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Article: Comprehensive software suite for functional analysis and synaptic input mapping of dendritic spines imaged

Yu, Yiyi / Adsit, Liam M / Smith, Ikuko T

2024 Volume 11, Issue 2, Page(s) 24307

Abstract: Significance: Advances in genetically encoded sensors and two-photon imaging have unlocked functional imaging at the level of single dendritic spines. Synaptic activity can be measured in real time in awake animals. However, tools are needed to ... ...

Abstract	Significance: Advances in genetically encoded sensors and two-photon imaging have unlocked functional imaging at the level of single dendritic spines. Synaptic activity can be measured in real time in awake animals. However, tools are needed to facilitate the analysis of the large datasets acquired by the approach. Commonly available software suites for imaging calcium transients in cell bodies are ill-suited for spine imaging as dendritic spines have structural characteristics distinct from those of the cell bodies. We present an automated tuning analysis tool (AUTOTUNE), which provides analysis routines specifically developed for the extraction and analysis of signals from subcellular compartments, including dendritic subregions and spines. Aim: Although the acquisition of Approach: We demonstrate the utility and effectiveness of our software with demo analyses of dendritic imaging data acquired from layer 2/3 pyramidal neurons in mouse V1 Results: AUTOTUNE provides a robust workflow for analyzing functional imaging data from neuronal dendrites. Features include source image registration, segmentation of regions-of-interest and detection of structural turnover, fluorescence transient extraction and smoothing, subtraction of signals from putative backpropagating action potentials, and stimulus and behavioral parameter response tuning analyses. Conclusions: AUTOTUNE is open-source and extendable for diverse functional synaptic imaging experiments. The ease of functional characterization of dendritic spine activity provided by our software can accelerate new functional studies that complement decades of morphological studies of dendrites, and further expand our understanding of neural circuits in health and in disease.
Language	English
Publishing date	2024-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2781943-7
ISSN	2329-4248 ; 2329-423X
ISSN (online)	2329-4248
ISSN	2329-423X
DOI	10.1117/1.NPh.11.2.024307
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Article ; Online: Asparaginyl endopeptidase contributes to cetuximab resistance via MEK/ERK signaling in RAS wide-type metastatic colorectal cancer.

Xu, Xiaojing / Liu, Mengling / Peng, Ke / Yu, Yiyi / Liu, Tianshu

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

2023 Volume 25, Issue 3, Page(s) 776–785

Abstract: Background: Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), is effective for RAS wild-type metastatic colorectal cancer (mCRC) patients. However, cetuximab resistance often occur and the mechanism has not been fully ... ...

Abstract	Background: Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), is effective for RAS wild-type metastatic colorectal cancer (mCRC) patients. However, cetuximab resistance often occur and the mechanism has not been fully elucidated. The purpose of this study was to investigate the role of asparaginyl endopeptidase (AEP) in cetuximab resistance. Methods: Differentially expressed genes between cetuximab responders and non-responders were identified by analyzing the gene expression profile GSE5851, retrieved from Gene Expression Omnibus (GEO). The potential genes were further validated in cetuximab-resistant CRC cell lines. The expression of AEP in the peripheral blood and tumor tissues of mCRC patients in our hospital were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The survival analysis was carried out by Kaplan-Meier method. The function and associated pathways of AEP were further investigated by lentivirus transfection, CCK8 assay, colony formation assay, real-time polymerase chain reaction (qPCR) and western blot. Results: Through bioinformatics analysis, we found that the expression of AEP gene was related to progress free survival (PFS) of mCRC patients treated with cetuximab alone (P = 0.00133). The expression of AEP was significantly higher in the cetuximab-resistant CRC cell lines, as well as in mCRC patients with shorter PFS treated with cetuximab-containing therapy. Furthermore, AEP could decrease the sensitivity of CRC cells to cetuximab in vitro. And the phosphorylation level of MEK and ERK1/2 was increased in AEP overexpression cells. The downregulation of AEP using specific inhibitors could partially restore the sensitivity of CRC cells to cetuximab. Conclusion: The higher expression of AEP could contribute to the shorter PFS of cetuximab treatment in mCRC. The reason might be that AEP could promote the phosphorylation of MEK/ERK protein in the downstream signal pathway of EGFR.
MeSH term(s)	Humans ; Cetuximab/pharmacology ; Cetuximab/therapeutic use ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/genetics ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Drug Resistance, Neoplasm/genetics ; ErbB Receptors/genetics ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Mutation ; Proto-Oncogene Proteins p21(ras)/genetics ; Rectal Neoplasms/drug therapy ; Rectal Neoplasms/genetics ; Signal Transduction ; Cysteine Endopeptidases/genetics ; Cysteine Endopeptidases/metabolism ; MAP Kinase Signaling System
Chemical Substances	asparaginylendopeptidase (EC 3.4.22.34) ; Cetuximab (PQX0D8J21J) ; ErbB Receptors (EC 2.7.10.1) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Cysteine Endopeptidases (EC 3.4.22.-)
Language	English
Publishing date	2023-01-07
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2397359-6
ISSN	1699-3055 ; 1699-048X
ISSN (online)	1699-3055
ISSN	1699-048X
DOI	10.1007/s12094-022-02986-6
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Article ; Online: Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review.

Xu, Xiaojing / Yu, Yiyi / Liu, Mengling / Liang, Li / Liu, Tianshu

Translational cancer research

2022 Volume 11, Issue 1, Page(s) 276–287

Abstract: Objective: The efficacy and safety of regorafenib and fruquintinib are studied extensively in different populations and trials across the world to determine their potential benefits. Here we review the efficacy and safety of regorafenib and fruquintinib ...

Abstract	Objective: The efficacy and safety of regorafenib and fruquintinib are studied extensively in different populations and trials across the world to determine their potential benefits. Here we review the efficacy and safety of regorafenib and fruquintinib as third-line treatment option for colorectal cancer (CRC). Background: CRC is the third most prevalent cancer worldwide, but the optimal third-line treatment option is still debatable. Regorafenib is a multikinase inhibitor that inhibits several cell signaling receptors, including vascular endothelial growth factor receptors (-1, -2, and -3) (VEGFRs), platelet-derived growth factor (PDGF), fibroblast growth factor, epidermal growth factor (EGF), angiotensin II, and Rapidly Accelerated Fibrosarcoma kinase pathway. On the other hand, fruquintinib inhibits signaling through the VEGFRs family. Regorafenib and fruquintinib have both received United States Food and Drug Administration (USFDA) approval for treating metastatic CRC (mCRC) in patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti- vascular endothelial growth factor therapy, and Rat sarcoma wild type, an anti- EGF receptor therapy. Methods: A review of literature was conducted in PubMed and Embase with the keywords "regorafenib" OR "fruquintinib" AND "colorectal cancer" for clinical studies performed in randomized controlled settings and real-world settings. Conclusions: Regorafenib and fruquintinib are effective and well tolerated options for the third-line treatment of patients with CRC. Both have a similar survival outcome with Regorafenib showing a slightly better toxicity profile.
Language	English
Publishing date	2022-03-04
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2901601-0
ISSN	2219-6803 ; 2218-676X
ISSN (online)	2219-6803
ISSN	2218-676X
DOI	10.21037/tcr-20-3539
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Article ; Online: Selective representations of texture and motion in mouse higher visual areas.

Yu, Yiyi / Stirman, Jeffrey N / Dorsett, Christopher R / Smith, Spencer L

Current biology : CB

2022 Volume 32, Issue 13, Page(s) 2810–2820.e5

Abstract: The mouse visual cortex contains interconnected higher visual areas, but their functional specializations are unclear. Here, we used a data-driven approach to examine the representations of complex visual stimuli by L2/3 neurons across mouse higher ... ...

Abstract	The mouse visual cortex contains interconnected higher visual areas, but their functional specializations are unclear. Here, we used a data-driven approach to examine the representations of complex visual stimuli by L2/3 neurons across mouse higher visual areas, measured using large-field-of-view two-photon calcium imaging. Using specialized stimuli, we found higher fidelity representations of texture in area LM, compared to area AL. Complementarily, we found higher fidelity representations of motion in area AL, compared to area LM. We also observed this segregation of information in response to naturalistic videos. Finally, we explored how receptive field models of visual cortical neurons could produce the segregated representations of texture and motion we observed. These selective representations could aid in behaviors such as visually guided navigation.
MeSH term(s)	Animals ; Mice ; Motion Perception/physiology ; Neurons/physiology ; Photic Stimulation/methods ; Visual Cortex/physiology ; Visual Fields ; Visual Pathways/physiology
Language	English
Publishing date	2022-05-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2022.04.091
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Zs.A 3208: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Pulmonary lymphangitis carcinomatosis: A peculiar presentation clustering in MET-amplified gastric cancer.

Zhang, Zhening / Yu, Yiyi / Xie, Tong / Qi, Changsong / Zhang, Xiaotian / Shen, Lin / Peng, Zhi

Cancer medicine

2023 Volume 12, Issue 19, Page(s) 19583–19594

Abstract: Background: The clinicopathological features of MET-amplified gastric cancer (GC) and real-world data on the efficacy of MET-targeted therapies remain unknown. Pulmonary lymphangitis carcinomatosis (PLC) is a peculiar manifestation of GC, whose ... ...

Abstract	Background: The clinicopathological features of MET-amplified gastric cancer (GC) and real-world data on the efficacy of MET-targeted therapies remain unknown. Pulmonary lymphangitis carcinomatosis (PLC) is a peculiar manifestation of GC, whose management has not been thoroughly described. Methods: This study analyzed patients diagnosed with MET-amplified GC or GC with PLC at any time point of the disease course from 2011 to 2021 in two centers. Clinicopathological features and survival outcomes of MET-amplified GC were analyzed. The clinical and molecular implications of GC with PLC were discussed. Results: Fifty-eight patients with MET-amplified GC and 20 patients with GC accompanied by PLC were finally enrolled for analysis (including 13 overlapped patients). GC with PLC was more common in female patients (p = 0.010), diagnosed at a younger age (p = 0.002), presented with a higher baseline ECOG PS (p = 0.016), and was more likely to develop lung metastasis (p < 0.001), and serous effusion (p = 0.026) than GC without PLC. Patients with primary MET-amplified GC had a worse prognosis than those with secondary MET-amplified GC (p = 0.005). The application of anti-MET therapy was associated with numerically prolonged survival, but the association was not statistically significant (p = 0.07). MET amplification was concentrated in patients with PLC, in which anti-MET therapies elicited a high response rate. Conclusions: MET-targeted therapies are efficacious in real-world populations with MET-amplified GC. Patients with PLC have distinct clinical and molecular features and might benefit from MET-targeted therapies.
MeSH term(s)	Female ; Humans ; Lung/pathology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/diagnosis ; Lymphangitis/etiology ; Lymphangitis/diagnosis ; Lymphangitis/pathology ; Prognosis ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Carcinoma
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6575
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Article ; Online: Synovial mesenchymal stem cell-derived exosomal microRNA-320c facilitates cartilage damage repair by targeting ADAM19-dependent Wnt signalling in osteoarthritis rats.

Kong, Ruina / Zhang, Ju / Ji, Lianmei / Yu, Yiyi / Gao, Jie / Zhao, Dongbao

Inflammopharmacology

2023 Volume 31, Issue 2, Page(s) 915–926

Abstract: Objective: Our previous study revealed that synovial mesenchymal stem cell (SMSC)-derived exosomal microRNA-302c enhanced chondrogenesis by targeting a disintegrin and metalloproteinase 19 (ADAM19) in vitro. This study aimed to validate the potential of ...

Abstract	Objective: Our previous study revealed that synovial mesenchymal stem cell (SMSC)-derived exosomal microRNA-302c enhanced chondrogenesis by targeting a disintegrin and metalloproteinase 19 (ADAM19) in vitro. This study aimed to validate the potential of SMSC-derived exosomal microRNA-302c for the treatment of osteoarthritis in vivo. Methods: After 4 weeks of destabilization of the medial meniscus surgery (DMM) to establish an osteoarthritis model, the rats received weekly articular cavity injection of SMSCs with or without GW4869 treatment (exosome inhibitor) or exosomes from SMSCs with or without microRNA-320c overexpression for another 4 weeks. Results: SMSCs and SMSC-derived exosomes reduced the Osteoarthritis Research Society International (OARSI) score, improved cartilage damage repair, suppressed cartilage inflammation, suppressed extracellular matrix (ECM) degradation, and inhibited chondrocyte apoptosis in DMM rats. However, these effects were largely hampered in rats that were injected with GW4869-treated SMSCs. Moreover, exosomes from microRNA-320c-overexpressing SMSCs exerted a better effect than exosomes from negative control SMSCs on decreasing the OARSI score, enhancing cartilage damage repair, suppressing cartilage inflammation, and inhibiting ECM degradation and chondrocyte apoptosis. Mechanistically, exosomes from microRNA-320c-overexpressing SMSCs reduced the levels of ADAM19, as well as β-catenin and MYC, which are two critical proteins in Wnt signalling. Conclusion: SMSC-derived exosomal microRNA-320c suppresses ECM degradation and chondrocyte apoptosis to facilitate cartilage damage repair in osteoarthritis rats by targeting ADAM19-dependent Wnt signalling.
MeSH term(s)	Rats ; Animals ; MicroRNAs/genetics ; Osteoarthritis/therapy ; Osteoarthritis/metabolism ; Mesenchymal Stem Cells ; Cartilage/metabolism ; Inflammation/metabolism
Chemical Substances	MicroRNAs ; GW 4869
Language	English
Publishing date	2023-03-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-023-01142-y
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Zs.A 3274: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Familial juvenile polyposis syndrome with a de novo germline missense variant in BMPR1A gene: a case report.

Liu, Qing / Liu, Mengling / Liu, Tianshu / Yu, Yiyi

BMC medical genetics

2020 Volume 21, Issue 1, Page(s) 196

Abstract: Background: Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline ... ...

Abstract	Background: Juvenile polyposis syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple distinct juvenile polyps in the gastrointestinal tract with an increased risk of colorectal cancer. Germline mutations in two genes, SMAD4 and BMPR1A, have been identified to cause JPS. Case presentation: Here, we report a germline heterozygous missense variant (c.299G > A) in exon 3 BMPR1A gene in a family with juvenile polyposis. This variant was absent from the population database, and concluded as de novo compared with the parental sequencing. Further sequencing of the proband's children confirmed the segregation of this variant with the disease, while the variant was also predicted to have damaging effect based on online prediction tools. Therefore, this variant was classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusions: Germline genetic testing revealed a de novo germline missense variant in BMPR1A gene in a family with juvenile polyposis. Identification of the pathogenic variant facilitates the cancer risk management of at-risk family members, and endoscopic surveillance is recommended for mutation carriers.
MeSH term(s)	Adenomatous Polyposis Coli/diagnosis ; Adenomatous Polyposis Coli/genetics ; Adult ; Bone Morphogenetic Protein Receptors, Type I/genetics ; Family Health ; Female ; Genetic Testing ; Germ-Line Mutation ; Heterozygote ; Humans ; Intestinal Polyposis/congenital ; Intestinal Polyposis/diagnosis ; Intestinal Polyposis/genetics ; Male ; Mutation, Missense ; Neoplastic Syndromes, Hereditary/diagnosis ; Neoplastic Syndromes, Hereditary/genetics ; Pedigree ; Smad4 Protein/genetics
Chemical Substances	SMAD4 protein, human ; Smad4 Protein ; BMPR1A protein, human (EC 2.7.11.30) ; Bone Morphogenetic Protein Receptors, Type I (EC 2.7.11.30)
Language	English
Publishing date	2020-10-08
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2350
ISSN (online)	1471-2350
DOI	10.1186/s12881-020-01135-6
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Article ; Online: China enters CAR-T cell therapy era.

Cao, Xin / Li, Wei / Yu, Yiyi / Liu, Tianshu / Zhou, Yuhong

Innovation (New York, N.Y.)

2021 Volume 3, Issue 1, Page(s) 100197

Language	English
Publishing date	2021-12-16
Publishing country	United States
Document type	News
ISSN	2666-6758
ISSN (online)	2666-6758
DOI	10.1016/j.xinn.2021.100197
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Article: Management of acute kidney injury in gastrointestinal tumor: An overview.

Su, Yi-Qi / Yu, Yi-Yi / Shen, Bo / Yang, Feng / Nie, Yu-Xin

World journal of clinical cases

2022 Volume 9, Issue 35, Page(s) 10746–10764

Abstract: Gastrointestinal tumors remain a global health problem. Acute kidney injury (AKI) is a common complication during the treatment of gastrointestinal tumors. AKI can cause a decrease in the remission rate and an increase in mortality. In this review, we ... ...

Abstract	Gastrointestinal tumors remain a global health problem. Acute kidney injury (AKI) is a common complication during the treatment of gastrointestinal tumors. AKI can cause a decrease in the remission rate and an increase in mortality. In this review, we analyzed the causes and risk factors for AKI in gastrointestinal tumor patients. The possible mechanisms of AKI were divided into three groups: pretreatment, intrafraction and post-treatment causes. Treatment and prevention measures were proposed according to various factors to provide guidance to clinicians and oncologists that can reduce the incidence of AKI and improve the quality of life and survival rate of gastrointestinal tumor patients.
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2307-8960
ISSN	2307-8960
DOI	10.12998/wjcc.v9.i35.10746
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Article: Nivolumab Combined With Ipilimumab Treatment Induced Hypophysitis and Immune-Mediated Liver Injury in Advanced Esophageal Squamous Cell Carcinoma: A Case Report.

Feng, Yi / Li, Chengyang / Ji, Yuan / Liu, Ying / Gan, Lu / Yu, Yiyi / Liu, Tianshu

Frontiers in oncology

2022 Volume 12, Page(s) 801924

Abstract: Immune checkpoint inhibitors (ICIs) have transformed the treatment in malignancies because of the impact on reactivating the immune cells to kill tumor cells. Because anti-CTLA-4 antibody and anti-PD-1 antibody (or anti-PD-L1 antibody) work in different ... ...

Abstract	Immune checkpoint inhibitors (ICIs) have transformed the treatment in malignancies because of the impact on reactivating the immune cells to kill tumor cells. Because anti-CTLA-4 antibody and anti-PD-1 antibody (or anti-PD-L1 antibody) work in different ways, they have synergistic effects when used in combination in many cancers. However, it has been found that a strong immune response may lead to more serious and multi-system immune-related adverse events (irAE). We describe an advanced esophageal squamous cell carcinoma patient who received nivolumab combined with ipilimumab resulting in hypophysitis and immune-mediated liver injury. He was enrolled into a CheckMate 648 global, multicenter, randomized phase 3 Clinical Trial (CTR20171227) investigating the combined potency of nivolumab and ipilimumab in the treatment of patients with advanced esophageal squamous cell carcinoma and admitted to our center (site 0200). The patient developed hypophysitis and immune-related hepatitis rapidly after ICIs therapy, leading to the interruption of anti-tumor therapy. Then the patient developed Herpes zoster and recurrence of tuberculosis after treatment of irAEs with glucocorticoids. We report this case in the hope that doctors need to have sufficient knowledge and attention to the occurrence of irAE during the anti-immune combination therapy and actively intervene as soon as possible to obtain better anti-tumor effects and less harm to patients.
Language	English
Publishing date	2022-04-01
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.801924
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