bluuebunny/crossref_metadata_2025_split huggingface dataset:
OTUB2 promotes the progression of endometrial cancer by regulating the PKM2‐mediated PI3K/AKT signaling pathway
Authors: Zhang Qian , Zhang Jing , Yao Anmei , Tian Xiaofei , Han Zhihong , Yuan Yuan , Tao Kai , Yang Xuemei 
Published: November 2022

AbstractEndometrial carcinoma (EC) morbidity and mortality have been increasing in recent years. Otubain 2 (OTUB2) was shown to be upregulated in EC patients, so the aim of this study was to explore the role of OTUB2 in EC. Cell Counting Kit‐8 (CCK‐8), colony formation, enzyme‐linked immunosorbent assay, the wound healing assay, and Transwell invasion assays were used to investigate the specific role of OTUB2 in EC tumorigenesis. Real‐time polymerase chain reaction and western blot analysis were used to detect the expression of OTUB2 in EC tissues and cells. OTUB2 is upregulated in EC patients and cell lines and is associated with a poor prognosis. The overexpression of OTUB2 promoted glycolysis and induced the proliferation, migration, and invasion of endometrial cancer cells. The silencing of OTUB2 had the opposite effect. In addition, the silencing of OTUB2 significantly suppressed the expression levels of PKM2. Importantly, inhibition of the PKM2/PI3K/AKT signaling pathway significantly reversed the promoting effect of OTUB2 overexpression on EC. OTUB2 regulated the proliferation and invasion of EC cells by regulating the PKM2/PI3K/AKT signaling pathway. OTUB2 may serve as a potential prognostic and therapeutic target in EC.
Human amniotic mesenchymal stem cells promote endometrium regeneration in a rat model of intrauterine adhesion
Authors: Mao Yanhua , Yang Yuan , Sun Congcong , Zou Yulong , Zhang Yingfeng , Wu Benyuan , Li Changjiang , Huang Jinglin , Zhang Wenwen , Wang Jia 
Published: November 2022

AbstractHuman amniotic transplantation has been proposed to improve the therapeutic efficacy of intrauterine adhesions (IUAs). Human amniotic mesenchymal stem stromal cells (hAMSCs) can differentiate into multiple tissue types. This study aimed to investigate the mechanism by which hAMSCs transplantation promotes endometrial regeneration. The rat models with IUA were established through mechanical and infective methods, and PKH26‐labeled hAMSCs were transplanted through the tail vein (combined with/without estrogen). Under three different conditions, hAMSCs differentiated into endometrium‐like cells. HE and Mason staining assays, and immunohistochemistry were used to compare the changes in rat models treated with hAMSCs and/or estrogen transplantation. To define the induction of hAMSCs to endometrium‐like cells in vitro, an induction medium (cytokines, estrogen) was used to investigate the differentiation of hAMSCs into endometrium‐like cells. qRT‐polymerase chain reaction (PCR) and western blotting were performed to detect the differentiation of hAMSCs into endometrium‐like cells. A greater number of glands, fewer endometrial fibrotic areas, and stronger expression of vascular endothelial growth factor and cytokeratin in the combined group (hAMSCs transplantation combined with estrogen) than in the other treatment groups were observed. hAMSCs could be induced into endometrium‐like cells by cytokine treatment (TGF‐β1, EGF, and PDGF‐BB). Transplantation of hAMSCs is an effective alternative for endometrial regeneration after injury in rats. The differentiation protocol for hAMSCs will be useful for further studies on human endometrial regeneration.
Celastrol acts as a new histone deacetylase inhibitor to inhibit colorectal cancer cell growth via regulating macrophage polarity
Authors: Wang Shuren , Hu Guanghui , Chen Lechuang , Ma Kai , Hu Chenfei , Zhu Hongxia , Xu Ningzhi , Zhou Changchun , Liu Mei 
Published: November 2022

AbstractThe tumorigenesis and progression of colorectal cancer are closely related to the tumor microenvironment, especially inflammatory response. Inhibitors of histone deacetylase (HDAC) have been reported as epigenetic regulators of the immune system to treat cancer and inflammatory diseases and our results demonstrated that Celastrol could act as a new HDAC inhibitor. Considering macrophages as important members of the tumor microenvironment, we further found that Celastrol could influence the polarization of macrophages to inhibit colorectal cancer cell growth. Specially, we used the supernatant of HCT116 and SW480 cells to induce Ana‐1 cells in vitro and chose the spontaneous colorectal cancer model APCmin/+ mice as an animal model to validate in vivo. The results indicated that Celastrol could reverse the polarization of macrophages from M2 to M1 through impacting the colorectal tumor microenvironment both in vitro and in vivo. Furthermore, using bioinformatics analysis, we found that Celastrol might mechanistically polarize the macrophages through MAPK signaling pathway. In conclusion, our findings identified that Celastrol as a new HDAC inhibitor and suggested that Celastrol could modulate macrophage polarization, thus inhibiting colorectal cancer growth, which may provide some novel therapeutic strategies for colorectal cancer.
Acute myocardial infarction caused by Kawasaki disease requires more intensive therapy: Insights from the Japanese registry of All Cardiac and Vascular Diseases—Diagnosis Procedure combination
Authors: Anzai Fumiya , Yoshihisa Akiomi , Takeishi Ryohei , Hotsuki Yu , Sato Yu , Sumita Yoko , Nakai Michikazu , Misaka Tomofumi , Takeishi Yasuchika 
Published: November 2022

AbstractBackgroundKawasaki disease (KD) induces coronary arteritis, which causes subsequent coronary aneurysms, and contributes to acute myocardial infarction (AMI). However, the differences regarding real‐world treatment selection and mortality between AMI‐complicated KD and AMI due to typical atherosclerosis (AMI‐non KD) are unknown.AimThe aim of the present study was to examine the current treatment strategy and prognosis of AMI‐complicated KD compared with AMI due to typical atherosclerosis.MethodWe used data from 2012 to 2019 from a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases—Diagnosis Procedure Combination.ResultsCompared to the AMI‐non KD patients (n = 70,227), the AMI‐complicated KD patients (n = 73): (1) underwent percutaneous coronary intervention (PCI) less often and more coronary artery bypass grafting, intracoronary thrombolysis or intravenous coronary thrombolysis more often; (2) underwent stentless PCI using old balloon angioplasty or rotablator, when they underwent PCI; and (3) needed in‐hospital cardiopulmonary resuscitation and intensive mechanical therapy such as intra‐aortic balloon pump, percutaneous cardiopulmonary support or a respirator. Both the AMI‐non KD and AMI‐complicated KD patients had similar in‐hospital mortality rates.ConclusionsCompared with AMI‐non KD patients, AMI‐complicated KD patients underwent non‐PCI strategies such as bypass surgery or thrombolysis, and required intensive therapy with mechanical supports more often, but presented similar in‐hospital mortality. When the AMI‐complicated KD patients underwent PCI, stentless PCI using balloon angioplasty or rotablator was performed more often compared with the AMI‐non KD patients.
Predictors of successful same‐day discharge and 1‐year outcomes after left atrial appendage closure
Authors: Wass Sojin Youn , Galo Jason , Yoon Sung‐Han , Dallan Luis A. P. , Mogalapalli Akhil , Ukaigwe Anene , Attizani Guilherme F. , Simon Daniel I. , Arruda Mauricio , Filby Steven J. 
Published: November 2022

AbstractBackgroundSame‐day discharge (SDD) following left atrial appendage closure (LAAC) is increasingly common but predictors of successful SDD and 1‐year clinical outcomes have not been described.ObjectiveThe purpose of this study was to explore predictors of successful SDD and report 1‐year outcomes in patients undergoing LAAC with SDD.MethodsA prospective analysis was performed over a 20‐month period of 225 consecutive patients that underwent LAAC in a large, academic hospital. All patients included in the study underwent a SDD protocol. Baseline characteristics and 1‐year outcomes of patients discharged same day of the procedure versus those that required at least one overnight stay were compared. Adverse events, procedural success, and procedure times were evaluated.ResultsOne hundred and sixty‐one patients (72%) of patients were discharged the same day and 64 patients (28%) required at least an overnight stay (non‐SDD: NSDD). NSDD patients were older and more often female. Procedure time was also longer in the NSDD group than in the SDD (63.4 vs. 55.1 min;p = 0.01). While overall procedural success rates were similar between the SDD and NSDD groups (99.4% vs. 98.4%;p = 0.39), NSDD patients had more complications (9.4% vs. 0%;p = 0.01) and higher number of devices per procedure (1.2 vs. 1.0;p = 0.01) as compared to SDD. At 1 year, there were no significant difference between the SDD and NSDD groups in stroke (1.1% vs. 0%; log‐rankp = 0.44) and all‐cause mortality (3.9% vs. 4.7%; log‐rankp = 0.70).ConclusionIn this single‐center LAAC experience, female sex, older age, and longer procedure duration were associated with higher likelihood for need of overnight stay. At 1‐year follow‐up, there were no significant differences in stroke events and death rates between SDD and NSDD groups.
Divergent Synthesis of Ultrabright and Dendritic Xanthenes for Enhanced Click‐Chemistry‐Based Bioimaging
Authors: Montiel Luis , Spada Fabio , Crisp Antony , Serdjukow Sascha , Carell Thomas , Frischmuth Thomas 
Published: November 2022

AbstractBiorthogonal labelling with fluorescent small molecules is an indispensable tool for diagnostic and biomedical applications. In dye‐based 5‐ethynyl‐2′‐deoxyuridine (EdU) cell proliferation assays, augmentation of the fluorescent signal entails an overall enhancement in the sensitivity and quality of the method. To this end, a rapid, divergent synthetic procedure that provides ready‐to‐click pH‐insensitive rhodamine dyes exhibiting outstanding brightness was established. Compared to the shortest available synthesis of related high quantum‐yielding rhodamines, two fewer synthetic steps are required. In a head‐to‐head imaging comparison involving copper(I)‐catalyzed azide alkyne cycloaddition reactions with in vitro administered EdU, our new 3,3‐difluoroazetidine rhodamine azide outperformed the popular 5‐TAMRA‐azide, making it among the best available choices when it comes to fluorescent imaging of DNA. In a further exploration of the fluorescence properties of these dyes, a set of bis‐MPA dendrons carrying multiple fluorescein or rhodamine units was prepared by branching click chemistry. Fluorescence self‐quenching of fluorescein‐ and rhodamine‐functionalized dendrons limited the suitability of the dyes as labels in EdU‐based experiments but provided new insights into these effects.
Closed Bipolar Electrode Array for Optical Reporting Reaction‐Coupled Electrochemical Sensing and Imaging
Authors: Qin Xiang , Gao Jiao , Jin Hua‐Jiang , Li Zhong‐Qiu , Xia Xing‐Hua 
Published: November 2022

AbstractThis review centers on a closed bipolar electrode (BPE) array using an electro‐fluorochromism (EFC) or electro‐chemiluminescence (ECL) reaction as the reporting reaction. Electrochemical signals at one pole of the closed BPE array can be transduced into the EFC or ECL signals at the opposite pole. Therefore, the current signal of a redox reaction can be easily detected and imaged by monitoring the luminescence signal. Recent developments in closed BPE array‐based EFC and ECL sensing and imaging are summarized and discussed in detail. Finally, we consider the challenges and opportunities for improving the spatial resolution of closed BPE array‐based electrochemical imaging, and emphasize the important application of this technique to the imaging of cellular activities at the single‐cell level.
Chiral Anthranyl Trifluoromethyl Alcohols: Structures, Oxidative Dearomatization and Chiroptical Properties
Authors: Sonet Dorian , Cayla Mattéo , Méreau Raphaël , Morvan Estelle , Lacoudre Aline , Vanthuyne Nicolas , Albalat Muriel , Bassani Dario M. , Scalabre Antoine , Pouget Emilie , Bibal Brigitte 
Published: November 2022

AbstractChiral trifluoromethyl alcohol groups were introduced at the hindered ortho positions of 9,10‐diphenylanthracenes to investigate their effects on the physical properties and reactivity towards oxidative dearomatization. In such compact structures, the position in different quadrants and the preferred orientation of the −CH(OH)CF3 groups were determined by the relative and absolute configurations of each stereoisomer, respectively. As a consequence, the stereochemistry governs the organization of the H‐bonded molecules in single crystals (homochiral dimers vs ribbon), whereas in chlorinated solvents, they all behave as discrete compounds. Concerning their reactivity, the stereospecific dearomative oxidation of these molecules leads to 9,10‐bis‐spiro‐isobenzofuran‐anthracenes, when using organic single‐electron transfer oxidants. The chiroptical properties of the alcohols and the corresponding dearomatized products were compared and showed an important modulation of the intensity.
Rapid 18F‐ and 19F‐Difluoromethylation through Desulfurative Fluorination of Transient N‐, O‐, and C‐Linked Dithioles
Authors: Newton Josiah J. , Engüdar Gökçe , Brooke Alan J. , Nodwell Matthew B. , Horngren‐Rhodes Holly , Martin Rainer E. , Schaffer Paul , Britton Robert , Friesen Chadron M. 
Published: November 2022

AbstractThe difluoromethyl group plays an important role in modern medicinal and agrochemistry. While several difluoromethylation reagents have been reported, these typically rely on difluoromethyl carbenes or anions, or target specific processes. Here, we describe a conceptually unique and general process for O−H, N−H and C−H difluoromethylation that involves the formation of a transient dithiole followed by facile desulfurative fluorination using silver(I) fluoride. We also introduce the 5,6‐dimethoxy‐1,3‐benzodithiole (DMBDT) function, which undergoes sufficiently rapid desulfurative fluorination to additionally support 18F‐difluoromethylation. This new process is compatible with the wide range of functional groups typically encountered in medicinal chemistry campaigns, and the use of Ag18F is demonstrated in the production of 18F‐labeled derivatives of testosterone, perphenazine, and melatonin, 58.0±2.2, 20.4±0.3 and 32.2±3.6 MBq μmol−1, respectively. We expect that the DMBDT group and this 18F/19F‐difluoromethylation process will inspire and support new efforts in medicinal chemistry, agrochemistry and radiotracer production.
Synthesis of Red‐Light‐Responsive Pheophorbide‐a Tryptamine Conjugated Photosensitizers for Photodynamic Therapy
Authors: Pandurang Taur Prakash , Kumar Bintu , Verma Narshimha , Dastidar Debabrata Ghosh , Yamada Risa , Nishihara Tatsuya , Tanabe Kazuhito , Kumar Dalip 
Published: November 2022

AbstractSix methyl pheophorbide‐a derivatives were prepared by linking a tryptamine side chain at the C‐131, C‐152 and C‐173 positions of pheophorbide‐a. Prepared conjugates were characterized and evaluated for their photocytotoxicity against A549 cells. The conjugate 6 a with strong absorption at 413 nm (Soret band), 663–671 nm (Q bands) and comparable fluorescence quantum yield (0.26) was found to exhibit significant cytotoxicity (659 nM). Molecular integration of pheophorbide‐a and tryptamines showed synergistic effects as the most potent conjugate 6 a was identified with enhanced photocytotoxicity when compared to methyl pheophorbide‐a. The conjugate 6 a was smoothly taken up by A549 cells and exhibited intracellular localization predominantly to lysosome in the cytoplasm. Upon photoirradiation 6 a generated singlet oxygen to show potent cytotoxicity toward A549 cells.
Inhibition of Amyloid Protein Aggregation Using Selected Peptidomimetics
Authors: Maity Debabrata 
Published: November 2022

AbstractAberrant protein aggregation leads to the formation of amyloid fibrils. This phenomenon is linked to the development of more than 40 irremediable diseases such as Alzheimer's disease, Parkinson's disease, type 2 diabetes, and cancer. Plenty of research efforts have been given to understanding the underlying mechanism of protein aggregation, associated toxicity, and the development of amyloid inhibitors. Recently, the peptidomimetic approach has emerged as a potential tool to modulate several protein‐protein interactions (PPIs). In this review, we discussed selected peptidomimetic‐based approaches for the modulation of important amyloid proteins (Islet Amyloid Polypeptide, Amyloid Beta, α‐synuclein, mutant p53, and insulin) aggregation. This approach holds a powerful platform for creating an essential stepping stone for the vital development of anti‐amyloid therapeutic agents.
Pharmacogenetics of ABCB1, CDA, DCK, GSTT1, GSTM1 and outcomes in a cohort of pediatric acute myeloid leukemia patients from Colombia
Authors: Yunis Luz K. , Linares‐Ballesteros Adriana , Aponte Nelson , Barros Gisela , García Johnny , Niño Laura , Uribe Gloria , Quintero Edna , Yunis Juan J. 
Published: November 2022

AbstractBackground and AimDifferent studies have shown pharmacogenetic variants related to drug toxicity in acute myeloid leukemia (AML) patients. Our aim was to identify the association between ABCB1, CDA, DCK, GSTT1, and GSTM1 variants with clinical outcomes and toxicity in pediatric patients with AML.MethodsFifty‐one confirmed de novo AML pediatric patients were included. A SNaPshot™ assay and conventional PCR were used to evaluate ABCB1, CDA, DCK, GSTT1, and GSTM1 variants. Clinical outcomes and toxicity associations were evaluated using odds ratios and Chi‐square analysis.ResultsPatients carrying ABCB1 (1236C > T, rs1128503) GG genotype in had a 6.8 OR (CI 95% 1.08–42.73, p = .044) for cardiotoxicity as compared to patients carrying either AA or GA genotypes 0.14 OR (CI 95% 0.023–0.92, p = .044). For ABCB1 (1236G > A rs1128503/2677C > A/T rs2032582/3435G > A rs1045642) AA/AA/AA combined genotypes had a strong association with death after HSTC OR 13.73 (CI 95% 1.94–97.17, p = .009). Combined genotypes GG/CC/GG with CDA (79A > C, rs2072671) CA genotype or CDA (‐451G > A, rs532545) CT genotype, had a 4.11 OR (CI 95% 2.32–725, p = .007) and 3.8 OR (CI 95% 2.23–6.47, p = .027) with MRD >0.1% after first chemotherapy cycle, respectively.ConclusionOur results highlight the importance of pharmacogenetic analysis in pediatric AML, particularly in populations with a high degree of admixture, and might be useful as a future tool for patient stratification for treatment.
Pleural metastasis from pulmonary primary signet‐ring squamous cell carcinoma. Case report and literature review
Authors: Torres‐Rivas Héctor‐Enrique , Ariza‐Prota Miguel , González Gutiérrez María de la Paz , Berrios Hernández Mario Luis , Bravo Peláez Belén , Fernández Fernández Luis Manuel 
Published: November 2022

AbstractSignet‐ring cells are morphologically defined by the presence of a large intracytoplasmic vacuole that compresses and displaces the nucleus to the periphery. In most cases, these cells are associated with adenocarcinomas of various locations, and with non‐epithelial neoplasms. To date, less than 20 cases of squamous cell carcinoma with signet‐ring morphology have been described, mainly located on the skin. We present the case of a 73‐year‐old male with pleural effusion and a left lower lobe mass. The cytological study of the pleural effusion allowed the diagnosis of metastasis of squamous cell carcinoma, signet‐ring cell variant. The treatment of lung cancer in advanced stages requires a precise diagnosis that allows the best therapy to be offered to the patient, depending on the clinical stage and the positivity of the biomarkers, among others. Our patient died 18 months after the initial diagnosis.
Current practice of colonoscopy surveillance in patients with lynch syndrome: A multicenter retrospective cohort study in Japan
Authors: Miyakura Yasuyuki , Chino Akiko , Tanakaya Kohji , Lefor Alan Kawarai , Akagi Kiwamu , Takao Akinari , Yamada Masayoshi , Ishida Hideyuki , Komori Koji , Sasaki Kazuhito , Miguchi Masashi , Hirata Keiji , Sudo Tomoya , Ishikawa Toshiaki , Yamaguchi Tatsuro , Tomita Naohiro , Ajioka Yoichi 
Published: November 2022

AbstractObjectivesColonoscopy surveillance reduces the incidence of colorectal cancer through the detection and endoscopic removal of adenomas. Current guidelines recommend that patients with Lynch syndrome should have colonoscopy surveillance every 1–2 years starting at the age of 20–25. However, insufficient data are available to evaluate the quality and safety of colonoscopy surveillance for patients with Lynch syndrome nationwide in Japan.MethodsPatients with Lynch syndrome (n = 309) from 13 institutions who underwent one or more colonoscopy procedures were enrolled in this retrospective analysis. Colonoscopy completion rate, colonoscopy‐related complication rate, proportion with an adequate colonoscopy interval, and adenoma detection rate were reviewed.ResultsThe colonoscopy completion rate was 98.8% and a history of previous colorectal cancer surgery was significantly associated with a higher completion rate. All complications were associated with endoscopic treatment and the rate of bleeding needing hemostasis and perforation needing surgical repair were both 0.16% after colonoscopy with polypectomy. The adenoma detection rate at the first colonoscopy was 25%. Although there was no difference in the completion and complication rates based on differences in the colonoscopy experience of the endoscopist, the detection rate of adenomas and intramucosal cancers was significantly higher with more experienced endoscopists. The proportion of patients developing cancer was significantly higher with a >24 months than a ≤24 months interval.ConclusionHigh‐volume experienced endoscopists and appropriate surveillance intervals may minimize the risk of developing colorectal cancers in patients with Lynch syndrome.
Direct Chan–Lam Amination and Etherification of Aryl BMIDA Reagents
Authors: Halford‐McGuff John M. , Israel Eva M. , West Matthew J. , Vantourout Julien C. , Watson Allan J. B. 
Published: November 2022

AbstractWe report a method for the direct Chan–Lam coupling of arylboronic acid N‐methyliminodiacetic acid esters (ArBMIDA) with amine and alcohol nucleophiles. A wide range of C−N and C−O cross‐coupled products are obtained in 34–99 % yield (34 examples). This method serves to expand the scope of organoboron components that can be used directly in this oxidative coupling reaction and provides opportunities for streamlining synthesis.
Electrochemical Sensing of Paracetamol Using 3D Porous Laser Scribed Graphene Platform
Authors: Berni Achraf , Lahcen Abdellatif Ait , Amine Aziz 
Published: November 2022

AbstractThis work presents a novel disposable electrochemical sensor for paracetamol (PCM). The sensing platform is based on graphene, manufactured via laser‐scribing technology (LSG) to produce a 3D‐porous structure that offers a large surface area. The analytical performances of LSG electrodes were greatly enhanced due to the high catalytic activity of graphene produced by LSG technology compared to conventional carbon electrodes. Moreover, the results showed an outstanding adsorption feature towards PCM, allowing its detection at nanomolar level from 5 nM to 100 nM through pre‐concentration. The proposed sensing strategy was successfully applied for the determination of PCM in human urine samples.