroptosis cells induced by HBx overexpression (all P < 0.05); The addition of miRNA-223 inhibitor and NLRP3 overexpression plasmid significantly increased the expression of NLRP3 inflammasome and cytokines, caspase-1 activity, and the number of pyroptosis cells (all P < 0.05). Conclusion: HBx may promote podocyte pyroptosis of HBV-GN via downregulating miRNA-223 targeting NLRP3 inflammasome, suggesting that miRNA-223 is expected to be a potential target for the treatment of HBV-GN.


Subject(s)
Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Podocytes/metabolism , Hepatitis B virus/genetics , Caspase 1/metabolism , Cytokines/metabolism , Carrier Proteins/metabolism , MicroRNAs/genetics , Glomerulonephritis/metabolism , RNA, Small Interfering
10.
Nat Commun ; 13(1): 7141, 2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36414676

ABSTRACT

Generation of continental crust in collision zones reflect the interplay between oceanic subduction and continental collision. The Gangdese continental crust in southern Tibet developed during subduction of the Neo-Tethyan oceanic slab in the Mesozoic prior to reworking during the India-Asia collision in the Cenozoic. Here we show that continental arc magmatism started with fractional crystallization to form cumulates and associated medium-K calc-alkaline suites. This was followed by a period commencing at ~70 Ma dominated by remelting of pre-existing lower crust, producing more potassic compositions. The increased importance of remelting coincides with an acceleration in the convergence rate between India and Asia leading to higher basaltic flow into the Asian lithosphere, followed by convergence deceleration due to slab breakoff, enabling high heat flow and melting of the base of the arc. This two-stage process of accumulation and remelting leads to the chemical maturation of juvenile continental crust in collision zones, strengthening crustal stratification.

11.
Cell Chem Biol ; 29(11): 1639-1648.e4, 2022 11 17.
Article in English | MEDLINE | ID: mdl-36356585

ABSTRACT

DNA-binding proteins are promising therapeutic targets but are notoriously difficult to drug. Here, we evaluate a chemoproteomic DNA interaction platform as a complementary strategy for parallelized compound profiling. To enable this approach, we determined the proteomic binding landscape of 92 immobilized DNA sequences. Perturbation-induced activity changes of captured transcription factors in disease-relevant settings demonstrated functional relevance of the enriched subproteome. Chemoproteomic profiling of >300 cysteine-directed compounds against a coverage optimized bead mixture, which specifically captures >150 DNA binders, revealed competition of several DNA-binding proteins, including the transcription factors ELF1 and ELF2. We also discovered the first compound that displaces the DNA-repair complex MSH2-MSH3 from DNA. Compound binding to cysteine 252 on MSH3 was confirmed using chemoproteomic reactive cysteine profiling. Overall, these results suggested that chemoproteomic DNA bead pull-downs enable the specific readout of transcription factor activity and can identify functional "hotspots" on DNA binders toward expanding the druggable proteome.


Subject(s)
Cysteine , DNA-Binding Proteins , Proteomics , Transcription Factors , Proteome
12.
World J Clin Oncol ; 13(9): 729-737, 2022 Sep 24.
Article in English | MEDLINE | ID: mdl-36212599

ABSTRACT

Immunotherapy has shown great promise in treating various types of malignant tumors. However, some patients with gastrointestinal cancer have been known to experience rapid disease progression after treatment, a situation referred to as hyperprogressive disease (HPD). This minireview focuses on the definitions and potential mechanisms of HPD, natural disease progression in gastrointestinal malignancies, and tumor immunological microenvironment.

13.
J Phys Chem B ; 126(43): 8771-8776, 2022 11 03.
Article in English | MEDLINE | ID: mdl-36278933

ABSTRACT

The unique tripeptide structure of green fluorescent protein (GFP), a Ser-Tyr-Gly motif, generates the mature chromophore in situ to define the emission profiles of GFP. Here, we describe the rational design and discovery of a biomimetic fluorescent emitter, MBP, by mimicking the key structure of the Ser-Tyr-Gly motif. Through systematically tailoring the tripeptide, a family of four chromophores were engineered, while only MBP exhibited bright fluorescence in different fluid solvents with highly enhanced quantum yields. Distinct to previous hydrogen-bonding-induced fluorescence quenching of GFP chromophore analogues, the emission of MBP was only slightly decreased in protic solvents. Heteronuclear multiple bond correlation techniques demonstrated the fundamental mechanism for enhanced fluorescence emission owing to the synergy of the formation of the intramolecular hydrogen-bonding-ring structure and the self-restricted effect, which was further illustrated via theoretical calculations. This work puts forward an extraordinary approach toward highly emissive biomimicking fluorophores, which gives new insights into the emission mechanisms and photophysics of GFP-like chromophores.


Subject(s)
Biomimetics , Hydrogen , Green Fluorescent Proteins/chemistry , Hydrogen Bonding , Spectrometry, Fluorescence , Solvents
14.
Biomaterials ; 290: 121824, 2022 11.
Article in English | MEDLINE | ID: mdl-36209580

ABSTRACT

Imaging and tracking macrophage behaviors in vivo are essential to reveal its biological function and fate in various diseases. Small molecular probes suffer from poor macrophage targeting and retention, rapid clearance, and deficient metabolizing stability. To overcome these limitations, a variety of functional nanoprobes have been developed for targeted imaging of macrophages in divergent diseases such as cancer, atherosclerosis and obesity. Generally, nanoprobes are functionalized with targeting peptides, ligands or antibodies to fulfill high macrophage affinity. In this review, the most recent advances of nanoprobes for imaging macrophages in vivo and ex vivo are systematically summarized. The challenges and perspectives of precisely imaging macrophages with improved signal-to-background ratios via nanoprobes are further discussed.


Subject(s)
Atherosclerosis , Nanoparticles , Neoplasms , Humans , Macrophages , Molecular Probes , Diagnostic Imaging , Nanoparticles/chemistry
15.
BMC Complement Med Ther ; 22(1): 253, 2022 Sep 30.
Article in English | MEDLINE | ID: mdl-36180911

ABSTRACT

BACKGROUND AND OBJECTIVE: Epimedii has long been used as a traditional medicine in Asia for the treatment of various common diseases, including Alzheimer's disease, cancer, erectile dysfunction, and stroke. Studies have reported the ameliorative effects of Icariside II (ICS II), a major metabolite of Epimedii, on acute ischemic stroke (AIS) in animal models. Based on network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we conducted a systematic review to evaluate the effects and neuroprotective mechanisms of ICS II on AIS. METHODS: First, we have searched 6 databases using studies with ICS II treatment on AIS animal models to explore the efficacy of ICS II on AIS in preclinical studies. The literature retrieval time ended on March 8, 2022 (Systematic Review Registration ID: CRD42022306291). There were no restrictions on the language of the search strategy. Systematic review follows the Patient, Intervention, Comparison and Outcome (PICO) methodology and framework. SYCLE's RoB tool was used to evaluate the the risk of bias. In network pharmacology, AIS-related genes were identified and the target-pathway network was constructed. Then, these targets were used in the enrichments of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO). Molecular docking and MD simulation were finally employed between ICS II and the potential target genes. RESULTS: Twelve publications were included describing outcomes of 1993 animals. The literature details, animal strains, induction models, doses administered, duration of administration, and outcome measures were extracted from the 12 included studies. ICS II has a good protective effect against AIS. Most of the studies in this systematic review had the appropriate methodological quality, but some did not clearly state the controlling for bias of potential study. Network pharmacology identified 246 targets with SRC, CTNNB1, HSP90AA1, MAPK1, and RELA as the core target proteins. Besides, 215 potential pathways of ICS II were identified, such as PI3K-Akt, MAPK, and cGMP-PKG signaling pathway. GO enrichment analysis showed that ICS II was significantly enriched in subsequent regulation such as MAPK cascade. Molecular docking and MD simulations showed that ICS II can closely bind with important targets. CONCLUSIONS: ICS II is a promising drug in the treatment of AIS. However, this systematic review reveals key knowledge gaps (i.e., the protective role of ICS II in women) that ICS II must address before it can be used for the treatment of human AIS. Our study shows that ICS II plays a protective role in AIS through multi-target and multi-pathway characteristics, providing ideas for the development of drugs for the treatment of AIS.


Subject(s)
Ischemic Stroke , Animals , Female , Flavonoids , Humans , Ischemic Stroke/drug therapy , Male , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt
16.
Anal Chim Acta ; 1223: 340204, 2022 Aug 29.
Article in English | MEDLINE | ID: mdl-35999002

ABSTRACT

The development of covalent organic framework nanosheet (COF NS) is becoming a vitally important research field by reason of its high permeability, ordered structure, high utilization of functional site, favourable dispersability and large aspect ratio, resulting in their widespread applications in separation, catalysis, sensing and optical device. In this work, a Tp-Bpy COF NS was prepared via an interfacial synthesis of 2,4,6-triformylphloroglucinol (Tp) and 5,5'-diamino-2,2'-bipyridine (Bpy), which has film morphology, high surface area, large pore, excellent stability and various functional site. It was utilized as a functional material to immobilize aptamers for constructing a sensitive electrochemical aptasensor. Compared with bulk Tp-Bpy COF, Tp-Bpy COF NS can significantly enhance the biosensing performance toward ultra-trace tobramycin. This work is benefit for the exploration of COF NSs and their electrochemical aptasensors in biosensing applications.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Metal-Organic Frameworks , Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods , Electrochemical Techniques/methods , Limit of Detection , Metal-Organic Frameworks/chemistry
17.
Pigment Cell Melanoma Res ; 35(3): 342-355, 2022 05.
Article in English | MEDLINE | ID: mdl-35266648

ABSTRACT

Melanogenesis (melanin pigment production) in melanocytes is canonically stimulated by the alpha melanocyte stimulating hormone (αMSH), which activates the cyclic-AMP-mediated expression of the melanocyte inducing transcription factor (MITF) and its downstream melanogenic genes, including the principal rate-limiting melanogenic enzyme tyrosinase (TYR). Here, we report that interferon-gamma (IFNG; type II interferon), but not interferon-alpha (a type I interferon), induces a noncanonical melanogenic pathway in mouse and human melanocytic cells. Inhibition of IFNG pathway by the JAK1/2 inhibitor ruxolitinib or knocking out Stat1 gene abrogated the IFNG-induced melanogenesis. Interestingly, IFNG-induced melanogenesis was independent of MITF. IFNG markedly increased the TYR protein expression but did not affect the mRNA expression, suggesting a post-translational regulatory mechanism. In contrast, IFNG had no effect on the expression of other melanogenesis-related proteins, for example, tyrosinase-related protein 1 (TYRP1) and dopachrome tautomerase (DCT). Glycosidase digestion assays revealed that IFNG treatment increased the mature glycosylated form of TYR, but not its de novo synthesis. Moreover, cycloheximide chase assay showed that degradation of TYR was decreased in IFNG-treated cells. These results suggest that the IFNG-STAT1 pathway regulates melanogenesis via regulation of the post-translational processing and protein stability of TYR.


Subject(s)
Interferon-gamma , Monophenol Monooxygenase , Animals , Interferon-gamma/metabolism , Interferon-gamma/pharmacology , Melanins/metabolism , Melanocytes/metabolism , Membrane Glycoproteins , Mice , Monophenol Monooxygenase/metabolism , Oxidoreductases , Protein Binding
18.
Neural Regen Res ; 17(7): 1582-1587, 2022 Jul.
Article in English | MEDLINE | ID: mdl-34916444

ABSTRACT

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder. In preclinical models of neurological and psychiatric diseases, Lycium barbarum polysaccharide (LBP) extracted from Goji berries had anti-depressant effects including but not limited to anti-oxidative and anti-inflammatory properties. However, the effect of LBP on subthreshold depression is unclear. To investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents, we conducted a randomized, double-blind, placebo-controlled trial (RCT) with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical University. The participants were randomly assigned to groups where they received either 300 mg LBP (LBP group, n = 15, 3 boys and 12 girls aged 15.13 ± 2.17 years) or a placebo (placebo group, n = 14, 2 boys and 12 girls aged 15 ± 1.71 years) for 6 successive weeks. Interim analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale (HAMD-24) scores relative to the baseline and a higher remission rate (HAMD-24 total score ≤ 7) at 6 weeks compared with the placebo group. Scores on the Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), Kessler Psychological Distress Scale (Kessler), and Screen for Child Anxiety-Related Emotional Disorders (SCARED) were similar between the LBP and placebo groups. No side effects related to the intervention were reported in either group. These results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold depression. Furthermore, LBP was well tolerated with no treatment-limiting adverse events. Clinical trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold depression. This study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University (Guangzhou, China; approval No. L2019-08) on April 4, 2019 and was registered on ClinicalTrials.gov (identifier: NCT04032795) on July 25, 2019.

19.
Front Surg ; 8: 783859, 2021.
Article in English | MEDLINE | ID: mdl-34957206

ABSTRACT

Double lumen endobronchial ventilation in McKeown esophagectomy is common for esophageal cancer. In spite of most patients could be extubated immediately after surgery under adequate multimodal analgesia, still some patients require extended mechanical ventilation or airway support post-surgery because of pain or difficult respiration. The present study reported a novel challenge for McKeown esophagectomy with discontinuous spontaneous ventilating anesthesia by the laryngeal mask. Three esophageal cancer patients underwent McKeown esophagectomy under discontinuous spontaneous ventilating anesthesia with local and regional analgesia and appropriate sedation. Two of them were accomplished under non-intubated video-assisted thoracoscopic surgery (NIVATS), and then, the abdominal and neck surgery was managed under laryngeal mask airway with appropriate muscle relaxation. One patient was endured high PetCO2 level, and converted to regular double lumen endobronchial intubation for safety. However, from the two successful cases, we still proved that the discontinuous spontaneous ventilating anesthesia achieved the same anesthetic effect as bronchial intubation under general anesthesia for McKeown esophagectomy, which reduced the postoperative pharyngeal discomfort, might be beneficial to the patients for enhanced recovery after surgery (ERAS).

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