tbuckley/cabot-search huggingface dataset:
Cerebellar Purkinje cell firing promotes conscious recovery from anesthesia state through coordinating neuronal communications with motor cortex
Authors: Jinpiao Zhu, Chang Chen, Xiaodong Liu, Mengying He, Yuanyuan Fang, Li Wang, Junke Jia, Juan Guo, Ziyue Zhao, Chenyi Gao, Jingang He, Chengshi Xu, Fuqiang Xu, Daqing Ma, Jie Wang, Zongze Zhang
Journal: Theranostics (2023)

Background:The neurobiological basis of gaining consciousness from unconscious state induced by anesthetics remains unknown.This study was designed to investigate the involvement of the cerebello-thalamus-motor cortical loop mediating consciousness transitions from the loss of consciousness (LOC) induced by an inhalational anesthetic sevoflurane in mice.Methods: The neural tracing and fMRI together with opto-chemogenetic manipulation were used to investigate the potential link among cerebello-thalamus-motor cortical brain regions.The fiber photometry of calcium and neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA) and norepinephrine (NE), were monitored from the motor cortex (M1) and the 5 th lobule of the cerebellar vermis (5Cb) during unconsciousness induced by sevoflurane and gaining consciousness after sevoflurane exposure.Cerebellar Purkinje cells were optogenetically manipulated to investigate their influence on consciousness transitions during and after sevoflurane exposure.Results: Activation of 5Cb Purkinje cells increased the Ca 2+ flux in the M1 CaMKIIα + neurons, but this increment was significantly reduced by inactivation of posterior and parafascicular thalamic nucleus.The 5Cb and M1 exhibited concerted calcium flux, and glutamate and GABA release during transitions from wakefulness, loss of consciousness, burst suppression to conscious recovery.Ca 2+ flux and Glu release in the M1, but not in the 5Cb, showed a strong synchronization with the EEG burst suppression, particularly, in the gamma-band range.In contrast, the Glu, GABA and NE release and Ca 2+ oscillations were coherent with the EEG gamma band activity only in the 5Cb during the pre-recovery of consciousness period.The optogenetic activation of Purkinje cells during burst suppression significantly facilitated emergence from anesthesia while the optogenetic inhibition prolonged the time to gaining consciousness.Conclusions: Our data indicate that cerebellar neuronal communication integrated with motor cortex through thalamus promotes consciousness recovery from anesthesia which may likely serve as arousal regulation.
Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles
Authors: Zewei Zhuo, Kehang Guo, Yujun Luo, Qi Yang, Huihuan Wu, Ruijie Zeng, Rui Jiang, Jingwei Li, Rui Wei, Qizhou Lian, Weihong Sha, Yuliang Feng, Hao Chen
Journal: Theranostics (2023)

Rationale:The therapeutic benefits of bilirubin in the treatment of ulcerative colitis (UC) are considerable, whereas the underlying mechanism of bilirubin on UC remains unclear remains unexplored.In addition, the weak hydrophilicity and toxicity have limited its translational applications.Methods: We have developed a colon dual-targeting nanoparticle, for orally delivering bilirubin through hydrogel encapsulation of hyaluronic acid (HA)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGABilirubin).Confocal microscopy and in vivo imaging were used to evaluate the uptake and the targeted property of HA-PLGABilirubin in UC.Immunohistochemistry, immunofluorescence, and transcriptomic analyses were applied to examine the therapeutic effect and potential mechanism of HA-PLGABilirubin in UC.Results: Our results indicated that HA-PLGAbilirubin can significantly enhance the release of bilirubin at simulated intestinal pH and demonstrate higher cellular uptake in inflammatory macrophages.Moreover, in vivo biodistribution studies revealed high uptake and retention of HA-PLGAbilirubin in inflamed colon tissue of UC mouse model, resulting in effective recovery of intestinal morphology and barrier function.Importantly, HA-PLGAbilirubin exerted potent therapeutic efficacy against ulcerative colitis through modulating the intestinal epithelial/stem cells regeneration, and the improvement of angiogenesis and inflammation.Furthermore, genome-wide RNA-seq analysis revealed transcriptional reprogramming of immune response genes in colon tissue upon HA-PLGAbilirubin treatment in UC mouse model.Conclusion: Overall, our work provides an efficient colon targeted drug delivery system to potentiate the treatment of ulcerative colitis via modulating intestinal epithelium regeneration and immune response in ulcerative colitis.
CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain: Erratum
Authors: Chun-Lin Mai, Zhi Tan, Ya-Nan Xu, Jing-Jun Zhang, Zhen-Hua Huang, Dong Wang, Hui Zhang, Wen-Shan Gui, Jun Zhang, Zhen-Jia Lin, Ying-Tong Meng, Xiao Wei, Ying-Tao Jie, Peter M. Grace, Long-Jun Wu, Li-Jun Zhou, Xian-Guo Liu
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.44364.].
Dual inhibition of PFKFB3 and VEGF normalizes tumor vasculature, reduces lactate production, and improves chemotherapy in glioblastoma: insights from protein expression profiling and MRI: Erratum
Authors: Junfeng Zhang, Wei Xue, Kai Xu, Liang Yi, Yu Guo, Tian Xie, Haipeng Tong, Bo Zhou, Shunan Wang, Qing Li, Heng Liu, Xiao Chen, Jingqin Fang, Weiguo Zhang
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.44427.].
Vitamin D binding protein (VDBP) hijacks twist1 to inhibit vasculogenic mimicry in hepatocellular carcinoma
Authors: Lu-ning Qin, Heng Zhang, Qing-qing Li, Ting Wu, Shan-bin Cheng, Kai-wen Wang, Yue Shi, Hao-ran Ren, Xue-wu Xing, Cheng Yang, Tao Sun
Journal: Theranostics (2023)

Rationale: Vitamin D (VD) has been suggested to have antitumor effects, however, research on the role of its transporter vitamin D-binding protein (VDBP, gene name as GC) in tumors is limited.In this study, we demonstrated the mechanism underlying the inhibition of vasculogenic mimicry (VM) by VDBP in hepatocellular carcinoma (HCC) and proposed an anti-tumor strategy of combining anti-PD-1 therapy with VD.Methods: Three-dimensional cell culture models and mice with hepatocyte-specific GC deletion were utilized to study the correlation between VDBP expression and VM.A patient-derived tumor xenograft (PDX) model was further applied to validate the therapeutic efficacy of VD in combination with an anti-PD-1 drug. Results:The study revealed that VDBP expression is negatively correlated with VM in HCC patients and elevated VDBP expression is associated with a favorable prognosis.The mechanism studies suggested VDBP hindered the binding of Twist1 on the promoter of VE-cadherin by interacting with its helix-loop-helix DNA binding domain, ultimately leading to the inhibition of VM.Furthermore, VD facilitated the translocation of the vitamin D receptor (VDR) into the nucleus where VDR interacts with Yin Yang 1 (YY1), leading to the transcriptional activation of VDBP.We further demonstrated that the combination of VD and anti-PD-1 led to an improvement in the anti-tumor efficacy of an anti-PD-1 drug.Conclusion: Collectively, we identified VDBP as an important prognostic biomarker in HCC patients and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.
Copper incorporated biomaterial-based technologies for multifunctional wound repair
Authors: Zhenhe Zhang, Hang Xue, Yuan Xiong, Yongtao Geng, Adriana C. Panayi, Samuel Knoedler, Guandong Dai, Mohammad-Ali Shahbazi, Bobin Mi, Gouhui Liu
Journal: Theranostics (2023)

The treatment of wounds is a worldwide challenge, and wound infection can affect the effectiveness of wound treatment and further increase the disease burden. Copper is an essential trace element that has been shown to have broad-spectrum antibacterial effects and to be involved in the inflammation, proliferation, and remodeling stages of wound healing. Compared to treatments such as bioactive factors and skin grafts, copper has the advantage of being low-cost and easily available, and has received a lot of attention in wound healing. Recently, biomaterials made by incorporating copper into bioactive glasses, polymeric scaffolds and hydrogels have been used to promote wound healing by the release of copper ions. In addition, copper-incorporated biomaterials with catalytic, photothermal, and photosensitive properties can also accelerate wound healing through antibacterial and wound microenvironment regulation. This review summarizes the antibacterial mechanisms of copper- incorporated biomaterials and their roles in wound healing, and discusses the current challenges. A comprehensive understanding of the role of copper in wounds will help to facilitate new preclinical and clinical studies, thus leading to the development of novel therapeutic tools.
The plasticity of neuropeptide Y-Y1 receptor system on <i>Tac2</i> neurons contributes to mechanical hyperknesis during chronic itch
Authors: Danqing Dai, Tiantian Zhao, Zhen Li, Wanrong Li, Aiwen Chen, Yali Tang, Xiao-Fei Gao, Lize Xiong
Journal: Theranostics (2023)

Rationale: In the physiological states, the act of scratching protects the person from harmful substances, while in certain pathological conditions, the patient suffers from chronic itch, both physically and mentally.Chronic itch sufferers are more sensitive to mechanical stimuli, and mechanical hyperknesis relief is essential for chronic itch treatment.While neuropeptide Y-Y1 receptor (NPY-Y1R) system is known to play a crucial role in modulating mechanical itch in physiological conditions, it is elusive how they are altered during chronic itch.We hypothesize that the negative regulatory effect of Y1Rs on Tac2 neurons, the key neurons that transmit mechanical itch, declines during chronic itch.Methods: We combined transgenic mice, chemogenetic manipulation, immunofluorescence, rabies virus circuit tracing, and electrophysiology to investigate the plasticity of Y1Rs on Tac2 neurons during chronic itch.Results: We found that Tac2 neurons receive direct input from Npy neurons and that inhibition of Npy neurons induces activation of Tac2 neurons.Moreover, the expression of Y1Rs on Tac2 neurons is reduced, and the regulatory effect is also reduced during chronic itch.Conclusion: Our study clarifies the plasticity of Y1Rs on Tac2 neurons during chronic itch and further elucidates the mechanism by which NPY-Y1R system is responsible for modulating mechanical itch.We highlight Y1Rs as a promising therapeutic target for mechanical hyperknesis during chronic itch.
Endosialin in Cancer: Expression Patterns, Mechanistic Insights, and Therapeutic Approaches
Authors: Shiqi Lu, Lunbiao Gan, Tong Lu, Keying Zhang, Jiayu Zhang, Xinjie Wu, Donghui Han, Chao Xu, Shaojie Liu, Fa Yang, Weijun Qin, Weihong Wen
Journal: Theranostics (2023)

Endosialin, also known as tumor endothelial marker 1 (TEM1) or CD248, is a single transmembrane glycoprotein with a C-type lectin-like domain. Endosialin is mainly expressed in the stroma, especially in cancer-associated fibroblasts and pericytes, in most solid tumors. Endosialin is also expressed in tumor cells of most sarcomas. Endosialin can promote tumor progression through different mechanisms, such as promoting tumor cell proliferation, adhesion and migration, stimulating tumor angiogenesis, and inducing an immunosuppressive tumor microenvironment. Thus, it is considered an ideal target for cancer treatment. Several endosialin-targeted antibodies and therapeutic strategies have been developed and have shown preliminary antitumor effects. Here, we reviewed the endosialin expression pattern in different cancer types, discussed the mechanisms by which endosialin promotes tumor progression, and summarized current therapeutic strategies targeting endosialin.
Generic design principles for antibody-based tumour necrosis factor (TNF) receptor 2 (TNFR2) agonists with FcγR-independent agonism
Authors: Mohamed A. Anany, Stefanie Haack, Isabell Lang, Julia Dahlhoff, Juan Gamboa Vargas, Tim Steinfatt, Lea Päckert, Daniela Weisenberger, Olena Zaitseva, Juliane Medler, Kirstin Kucka, Tengyu Zhang, Tom Van Belle, Luc van Rompaey, Andreas Beilhack, Harald Wajant
Journal: Theranostics (2023)

Selective TNFR2 activation can be used to treat immune pathologies by activating and expanding regulatory T-cells (Tregs) but may also restore anti-tumour immunity by co-stimulating CD8
Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation
Authors: Xiaoyao Zhang, Li Li, Huishi Tan, Xue Hong, Qian Yuan, Fan Fan Hou, Lili Zhou, Youhua Liu
Journal: Theranostics (2023)

Klotho deficiency is a common feature of premature aging and chronic kidney disease (CKD). As such, restoring Klotho expression could be a logic strategy for protecting against various nephropathies. In this study, we demonstrate that KP1, a Klotho-derived peptide, inhibits cellular senescence by restoring endogenous Klotho expression.
Exosomes derived from CD271<sup>+</sup>CD56<sup>+</sup> bone marrow mesenchymal stem cell subpopoulation identified by single-cell RNA sequencing promote axon regeneration after spinal cord injury
Authors: Yi Sun, Quanbo Liu, Yiming Qin, Yan Xu, Jinyun Zhao, Yong Xie, Chengjun Li, Tian Qin, Yuxin Jin, Liyuan Jiang, Yong Cao, Hongbin Lu, Jianzhong Hu
Journal: Theranostics (2023)

Spinal cord injury (SCI) results in neural tissue damage. However, the limited regenerative capacity of adult mammals' axons upon SCI leads to persistent neurological dysfunction. Thus, exploring the pathways that can enhance axon regeneration in injured spinal cord is of great significance.
Differential effect of cancer-associated fibroblast-derived extracellular vesicles on cisplatin resistance in oral squamous cell carcinoma <i>via</i> miR-876-3p
Authors: Soo Hyun Kang, Su Young Oh, Kah-Young Lee, Heon-Jin Lee, Mee-Seon Kim, Tae-Geon Kwon, Jin-Wook Kim, Sung-Tak Lee, So-Young Choi, Su-Hyung Hong
Journal: Theranostics (2023)

Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism.
Long-term Nephrotoxicity after PRRT: Myth or Reality
Authors: Richard P. Baum, Xin Fan, Vivianne Jakobsson, Fei Yu, Christiane Schuchardt, Xiaoyuan Chen, Jingjing Zhang
Journal: Theranostics (2023)

The kidneys are commonly considered as the potential dose-limiting organ for peptide receptor radionuclide therapy (PRRT), making the risk of nephrotoxicity a primary concern. This retrospective analysis with prospective documentation and long-term follow-up aims to assess the risk of nephrotoxicity after PRRT in a large cohort of patients with neuroendocrine neoplasms (NENs) treated at our institution over the past 18 years.
Imaging diagnosis and efficacy monitoring by [<sup>89</sup>Zr]Zr-DFO-KN035 immunoPET in patients with PD-L1-positive solid malignancies
Authors: Huihui He, Xiaowei Qi, Haitian Fu, Jianfeng Xu, Qihuang Zheng, Liping Chen, Yu Zhang, Haiying Hua, Wenhuan Xu, Zhenyu Xu, Xiaoping Chen, Qingjun You, Jianguo Lin, Gang Huang, Yong Mao, Chunjing Yu
Journal: Theranostics (2023)

Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments.
Significant CircRNAs in liver cancer stem cell exosomes: mediator of malignant propagation in liver cancer?
Authors: Tao Han, Lujun Chen, Kerui Li, Qilin Hu, Yue Zhang, Xuan You, Lei Han, Tingsong Chen, Kai Li
Journal: Molecular Cancer (2023)

Abstract Hepatocellular carcinoma (HCC), one of the most prevalent forms of cancer worldwide, presents a significant global healthcare challenge. Cancer stem cells (CSCs), which can influence neighboring non-CSCs, are believed to play a crucial role in tumor growth and resistance to treatment, but the specific mechanisms and mediators are not fully understood. Regulation of the CSC state is considered an ideal therapeutic strategy both in the early stages of tumor formation and within established tumors. Exosomes have emerged as key players in intercellular communication, similar to classical hormone signaling, and are essential for facilitating communication between cells in liver cancer. Here, by coupling immunomagnetic bead sorting and exosomal sequencing, we found that exosome-derived circRNAs enriched in liver cancer CSCs were the key subsets with stemness characteristics and ultimately promoted HCC development. Of interest, we found that circ-ZEB1 and circ-AFAP1 are strongly correlated with liver cancer stemness and a poor prognosis, and can regulate the epithelial-mesenchymal transition (EMT) process. Our novel exosome-derived circRNAs play a vital role as key components of various intercellular crosstalk and communication systems in malignant transmission. This finding not only provides valuable support for utilizing plasma exosomal circRNAs as clinical prognostic indicators for HCC patients but also highlights a new research direction in exploring the signaling between liver CSCs and the messenger molecules contained within exosomes.
Response letter to “Tracing the origins of setons in hidradenitis suppurativa: A commentary to Vilarrasa et al’s ‘Drainage setons for the management of sinus tracts in hidradenitis suppurativa’”
Authors: Gemma Camiña-Conforto, Eva Vilarrasa, Fernando Cabo, Javier Fernández-Vela, María Pousa, Jorge Romaní
Journal: Journal of the American Academy of Dermatology (2023)
Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells
Authors: C. Cattaneo, E. Enzo, L. De Rosa, L. Sercia, F. Consiglio, M. Forcato, S. Bicciato, A. Paiardini, G. Basso, E. Tagliafico, A. Paganelli, C. Fiorentini, C. Magnoni, M.C. Latella, M. De Luca
Journal: Molecular Therapy (2023)
Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group
Authors: Dan-Ping Huang, Liang-Chun Yang, Yi-Qiao Chen, Wu-Qing Wan, Dun-Hua Zhou, Hui-Rong Mai, Wan-Li Li, Li-Hua Yang, He-Kui Lan, Hui-Qin Chen, Bi-Yun Guo, Zi-Jun Zhen, Ri-Yang Liu, Guo-Hua Chen, Xiao-Qin Feng, Cong Liang, Li-Na Wang, Yu Li, Jie-Si Luo, Zhong Fan, Xue-Qun Luo, Bin Li, Yan-Lai Tang, Xiao-Li Zhang, Li-Bin Huang
Journal: Blood Cancer Journal (2023)

Abstract Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As 4 S 4 ), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.
Cannabinoid receptor 2 as a regulator of inflammation induced oleoylethanolamide in eosinophilic asthma
Authors: Eun-Kyung Kwon, Youngwoo Choi, Soyoon Sim, Young-Min Ye, Yoo Seob Shin, Hae-Sim Park, Ga-Young Ban
Journal: Journal of Allergy and Clinical Immunology (2023)
11C-Acetate PET/CT for Reactive Astrogliosis Outperforms 11C-Methionine PET/CT in Glioma Classification and Survival Prediction
Authors: Dongwoo Kim, Ju Hyeon Yi, Youngjoo Park, Sun Jung Kim, Seok-Gu Kang, Se Hoon Kim, Joong-Hyun Chun, Jong Hee Chang, Mijin Yun
Journal: Clinical Nuclear Medicine (2023)

Purpose 11 C-acetate (ACE) PET/CT visualizes reactive astrogliosis in tumor microenvironment. This study compared 11 C-ACE and 11 C-methionine (MET) PET/CT for glioma classification and predicting patient survival. Patients and Methods In this prospective study, a total of 142 patients with cerebral gliomas underwent preoperative MRI, 11 C-MET PET/CT, and 11 C-ACE PET/CT. Tumor-to-contralateral cortex (TNR MET ) and tumor-to-choroid plexus ratios (TNR ACE ) were calculated for 11 C-MET and 11 C-ACE. The Kruskal-Wallis test and Bonferroni post hoc analysis were used to compare the differences in 11 C-TNR MET and 11 C-TNR ACE . The Cox proportional hazards regression analysis and classification and regression tree models were used to assess progression-free survival (PFS) and overall survival (OS). Results The median 11 C-TNR MET and 11 C-TNR ACE for oligodendrogliomas (ODs), IDH1 -mutant astrocytomas, IDH1 -wildtype astrocytomas, and glioblastomas were 2.75, 1.40, 2.30, and 3.70, respectively, and 1.40, 1.20, 1.77, and 2.87, respectively. The median 11 C-TNR MET was significantly different among the groups, except between ODs and IDH1 -wildtype astrocytomas, whereas the median 11 C-TNR ACE was significantly different among all groups. The classification and regression tree model identified 4 risk groups ( IDH1 -mutant with 11 C-TNR ACE ≤ 1.4, IDH1 -mutant with 11 C-TNR ACE &gt; 1.4, IDH1 -wildtype with 11 C-TNR ACE ≤ 1.8, and IDH1 -wildtype with 11 C-TNR ACE &gt; 1.8), with median PFS of 52.7, 44.5, 25.9, and 8.9 months, respectively. Using a 11 C-TNR ACE cutoff of 1.4 for IDH1 -mutant gliomas and a 11 C-TNR ACE cutoff of 2.0 for IDH1 -wildtype gliomas, all gliomas were divided into 4 groups with median OS of 52.7, 46.8, 27.6, and 12.0 months, respectively. Significant differences in PFS and OS were observed among the 4 groups after correcting for multiple comparisons. Conclusions 11 C-ACE PET/CT is better for glioma classification and survival prediction than 11 C-MET PET/CT, highlighting its potential role in cerebral glioma patients.
177Lu-DOTATATE in the Treatment of Recurrent Pheochromocytoma With Multiple Metastases
Authors: Dan Su, Yu Zhang, Zhuoyuan Li, Hongyu Yang, Yue Chen
Journal: Clinical Nuclear Medicine (2023)

Abstract The treatment of metastatic pheochromocytoma is challenging. We report a case of a woman with recurrent pheochromocytoma with multiple metastases who achieved excellent response after 4 cycles of 177 Lu-DOTATATE therapy. She did not experience any observable adverse effects. Her disease was still stable 6 months after the fourth cycle of treatment.