Publications by authors named "Xiaoying Wang"

936 Publications

Diagnostic value of maternal alpha-fetoprotein variants in second-trimester biochemical screening for trisomy 21 and 18.

Sci Rep 2022 Aug 10;12(1):13605. Epub 2022 Aug 10.

The Fourth School of Clinical Medicine of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.

To evaluate the clinical predictive value of serum alpha-fetoprotein variants (AFP-L2, AFP-L3) in combination with maternal serum prenatal screening biomarkers in predicting fetal trisomy 21 and trisomy 18. We analyze the data of singleton pregnant women at 15-20 weeks of 731,922 gravidas from October 2007 to September 2019. The research objects were separated into the following groups: control (n = 569), trisomy 21 (n = 116), and trisomy 18 (n = 52). The cases were diagnosed by chromosomal karyotypic analysis of amniotic fluid cells. Level of AFP-L2 and AFP-L3 were detected in maternal serum among control women and patients. Receiver operator characteristic analysis, detection rate, false positive rate, false negative rate, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio, comprehensive discriminant improvement, net weight classification improvement, decision curve analysis and Hosmer-lemeshow (H-L) test were used to investigate the predictive value of free β-hCG, AFP, AFP-L2 and AFP-L3 on the risk models of trisomy 21, 18. There was a statistically significant difference in maternal serum AFP-L2 and AFP-L3 multiple of the median (MoM) among the trisomy 21, trisomy 18, and control groups. The AUCs of AFP-L2 and AFP-L3 for the screening trisomy 21 and trisomy 18 fetus were 0.785, 0.758 and 0.775, 0.754. According to ROC, the optimal cut-off values of AFP-L2 and AFP-L3 for predicting trisomy 21 and trisomy 18 fetuses all were 1.09 MoM and 1.30 MoM, respectively. The risk-calculation model constructed by AFP-L2 + AFP-L3 MoM manifested better efficiency than the original single-value truncation method using AFP MoM alone. Compared with different modeling methods, the AUC of trisomy 21 fetuses predicted by AFP-L2 + AFP-L3 + free β-hCG achieved an optimal value (0.938), while the AUC of trisomy 18 fetus predicted by AFP-L2 + free β-hCG was the best (0.991). Compared with AFP, the IDI of AFP-L2 or AFP-L3 alone increased 9.56% and 12.34%; the NRI increased 26.50% and 26.70 in predicting trisomy 21. For trisomy 18, the IDI of AFP-L2 or AFP-L3 alone declined with 8.12% and 1.52%; the NRI declined with 13.84% and 8.54%. In the combined model, the model with best detection rate, false positive rate and positive likelihood ratio was AFP-L2 + AFP-L3 + free β-hCG, followed by AFP-L2 + free β-hCG and AFP-L3 + free β-hCG, and finally AFP + free β-hCG. Maternal serum AFP-L2 and AFP-L3 in the second trimester is a good marker for screening trisomy 21 and trisomy18 with high sensitivity and specificity. The combined screening results are better than the single marker, and the efficiency of AFP-L2 + AFP-L3 + free β-hCG is the best.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-16807-xDOI Listing
August 2022

Puerarin attenuates isoproterenol‑induced myocardial hypertrophy via inhibition of the Wnt/β‑catenin signaling pathway.

Mol Med Rep 2022 Oct 10;26(4). Epub 2022 Aug 10.

Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.

Myocardial hypertrophy (MH) is an independent risk factor for cardiovascular disease, which in turn lead to arrhythmia or heart failure. Therefore, attention must be paid to formulation of therapeutic strategies for MH. Puerarin is a key bioactive ingredient isolated from genera of plants that is beneficial for the treatment of MH. However, its molecular mechanism of action has not been fully determined. In the present study, 40 µM puerarin was demonstrated to be a safe dose for human AC16 cells using Cell Counting Kit‑8 assay. The protective effects of puerarin against MH were demonstrated in AC16 cells stimulated with isoproterenol (ISO). These effects were characterized by a significant decrease in surface area of cells (assessed using fluorescence staining) and mRNA and protein expression levels of MH‑associated biomarkers, including atrial and brain natriuretic peptide, assessed using reverse transcription‑quantitative PCR and western blotting, as well as β‑myosin heavy chain mRNA expression levels. Mechanistically, western blotting demonstrated that puerarin inhibited activation of the Wnt signaling pathway. Puerarin also significantly decreased phosphorylation of p65; this was mediated via crosstalk between the Wnt and NF‑κB signaling pathways. An inhibitor (Dickkopf‑1) and activator (IM‑12) of the Wnt signaling pathway were used to demonstrate that puerarin‑mediated effects alleviated ISO‑induced MH via the Wnt signaling pathway. The results of the present study demonstrated that puerarin pre‑treatment may be a potential therapeutic strategy for preventing ISO‑induced MH and managing MH in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2022.12822DOI Listing
October 2022

CuS NP-based nanocomposite with photothermal and augmented-photodynamic activity for magnetic resonance imaging-guided tumor synergistic therapy.

J Inorg Biochem 2022 Jul 23;235:111940. Epub 2022 Jul 23.

State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China. Electronic address:

Although many treatments have been developed for oncotherapy, the lack of effective imaging guidance in the therapeutic process is still an urgent problem to be solved. In this study, magnetic resonance contrast agent (Gd) chelated on CuS nanoparticles and glucose oxidase (GOx) were coloaded into mesoporous silica nanoparticles (MSNs) to form [email protected], in which the Gd provided magnetic resonance imaging (MRI) for therapeutic process monitor while GOx could catalyze the generation of HO to enhance the photodynamic therapy (PDT). The in vitro results show that under near-infrared (NIR) laser irradiation (2 W·cm, 5 min), temperature rapidly increased by approximately 30 °C for the accumulation of heat. At the same time, GOx on [email protected] effectively consumed glucose to produce a large amount of HO, which was used to augment PDT through producing highly toxic hydroxyl radicals (·OH) and singlet oxygen (O). The photothermal and augmented-photodynamic could induce apoptosis and death of tumor cells. More importantly, the study found that [email protected] had MRI performance, which provided imaging guidance during the treatment process, and it can monitor the diffusion of water molecules in the tumor tissue during the treatment and microcirculation perfusion of capillary network. These results indicate that the nanomaterial produced significant synergistic therapeutic effects through photothermal and photodynamic forces, meanwhile showed excellent spatial resolution and deep tissue penetration in imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2022.111940DOI Listing
July 2022

Correction to: bFGF Protects Against Oxygen Glucose Deprivation/ Reoxygenation-Induced Endothelial Monolayer Permeability via S1PR1- Dependent Mechanisms.

Mol Neurobiol 2022 Jul 20. Epub 2022 Jul 20.

Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 2401, Charlestown, Boston, MA, 02129, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-022-02939-8DOI Listing
July 2022

N-glycosylation of GDF15 abolishes its inhibitory effect on EGFR in AR inhibitor-resistant prostate cancer cells.

Cell Death Dis 2022 Jul 19;13(7):626. Epub 2022 Jul 19.

Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu Province, 214122, China.

Castration-resistance of prostate cancer is one of the most challenging clinical problems. In the present study, we have performed proteomics and glycomics using LNCaP model. Growth differentiation factor-15 (GDF15) level is increased in androgen receptor (AR) inhibitor-resistant cells and the inhibitory effect of GDF15 on epithelial growth factor receptor (EGFR) pathway is relieved by GDF15 N70 glycosylation. Interference of GDF15 (siRNA or N70Q dominant negative) or EGFR pathway (inhibitor or siRNA for EGFR, SRC or ERK) decreases the resistant-cell survival in culture and tumor growth in mice. Our study reveals a novel regulatory mechanism of prostate cancer AR inhibitor resistance, raises the possibility of AR/SRC dual-targeting of castration-resistance of prostate cancer, and lays foundation for the future development of selective inhibitors of GDF15 glycosylation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-022-05090-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296468PMC
July 2022

Geospatial immune heterogeneity reflects the diverse tumor-immune interactions in intrahepatic cholangiocarcinoma.

Cancer Discov 2022 Jul 19. Epub 2022 Jul 19.

Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Fudan University,, Shanghai, China.

Intrahepatic cholangiocarcinoma (iCCA) exhibits extensive intratumoral heterogeneity and extremely high mortality rate. Here, we performed WES, RNA-seq, TCR-seq and multiplexed immunofluorescence on 207 tumor regions from 45 iCCA patients. Over half of iCCA displayed intratumoral heterogeneity of immune infiltration, and iCCA were classified into sparsely, heterogeneously, and highly infiltrated subgroups with distinct immunogenomic characteristics. Sparsely infiltrated tumors displayed active copy number loss of clonal neoantigens and heterogeneous immune infiltration played an important role in the subclonal evolution across tumor subregions. Highly infiltrated tumors were characterized by extensive immune activation and similar TCR repertoire across tumor subregions, but counteracted with T cell exhaustion and pervasive antigen presentation defects. Notably, FGFR2 mutations and fusions correlated with low mutation burden and reduced immune infiltration. Our work sculpted the dynamic tumor-immune interactions and developed a robust classification system to divide iCCA patients into high and low immune evasion groups with different prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2159-8290.CD-21-1640DOI Listing
July 2022

Utility of the Iwate difficulty scoring system for laparoscopic right posterior sectionectomy: do surgical outcomes differ for tumors in segments VI and VII?

Surg Endosc 2022 Jul 18. Epub 2022 Jul 18.

General and Hepatobiliary Surgery, Department of Surgery, Dentistry, Gynecology and Pediatrics, GB Rossi Hospital, University of Verona, Verona, Italy.

Introduction: The Iwate Score (IS) have not been well-validated for specific procedures, especially for right posterior sectionectomy (RPS). In this study, the utility of the IS was determined for laparoscopic (L)RPS and the effect of tumor location on surgical outcomes was investigated.

Methods: Post-hoc analysis of 647 L-RPS performed in 40 international centers of which 596L-RPS cases met the inclusion criteria. Baseline characteristics and perioperative outcomes of patients stratified based on the Iwate score were compared to determine whether a correlation with surgical difficulty existed. A 1:1 Mahalanobis distance matching was utilized to investigate the effect of tumor location on L-RPS outcomes.

Results: The patients were stratified into 3 levels of difficulty (31 intermediate, 143 advanced, and 422 expert) based on the IS. When using a stepwise increase of the IS excluding the tumor location score, only Pringle's maneuver was more frequently used in the higher surgical difficulty level (35.5%, 54.6%, and 65.2%, intermediate, advanced, and expert levels, respectively, Z = 3.34, p = 0.001). Other perioperative results were not associated with a statistical gradation toward higher difficulty level. 80 of 85 patients with a segment VI lesion and 511 patients with a segment VII lesion were matched 1:1. There were no significant differences in the perioperative outcomes of the two groups including open conversion, operating time, blood loss, intraoperative blood transfusion, postoperative stay, major morbidity, and mortality.

Conclusion: Among patients undergoing L-RPS, the IS did not significantly correlate with most outcome measures associated with intraoperative difficulty and postoperative outcomes. Similarly, tumor location had no effect on L-RPS outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-022-09404-6DOI Listing
July 2022

LncRNA MINCR attenuates osteoarthritis progression via sponging miR-146a-5p to promote BMPR2 expression.

Cell Cycle 2022 Jul 18:1-16. Epub 2022 Jul 18.

Department of Preventive Treatment of Disease, the Third Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, China.

The purposes of this study are to explore the function and regulatory mechanism of a novel lncRNA MYC-Induced Long non-coding RNA (MINCR) in osteoarthritis (OA). The expression of lncRNA MINCR, miR-146a-5p, and bone morphogenetic protein receptor 2 (BMPR2), Sry-type high-mobility-group box 9 (SOX9), collagen type II alpha 1 (COL2A1), Aggrecan, metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), Matrix metalloproteinase 3 (MMP3), MMP13, COL2A1, and Aggrecan were determined using quantitative real-time PCR (qRT-PCR), western blot, immunohistochemistry (IHC) and immunofluorescence (IF) and . And distribution and expression of MINCR were examined by fluorescence in situ hybridization (FISH). Cell proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining, Annexin V-FITC/Propidium Iodide (PI), and Terminal Deoxynucleotidyl transferase-mediated dUTP Nick-End Labeling (TUNEL) staining and . The anterior cruciate ligament transection (ACLT) rat model was constructed to analyze the MINCR/miR-146a-5p/BMPR2 axis . The cartilage degeneration was determined by pathological staining with Hematoxylin and Eosin (H&E) and Safranin O staining. The binding relationship between MINCR and miR-146a-5p, and between miR-146a-5p and BMPR2 were determined by a dual-luciferase reporter gene, RNA Immunoprecipitation (RIP) assay, and RNA-pull down assays. Here, MINCR and BMPR2 were downregulated whereas miR-146a-5p was upregulated in OA cartilage tissues compared with control as well as IL-1β-induced chondrocytes compared with normal chondrocytes. Function experiments indicated that MINCR upregulation promoted cell proliferation and inhibited apoptosis and extracellular matrix (ECM)-degeneration. We also proved the binding relationship between MINCR and miR-146a-5p, and the BMPR2 acted as a target of miR-146a-5p. Mechanism analysis using rescue experiments and , MINCR silencing reversed the effects of miR-146a-5p downregulation in OA. Overexpression of miR-146a-5p also reversed the function of BMPR2 overexpression in OA. These data indicated that MINCR prevented OA progression via targeting miR-146a-5p to promote BMPR2 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384101.2022.2099191DOI Listing
July 2022

Clinical efficacy of endoscopic antireflux mucosectomy . Stretta radiofrequency in the treatment of gastroesophageal reflux disease: a retrospective, single-center cohort study.

Ann Transl Med 2022 Jun;10(12):660

Department of Gastroenterology, Strategic Support Force Medical Center, Beijing, China.

Background: Currently, antireflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) are the most commonly used minimally invasive antireflux therapies. To date, there have not been any reports comparing ARMS and SRF. Our aim was to compare the clinical efficacies of these two therapeutic methods.

Methods: We analyzed data from gastroesophageal reflux disease (GERD) patients, including 39 who received ARMS treatment and 30 who received SRF treatment between January 2020 and May 2021. Symptom control, gastroesophageal reflux disease questionnaire (GERDQ) score, gastroesophageal reflux disease health-related quality of life (GERD-HRQL) score, proton pump inhibitor (PPI) withdrawal, and PPI reduction were analyzed and compared.

Results: After 6 months of follow-up, the results showed that both therapies were effective in improving symptoms and quality of life. No difference was found between the ARMS group and SRF group in GERDQ score, GERD-HRQL score, PPI withdrawal rate, or PPI reduction rate (P>0.05). There was no significant difference in the PPI withdrawal rate between the two therapies among patients with gastroesophageal flap valve (GEFV) grade II and grade III (P>0.05), but the PPI withdrawal rate in the ARMS group was significantly higher than that in the SRF group among patients with GEFV grade IV (P<0.05).

Conclusions: The clinical efficacies of ARMS and SRF 6 months postoperation were equivalent. The results showed that both ARMS and SRF treatment were acceptable for patients with GEFV grades II and III, while ARMS should be selected for patients with GEFV grade IV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-22-2071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279761PMC
June 2022

Defining Global Benchmarks for Laparoscopic Liver Resections: An International Multicenter Study.

Ann Surg 2022 Jul 15. Epub 2022 Jul 15.

General and Digestive Surgery, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.

Objective: To establish global benchmark outcomes indicators after laparoscopic liver resections (L-LR).

Background: There is limited published data to date on the best achievable outcomes after L-LR.

Methods: This is a post hoc analysis of a multicenter database of 11,983 patients undergoing L-LR in 45 international centers in 4 continents between 2015 and 2020. Three specific procedures: left lateral sectionectomy (LLS), left hepatectomy (LH), and right hepatectomy (RH) were selected to represent the 3 difficulty levels of L-LR. Fifteen outcome indicators were selected to establish benchmark cutoffs.

Results: There were 3519 L-LR (LLS, LH, RH) of which 1258 L-LR (40.6%) cases performed in 34 benchmark expert centers qualified as low-risk benchmark cases. These included 659 LLS (52.4%), 306 LH (24.3%), and 293 RH (23.3%). The benchmark outcomes established for operation time, open conversion rate, blood loss ≥500 mL, blood transfusion rate, postoperative morbidity, major morbidity, and 90-day mortality after LLS, LH, and RH were 209.5, 302, and 426 minutes; 2.1%, 13.4%, and 13.0%; 3.2%, 20%, and 47.1%; 0%, 7.1%, and 10.5%; 11.1%, 20%, and 50%; 0%, 7.1%, and 20%; and 0%, 0%, and 0%, respectively.

Conclusions: This study established the first global benchmark outcomes for L-LR in a large-scale international patient cohort. It provides an up-to-date reference regarding the "best achievable" results for L-LR for which centers adopting L-LR can use as a comparison to enable an objective assessment of performance gaps and learning curves.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000005530DOI Listing
July 2022

Ursolic acid alleviates tetrandrine-induced hepatotoxicity by competitively binding to the substrate-binding site of glutathione S-transferases.

Phytomedicine 2022 Sep 6;104:154325. Epub 2022 Jul 6.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, PR China. Electronic address:

Background: Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra S. Moore, is the only approved medicine in China for silicosis. However, TET-induced hepatotoxicity has raised safety concerns. The underlying toxic targets and mechanism induced by TET remain unclear; there are no targeted detoxification strategies developed for TET-induced hepatotoxicity. Ursolic acid (UA), a pentacyclic triterpene with liver protective effects, may have detoxification effects on TET-induced hepatotoxicity.

Purpose: This study aims to explore toxic targets and mechanism of TET and present UA as a potential targeted therapy for alleviating TET-induced hepatotoxicity.

Methods: A TET-induced liver-injury model was established to evaluate TET toxicity and the potential UA detoxification effect. Alkenyl-modified TET and UA probes were designed to identify potential liver targets. Pharmacological and molecular biology methods were used to explore the underlying toxicity/detoxification mechanism.

Results: TET induced liver injury by covalently binding to the substrate-binding pocket (H-site) of glutathione S-transferases (GSTs) and inhibiting GST activity. The covalent binding led to toxic metabolite accumulation and caused redox imbalance and liver injury. UA protected the liver from TET-induced damage by competitively binding to the GST H-site.

Conclusion: The mechanism of TET-induced hepatotoxicity is related to irreversible binding with the GST H-site and GST-activity inhibition. UA, a natural antidote, competed with TET on H-site binding and reversed the redox imbalance. This study revealed the hepatotoxic mechanism of TET and provided a targeted detoxifying agent, UA, to alleviate hepatotoxicity caused by GST inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2022.154325DOI Listing
September 2022

Simultaneous vessel segmentation and unenhanced prediction using self-supervised dual-task learning in 3D CTA (SVSUP).

Comput Methods Programs Biomed 2022 Jul 3;224:107001. Epub 2022 Jul 3.

Academy for Advanced Interdisciplinary Studies, Peking University, No.5 Yiheyuan Rd., Beijing, 100871, China; College of Engineering, Peking University, No.5 Yiheyuan Rd., Beijing, 100871, China. Electronic address:

Background And Objective: The vessel segmentation in CT angiography (CTA) provides an important basis for automatic diagnosis and hemodynamics analysis. Virtual unenhanced (VU) CT images obtained by dual-energy CT can assist clinical diagnosis and reduce radiation dose by obviating true unenhanced imaging (UECT). However, accurate segmentation of all vessels in the head-neck CTA (HNCTA) remains a challenge, and VU images are currently not available from conventional single-energy CT imaging.

Methods: In this paper, we proposed a self-supervised dual-task deep learning strategy to fully automatically segment all vessels and predict unenhanced CT images from single-energy HNCTA based on a developed iterative residual-sharing scheme. The underlying idea was to use the correlation between the two tasks to improve task performance while avoiding manual annotation for model training.

Results: The feasibility of the strategy was verified using the data of 24 patients. For vessel segmentation task, the proposed model achieves a significantly higher average Dice coefficient (84.83%, P-values 10 in paired t-test) than the state-of-the-art segmentation model, vanilla VNet (78.94%), and several popular 3D vessel segmentation models, including Hessian-matrix based filter (62.59%), optically-oriented flux (66.33%), spherical flux model (66.91%), and deep vessel net (66.47%). For the unenhanced prediction task, the average ROI-based error compared to the UECT in the artery tissue is 6.1±4.5 HU, similar to previously reported 6.4±5.1 HU for VU reconstruction.

Conclusions: Results show that the proposed dual-task framework can effectively improve the accuracy of vessel segmentation in HNCTA, and it is feasible to predict the unenhanced image from single-energy CTA, providing a potential new approach for radiation dose saving. Moreover, to our best knowledge, this is the first reported annotation-free deep learning-based full-image vessel segmentation for HNCTA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmpb.2022.107001DOI Listing
July 2022

T-Lymphocyte Interactions with the Neurovascular Unit: Implications in Intracerebral Hemorrhage.

Cells 2022 06 24;11(13). Epub 2022 Jun 24.

Clinical Neuroscience Research Center, Department of Neurosurgery & Neurology, Tulane University School of Medicine, New Orleans, LA 70112, USA.

In the pathophysiology of hemorrhagic stroke, the perturbation of the neurovascular unit (NVU), a functional group of the microvascular and brain intrinsic cellular components, is implicated in the progression of secondary injury and partially informs the ultimate patient outcome. Given the broad NVU functions in maintaining healthy brain homeostasis through its maintenance of nutrients and energy substrates, partitioning central and peripheral immune components, and expulsion of protein and metabolic waste, intracerebral hemorrhage (ICH)-induced dysregulation of the NVU directly contributes to numerous destructive processes in the post-stroke sequelae. In ICH, the damaged NVU precipitates the emergence and evolution of perihematomal edema as well as the breakdown of the blood-brain barrier structural coherence and function, which are critical facets during secondary ICH injury. As a gateway to the central nervous system, the NVU is among the first components to interact with the peripheral immune cells mobilized toward the injured brain. The release of signaling molecules and direct cellular contact between NVU cells and infiltrating leukocytes is a factor in the dysregulation of NVU functions and further adds to the acute neuroinflammatory environment of the ICH brain. Thus, the interactions between the NVU and immune cells, and their reverberating consequences, are an area of increasing research interest for understanding the complex pathophysiology of post-stroke injury. This review focuses on the interactions of T-lymphocytes, a major cell of the adaptive immunity with expansive effector function, with the NVU in the context of ICH. In cataloging the relevant clinical and experimental studies highlighting the synergistic actions of T-lymphocytes and the NVU in ICH injury, this review aimed to feature emergent knowledge of T cells in the hemorrhagic brain and their diverse involvement with the neurovascular unit in this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells11132011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266108PMC
June 2022

Psoralen induces hepatotoxicity by covalently binding to glutathione-S-transferases and the hepatic cytochrome P450.

Phytomedicine 2022 Sep 13;104:154165. Epub 2022 May 13.

Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. Electronic address:

Background: Psoraleae Fructus has been widely used in China and its surroundings; however, Psoraleae Fructus and its compound preparation have been reported recently to cause liver injury in clinics. Thus, its safe use has attracted increasing attention. The possible mechanism is related to the metabolism of psoralen, but it still needs further clarification.

Purpose: The present study was designed to evaluate the toxicity of psoralen and investigate the potentially related molecular mechanisms using chemical biology methods combined with animal experiments to provide evidence for the rational clinical use of psoralen.

Methods: An in vivo experiment was conducted with a time series of 20-80 mg/kg psoralen to verify its toxic performance. Target capture and click reactions were used to investigate direct targets of psoralen. Selectivity for different glutathione-S-transferase (GST) subtypes in the liver and inhibition of cytochrome P450 (CYP450) were also detected.

Results: Psoralen build-up in the liver is the primary cause of liver damage. Our study revealed the mechanism by which psoralen induces liver injury. Psoralen can bind directly to CYP2D6, CYP3A4, GST-α, and GST-μ and inhibit their activities, causing the depletion of glutathione (GSH) in vivo, which in turn induces hepatic damage. The special structure of α,β-unsaturated lactones in psoralen facilitates its attachment to its target; therefore, complementing psoralen with GSH can efficiently protect the liver from damage.

Conclusions: Psoralen causes a disorder in drug metabolism by inhibiting the activity of CYPs and GSTs, causing exhaustion of GSH, and subsequently leading to liver damage. The co-administration of GSH and psoralen is an effective way to avoid liver injury in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2022.154165DOI Listing
September 2022

Automatic measurement of the patellofemoral joint parameters in the Laurin view: a deep learning-based approach.

Eur Radiol 2022 Jul 5. Epub 2022 Jul 5.

Department of Radiology, Peking University First Hospital, No.8 Xishiku Street, Xicheng District, Beijing, 100034, China.

Objectives: To explore the performance of a deep learning-based algorithm for automatic patellofemoral joint (PFJ) parameter measurements from the Laurin view.

Methods: A total of 1431 consecutive Laurin views of the PFJ were retrospectively collected and divided into two parts: (1) the model development dataset (dataset 1, n = 1230) and (2) the hold-out test set (dataset 2, n = 201). Dataset 1 was used to develop the U-shaped fully convolutional network (U-Net) model to segment the landmarks of the PFJ. Based on the predicted landmarks, the PFJ parameters were calculated, including the sulcus angle (SA), congruence angle (CA), patellofemoral ratio (PFR), and lateral patellar tilt (LPT). Dataset 2 was used to assess the model performance. The mean of three radiologists who independently measured the PFJ parameters was defined as the reference standard. Model performance was assessed by the intraclass correlation coefficient (ICC), mean absolute difference (MAD), and root mean square (RMS) compared to the reference standard. Ninety-five percent limits of agreement (95% LoA) were calculated pairwise for each radiologist, reference standard, and model.

Results: Compared with the reference standard, U-Net showed good performance for predicting SA, CA, PFR, and LPT, with ICC = 0.85-0.97, MAD = 0.06-5.09, and RMS = 0.09-6.90 in the hold-out test set. Except for the PFR, the remaining parameters measured between the reference standard and the model were within the 95% LoA in the hold-out test dataset.

Conclusions: The U-Net-based deep learning approach had a relatively high model performance in automatically measuring SA, CA, PFR, and LPT.

Key Points: • The U-Net model could be used to segment the landmarks of the PFJ and calculate the SA, CA, PFR, and LPT, which could be used to evaluate the patellar instability. • In the hold-out test, the automatic measurement model yielded comparable performance with reference standard. • The automatic measurement model could still accurately predict SA, CA, PFR, and LPT in patients with PI and/or PFOA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-022-08967-1DOI Listing
July 2022

DESSO-DB: A web database for sequence and shape motif analyses and identification.

Comput Struct Biotechnol J 2022 16;20:3053-3058. Epub 2022 Jun 16.

Department of Mathematics, Shandong University, Shandong, China.

-regulatory motif (motif for short) identification and analyses are essential steps in detecting gene regulatory mechanisms. Deep learning (DL) models have shown substantial advances in motif prediction. In parallel, intuitive and integrative web databases are needed to make effective use of DL models and ensure easy access to the identified motifs. Here, we present DESSO-DB, a web database developed to allow efficient access to the identified motifs and diverse motif analyses. DESSO-DB provides motif prediction results and visualizations of 690 ENCODE human Chromatin Immunoprecipitation sequencing (ChIP-seq) data (including 161 transcription factors (TFs) in 91 cell lines) and 1,677 human ChIP-seq data (including 547 TFs in 359 cell lines) from Cistrome DB using DESSO, which is an in-house developed DL tool for motif prediction. It also provides online motif finding and scanning functions for new ChIP-seq/ATAC-seq datasets and downloadable motif results of the above 690 DECODE datasets, 126 cancer ChIP-seq, 55 RNA Crosslinking-Immunoprecipitation and high-throughput sequencing (CLIP-seq) data. DESSO-DB is deployed on the Google Cloud Platform, providing stabilized and efficient resources freely to the public. DESSO-DB is free and available at http://cloud.osubmi.com/DESSO/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.csbj.2022.06.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233226PMC
June 2022

Preoperative prediction of pelvic lymph nodes metastasis in prostate cancer using an ADC-based radiomics model: comparison with clinical nomograms and PI-RADS assessment.

Abdom Radiol (NY) 2022 Jun 28. Epub 2022 Jun 28.

Department of Radiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.

Purpose: To develop and test radiomics models based on manually corrected or automatically gained masks on ADC maps for pelvic lymph node metastasis (PLNM) prediction in patients with prostate cancer (PCa).

Methods: A primary cohort of 474 patients with PCa who underwent prostate mpMRI were retrospectively enrolled for PLNM prediction between January 2017 and January 2020. They were then randomly split into training/validation (n = 332) and test (n = 142) groups for model development and internal testing. Four radiomics models were developed using four masks (manually corrected/automatic prostate gland and PCa lesion segmentation) based on the ADC maps using the primary cohort. Another cohort of 128 patients who underwent radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND) for PCa was used as the testing cohort between February 2020 and October 2021. The performance of the models was evaluated in terms of discrimination and clinical usefulness using the area under the curve (AUC) and decision curve analysis (DCA). The optimal radiomics model was further compared with Memorial Sloan Kettering Cancer Center (MSKCC) and Briganti 2017 nomograms, and PI-RADS assessment.

Results: 17 (13.28%) Patients with PLNM were included in the testing cohort. The radiomics model based on the mask of automatically segmented prostate obtained the highest AUC among the four radiomics models (0.73 vs. 0.63 vs. 0.70 vs. 0.56). Briganti 2017, MSKCC nomograms, and PI-RADS assessment-yielded AUCs of 0.69, 0.71, and 0.70, respectively, and no significant differences were found compared with the optimal radiomics model (P = 0.605-0.955).

Conclusion: The radiomics model based on the mask of automatically segmented prostate offers a non-invasive method to predict PLNM for patients with PCa. It shows comparable accuracy to the current MKSCC and Briganti nomograms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00261-022-03583-5DOI Listing
June 2022

Comparison between the difficulty of laparoscopic limited liver resections of tumors located in segment 7 versus segment 8: An international multicenter propensity-score matched study.

J Hepatobiliary Pancreat Sci 2022 Jun 27. Epub 2022 Jun 27.

Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China.

Background: Presently, according to different difficulty scoring systems, there is no difference in complexity estimation of laparoscopic liver resection (LLR) of segments 7 and 8. However, there is no published data supporting this assumption. To date, no studies have compared the outcomes of laparoscopic parenchyma-sparing resection of the liver segments 7 and 8.

Methods: A post hoc analysis of patients undergoing LLR of segments 7 and 8 in 46 centers between 2004 and 2020 was performed. 1:1 Propensity score matching (PSM) was used to compare isolated LLR of segments 7 and 8. Subset analyses were also performed to compare atypical resections and segmentectomies of 7 and 8.

Results: A total of 2411 patients were identified, and 1691 patients met the inclusion criteria. Comparison after PSM between the entire cohort of segment 7 and segment 8 resections revealed inferior results for segment 7 resection in terms of increased blood loss, blood transfusions, and conversions to open surgery. Subset analyses of only atypical resections similarly demonstrated poorer outcomes for segment 7 in terms of increased blood loss, operation time, blood transfusions, and conversions to open surgery. Conversely, a subgroup analysis of segmentectomies after PSM found better outcomes for segment 7 in terms of a shorter operation time and hospital stay.

Conclusion: Differences in the outcomes of segments 7 and 8 resections suggest a greater difficulty of laparoscopic atypical resection of segment 7 compared to segment 8, and greater difficulty of segmentectomy 8 compared to segmentectomy 7.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.1210DOI Listing
June 2022

Refractive Outcomes of Implantable Collamer Lens Implantation in 1212 Eyes with Suboptimal Corrected Distance Vision Acuity.

Curr Eye Res 2022 Jul 10:1-5. Epub 2022 Jul 10.

Department of Ophthalmology, Eye, ENT Hospital of Fudan University, Shanghai, PR China.

Purpose: To analyze the factors related to corrected distance vision acuity (CDVA) after implantable collamer lens (ICL) implantation in patients with preoperative suboptimal CDVA.

Methods: This retrospective study included patients with suboptimal preoperative CDVA (CDVA ≤ 20/25) who underwent ICL implantation (V4 or V4c). Preoperative and postoperative clinical evaluations included CDVA, uncorrected distance visual acuity (UDVA), and refraction.

Results: A total of 1212 eyes from 731 patients were identified. CDVA increased in 90.8% of the eyes after surgery. Among them, 57.5% of the eyes (697 eyes) gained more than one line. The preoperative LogMAR CDVA was 0.32 ± 0.23, which significantly improved to 0.13 ± 0.17 postoperatively ( < 0.001). There was no significant difference between ICL V4c and ICL V4 in the LogMAR UDVA, sphere, cylinder, SE, LogMAR CDVA, efficacy index, and safety index after surgery ( > 0.05). For eyes with full correction, the postoperative LogMAR CDVA = 0.575 * preoperative LogMAR CDVA - 0.061 ( < 0.001, = 0.53). For eyes with partial correction, the postoperative LogMAR CDVA = 0.536 * preoperative LogMAR CDVA - 0.007 * SE - 0.196 ( < 0.001, = 0.55).

Conclusions: ICL implantation can improve CDVA in eyes with suboptimal CDVA. This study provides the postoperative outcomes of eyes with different preoperative CDVA, which makes it convenient for surgeons to communicate with such patients before surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2022.2094418DOI Listing
July 2022

Corrigendum: Chlorine Dioxide Inhibits African Swine Fever Virus by Blocking Viral Attachment and Destroying Viral Nucleic Acids and Proteins.

Front Vet Sci 2022 9;9:937653. Epub 2022 Jun 9.

Guangzhou Higher Education Mega Center, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

[This corrects the article DOI: 10.3389/fvets.2022.844058.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fvets.2022.937653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222332PMC
June 2022

A Radiomics Model for Preoperative Predicting Sentinel Lymph Node Metastasis in Breast Cancer Based on Dynamic Contrast-Enhanced MRI.

Front Oncol 2022 6;12:884599. Epub 2022 Jun 6.

Department of Radiology, Peking University First Hospital, Beijing, China.

Purpose: To develop a radiomics model based on preoperative dynamic contrast-enhanced MRI (DCE-MRI) to identify sentinel lymph node (SLN) metastasis in breast cancer (BC) patients.

Materials And Methods: The MRI images and clinicopathological data of 142 female primary BC patients from January 2017 to December 2018 were included in this study. The patients were randomly divided into the training and testing cohorts at a ratio of 7:3. Four types of radiomics models were built: 1) a radiomics model based on the region of interest (ROI) of breast tumor; 2) a radiomics model based on the ROI of intra- and peri-breast tumor; 3) a radiomics model based on the ROI of axillary lymph node (ALN); 4) a radiomics model based on the ROI of ALN and breast tumor. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to assess the performance of the three radiomics models. The technique for order of preference by similarity to ideal solution (TOPSIS) through decision matrix analysis was used to select the best model.

Results: Models 1, 2, 3, and 4 yielded AUCs of 0.977, 0.999, 0.882, and 1.000 in the training set and 0.699, 0.817, 0.906, and 0.696 in the testing set, respectively, in terms of predicting SLN metastasis. Model 3 had the highest AUC in the testing cohort, and only the difference from Model 1 was statistically significant ( = 0.022). DCA showed that Model 3 yielded a greater net benefit to predict SLN metastasis than the other three models in the testing cohort. The best model analyzed by TOPSIS was Model 3, and the method's names for normalization, dimensionality reduction, feature selection, and classification are mean, principal component analysis (PCA), ANOVA, and support vector machine (SVM), respectively.

Conclusion: ALN radiomics feature extraction on DCE-MRI is a potential method to evaluate SLN status in BC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2022.884599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207247PMC
June 2022

Preoperative Prediction of Inferior Vena Cava Wall Invasion of Tumor Thrombus in Renal Cell Carcinoma: Radiomics Models Based on Magnetic Resonance Imaging.

Front Oncol 2022 6;12:863534. Epub 2022 Jun 6.

Department of Radiology, Peking University First Hospital, Peking University, Beijing, China.

Objective: To develop radiomics models to predict inferior vena cava (IVC) wall invasion by tumor thrombus (TT) in patients with renal cell carcinoma (RCC).

Methods: Preoperative MR images were retrospectively collected from 91 patients with RCC who underwent radical nephrectomy (RN) and thrombectomy. The images were randomly allocated into a training (n = 64) and validation (n = 27) cohort. The inter-and intra-rater agreements were organized to compare masks delineated by two radiologists. The masks of TT and IVC were manually annotated on axial fat-suppression T2-weighted images (fsT2WI) by one radiologist. The following models were trained to predict the probability of IVC wall invasion: two radiomics models using radiomics features extracted from the two masks (model 1, radiomics model_IVC; model 2, radiomics model_TT), two combined models using radiomics features and radiological features (model 3, combined model_IVC; model 4, combined model_TT), and one radiological model (model 5) using radiological features. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were applied to validate the discriminatory effect and clinical benefit of the models.

Results: Model 1 to model 5 yielded area under the curves (AUCs) of 0.881, 0.857, 0.883, 0.889, and 0.769, respectively, in the validation cohort. No significant differences were found between these models ( = 0.108-0.951). The dicision curve analysis (DCA) showed that the model 3 had a higher overall net benefit than the model 1, model 2, model 4, and model 5.

Conclusions: The combined model_IVC (model 3) based on axial fsT2WI exhibited excellent predictive performance in predicting IVC wall invasion status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2022.863534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207178PMC
June 2022

Evapotranspiration dynamics and their drivers in a temperate mixed forest in northeast China.

PeerJ 2022 8;10:e13549. Epub 2022 Jun 8.

Yichun Wuying District Meteorological Service, Yichun, People's Republic of China.

Evapotranspiration (ET) is a vital part of the global water cycle and is closely related to carbon sequestration. Analysing ET dynamics and their drivers would benefit for improving our understanding of the global water and carbon cycles. Using an eddy covariance (EC) approach, we analysed ET dynamics and their drivers in a temperate mixed forest over northeast China from 2016 to 2017. The results showed that 43.55% of our eddy covariance data passed the quality control. In addition, the energy balance ratio was 0.62, indicating that measurements were reliable. The measured ET showed clear single peak patterns with seasonal and diurnal variations. The daily ET ranged from 0 to 7.75 mm d and the hourly ET ranged from 0 to 0.28 mm h. The ranges of hourly ET floated from 0 to 0.05 mm h at non-growing season (November to April) while ranged from 0 to 0.28 mm h at active growing season (May to October). The diurnal ET dynamics during the non-growing season were driven by air temperature ( ) but were governed by global radiation ( ) during the active growing season. Leaf area index (LAI) comprehensively reflected the variations of and , and was found to be the primary factor shaping the seasonal dynamics of ET. The annual ET rates were 501.91 ± 5.30 mm year and 554.60 ± 11.24 mm year for 2016 and 2017, respectively. Therefore, energy supply, represented by and , governed ET dynamics in our temperate mixed forest, while variables representing the energy supply affecting ET dynamics differed among seasons and time scales. ET dynamics indicated that a temperate mixed forest is important to the global water cycle. Our results improved our understanding of ET dynamics in the studied region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.13549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188314PMC
June 2022

Thermo-processable chitosan-based plastic substitute with self-adaptiveness and closed-loop recyclability.

Carbohydr Polym 2022 Sep 26;291:119479. Epub 2022 Apr 26.

State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510640, China. Electronic address:

The increasing environmental burden generated by disposable plastic wastes makes the development of sustainable substitute materials an emergent task. As one of the most abundant bioresources, chitosan (CS) has been considered as a potential candidate for plastic substitution. Conventionally, CS-based materials are fabricated through a solution-processing procedure due to the high crystallinity of CS. Herein, we designed a CS-based material via integrating CS into the network of polyimine (PI), which shows thermomechanical processability similar to plastics. Strong interactions were achieved through dynamic imine bond and hydrogen bond and thus formed a thermo-processable dynamic composite network. These CS-based plastic substitutes exhibit exceptional mechanical performances, excellent thermal/chemical stability, and a series of self-adaptiveness, including re-healing, reprocessing and multi-layer laminating. Notably, CPs can be easily degraded and 100% recycled for the production of next-generation materials. This work provides an alternative route to produce green and sustainable biomass materials as a plastic substitute.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2022.119479DOI Listing
September 2022

Factors associated with and impact of open conversion on the outcomes of minimally invasive left lateral sectionectomies: An international multicenter study.

Surgery 2022 Aug 7;172(2):617-624. Epub 2022 Jun 7.

General and Hepatobiliary Surgery, Department of Surgery, Dentistry, Gynecology and Pediatrics University of Verona, GB Rossi Hospital, Verona, Italy.

Background: Despite the rapid advances that minimally invasive liver resection has gained in recent decades, open conversion is still inevitable in some circumstances. In this study, we aimed to determine the risk factors for open conversion after minimally invasive left lateral sectionectomy, and its impact on perioperative outcomes.

Methods: This is a post hoc analysis of 2,445 of 2,678 patients who underwent minimally invasive left lateral sectionectomy at 45 international centers between 2004 and 2020. Factors related to open conversion were analyzed via univariate and multivariate analyses. One-to-one propensity score matching was used to analyze outcomes after open conversion versus non-converted cases.

Results: The open conversion rate was 69/2,445 (2.8%). On multivariate analyses, male gender (3.6% vs 1.8%, P = .011), presence of clinically significant portal hypertension (6.1% vs 2.6%, P = .009), and larger tumor size (50 mm vs 32 mm, P < .001) were identified as independent factors associated with open conversion. The most common reason for conversion was bleeding in 27/69 (39.1%) of cases. After propensity score matching (65 open conversion vs 65 completed via minimally invasive liver resection), the open conversion group was associated with increased operation time, blood transfusion rate, blood loss, and postoperative stay compared with cases completed via the minimally invasive approach.

Conclusion: Male sex, portal hypertension, and larger tumor size were predictive factors of open conversion after minimally invasive left lateral sectionectomy. Open conversion was associated with inferior perioperative outcomes compared with non-converted cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surg.2022.03.037DOI Listing
August 2022

Structural insights into G protein activation by D1 dopamine receptor.

Sci Adv 2022 06 10;8(23):eabo4158. Epub 2022 Jun 10.

Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors and are the most important drug targets. An agonist-bound GPCR engages heterotrimeric G proteins and triggers the exchange of guanosine diphosphate (GDP) with guanosine triphosphate (GTP) to promote G protein activation. A complete understanding of molecular mechanisms of G protein activation has been hindered by a lack of structural information of GPCR-G protein complex in nucleotide-bound states. Here, we report the cryo-EM structures of the D1 dopamine receptor and mini-G complex in the nucleotide-free and nucleotide-bound states. These structures reveal major conformational changes in Gα such as structural rearrangements of the carboxyl- and amino-terminal α helices that account for the release of GDP and the GTP-dependent dissociation of Gα from Gβγ subunits. As validated by biochemical and cellular signaling studies, our structures shed light into the molecular basis of the entire signaling events of GPCR-mediated G protein activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abo4158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187227PMC
June 2022

miR-18a-5p derived from mesenchymal stem cells-extracellular vesicles inhibits ovarian cancer cell proliferation, migration, invasion, and chemotherapy resistance.

J Transl Med 2022 06 7;20(1):258. Epub 2022 Jun 7.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China.

Objective: Ovarian cancer (OC) is a major threat to women's health. Mesenchymal stem cells (MSCs) are key regulators in cellular communication by secreting extracellular vesicles (EVs) that are involved in OC. This study probed into the mechanism of human MSCs derived-EVs (hMSC-EVs) in regulating OC cell growth and chemotherapy resistance.

Methods: hMSCs and EVs were isolated and identified. After adding EVs, the uptake of EVs by OC CAOV3/ES2 cells (for in vitro studies), and cell proliferation, migration, and invasion were detected. Downregulated miRNAs in hMSC-EVs were screened and miR-18a-5p expression in OC patients was detected. The prognosis of OC patients was analyzed. Binding sites of miR-18a-5p and NACC1 were predicted and validated. NACC1 expression in OC tissues was measured by RT-qPCR, and its correlation with miR-18a-5p was analyzed by Pearson method. AKT/mTOR pathway activation was assessed by WB. The cisplatin sensitivity of EVs-treated CAOV3 cells was evaluated via MTT assay and tested by tumor formation assay in nude mice.

Results: hMSC-EVs suppressed OC cell proliferation, migration, and invasion. miR-18a-5p was downregulated in OC and miR-18a-5p low expression was associated with a poor prognosis. EV-encapsulated miR-18a-5p targeted NACC1. NACC1 was upregulated in OC tissues. miR-18a-5p knockdown and NACC1 overexpression both annulled the inhibition of hMSC-EVs on OC cell growth. AKT and mTOR were elevated in OC and NACC1 activated the AKT/mTOR pathway in OC cells. hMSC-EVs promoted cisplatin sensitivity of OC cells by carrying miR-18a-5p.

Conclusion: hMSC-EVs-derived miR-18a-5p inhibits OC cell proliferation, migration, invasion, and chemotherapy resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-022-03422-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172103PMC
June 2022

Studying the mixed transmission in a community with age heterogeneity: COVID-19 as a case study.

Infect Dis Model 2022 Jun 28;7(2):250-260. Epub 2022 May 28.

Africa-Canada Artificial Intelligence and Data Innovation Consortium (ACADIC) Laboratory for Industrial and Applied Mathematics (LIAM) Department of Mathematics and Statistics, York University Toronto, ON, M3J 1P3, Canada.

COVID-19 has been prevalent worldwide for about 2 years now and has brought unprecedented challenges to our society. Before vaccines were available, the main disease intervention strategies were non-pharmaceutical. Starting December 2020, in Ontario, Canada, vaccines were approved for administering to vulnerable individuals and gradually expanded to all individuals above the age of 12. As the vaccine coverage reached a satisfactory level among the eligible population, normal social activities resumed and schools reopened starting September 2021. However, when schools reopen for in-person learning, children under the age of 12 are unvaccinated and are at higher risks of contracting the virus. We propose an age-stratified model based on the age and vaccine eligibility of the individuals. We fit our model to the data in Ontario, Canada and obtain a good fitting result. The results show that a relaxed between-group contact rate may trigger future epidemic waves more easily than an increased within-group contact rate. An increasing mixed contact rate of the older group quickly amplifies the daily incidence numbers for both groups whereas an increasing mixed contact rate of the younger group mainly leads to future waves in the younger group alone. The results indicate the importance of accelerating vaccine rollout for younger individuals in mitigating disease spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.idm.2022.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142179PMC
June 2022

Platelets involved tumor cell EMT during circulation: communications and interventions.

Cell Commun Signal 2022 06 3;20(1):82. Epub 2022 Jun 3.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, People's Republic of China.

Distant spreading of metastatic tumor cells is still the leading cause of tumor death. Metastatic spreading is a complex process, in which epithelial-mesenchymal transition (EMT) is the primary and key event to promote it. Presently, extensive reviews have given insights on the occurrence of EMT at the primary tumor site that depends on invasive properties of tumor cells and the tumor-associated microenvironment. However, essential roles of circulation environment involved in tumor cell EMT is not well summarized. As a main constituent of the blood, platelet is increasingly found to work as an important activator to induce EMT. Therefore, this review aims to emphasize the novel role of platelet in EMT through signal communications between platelets and circulation tumor cells, and illustrate potent interventions aiming at their communications. It may give a complementary view of EMT in addition to the tissue microenvironment, help for better understand the hematogenous metastasis, and also illustrate theoretical and practical basis for the targeted inhibition. Video abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12964-022-00887-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166407PMC
June 2022

Brain intrinsic connection patterns underlying tool processing in human adults are present in neonates and not in macaques.

Neuroimage 2022 09 29;258:119339. Epub 2022 May 29.

State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China; IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China; Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing 100875, China; Chinese Institute for Brain Research, Beijing 102206, China. Electronic address:

Tool understanding and use are supported by a dedicated left-lateralized, intrinsically connected network in the human adult brain. To examine this network's phylogenetic and ontogenetic origins, we compared resting-state functional connectivity (rsFC) among regions subserving tool processing in human adults to rsFC among homologous regions in human neonates and macaque monkeys (adolescent and mature). These homologous regions formed an intrinsic network in human neonates, but not in macaques. Network topological patterns were highly similar between human adults and neonates, and significantly less so between humans and macaques. The premotor-parietal rsFC had most significant contribution to the formation of the neonatal tool network. These results suggest that an intrinsic brain network potentially supporting tool processing exists in the human brain prior to individual tool use experiences, and that the premotor-parietal functional connection in particular offers a brain basis for complex tool behaviors specific to humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2022.119339DOI Listing
September 2022
-->