Publications by authors named "Xin Tang"

672 Publications

Effectiveness and safety of tafluprost in primary open-angle glaucoma and ocular hypertension: a post-marketing phase IV study in China.

BMC Ophthalmol 2022 Aug 5;22(1):332. Epub 2022 Aug 5.

Department of Cataract and Glaucoma, Wuhan Eyegood Ophthalmic Hospital, Wuhan, 430064, Hubei Province, China.

Background: Prostaglandin analogs (PGAs) are the first-line treatment for primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study aimed to confirm the effectiveness and safety of Tapros® (0.0015% tafluprost eye drops) in Chinese patients with POAG and OH.

Methods: This phase IV, multicenter, non-comparative, prospective study enrolled patients with POAG and OH in China between 12/27/2017 and 04/15/2020. Patients who were treatment-naïve or untreated within one month (group A) or with unreached intraocular pressure (IOP) target after previous monotherapy of other PGAs (group B) or non-PGA IOP-lowering drugs (group C) were treated with 0.0015% tafluprost for three months. The IOP reduction, response rate, and safety were observed.

Results: There were 165, 89, and 31 patients in groups A, B, and C, with baseline IOPs of 22.4 ± 4.7, 21.0 ± 3.5, and 22.5 ± 3.2 mmHg, respectively. The least-square means and percentages of IOP reduction at 3 months for groups A, B, and C were 4.7 (19.8%), 1.6 (6.1%), and 4.6 mmHg (20.3%), respectively. A significant reduction in IOP was observed at each visit compared with baseline (all P < 0.05). At the final visit, 57.0% of the participants in group A achieved an IOP reduction of ≥ 20%, while 40.4% and 77.4% in groups B and C achieved an IOP reduction of ≥ 10%. Fifty-eight treatment-related adverse events occurred in 46 participants (15.7%), of which the most common one was conjunctival hyperemia (34/293, 11.6%).

Conclusions: Tafluprost showed a sustained and significant effect with tolerable adverse events in Chinese patients with POAG and OH who were treatment-naïve or untreated within one month or received prior treatments with unsatisfying outcomes.
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http://dx.doi.org/10.1186/s12886-022-02553-1DOI Listing
August 2022

Automatic Multi-functional Integration Program (AMFIP) towards all-optical mechano-electrophysiology interrogation.

PLoS One 2022 28;17(7):e0266098. Epub 2022 Jul 28.

Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, UF, Gainesville, Florida, United States of America.

Automatic operations of multi-functional and time-lapse live-cell imaging are necessary for the biomedical science community to study active, multi-faceted, and long-term biological phenomena. To achieve automatic control, most existing solutions often require the purchase of extra software programs and hardware that rely on the manufacturers' own specifications. However, these software programs are usually non-user-programmable and unaffordable for many laboratories. To address this unmet need, we have developed a novel open-source software program, titled Automatic Multi-functional Integration Program (AMFIP), as a new Java-based and hardware-independent system that provides proven advantages over existing alternatives to the scientific community. Without extra hardware, AMFIP enables the functional synchronization of the μManager software platform, the Nikon NIS-Elements platform, and other 3rd party software to achieve automatic operations of most commercially available microscopy systems, including but not limited to those from Nikon. AMFIP provides a user-friendly and programmable graphical user interface (GUI), opening the door to expanding the customizability for myriad hardware and software systems according to user-specific experimental requirements and environments. To validate the intended purposes of developing AMFIP, we applied it to elucidate the question whether single cells, prior to their full spreading, can sense and respond to a soft solid substrate, and if so, how does the interaction depend on the cell spreading time and the stiffness of the substrate. Using a CRISPR/Cas9-engineered human epithelial Beas2B (B2B) cell line that expresses mNeonGreen2-tagged mechanosensitive Yes-associated protein (YAP), we show that single B2B cells develop distinct substrate-stiffness-dependent YAP expressions within 10 hours at most on the substrate, suggesting that cells are able to sense, distinguish, and respond to mechanical cues prior to the establishment of full cell spreading. In summary, AMFIP provides a reliable, open-source, and cost-free solution that has the validated long-term utility to satisfy the need of automatic imaging operations in the scientific community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266098PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333221PMC
August 2022

Treatment of Pediatric Intercondylar Humerus Fracture With External Fixation and Percutaneous Pinning After Closed Reduction.

Front Pediatr 2022 11;10:916604. Epub 2022 Jul 11.

Department of Orthopaedic Surgery, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.

Background: It is uncommon for young children to suffer an intercondylar fracture of the distal humerus. Although many approaches have been described to manage, there is no specific and accepted treatment protocol for such fracture patterns. This study aimed to identify the incidence of intercondylar fracture of the distal humerus in the pediatric population and report the clinical outcome of external fixation and percutaneous pinning in such injury patterns.

Methods: Pediatric patients under the age of 14 years who had an intercondylar fracture of the distal humerus treated with external fixation and percutaneous pinning between January 2013 and December 2018 at the author's Wuhan Union Hospital were retrospectively evaluated. The detailed baseline information of the patients, operating time, time to union time, and carrying angle difference (CAD) of the injured extremity were collected. During the follow-up visit, clinical results were evaluated using the Mayo Elbow Performance Score (MEPS) and the Flynn criteria.

Results: A total of eight patients (2 women and 6 men) with an average age of 8 years (5-12 years) who had an intercondylar fracture of the distal humerus (1 C2 and 7 C1) were included. All the patients achieved union, and the average MEPS score was 95 points 24 months after the surgery.

Conclusion: The intercondylar fracture of the distal humerus in children is rare, and closed reduction and external fixation is a viable treatment option, especially for the C1 type of fracture pattern.
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http://dx.doi.org/10.3389/fped.2022.916604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309387PMC
July 2022

The application of the 150° oblique tangential fluoroscopic view to detect the posterosuperior femoral neck screw in-out-in intraoperatively.

Authors:
Jian Zhang Xin Tang

Sci Rep 2022 Jul 27;12(1):12790. Epub 2022 Jul 27.

Department of Orthopedic Trauma, The First Affiliated Hospital of Dalian Medical University, 222 Zhong Shan Road, Xi Gang District, Dalian, 116011, Liaoning Province, China.

This study investigates the application of the 150° tangential fluoroscopic projection as a novel fluoroscopic view to detect the posterosuperior screw in-out-in (IOI) in the cannulated screws fixation of femoral neck fractures. A retrospective analysis was conducted including 33 patients with femoral neck fractures enrolled from April to November 2021. All patients underwent closed reduction and internal fixation with cannulated screws under intra-operative C-arm fluoroscopy. The posterosuperior femoral neck screw position (whether in-out-in and the distance to the femoral neck cortex) was evaluated from the standard anteroposterior (AP), lateral view, and tangential view images. Postoperative computed tomography (CT) scan results are considered the gold standard for detecting the femoral neck screw locations. Of 33 patients, no femoral neck screws were found to be placed IOI under the standard AP and lateral views. The tangential view revealed the posterosuperior screw was IOI in 8 patients, whereas the average distance between the posterosuperior screw and the posterior femoral neck cortex was 2.73 ± 1.06 mm under the standard lateral view. Postoperative CT verified that posterosuperior screw was placed IOI in these 8 patients. In the other 25 patients with the tangential view showed the posterosuperior screw completely contained in the femoral neck, the average distance between the posterosuperior screw and the posterior femoral neck cortex was 5.48 ± 1.26 mm under the standard lateral view and 2.76 ± 1.08 mm under the tangential view, with a statistically significant difference between the two groups (p < 0.05). Post-operative CT demonstrated that the femoral neck screws were completely contained in the femoral neck in these 25 patients. Intra-operative tangential view of 150° can effectively identify the posterosuperior screw IOI in the cannulated screws fixation of femoral neck fractures. Based on our study, we highly recommend the tangential view as a routine intraoperative fluoroscopic angle to detect the posterosuperior screw IOI.
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http://dx.doi.org/10.1038/s41598-022-17221-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329380PMC
July 2022

Inosine Pretreatment Attenuates LPS-Induced Lung Injury through Regulating the TLR4/MyD88/NF-κB Signaling Pathway In Vivo.

Nutrients 2022 Jul 9;14(14). Epub 2022 Jul 9.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Inosine is a type of purine nucleoside, which is considered to a physiological energy source, and exerts a widely range of anti-inflammatory efficacy. The TLR4/MyD88/NF-κB signaling pathway is essential for preventing host oxidative stresses and inflammation, and represents a promising target for host-directed strategies to improve some forms of disease-related inflammation. In the present study, the results showed that inosine pre-intervention significantly suppressed the pulmonary elevation of pro-inflammatory cytokines (including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)), malondialdehyde (MDA), nitric oxide (NO), and reactive oxygen species (ROS) levels, and restored the pulmonary catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and myeloperoxidase (MPO) activities ( < 0.05) in lipopolysaccharide (LPS)-treated mice. Simultaneously, inosine pre-intervention shifted the composition of the intestinal microbiota by decreasing the ratio of Firmicutes/Bacteroidetes, elevating the relative abundance of Tenericutes and Deferribacteres. Moreover, inosine pretreatment affected the TLR4/MyD88/NF-κB signaling pathway in the pulmonary inflammatory response, and then regulated the expression of pulmonary iNOS, COX2, Nrf2, HO-1, TNF-α, IL-1β, and IL-6 levels. These findings suggest that oral administration of inosine pretreatment attenuates LPS-induced pulmonary inflammatory response by regulating the TLR4/MyD88/NF-κB signaling pathway, and ameliorates intestinal microbiota disorder.
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http://dx.doi.org/10.3390/nu14142830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318366PMC
July 2022

CCFM1223 Protects against Lipopolysaccharide-Induced Acute Liver Injury in Mice by Regulating the "Gut-Liver" Axis.

Microorganisms 2022 Jun 30;10(7). Epub 2022 Jun 30.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Background: CCFM1223, a probiotic previously isolated from the healthy people's intestine, exerts the beneficial influence of preventing the development of inflammation.

Methods: The aim of this research was to explore the beneficial effects of CCFM1223 to prevent lipopolysaccharide (LPS)-induced acute liver injury (ALI) and elaborate on its hepatoprotective mechanisms.

Results: CCFM1223 pretreatment remarkably decreased the activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in mice with LPS treatment and remarkably recovered LPS-induced the changes in inflammatory cytokines (tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interleukin (IL)-1β, IL-6, IL-17, IL-10, and LPS) and antioxidative enzymes activities (total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)). Metagenomic analysis showed that CCFM1223 pretreatment remarkably increased the relative abundance of compared with the LPS group but remarkably reduced the relative abundance of [] , , , and , which is closely associated with the inflammation cytokines and antioxidative enzymes. Furthermore, CCFM1223 pretreatment remarkably increased the colonic, serum, and hepatic IL-22 levels in ALI mice. In addition, CCFM1223 pretreatment remarkably down-regulated the hepatic Tlr4 and Nf-kβ transcriptions and significantly up-regulated the hepatic Tlr9, Tak1, Iκ-Bα, and Nrf2 transcriptions in ALI mice.

Conclusions: CCFM1223 has a hepatoprotective function in ameliorating LPS-induced ALI by regulating the "gut-liver" axis.
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http://dx.doi.org/10.3390/microorganisms10071321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319883PMC
June 2022

Combining 3D Magnetic Force Actuator and Multi-Functional Fluorescence Imaging to Study Nucleus Mechanobiology.

J Vis Exp 2022 Jul 5(185). Epub 2022 Jul 5.

Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida; UF Health Cancer Center, University of Florida; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida; Department of Physiology and Functional Genomics, University of Florida;

A fundamental question in mechanobiology is how living cells sense extracellular mechanical stimuli in the context of cell physiology and pathology. The cellular mechano-sensation of extracellular mechanical stimuli is believed to be through the membrane receptors, the associated protein complex, and the cytoskeleton. Recent advances in mechanobiology demonstrate that the cell nucleus in cytoplasm itself can independently sense mechanical stimuli simultaneously. However, a mechanistic understanding of how the cell nucleus senses, transduces, and responds to mechanical stimuli is lacking, mainly because of the technical challenges in accessing and quantifying the nucleus mechanics by conventional tools. This paper describes the design, fabrication, and implementation of a new magnetic force actuator that applies precise and non-invasive 3D mechanical stimuli to directly deform the cell nucleus. Using CRISPR/Cas9-engineered cells, this study demonstrates that this tool, combined with high-resolution confocal fluorescent imaging, enables the revelation of the real-time dynamics of a mechano-sensitive yes-associated protein (YAP) in single cells as a function of nucleus deformation. This simple method has the potential to bridge the current technology gap in the mechanobiology community and provide answers to the knowledge gap that exists in the relation between nucleus mechanotransduction and cell function.
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http://dx.doi.org/10.3791/64098DOI Listing
July 2022

Weak electro-stimulation promotes microbial uranium removal: Efficacy and mechanisms.

J Hazard Mater 2022 Jul 16;439:129622. Epub 2022 Jul 16.

School of Ecology and Environment, Northwestern Polytechnical University, Xi'an 710129, PR China. Electronic address:

Removal and recovery of uranium from uranium-mine wastewater is beneficial to environmental protection and resource preservation. Reduction of soluble hexavalent U (U(VI)) to insoluble tetravalent uranium (U(IV)) by microbes is a plausible approach for this purpose, but its practical implementation has long been restricted by its intrinsic drawbacks. The electro-stimulated microbial process offers promise in overcoming these drawbacks. However, its applicability in real wastewater has not been evaluated yet, and its U(VI) removal mechanisms remain poorly understood. Herein, we report that introducing a weak electro-stimulation considerably boosted microbial U(VI) removal activities in both synthetic and real wastewater. The U(VI) removal has proceeded via U(VI)-to-U(IV) reduction in the biocathode, and the electrochemical characterization demonstrates the crucial role of the electroactive biofilm. Microbial community analysis shows that the broad biodiversity of the cathode biofilm is capable of U(VI) reduction, and the molecular ecological network indicates that synthetic metabolisms among electroactive and metal-reducing bacteria play major roles in electro-microbial-mediated uranium removal. Metagenomic sequencing elucidates that the electro-stimulated U(VI) bioreduction may proceed via e-pili, extracellular electron shuttles, periplasmic and outer membrane cytochrome, and thioredoxin pathways. These findings reveal the potential and mechanism of the electro-stimulated U(VI) bioreduction system for the treatment of U-bearing wastewater.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129622DOI Listing
July 2022

Metformin Alleviates Delayed Hydrocephalus after Intraventricular Hemorrhage by Inhibiting Inflammation and Fibrosis.

Transl Stroke Res 2022 Jul 19. Epub 2022 Jul 19.

Department of Neurosurgery and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.

Intraventricular hemorrhage (IVH) is a subtype of intracerebral hemorrhage (ICH) with high morbidity and mortality. Posthemorrhagic hydrocephalus (PHH) is a common and major complication that affects prognosis, but the mechanism is still unclear. Inflammation and fibrosis have been well established as the major causes of PHH after IVH. In this study, we aimed to investigate the effects of metformin on IVH in adult male mice and further explored the underlying molecular mechanisms of these effects. In the acute phase, metformin treatment exerted dose-dependent neuroprotective effects by reducing periependymal apoptosis and neuronal degeneration and decreasing brain edema. Moreover, high-dose metformin reduced inflammatory cell infiltration and the release of proinflammatory factors, thus protecting ependymal structure integrity and subependymal neurons. In the chronic phase, metformin administration improved neurocognitive function and reduced delayed hydrocephalus. Additionally, metformin significantly inhibited basal subarachnoid fibrosis and ependymal glial scarring. The ependymal structures partially restored. Mechanically, IVH reduced phospho-AMPK (p-AMPK) and SIRT1 expression and activated the phospho-NF-κB (p-NF-κB) inflammatory signaling pathway. However, metformin treatment increased AMPK/SIRT1 expression and lowered the protein expression of p-NF-κB and its downstream inflammation. Compound C and EX527 administration reversed the anti-inflammatory effect of metformin. In conclusion, metformin attenuated neuroinflammation and subsequent fibrosis after IVH by regulating AMPK /SIRT1/ NF-κB pathways, thereby reducing delayed hydrocephalus. Metformin may be a promising therapeutic agent to prevent delayed hydrocephalus following IVH.
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http://dx.doi.org/10.1007/s12975-022-01026-3DOI Listing
July 2022

LRP-1 receptor combines EGFR signalling and eHsp90α autocrine to support constitutive breast cancer cell motility in absence of blood supply.

Sci Rep 2022 Jul 14;12(1):12006. Epub 2022 Jul 14.

Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre, Los Angeles, CA, 90033, USA.

Tumor cells face constant stress of ischemic (nutrient paucity and hypoxia) environment when they migrate and invade too fast to outgrow the nearest blood vessels. During the temporary loss of support from circulation, the tumor cells must act self-sufficient to survive and then to migrate to re-connect with the nearest blood supply or die. We have previously reported that ablation of the low-density lipoprotein receptor-related protein 1 (LRP-1) completely nullified the ability of tumour cells to migrate and invade under serum-free conditions in vitro and to form tumours in vivo. The mechanism behind the important function by cell surface LRP-1 was not fully understood. Herein we show that LRP-1 orchestrates two parallel cell surface signalling pathways to support the full constitutive tumour cell migration. First, LRP-1 stabilizes activated epidermal growth factor receptor (EGFR) to contribute half of the pro-motility signalling. Second, LRP-1 mediates secreted Hsp90α autocrine signalling to bring the other half of pro-motility signalling. Only combined inhibitions of the EGFR signalling and the eHsp90α autocrine signalling led to the full blockade of the tumour cell migration as the LRP-1 depletion did. This finding uncovers a novel mechanism by which certain breast cancer cells use LRP-1 to engage parallel signalling pathways to move when they lose contact with blood support.
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http://dx.doi.org/10.1038/s41598-022-16161-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283467PMC
July 2022

Platelet-rich Plasma Injection Can Be a Viable Alternative to Corticosteroid Injection for Conservative Treatment of Rotator Cuff Disease: A Meta-analysis of Randomized Controlled Trials.

Arthroscopy 2022 Jul 7. Epub 2022 Jul 7.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University; Chengdu, China. Electronic address:

Purpose: The purpose of this study was to explore whether PRP injection can be a viable alternative to CS injection for conservative treatment of rotator cuff disease.

Methods: The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, The Cochrane Library, and Web of Science were searched for English-written randomized controlled trials (RCTs) which compared PRP and CS injections for patients with rotator cuff disease from January 1, 1990, to March 20, 2022. Two evaluators independently screened the literature, extracted data, and assessed the level of evidence and methodological quality of the enrolled studies. The meta-analysis was conducted using RevMan 5.3.3 software.

Results: Thirteen non-surgical RCTs with 725 patients were included. Compared with CS, PRP provided statistically worse short-term (<2 months) changes (Δ) of the American Shoulder and Elbow Surgeons (ASES) assessment, Δ the Simple Shoulder Test (SST), Δ the Disability of Arm, Shoulder and Hand (DASH) questionnaires but better medium-term (2 to 6 months) Δ DASH, long-term (≥ 6 months) Δ Constant-Murley Score (CMS), Δ ASES and Δ SST. No statistical differences regarding pain reduction were found between the two groups. PRP injections led to worse short-term Δ forward flexion, Δ internal rotation but better medium-term Δ forward flexion and Δ external rotation. PRP had significantly lower rates of postinjection failure (requests for a subsequent injection or surgical intervention prior to 12 months) than CS. No outcome reached the minimal clinically important difference (MCID). After sensitivity analyses by excluding studies with substantial clinical and/or methodological heterogeneity, PRP showed better medium-term Δ ASES, Δ VAS, and long-term Δ VAS which reached the MCID.

Conclusions: Without the drawbacks of CS injection, PRP injection is not worse than CS injection in pain relief and function recovery at any time point of the follow-up. PRP injection may reduce rates of subsequent injection or surgery, and might provide better improvement in pain and function in the medium- to long-term. PRP injection can be a viable alternative to CS injection for conservative treatment of rotator cuff disease.

Level Of Evidence: Systematic review of Level I and II studies.
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http://dx.doi.org/10.1016/j.arthro.2022.06.022DOI Listing
July 2022

Mid-Infrared Intraband Photodetector High Carrier Mobility HgSe Colloidal Quantum Dots.

ACS Nano 2022 Jul 6. Epub 2022 Jul 6.

School of Optics and Photonics, Beijing Institute of Technology, No. 5, Zhongguancun South Street, Beijing, 100081, China.

In this work, a room-temperature mixed-phase ligand exchange method is developed to obtain a relatively high carrier mobility (∼1 cm/(V s)) on HgSe intraband colloidal quantum dot solids without any observable trap state. What is more, the doping from 1S to 1P state in the conduction band could be precisely controlled by additional salts during this method, proved by optical and transport experiments. The high mobility and controllable doping benefit the mid-infrared photodetector utilizing the 1S to 1P transition, with a 1000-fold improvement in response speed, which is several μs, a 55-fold increase in responsivity, which is 77 mA/W, and a 10-fold increase in specific detectivity, which is above 1.7 × 10 Jones at 80 K. The high-performance photodetector could serve as an intraband infrared camera for thermal imaging, as well as a CO gas sensor with a range from 0.25 to 2000 ppm.
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http://dx.doi.org/10.1021/acsnano.2c03631DOI Listing
July 2022

TNF-α-inducing protein of Helicobacter pylori promotes EMT and cancer stem-like cells properties via activation of Wnt/β-catenin signaling pathway in gastric cancer cells.

Pathog Dis 2022 Jul 1. Epub 2022 Jul 1.

Institute of Pathogenic Biology, Hengyang Medical College, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control; Hunan Province Innovative Training Base for Postgraduates, University of South China and Nanyue Biopharmaceutical Co. Ltd., Hengyang 421001, Hunan, China.

Tumor necrosis factor-α-inducing protein (Tipα) is a newly identified toxin, which promotes the inflammation and carcinogenesis caused by Helicobacter pylori (H. pylori). However, its mechanism of pathogenesis is still unclear. To investigate the carcinogenic mechanisms of Tipα, SGC7901 cells and SGC7901-derived cancer stem-like cells (CSCs) were stimulated by recombinant Tipα protein with or without Wnt/β-catenin signaling inhibitor XAV939. qRT-PCR and Western blotting were employed to detect expression of epithelial-mesenchymal transition (EMT), CSCs markers, and downstream target genes of this signaling pathway. The cell migration ability was measured by wound healing assay and transwell assay. Our results indicated that Tipα promoted CSC properties of SGC7901 spheroids, including increased expression of CSC specific surface markers CD44, Oct4, Nanog, and an increased capacity for self-renewal. Tipα activated Wnt/β-catenin signaling in both SGC7901 cells or CSCs. Furthermore, Tipα induced the EMT and increased the expressions of downstream target genes of this signaling, including c-myc, cyclin D1, and CD44. However, XAV939 pretreatment inhibited Tipα-induced EMT and CSC properties in SGC7901 cells or CSCs. These results suggest that Tipα promotes EMT and CSC-like properties in gastric cancer cells through activation of Wnt/β-catenin signaling pathway, thereby accelerating the progression of gastric cancer.
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http://dx.doi.org/10.1093/femspd/ftac025DOI Listing
July 2022

Molecular mechanism of -adenosylmethionine sensing by SAMTOR in mTORC1 signaling.

Sci Adv 2022 07 1;8(26):eabn3868. Epub 2022 Jul 1.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

The mechanistic target of rapamycin-mLST8-raptor complex (mTORC1) functions as a central regulator of cell growth and metabolism in response to changes in nutrient signals such as amino acids. SAMTOR is an -adenosylmethionine (SAM) sensor, which regulates the mTORC1 activity through its interaction with the GTPase-activating protein activity toward Rags-1 (GATOR1)-KPTN, ITFG2, C12orf66 and SZT2-containing regulator (KICSTOR) complex. In this work, we report the crystal structures of SAMTOR in apo form and in complex with SAM. SAMTOR comprises an N-terminal helical domain and a C-terminal SAM-dependent methyltransferase (MTase) domain. The MTase domain contains the SAM-binding site and the potential GATOR1-KICSTOR-binding site. The helical domain functions as a molecular switch, which undergoes conformational change upon SAM binding and thereby modulates the interaction of SAMTOR with GATOR1-KICSTOR. The functional roles of the key residues and the helical domain are validated by functional assays. Our structural and functional data together reveal the molecular mechanism of the SAM sensing of SAMTOR and its functional role in mTORC1 signaling.
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http://dx.doi.org/10.1126/sciadv.abn3868DOI Listing
July 2022

Genome-scale CRISPR-Cas9 screen reveals novel regulators of B7-H3 in tumor cells.

J Immunother Cancer 2022 06;10(6)

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, Sichuan, China

Background: Despite advances in B7 homolog 3 protein (B7-H3) based immunotherapy, the development of drug resistance remains a major clinical concern. The heterogeneity and emerging loss of B7-H3 expression are the main causes of drug resistance and treatment failure in targeted therapies, which reveals an urgent need to elucidate the mechanism underlying the regulation of B7-H3 expression. In this study, we identified and explored the crucial role of the transcription factor SPT20 homolog (SP20H) in B7-H3 expression and tumor progression.

Methods: Here, we performed CRISPR/Cas9-based genome scale loss-of-function screening to identify regulators of B7-H3 in human ovarian cancer cells. Signaling pathways altered by SP20H knockout were revealed by RNA sequencing. The regulatory role and mechanism of SP20H in B7-H3 expression were validated using loss-of-function and gain-of-function assays in vitro. The effects of inhibiting SP20H on tumor growth and efficacy of anti-B7-H3 treatment were evaluated in tumor-bearing mice.

Results: We identified SUPT20H (SP20H) as negative and eIF4E as positive regulators of B7-H3 expression in various cancer cells. Furthermore, we provided evidence that either SP20H loss or TNF-α stimulation in tumor cells constitutively activates p38 MAPK-eIF4E signaling, thereby upregulating B7-H3 expression. Loss of SP20H upregulated B7-H3 expression both in vitro and in vivo. Additionally, deletion of SP20H significantly suppressed tumor growth and increased immune cells infiltration in tumor microenvironment. More importantly, antibody-drug conjugates targeting B7-H3 exhibited superior antitumor performance against SP20H-deficient tumors relative to control groups.

Conclusions: Activation of p38 MAPK-eIF4E signaling serves as a key event in the transcription initiation and B7-H3 protein expression in tumor cells. Genetically targeting SP20H upregulates target antigen expression and sensitizes tumors to anti-B7-H3 treatment. Collectively, our findings provide new insight into the mechanisms underlying B7-H3 expression and introduce a potential synergistic target for existing antibody-based targeted therapy against B7-H3.
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http://dx.doi.org/10.1136/jitc-2022-004875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244714PMC
June 2022

How steaming and drying processes affect the active compounds and antioxidant types of Gastrodia elata Bl. f. glauca S. chow.

Food Res Int 2022 Jul 21;157:111277. Epub 2022 Apr 21.

Chongqing Academy of Chinese Materia Medica, Chongqing College of Traditional Chinese Medicine, Chongqing 400065, PR China.

As both a traditional medicine and food material, fresh Gastrodia elata requires a curing process for quality improvement. The effects of steaming and various drying methods (sun-, hot-air-, microwave-vacuum-, freeze- and vacuum-drying) on the total phenolic, total flavonoid, ascorbic acid, adenosine, and phenolic compound contents, antioxidant activities (scavenging DPPH•, ABTS•, OH• and reducing power) and microstructures were investigated in this study. The contents of adenosine and individual phenolic compounds were analyzed using high-performance liquid chromatography. The results showed that steaming had adverse effects on the total phenolic, total flavonoid, adenosine, parishin C, vanillyl alcohol, quercetin and cinnamic acid contents, while subsequent hot-air- and freeze-drying showed compensatory effects. Steaming significantly increased the levels of gastrodin, p-hydroxybenzylalcohol, p-hydroxybenzaldehyde, parishins (A, B and E) and catechin (by 3.4-, 1.1-, 1.1-, 3.8-, 6-, 1.4- and 1.5-fold, respectively, p < 0.05) compared to the fresh samples, which were further increased by hot-air- and freeze-drying. Hot-air- and freeze-drying significantly increased the levels of adenosine, gastrodin, p-hydroxybenzylalcohol, p-hydroxybenzaldehyde, parishins (A, B and C), vanillyl alcohol, catechin, caffeic acid, quercetin and cinnamic acid by 1.1-11.6-fold (p < 0.05) compared to steaming treatment. Steaming reduced all the antioxidant activities, which were restored partially by hot-air- and freeze-drying. Principal component and clustering analyses revealed the relationship among the samples, phenolics, and antioxidant activities, which suggested a steaming-then-drying action mechanism in which steaming changes enzymes and starch hydrolysis and drying promote condensation reactions. Collectively, steaming-then-hot-air- or freeze-drying is a promising method for enhancing the quality of Gastrodia elata for food applications.
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http://dx.doi.org/10.1016/j.foodres.2022.111277DOI Listing
July 2022

Resolution of inflammation is disturbed in acute ischemic stroke with diabetes mellitus and rescued by resolvin D2 treatment.

Free Radic Biol Med 2022 Aug 21;188:194-205. Epub 2022 Jun 21.

Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address:

Background: Inflammation plays an important role in diabetes mellitus (DM)-related acute ischemic stroke (AIS). The mechanisms of un-resolved inflammation in DM-related AIS are not fully understood. Specialized pro-resolving mediators (SPMs) are key regulators that promote resolution of inflammation. We aimed to examine resolution function in patients with AIS complicated with DM, and explore potential treatment effects of one of the SPMs, resolvin D2 (RvD2) ex vivo and in vivo.

Methods: Cultured human macrophages, which were derived from peripheral blood mononuclear cells of AIS and none-AIS patients with or without DM, were stimulated with oxidized-low density lipoprotein (ox-LDL). Levels of SPMs and inflammatory markers were analysed, and RvD2 treatment effects were evaluated in these cells. For experiments in vivo, challenges with high fat diet and low-dose streptozotocin (STZ) were used to induce DM in C57BL/6J mice. AIS model was established by permanent middle cerebral artery occlusion (pMCAO) followed by intra-cerebroventricular injection of RvD2.

Results: Compared with macrophages of AIS patients without DM, the ratios of SPMs to leukotriene B4 (LTB) were decreased in AIS patients with DM, accompanied by reduced expression of SPM synthesis enzyme, 15-lipoxygenase-1. Moreover, the levels of pro-inflammatory pathway markers were increased, and the macrophages were skewed to M1 polarization in AIS patients with DM. In mice, treatment with RvD2 ameliorated pMCAO-induced brain injury, neurological dysfunction, and inflammatory response. Furthermore, RvD2 rescued resolution of inflammation by promoting macrophage/microglia polarization to pro-resolving M2 phenotype ex vivo and in vivo.

Conclusions: Our data demonstrate resolution of inflammation is impaired by DM in AIS patients, implicating a novel mechanism of un-resolved inflammation in DM-related AIS. Furthermore, RvD2 promotes inflammation resolution in macrophages/microglia and protects DM-related AIS, and may thus serve as a novel therapeutic target.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.06.231DOI Listing
August 2022

Comparison of Selenium-Enriched , Selenium-Enriched Yeast, and Selenite for the Alleviation of DSS-Induced Colitis in Mice.

Nutrients 2022 Jun 12;14(12). Epub 2022 Jun 12.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Patients with inflammatory bowel disease (IBD) have been found to have decreased immune function. Selenium (Se) is an essential trace element that is beneficial for human health, which has a significant stimulating effect on immune function. We compared the effects of different Se forms on the alleviation of colitis in DSS-induced mice. Moreover, we also aimed to determine whether Se-enriched CCFM 1089 could be used as a new organic Se supplement. Different Se supplements (Se-enriched CCFM 1089, Se-enriched yeast and sodium selenite) were given to Se-deficient mice suffering from colitis. Se-enriched CCFM 1089, which is based on selenocysteine (SeCys), had similar effects in terms of reducing oxidative stress and inhibiting pro-inflammatory factors to Se-enriched yeast; however, selenase activity in the Se-enriched CCFM 1089-treated mice was higher than that in other treatment groups. In addition, Se-enriched CCFM 1089 could better protect the intestinal mucosa, which increased the expression of tight junction proteins (ZO-1 and occludin) in mice. Thus Se-enriched CCFM 1089 was shown to alleviate IBD, suggesting that it has potential as a good organic Se supplement.
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http://dx.doi.org/10.3390/nu14122433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231187PMC
June 2022

Use of Ilizarov Device to Gain Early Range of Motion in the Treatment of Pediatric Talus Body Fractures: A Series of Four Cases and Literature Review.

Orthop Surg 2022 Jun 22. Epub 2022 Jun 22.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Talus fractures are rare in children but can lead to severe outcomes if untreated. The Ilizarov external fixator has been used in the treatment of a variety of lower extremity pathologies. The purpose of this study was to investigate the clinical outcomes of talus body fractures treated with the Ilizarov external fixator.

Case Presentation: Four male pediatric patients (age range, 5-11 years) with talus body fractures who were treated by open reduction and internal fixation combined with Ilizarov external fixator between November 2015 and April 2016 were reviewed. Mean follow-up period was 4 years (range, 4-5). Clinical outcome was evaluated using the clinical rating scale of the American Orthopaedic Foot and Ankle Society (AOFAS). All four patients achieved good to excellent results at the last follow-up. None of the patients developed avascular necrosis. One patient developed automatic fusion of tibiotalar joint.

Conclusion: Use of the Ilizarov external fixator to gain early range of motion is a valuable option for treatment of talus body fractures in children.
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http://dx.doi.org/10.1111/os.13376DOI Listing
June 2022

Lisfranc injuries with dislocation the first tarsometatarsal joint: primary arthrodesis or internal fixation (a randomized controlled trial).

Int Orthop 2022 Jun 20. Epub 2022 Jun 20.

Department of Orthopedics, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.

Background: Open reduction and internal fixation (ORIF) is a popular method for treatment of displaced Lisfranc injuries. However, even with anatomic reduction and solid internal fixation, treatment does not provide good outcomes in certain severe dislocations. The purpose of this study was to compare ORIF and primary arthrodesis (PA) of the first tarsometatarsal (TMT) joint for Lisfranc injuries with the first TMT joint dislocation.

Methods: Seventy-eight Lisfranc injuries with first TMT joint dislocation were finally enrolled and analyzed in a prospective, randomized trial comparing ORIF and PA. They were 50 males and females with a mean age of 40.7 years and randomized to ORIF group and PA group. Outcome measures included radiographs, American Orthopaedic Foot and Ankle Society (AOFAS) midfoot scale, Foot and Ankle Ability Measure (FAAM) Sports subscale, visual analog scale (VAS), and the 36-Item Short Form Health Survey (SF-36). Complications and revision rate were also analyzed.

Results: Forty patients were treated by ORIF, while PA group includes 38 cases. Patients were followed up for 37.8(range, 24-48) months. At final follow-up, the mean AOFAS midfoot score (P < 0.01), the FAAM Sports subscale (P < 0.01), the physical function score (P < 0.05), and the Bodily Pain score of SF-36 (P < 0.05) after ORIF treatment were significantly lower than PA group. The mean VAS score in ORIF group was higher (P < 0.01). In ORIF group, redislocation of the first TMT joint was observed in ten cases, and thirteen patients had pain in midfoot. No redislocation and no hardware failure were identified in PA group.

Conclusion: PA of the first TMT joint provided a better medium-term outcome than ORIF for Lisfranc injuries with the first TMT dislocation. Possible complications and revision could be avoided by PA for dislocated first ray injuries.
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http://dx.doi.org/10.1007/s00264-022-05478-yDOI Listing
June 2022

Long noncoding RNA (lncRNA) metallothionein 1 J, pseudogene (MT1JP) is downregulated in triple-negative breast cancer and upregulates microRNA-138 (miR-138) to downregulate hypoxia-inducible factor-1α (HIF-1α).

Bioengineered 2022 05;13(5):13718-13727

Department of Breast, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study explored the molecular mechanism and influences of metallothionein 1 J, pseudogene (MT1JP), microRNA-138 (miR-138), and hypoxia-inducible factor-1α (HIF-1α) on TNBC cell proliferation and migration. We confirmed TNBC cases by immunohistochemistry (IHC) staining. The expression of MT1JP in two types of tissue collected from 78 TNBC patients was detected by performing real-time quantitative fluorescence PCR (RT-qPCR). To further evaluate the relationship among MT1JP, miR-138 and HIF-1α, expression vectors of MT1JP and HIF-1α, as well as miR-138 mimic and inhibitor, were delivered into BT-549 cells. We observed that MT1JP was downregulated in TNBC. MT1JP was positively correlated with miR-138 but negatively correlated with HIF-1α in TNBC tissues. In TNBC cells, upregulation of miR-138 and downregulation of HIF-1α were observed after overexpression of MT1JP. In addition, overexpression of miR-138 resulted in downregulation of HIF-1α but did not affect the expression of MT1JP. Decreased proliferation rate of TNBC cells was observed after overexpression of MT1JP and miR-138. HIF-1α increased cell proliferation and migration. HIF-1α also suppressed the role of MT1JP and miR-138 in TNBC cell proliferation and migration. In conclusion, our findings demonstrated that MT1JP inhibited TNBC by regulating the miR-138/HIF-1α axis, indicating that MT1JP might serve as a biomarker or target for TNBC treatment.
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http://dx.doi.org/10.1080/21655979.2022.2077906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276039PMC
May 2022

An inactivated vaccine against infectious pancreatic necrosis virus in rainbow trout (Oncorhynchus mykiss).

Fish Shellfish Immunol 2022 Jun 10;127:48-55. Epub 2022 Jun 10.

Department of Aquatic Animal Diseases and Control, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Harbin, 150070, China. Electronic address:

Infectious pancreatic necrosis virus (IPNV), belonging to the genus Aquabirnavirus within the family Birnaviridae, causes huge economic loss to the global salmonid industry every year. Recently, outbreaks of disease caused by genogroup I IPNV were found in many rainbow trout (Oncorhynchus mykiss) farms worldwide. An inactivated vaccine was prepared using a genogroup I IPNV isolate with an optimized procedure as incubation with β-propanolactone (BPL) at the final concentration of 0.5% at room temperature for 48 h. The inactivated vaccine was used to immunize rainbow trout, and the protection efficiency was evaluated by viral loads determination, immune-related genes quantification, and neutralizing antibody tests. The viral loads in immunized rainbow trout were significantly decreased and the strongest antiviral effect was observed on 30 days post-immunization (d.p.i). The expression of innate immune-related genes IFN-1, and Mx-1 genes were significantly up-regulated on 3, 7, and 15 d.p.i (p < 0.05), and adaptive immune-related genes CD4, CD8, and IgM genes were significantly up-regulated on 15 and 30 d.p.i (p < 0.05). Neutralizing antibodies were firstly detected on 30 d.p.i and the highest titer was observed on 45 d.p.i, which began to decrease on 60 d.p.i, but was still significantly higher than that in negative control fish. The results indicated that the vaccine prepared in this study could stimulate the non-specific and specific immune response and provide significant immune protection to the vaccinated rainbow trout.
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http://dx.doi.org/10.1016/j.fsi.2022.06.008DOI Listing
June 2022

Protective Effects of a Novel Probiotic on the Intestinal Barrier of Colitis Mice via Modulating the Pparγ/STAT3 Pathway and Intestinal Microbiota.

Foods 2022 May 25;11(11). Epub 2022 May 25.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Colitis has become a major health concern worldwide. The objective of the present study was to determine the probiotic influence of different strains of (Bp7 and Bp8) on alleviating colitis and to explore its possible potential mechanisms. Our results displayed that Bp7 and Bp8 intervention effectively reduced dextran sodium sulfate (DSS)-caused body weight loss and the release of several pro-inflammatory factors (interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α)) and increased the activities of antioxidant enzymes (T-AOC, SOD, and GSH) and the concentrations of tight junction proteins (occludin, claudin-1, and ZO-1). Moreover, Bp7 and Bp8 intervention drastically down-regulated the expression of colonic MyD88, NF-κB, iNOS and COX2 and drastically elevated the expression of colonic STAT3, Nrf2, and PPARγ. Gas chromatography-mass spectrometry results revealed that the cecal levels of isobutyric, butyric, and isovaleric acids were drastically increased in colitis mice intervened with Bp7 and Bp8. Moreover, 16S rRNA sequencing revealed that Bp7 and Bp8 intervention modulated the intestinal microbiota structure, particularly by enhancing the proportion of , , , , UCG 002, and , which are relevant to the levels of cecal isobutyric acid, butyric acid, isovaleric acid, and inflammatory cytokines. Collectively, these findings suggest that Bp7 and Bp8 intervention alleviates the intestinal barrier function, possibly by blocking the secretion of proinflammatory cytokines, maintaining the intestinal physical barrier integrity, activating the PPARγ/STAT3 pathway, and modulating intestinal microbiota composition. Our study also suggested that is a promising probiotic for colitis treatment.
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http://dx.doi.org/10.3390/foods11111551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180506PMC
May 2022

Molecular mechanism of interaction between fatty acid delta 6 desaturase and acyl-CoA by computational prediction.

AMB Express 2022 Jun 9;12(1):69. Epub 2022 Jun 9.

State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People's Republic of China.

Enzyme catalyzed desaturation of intracellular fatty acids plays an important role in various physiological and pathological processes related to lipids. Limited to the multiple transmembrane domains, it is difficult to obtain their three-dimensional structure of fatty acid desaturases. So how they interact with their substrates is unclear. Here, we predicted the complex of Micromonas pusilla delta 6 desaturase (MpFADS6) with the substrate linoleinyl-CoA (ALA-CoA) by trRosetta software and docking poses by Dock 6 software. The potential enzyme-substrate binding sites were anchored by analysis of the complex. Then, site-directed mutagenesis and activity verification clarified that W290, W224, and F352 were critical residues of the substrate tunnel and directly bonded to ALA-CoA. H94 and H69 were indispensable for transporting electrons with heme. H452, N445, and H358 significantly influenced the recognition and attraction of MpFADS6 to the substrate. These findings provide new insights and methods to determine the structure, mechanisms and directed transformation of membrane-bound desaturases.
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http://dx.doi.org/10.1186/s13568-022-01410-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184693PMC
June 2022

Ultrafast construction of 3D ultrathin [email protected] heteronanosheet array by plasma magnetron sputtering for non-enzymatic glucose sensing in beverage and human serum.

Food Chem 2022 Nov 3;393:133399. Epub 2022 Jun 3.

College of Chemistry and Materials, Sichuan Normal University, Chengdu, Sichuan 610068, China. Electronic address:

In this work, a 3D ultra-thin NiCo-LDH nanosheet array coated Cu nanoparticles on carbon cloth ([email protected] NSA/CC) was ultrafast synthesized by plasma magnetron sputtering for the first time. This method has low toxicity and is easy to operate. As a durable and efficient 3D heteronanoarray electrocatalyst for glucose detection, [email protected] NSA/CC has higher stable conductivity and faster electron transport rate than NiCo-LDH NSA/CC and Cu nanoparticles, which work through synergistic effect to form a high-performance sensing platform. The [email protected] NSA/CC heteronanosheet structure has good electrocatalytic performance for glucose oxidation, with the sensitivity of the two linear ranges (0.001-1 mmol L and 1-6 mmol L) being 9710 μA L mmol cm and 4870 μA L mmol cm, respectively, and the detection limit (LOD) is 157 nmol L (S/N = 3). The sensor has been successfully applied to detect glucose in beverages and serum.
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http://dx.doi.org/10.1016/j.foodchem.2022.133399DOI Listing
November 2022

The roles of social-emotional skills in students' academic and life success: A multi-informant and multicohort perspective.

J Pers Soc Psychol 2022 Jun 6. Epub 2022 Jun 6.

Department of Education.

Social-emotional skills have been shown to be beneficial for many important life outcomes for students. However, previous studies on the topic have suffered from many issues (e.g., consideration of only a small subset of skills, single-informant, and single-cohort design). To address these limitations, this study used a multi-informant (self, teacher, and parent) and multicohort (ages 10-15 from Finland, = 5,533) perspective to study the association between 15 social-emotional skills and 20 educational (e.g., school grades), social (e.g., relationships with teachers), psychological health (e.g., life satisfaction), and physical health outcomes (e.g., sleep trouble). Results showed that (a) there was a modest level of interrater agreement on social-emotional skills, with the highest agreement between students and parents (mean = .41); (b) inclusion of multi-informant ratings substantially enhanced the ability of social-emotional skills in predicting outcome variables, with parent- and self-rated skills playing important, unique roles; (c) by modeling skills at the facet level rather than at the domain level, we identified the key skills for different outcomes and found significant variation in facets' predictive utility even within the same domain; and (d) although the older cohort showed lower levels of most social-emotional skills (9/15), there were only minor changes in the interrater agreement and predictive utility on outcomes. Overall, self-control, trust, optimism, and energy were found among the four most important skills for academic and life success. We further identified the unique contribution of each skill for specific outcomes, pointing the way to effective and precise interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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http://dx.doi.org/10.1037/pspp0000426DOI Listing
June 2022

β(2→1) chicory and β(2→1)-β(2→6) agave fructans protect the human intestinal barrier function in a stressor-dependent fashion.

Food Funct 2022 Jun 20;13(12):6737-6748. Epub 2022 Jun 20.

Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

Dietary fibers such as fructans can protect the intestinal epithelial barrier integrity, but the mechanisms underlying this protection are not completely understood. We aimed to study the protective effect of β(2→1)-β(2→6) branched graminan-type fructans (GTFs) on gut epithelial barrier function that was disrupted by three different agents which impact the barrier function different cellular mechanisms. The effects of GTFs were compared with those of linear β(2→1) inulin-type fructans (ITFs). T84 intestinal epithelial monolayers were incubated with GTFs and ITFs. Afterwards, the monolayers were challenged with the barrier disruptors calcium ionophore A23187, 12-myristate 13-acetate (PMA) and deoxynivalenol (DON). Transepithelial resistance was measured with an electric cell-substrate impedance sensing system. All fructans studied prevented the barrier disruption induced by A23187. ITF II protected from the disruptive effects of PMA. However, none of the studied fructans influenced the disruption induced by DON. As a measure of disruption-induced inflammation, interleukin-8 (IL-8) production by the intestinal epithelium was determined by ELISA. The production of IL-8 induced by A23187 was decreased by all fructans, whereas IL-8 production induced by DON decreased only upon pre-treatment with ITF II. None of the studied fructans prevented PMA induced IL-8 production. GTFs just like ITFs can influence the barrier function and inflammatory processes in gut epithelial cells in a structure-dependent fashion. These distinct protective effects are dependent on the different signaling pathways that lead to gut barrier disruption.
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http://dx.doi.org/10.1039/d2fo00534dDOI Listing
June 2022

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis the TFEB-P300-BRD4 axis.

Acta Pharm Sin B 2022 May 29;12(5):2280-2299. Epub 2021 Dec 29.

Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific overexpression or knock-out in knock-out mice bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.
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http://dx.doi.org/10.1016/j.apsb.2021.12.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136579PMC
May 2022

Serum 25(OH)D Levels Modify the Association between Triglyceride and IR: A Cross-Sectional Study.

Int J Endocrinol 2022 10;2022:5457087. Epub 2022 May 10.

Renal Department, Dezhou People's Hospital, Dezhou, Shandong Province 25300, China.

Background: Triglycerides and 25(OH)D had been reported as correlates of IR, but the results suggest substantial heterogeneity across races. In addition, little research reported on whether different 25(OH)D levels affect triglycerides and IR. Therefore, a similar study on the US population would be a great addition to the current one. This study investigated the association between triglycerides and IR at different 25(OH)D levels.

Methods: A total of 19,926 participants were included, each containing specific indicators for the study project. IR was estimated as a HOMA-IR index ≥2.73. Four multivariate logistic regression models were developed to analyze the association between TG and IR and whether different 25(OH)D levels influenced this association. Smoothed fitting curves were plotted.

Results: Triglyceride was significantly associated with IR (OR: 1.3, 95 CI %), while this association received different 25(OH)D levels ( for interaction <0.001). The effect value OR was 1.33 with the high levels, and its effect value OR was 1.28 with the low levels.

Conclusion: This study demonstrates that triglyceride levels are significantly associated with insulin in the US adult population and can be used as a predictor of IR. This correlation was compromised at different 25 (OH)D levels, so future studies need to be explored in more ethnically diverse contexts.
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http://dx.doi.org/10.1155/2022/5457087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9113899PMC
May 2022

Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Promote Peritoneal Healing by Activating MAPK-ERK1/2 and PI3K-Akt to Alleviate Postoperative Abdominal Adhesion.

Stem Cells Int 2022 5;2022:1940761. Epub 2022 May 5.

Department of Pediatric Surgery, Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin 150001, China.

Peritoneal regeneration and repair can alleviate postoperative intraperitoneal adhesions, and mesenchymal stem cells (MSCs) have demonstrated the potential for peritoneal repair and regeneration. However, extracellular vesicles (EVs) are the main carriers for the MSC activity. Thus far, the roles of MSC-derived EVs on peritoneal repair are not well understood. To investigate the therapeutic effect of adipose-derived mesenchymal stem cell-derived EVs (ADSC-EVs) in peritoneal injuries, ADSC-EVs were injected in vivo via the tail vein of rats. The antiadhesion effects were evaluated following abdominal surgery. In addition, the levels of the peritoneal fibrinolysis system were determined via enzyme-linked immunosorbent assay. Expression differences in inflammatory and apoptotic markers were detected using immunofluorescence. The expression of extracellular matrix-related indexes and peritoneal healing were observed using immunohistochemistry. In vitro, rat peritoneal mesothelial cell proliferation was assessed via a 5-ethynyl-2-deoxyuridine assay. Cell migration was determined using scratch wound and transwell assays. Related signaling networks were estimated based on sequencing and bioinformatics analyses. The roles of the MAPK-ERK1/2 and PI3K-Akt signaling networks were analyzed using immunoblotting. This is the first report of the effectiveness of ADSC-EVs in the treatment of postoperative adhesions. ADSC-EVs were incorporated in vitro and induced rat peritoneal mesothelial cell proliferation and migration. This was mediated by stimulation of the MAPK-ERK1/2 and PI3K-Akt axes. ADSC-EVs promote the healing of the injured peritoneum, suggesting a promising therapeutic approach for peritoneal adhesions.
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http://dx.doi.org/10.1155/2022/1940761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107054PMC
May 2022
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