endoscopic-ultrasound-based-differentiation-pancreatic-neuroendocrine

Endoscopic Ultrasound-Based Differentiation of Pancreatic Neuroendocrine Tumors and Pancreatic Duct Adenocarcinoma

Endoscopic ultrasound (EUS) is one of the most critical imaging modalities for evaluating pancreatic masses, providing high-resolution visualization of ...

Fudan University

Semen-derived enhancer of viral infection (SEVI) is composed of amyloid fibrils that can greatly enhance HIV-1 infectivity. By its cationic property, SEVI promotes viral sexual transmission by facilitating the attachment and internalization of HIV-1 to target cells. Therefore, semen-derived amyloid fibrils are potential targets for microbicide design. ADS-J1 is an anionic HIV-1 entry inhibitor. In this study, we explored an additional function of ADS-J1: inhibition of SEVI fibril formation and blockage of SEVI-mediated enhancement of viral infection. We found that ADS-J1 bound to an amyloidogenic peptide fragment (PAP248-286, comprising amino acids 248 to 286 of the enzyme prostatic acid phosphatase), thereby inhibiting peptide assembly into amyloid fibrils. In addition, ADS-J1 binds to mature amyloid fibrils and antagonizes fibril-mediated enhancement of viral infection. Unlike cellulose sulfate, a polyanion that failed in clinical trial to prevent HIV-1 sexual transmission, ADS-J1 shows no ability to facilitate fibril formation. More importantly, the combination of ADS-J1 with several antiretroviral drugs exhibited synergistic effects against HIV-1 infection in semen, with little cytotoxicity to vaginal epithelial cells. Our results suggest that ADS-J1 or a derivative may be incorporated into a combination microbicide for prevention of the sexual transmission of HIV-1.

ADS-J1 inhibits semen-derived amyloid fibril formation and blocks fibril-mediated enhancement of HIV-1 infection.

The correlation of genetic alterations with response to neoadjuvant chemotherapy (NAC) has not been fully revealed. In this study, we enrolled 247 breast cancer patients receiving anthracycline-taxane-based NAC treatment. A next generation sequencing (NGS) panel containing 36 hotspot breast cancer-related genes was used in this study. Two different standards for the extent of pathologic complete response (pCR), ypT0/isypN0 and ypT0/is, were used as indicators for NAC treatment. TP53 mutation (n = 149, 60.3%), PIK3CA mutation (n = 109, 44.1%) and MYC amplification (n = 95, 38.5%) were frequently detected in enrolled cases. TP53 mutation (P = 0.019 for ypT0/isypN0 and P = 0.003 for ypT0/is) and ERBB2 amplification (P < 0.001 for both ypT0/isypN0 and ypT0/is) were related to higher pCR rates. PIK3CA mutation (P = 0.040 for ypT0/isypN0) and CCND2 amplification (P = 0.042 for ypT0/is) showed reduced sensitivity to NAC. Patients with MAPK pathway alteration had low pCR rates (P = 0.043 for ypT0/is). Patients with TP53 mutation (-) PIK3CA mutation (-) ERBB2 amplification (+) CCND1 amplification (-), TP53 mutation (+) PIK3CA mutation (-) ERBB2 amplification (+) CCND1 amplification (-) or TP53 mutation (+) PIK3CA mutation (+) ERBB2 amplification (+) CCND1 amplification (-)had significantly higher pCR rates (P < 0.05 for ypT0/isypN0 and ypT0/is) than wild type genotype tumors. Some cancer genetic alterations as well as pathway alterations were associated with chemosensitivity to NAC treatment. Our study may shed light on the molecular characteristics of breast cancer for prediction of NAC expectations when breast cancer is first diagnosed by biopsy.

Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 are associated with chemosensitivity for breast cancers.

Prostate cancer (PCa) remains the second leading cause of cancer-related death among men in the United States, and its molecular mechanism remains to be elucidated. Recent studies have suggested that microRNAs may play an important role in cancer development and progression. By analyzing the Gene Expression Omnibus dataset, we found lower expression for miR-488 in PCa than in normal tissues. Moreover, CCK-8, EdU, glucose uptake, and lactate secrete assays revealed that overexpression of miR-488 in PCa cell lines PC3 and DU145 resulted in inhibition of proliferation and glycolysis. In contrast, downregulation of miR-488 expression promoted proliferation and glycolysis in PCa cells. Using a bioinformatic approach and dual-luciferase reporter assays, we identified 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, isoform3 (PFKFB3), as a direct target of miR-488. Inhibition of PFKFB3 also suppressed PCa cell glycolysis and proliferation. Our study suggests that miR-488 inhibits PCa cell proliferation and glycolysis by targeting PFKFB3, and thus, miR-488 may be a novel therapeutic candidate for PCa.

MicroRNA-488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3.

To investigate the serum changes of oxidative stress markers and the relationship between these factors and visual field (VF) progression in patients with primary angle closure glaucoma (PACG).

Relationship between Oxidative Stress Biomarkers and Visual Field Progression in Patients with Primary Angle Closure Glaucoma.

The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus . It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice . Therefore, SRT shows promise as a treatment option for COVID-19.  The study shows SRT is an effective entry inhibitor against infection of SARS-CoV-2, which is currently prevalent globally. SRT targets the S protein of SARS-CoV-2 and is effective against a panel of SARS-CoV-2 variants. It also could be used in combination to prevent SARS-CoV-2 infection. More importantly, with long history of clinical use and proven safety, SRT might be particularly suitable to treat infection of SARS-CoV-2 in the central nervous system and optimized for treatment in older people, pregnant women, and COVID-19 patients with heart complications, which are associated with severity and mortality of COVID-19.

Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein.

We explored developing an internal validation model to predict the moderate to severe endoscopic activity of ulcerative colitis (UC) patients based on non-invasive or minimally-invasive parameters.

Risk prediction model based on blood biomarkers for predicting moderate to severe endoscopic activity in patients with ulcerative colitis.

Y-box binding protein 1 (YBX1) has been reported to be involved in the transcriptional regulation of various pathophysiological processes, such as inflammation, oxidative stress, and epithelial-mesenchymal transformation. However, its precise role and mechanism in regulating hepatic fibrosis remain unclear. In this study, we aimed to investigate the effects of YBX1 on liver fibrosis and its potential mechanism. The expression of YBX1 in human liver microarray, mice tissues and primary mouse hepatic stellate cells (HSCs) was validated to be upregulated in several hepatic fibrosis models (CCl injection, TAA injection, and BDL). Hepatic-specific Ybx1 overexpression exacerbated the liver fibrosis phenotypes in vivo and in vitro. Moreover, the knockdown of YBX1 significantly improved TGF-β-induced fibrosis in the LX2 cell (a hepatic stellate cell line). Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) of hepatic-specific Ybx1 overexpression (Ybx1-OE) mice with CCl injection showed increasing chromatin accessibility than CCl only group. Functional enrichments of open regions in the Ybx1-OE group indicated that extracellular matrix (ECM) accumulation, lipid purine metabolism, and oxytocin-related pathways were more accessible in the Ybx1-OE group. Accessible regions of the Ybx1-OE group in the promoter also suggested significant activation of genes related to liver fibrogenesis, such as response to oxidative stress and ROS, lipid localization, angiogenesis and vascular development, and inflammatory regulation. Moreover, we screened and validated the expression of candidate genes (Fyn, Axl, Acsl1, Plin2, Angptl3, Pdgfb, Ccl24, and Arg2), which might be potential targets of Ybx1 in the pathogenesis of liver fibrosis.

Y-box binding protein 1 promotes chromatin accessibility to aggravate liver fibrosis.

Early intervention of liver fibrosis can prevent its further irreversible progression. Both excess reactive oxygen species (ROS) and transforming growth factor beta(TGF-β)/drosophila mothers against decapentaplegic protein (SMADS) pathway balance disorder promote the progression of hepatic stellate cell (HSC) activation, but existing therapeutic strategies failed to focus on those two problems. A new biomimetic mesoporous polydopamine nandrug (MPO) was constructed for liver fibrosis therapy with multiple targets and reliable biosafety. The MPO was formed by mesoporous polydopamine (mPDA) which has the effect of ROS elimination and encapsulated with anti-fibrotic drug -oxymatrine (OMT) which can intervene liver fibrosis targeting TGF-β/SMADSpathway. Particularly, the nanodrug was completed by macrophage-derived exosome covering. The MPO was confirmed to possess a desired size distribution with negative zeta potential and exhibite strong ROS scavenger ability. Besides, in vitro studies, MPO showed efficient endocytosis and superior intracellular ROS scavenging without cytotoxicity; in vivo studies, MPO effectively cleared the excessive ROS in liver tissue and balanced the TGF-β/SMADS pathways, which in turn inhibited HSC activation and showed superior anti-liver fibrosis therapeutic efficiency with good biological safety. Taken together, this work showed highlights the great potential of the MPO for ameliorating liver fibrosis via ROS elimination and TGF-β/SMADS balancing.

Mesoporous polydopamine based biominetic nanodrug ameliorates liver fibrosis via antioxidation and TGF-β/SMADS pathway.

We conducted this randomized controlled trial (RCT) to evaluate the effectiveness and safety of moxibustion at Sanyinjiao (SP6) acupoint for treatment of negative mood and sleep quality in healthcare workers during the 2019 coronavirus disease (COVID-19).

Moxibustion for medical personnel with negative emotion and insomnia during COVID-19 pandemic: A randomized, controlled trial.

Most colorectal cancers originate from precancerous polyps. This study aimed to determine the prevalence of colorectal polyps with diverse pathological morphologies and to explore the risk factors for colorectal carcinoma in situ (CCS) and neoplastic polyps.

Prevalence of diverse colorectal polyps and risk factors for colorectal carcinoma in situ and neoplastic polyps.

An accurate and non-invasive diagnosis of the clinical stage is critical for effectively managing liver cirrhosis. This study aimed to identify serum metabolite biomarkers and clinical features that may reliably predict high-risk cirrhosis. This cross-sectional study recruited 94 cirrhotic patients (70 for identification cohort, 24 for validation cohort) from Minhang Hospital Affiliated with Fudan University between 2018 and 2021, who were analyzed by targeted quantitative metabolomics technique. Baseline clinical characteristics were collected, and different stage cirrhosis classification was performed according to the presence or absence of decompensated events. Potential metabolite biomarkers were screened, and a model for predicting the decompensation stage was created. Finally, the incidence of decompensated outcomes was analyzed. A total of 560 metabolites were detected in the identification cohort. Indole-3-propionic acid (IPA) was the most significantly decreased metabolic biomarker in the decompensated group (P<0.01, |log2FC| >2), having the strongest correlation with hyaluronic acid (r=-0.50, P<0.01). It also performed well for differentiating decompensated cirrhosis with an area under the curve (AUC) of 0.79(0.75 at internal validation). Another diagnostic model consisting of indole-3-propionic acid, hemoglobin, and albumin showed better predictive performance with an AUC of 0.97 (0.91 at internal validation). Also, 31 (44.29%) patients developed decompensated events at a median follow-up of 22.76±15.24 months. The cumulative incidence of decompensated events based on IPA subgroups (IPA <39.67ng/ml and ≥39.67ng/ml) showed a significant difference (P<0.01). "Indole-3-propionic acid" and a diagnostic model of hemoglobin and albumin can non-invasively identify cirrhotic populations at risk for decompensation, aiding in future management of liver cirrhosis.

Serum metabolomic profiling of patients with liver cirrhosis at different stages.

Indole‑3‑propionic acid (IPA), a product of  metabolism, has been shown to improve intestinal barrier function. In the present study, in vitro experiments using NCM460 human colonic epithelial cells were performed to investigate how IPA alleviates lipopolysaccharide (LPS)‑induced intestinal epithelial cell injury, with the aim of improving intestinal barrier function. In addition, the underlying mechanism was explored. NCM460 cell viability and apoptosis were measured using the Cell Counting Kit‑8 assay and flow cytometry, respectively. The integrity of the intestinal epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER). The underlying molecular mechanism was explored using western blotting, immunofluorescence staining, a dual luciferase reporter gene assay and quantitative PCR. The results showed that 10 µg/ml LPS induced the most prominent decrease in cell viability after 24 h of treatment. By contrast, IPA effectively inhibited LPS‑induced apoptosis in the intestinal epithelial cells. Additionally, >0.5 mM IPA improved intestinal barrier function by increasing TEER and upregulating the expression of tight junction proteins (zonula occludens‑1, claudin‑1 and occludin). Furthermore, IPA inhibited the release of pro‑inflammatory cytokines (IL‑1β, IL‑6 and TNF‑α) in a dose‑dependent manner and this was achieved via regulation of the Toll‑like receptor 4 (TLR4)/myeloid differentiation factor 88/NF‑κB and TLR4/TRIF/NF‑κB pathways. In conclusion, IPA may alleviate LPS‑induced inflammatory injury in human colonic epithelial cells. Taken together, these results suggest that IPA may be a potential therapeutic approach for the management of diseases characterized by LPS‑induced intestinal epithelial cell injury and intestinal barrier dysfunction.

Indole‑3‑propionic acid alleviates intestinal epithelial cell injury via regulation of the TLR4/NF‑κB pathway to improve intestinal barrier function.

Creating chirality in achiral graphene and other two-dimensional materials has attracted broad scientific interest due to their potential application in advanced optics, electronics and spintronics. However, investigations into their optical activities and related chiro-electronic properties are constrained by experimental challenges, particularly in the precise control over the chirality of these materials. Here a universal wax-aided immersion method is developed to yield graphene rolls with controllable chiral angles, and the method can be generalized in other two-dimensional materials for high-yield fabrication. The left-handed and right-handed rolls exhibit optical activity and excellent spin selectivity effects with a spin polarization over 90% at room temperature. The discovery of tunable chirality-induced spin selectivity in tailored roll-shaped allotropes, achievable only through precise control of chirality, distinguishes itself from other carbon materials or existing chiral materials. Our Dirac fermion model shows that the electrons moving predominately along one side of the chiral roll develop a preferred spin polarization, and the rolling-chirality-induced spin selectivity is a result of this finite spin selectivity effect. Our method opens up opportunities for endowing achiral two-dimensional materials with tunable chirality, and may enable the emergence of quantum behaviours and room-temperature spintronic technologies.

Graphene rolls with tunable chirality.

To address the clinical challenge of wound infection and secondary injury caused by frequent dressing changes during wound healing, this study aims to develop a chitosan-based aerogel dressing with on-demand dissoluble and efficient antibacterial functionality. A low-temperature alkaline urea dissolution strategy enabled the fabrication of chitosan aerogels (CS) through thermally induced gelation, solvent exchange, and freeze-drying. Subsequent ultrasonic-assisted adsorption of N-halamine 1,3-dichloro-5,5-dimethylhydantoin (MC) yielded functionalized N-halamine-loaded chitosan aerogels (CS-MC). Systematic optimization established 2.0 % CS (based on apparent density, porosity, and ethanol adsorption) and 1.5 % MC loading (determined via swelling kinetics, chlorine release profiles, and antibacterial efficacy) as optimal parameters. 2.0 % CS-1.5 % MC had high effective antibacterial effect. The killing rates of E. coli and S. aureus were 78.57 % and 80.30 % at 1 min, respectively, and the killing rates of both bacterial reached 100 % within 5 min. CS-MC dressings were completely dissolved in a dilute acetic acid solution within 20 min. CS-MC aerogels maintain high fibroblast viability, above the 70 % defined by ISO 10993-5 cytotoxicity threshold, achieving an optimal balance between efficient bactericide and histocompatibility. In summary, CS-MC exhibit high antibacterial efficacy and on-demand dissoluble properties, making them suitable for medical dressings.

Article	Year
ADS-J1 inhibits semen-derived amyloid fibril formation and blocks fibril-mediated enhancement of HIV-1 infection. Antimicrobial agents and chemotherapy\| PubMed ID: 26055369	2015
Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 are associated with chemosensitivity for breast cancers. Cancer science\| PubMed ID: 30776175	2019
MicroRNA-488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3. FEBS open bio\| PubMed ID: 31410981	2019
Relationship between Oxidative Stress Biomarkers and Visual Field Progression in Patients with Primary Angle Closure Glaucoma. Oxidative medicine and cellular longevity\| PubMed ID: 32831992	2020
Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein. Journal of virology\| PubMed ID: 36468859	2022
Risk prediction model based on blood biomarkers for predicting moderate to severe endoscopic activity in patients with ulcerative colitis. Frontiers in medicine\| PubMed ID: 36895716	2023
Y-box binding protein 1 promotes chromatin accessibility to aggravate liver fibrosis. Cellular signalling\| PubMed ID: 37290675	2023
Mesoporous polydopamine based biominetic nanodrug ameliorates liver fibrosis via antioxidation and TGF-β/SMADS pathway. International journal of biological macromolecules\| PubMed ID: 37482153	2023
Moxibustion for medical personnel with negative emotion and insomnia during COVID-19 pandemic: A randomized, controlled trial. Integrative medicine research\| PubMed ID: 37637182	2023
Prevalence of diverse colorectal polyps and risk factors for colorectal carcinoma in situ and neoplastic polyps. Journal of translational medicine\| PubMed ID: 38632639	2024
Serum metabolomic profiling of patients with liver cirrhosis at different stages. Cellular and molecular biology (Noisy-le-Grand, France)\| PubMed ID: 38678625	2024
Indole‑3‑propionic acid alleviates intestinal epithelial cell injury via regulation of the TLR4/NF‑κB pathway to improve intestinal barrier function. Molecular medicine reports\| PubMed ID: 39219265	2024
Graphene rolls with tunable chirality. Nature materials\| PubMed ID: 39984739	2025
Construction of aerogels based on N-halamine and chitosan as wound dressing materials with excellent bactericidal and on-demand dissoluble properties. International journal of biological macromolecules\| PubMed ID: 40324493	2025

Xiaojuan Li

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