tbuckley/cabot-search huggingface dataset:
Multifunctional Sr/Se co-doped ZIF-8 nanozyme for chemo/chemodynamic synergistic tumor therapy <i>via</i> apoptosis and ferroptosis
Authors: Aimin Wu, Ming Han, Zihan Ni, Haoran Li, Yinyin Chen, Zhouping Yang, Yumei Feng, Zufeng He, Hua Zhen, Xianxiang Wang
Journal: Theranostics (2024)

Rationale: Cancer continues to be a significant public health issue.Traditional treatments such as surgery, radiotherapy, and chemotherapy often fall short because of intrinsic issues such as lack of specificity and poor drug delivery, leading to insufficient drug concentration at the tumor site and/or potential side effects.Consequently, improving the delivery of conventional chemotherapy drugs like doxorubicin (DOX) is crucial for their therapeutic efficacy.Successful cancer treatment is achieved when regulated cell death (RCD) of cancer cells, which includes apoptotic and non-apoptotic processes such as ferroptosis, is fundamental to successful cancer treatment.The developing field of nanozymes holds considerable promise for innovative cancer treatment approaches.Methods: A dual-metallic nanozyme system encapsulated with DOX was created, derived from metal-organic frameworks (MOFs), designed to combat tumors by depleting glutathione (GSH) and concurrently liberating DOX.The initial phase of the study examined the GSH oxidase-mimicking function of the dimetallic nanozyme (ZIF-8/SrSe) through enzyme kinetic assays and Density Functional Theory (DFT) simulations.Following this, we probed the ability of ZIF-8/SrSe@DOX to release DOX in response to the tumor microenvironment in vitro, alongside examining its anticancer capabilities and mechanisms prompting apoptosis or ferroptosis in cancer cells.Moreover, we established tumor-bearing animal models to corroborate the anti-tumor effectiveness of our nanozyme complex and to identify the involved apoptotic and ferroptotic pathways implicated.Results: Enzyme kinetic analyses demonstrated that the ZIF-8/SrSe nanozyme exhibits substantial GSH oxidase-like activity, effectively oxidizing reduced GSH to glutathione disulfide (GSSG), while also inhibiting glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11).This inhibition led to an imbalance in iron homeostasis, pronounced caspase activation, and subsequent induction of apoptosis and ferroptosis in tumor cells.Additionally, the ZIF-8/SrSe@DOX nanoparticles efficiently delivered DOX, causing DNA damage and further promoting apoptotic and ferroptotic pathways.Conclusions: This research outlines the design of a novel platform that combines chemotherapeutic agents with a Fenton reaction catalyst, offering a promising strategy for cancer therapy that leverages the synergistic effects of apoptosis and ferroptosis.
Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage
Authors: Qiang Zhang, Yujie Chen, Yingpei Li, Zhou Feng, Liang Liang, Xiaoke Hao, Wenbo Kang, Zhaoqi Zhang, Xuyang Zhang, Rong Hu, Hua Feng, Zhi Chen
Journal: Theranostics (2024)

Rationale: Hydrocephalus is a substantial complication after intracerebral hemorrhage (ICH) or intraventricular hemorrhage (IVH) that leads to impaired cerebrospinal fluid (CSF) circulation.Recently, brain meningeal lymphatic vessels (mLVs) were shown to serve as critical drainage pathways for CSF.Our previous studies indicated that the degradation of neutrophil extracellular traps (NETs) after ICH/IVH alleviates hydrocephalus.However, the mechanisms by which NET degradation exerts beneficial effects in hydrocephalus remain unclear.Methods: A mouse model of hydrocephalus following IVH was established by infusing autologous blood into both wildtype and Cx3cr1 -/-mice.By studying the features and processes of the model, we investigated the contribution of mLVs and NETs to the development and progression of hydrocephalus following secondary IVH.Results: This study observed the widespread presence of neutrophils, fibrin and NETs in mLVs following IVH, and the degradation of NETs alleviated hydrocephalus and brain injury.Importantly, the degradation of NETs improved CSF drainage by enhancing the recovery of lymphatic endothelial cells (LECs).Furthermore, our study showed that NETs activated the membrane protein CX3CR1 on LECs after IVH.In contrast, the repair of mLVs was promoted and the effects of hydrocephalus were ameliorated after CX3CR1 knockdown and in Cx3cr1 -/-mice.Conclusion: Our findings indicated that mLVs participate in the development of brain injury and secondary hydrocephalus after IVH and that NETs contribute to acute LEC injury and lymphatic thrombosis.CX3CR1 is a key molecule in NET-induced LEC damage and meningeal lymphatic thrombosis, which leads to mLV dysfunction and exacerbates hydrocephalus and brain injury.NETs may be a critical target for preventing the obstruction of meningeal lymphatic drainage after IVH.
Intravital imaging of splenic classical monocytes modifying the hepatic CX3CR1<sup>+</sup> cells motility to exacerbate liver fibrosis via spleen-liver axis
Authors: Chenlu Han, Yujie Zhai, Yuke Wang, Xuwen Peng, Xian Zhang, Bolei Dai, Yuehong Leng, Zhihong Zhang, Shuhong Qi
Journal: Theranostics (2024)

CX3CR1 + cells play a crucial role in liver fibrosis progression.However, changes in the migratory behavior and spatial distribution of spleen-derived and hepatic CX3CR1 + cells in the fibrotic liver as well as their influence on the liver fibrosis remain unclear. Methods:The CX3CR1 GFP/+ transgenic mice and CX3CR1-KikGR transgenic mice were used to establish the CCl4-induced liver fibrosis model.Splenectomy, adoptive transfusion of splenocytes, in vivo photoconversion of splenic CX3CR1 + cells and intravital imaging were performed to study the spatial distribution, migration and movement behavior, and regulatory function of CX3CR1 + cells in liver fibrosis. Results:Intravital imaging revealed that the CX3CR1 GFP cells accumulated into the fibrotic liver and tended to accumulate towards the central vein (CV) in the hepatic lobules.Two subtypes of hepatic CX3CR1 + cells existed in the fibrotic liver.The first subtype was the interacting CX3CR1 GFP cells, most of which were observed to distribute in the liver parenchyma and had a higher process velocity; the second subtype was mobile CX3CR1 GFP cells, most of which were present in the hepatic vessels with a faster moving speed.Splenectomy ameliorated liver fibrosis and decreased the number of CX3CR1 + cells in the fibrotic liver.Moreover, splenectomy rearranged CX3CR1 GFP cells to the boundary of the hepatic lobule, reduced the process velocity of interacting CX3CR1 GFP cells and decreased the number and mobility of mobile CX3CR1 GFP cells in the fibrotic liver.Transfusion of spleen-derived classical monocytes increased the process velocity and mobility of hepatic endogenous CX3CR1 GFP cells and facilitated liver fibrosis progression via the production of proinflammatory and profibrotic cytokines.The photoconverted splenic CX3CR1 + KikRed + cells were observed to leave the spleen, accumulate into the fibrotic liver and contact with hepatic CX3CR1 + KikGreen + cells during hepatic fibrosis. Conclusion:The splenic CX3CR1 + monocytes with classical phenotype migrated from the spleen to the fibrotic liver, modifying the migratory behavior of hepatic endogenous CX3CR1 GFP cells and exacerbating liver fibrosis via the secretion of cytokines.This study reveals that splenic CX3CR1 + classical monocytes are a key driver of liver fibrosis via the spleen-liver axis and may be potential candidate targets for the treatment of chronic liver fibrosis.
G protein subunit alpha i2's pivotal role in angiogenesis
Authors: Chao-wen Bai, Lu Lu, Jia-nan Zhang, Chengyu Zhou, Yi-chao Ni, Ke-ran Li, Jin Yao, Xiao-zhong Zhou, Chang-gong Lan, Cong Cao
Journal: Theranostics (2024)

Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis.Methods: Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function.Their effects on endothelial cell functions were assessed in vitro.In vivo, the endothelial-specific Gαi2 shRNA adeno-associated virus (AAV) was utilized to silence Gαi2 expression.The impact of this suppression on retinal angiogenesis in control mice and streptozotocin (STZ)-induced diabetic retinopathy (DR) mice was analyzed.Results: Analysis of single-cell RNA sequencing data revealed Gαi2 (GNAI2) was predominantly expressed in retinal endothelial cells and expression was increased in retinal endothelial cells following oxygen-induced retinopathy (OIR) in mice.Moreover, transcriptome analysis linking Gαi2 to angiogenesis-related processes/pathways, supported by increased Gαi2 expression in experimental OIR mouse retinas, highlighted its possible role in angiogenesis.In various endothelial cell types, shRNA-induced silencing and CRISPR/Cas9-mediated knockout (KO) of Gαi2 resulted in substantial reductions in cell proliferation, migration, invasion, and capillary tube formation.Conversely, Gαi2 over-expression in endothelial cells induced pro-angiogenic activities, enhancing cell proliferation, migration, invasion, and capillary tube formation.Furthermore, our investigation revealed a crucial role of Gαi2 in NFAT (nuclear factor of activated T cells) activation, as evidenced by the down-regulation of NFAT-luciferase reporter activity and pro-angiogenesis NFAT-targeted genes (Egr3, CXCR7, and RND1) in Gαi2-silenced or -KO HUVECs, which were up-regulated in Gαi2-overexpressing endothelial cells.Expression of a dominant negative Gαi2 mutation (S48C) also down-regulated NFAT-targeted genes, slowing proliferation, migration, invasion, and capillary tube formation in HUVECs.Importantly, in vivo experiments revealed that endothelial Gαi2 knockdown inhibited retinal angiogenesis in mice, with a concomitant down-regulation of NFAT-targeted genes in mouse retinal tissue.In contrast, Gαi2 over-expression in endothelial cells enhanced retinal angiogenesis in mice.Single-cell RNA sequencing data confirmed increased levels of Gαi2 specifically in retinal endothelial cells of mice with streptozotocin (STZ)-induced diabetic retinopathy (DR).Importantly, endothelial Gαi2 silencing ameliorated retinal pathological angiogenesis in DR mice. Conclusion:Our study highlights a critical role for Gαi2 in NFAT activation, endothelial cell activation and angiogenesis, offering valuable insights into potential therapeutic strategies for modulating these processes.
NPC1 is required for postnatal islet β cell differentiation by maintaining mitochondria turnover
Authors: Bei Liu, Duanyi Hua, Linyan Shen, Tingting Li, Zheying Tao, Chenyang Fu, Zhongzheng Tang, Jie Yang, Li Zhang, Aifang Nie, Yiran Jiang, Jiqiu Wang, Yang Li, Yanyun Gu, Guang Ning
Journal: Theranostics (2024)

Rationale: NPC1 is a protein localized on the lysosome membrane regulating intracellular cholesterol transportation and maintaining normal lysosome function.GWAS studies have found that NPC1 variants in T2D was a pancreatic islet expression quantitative trait locus, suggesting a potential role of NPC1 in T2D islet pathophysiology.Methods: Two-week-old Npc1 -/-mice and wild type littermates were employed to examine pancreatic β cell morphology and functional changes induced by loss of Npc1.Single cell RNA sequencing was conducted on primary islets.Npc1 -/-Min6 cell line was generated using CRISPR/Cas9 gene editing.Seahorse XF24 was used to analyze primary islet and Min6 cell mitochondria respiration.Ultra-high-resolution cell imaging with Lattice SIM 2 and electron microscope imaging were used to observe mitochondria and lysosome in primary islet β and Min6 cells.Mitophagy Dye and mt-Keima were used to measure β cell mitophagy.Results: In Npc1 -/-mice, we found that β cell survival and pancreatic β cell mass expansion as well as islet glucose induced insulin secretion in 2-week-old mice were reduced.Npc1 loss retarded postnatal β cell differentiation and growth as well as impaired mitochondria oxidative phosphorylation (OXPHOS) function to increase mitochondrial superoxide production, which might be attributed to impaired autophagy flux particularly mitochondria autophagy (mitophagy) induced by dysfunctional lysosome in Npc1 null β cells. Conclusion:Our study revealed that NPC1 played an important role in maintaining normal lysosome function and mitochondria turnover, which ensured establishment of sufficient mitochondria OXPHOS for islet β cells differentiation and maturation.
Engineered exosomes and composite biomaterials for tissue regeneration
Authors: Weikang Hu, Wang Wang, Zesheng Chen, Yun Chen, Zijian Wang
Journal: Theranostics (2024)

Exosomes, which are small vesicles enclosed by a lipid bilayer and released by many cell types, are widely dispersed and have garnered increased attention in the field of regenerative medicine due to their ability to serve as indicators of diseases and agents with therapeutic potential. Exosomes play a crucial role in mediating intercellular communication through the transfer of many biomolecules, including proteins, lipids, RNA, and other molecular constituents, between cells. The targeted transport of proteins and nucleic acids to specific cells has the potential to enhance or impair specific biological functions. Exosomes have many applications, and they can be used alone or in combination with other therapeutic approaches. The examination of the unique attributes and many functions of these factors has emerged as a prominent field of study in the realm of biomedical research. This manuscript summarizes the origins and properties of exosomes, including their structural, biological, physical, and chemical aspects. This paper offers a complete examination of recent progress in tissue repair and regenerative medicine, emphasizing the possible implications of these methods in forthcoming tissue regeneration attempts.
Unleashing the potential of adipose organoids: A revolutionary approach to combat obesity-related metabolic diseases
Authors: Xingran Liu, Jing Yang, Yuxin Yan, Qingfeng Li, Ru-Lin Huang
Journal: Theranostics (2024)

Obesity-related metabolic diseases, including obesity, diabetes, hyperlipidemia, and non-alcoholic fatty liver diseases pose a significant threat to health.However, comprehensive pathogenesis exploration and effective therapy development are impeded by the limited availability of human models.Notably, advances in organoid technology enable the generation of adipose organoids that recapitulate structures and functions of native human adipose tissues to investigate mechanisms and develop corresponding treatments for obesity-related metabolic diseases.Here, we review the general principles, sources, and three-dimensional techniques for engineering adipose organoids, along with strategies to promote maturation.We also outline the application of white adipose organoids, primarily for disease modeling and drug screening, and highlight the therapeutic potential of thermogenic beige and brown adipose organoids in promoting weight loss and glucose and lipid metabolic homeostasis.We also discuss the challenges and prospects in the establishment and bench-to-bedside of adipose organoids, as well as their potential applications.
FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation
Authors: Xingyan Xu, Xuefen Zhuang, Haowei Yu, Ping Li, Xiaosa Li, Huiping Lin, Jian-peng Teoh, Yiwen Chen, Yuanlan Yang, Yang Cheng, Weiyu Chen, Xiaodong Fu
Journal: Theranostics (2024)

Background:The therapeutic benefits of targeting follicle-stimulating hormone (FSH) receptor in treatment of ovarian cancer are significant, whereas the role of FSH in ovarian cancer progresses and the underlying mechanism remains to be developed.Methods: Tissue microarray of human ovarian cancer, tumor xenograft mouse model, and in vitro cell culture were used to investigate the role of FSH in ovarian carcinogenesis.siRNA, lentivirus and inhibitors were used to trigger the inactivation of genes, and plasmids were used to increase transcription of genes.Specifically, pathological characteristic was assessed by histology and immunohistochemistry (IHC), while signaling pathway was studied using western blot, quantitative RT-PCR, and immunofluorescence.Results: Histology and IHC of human normal ovarian and tumor tissue confirmed the association between FSH and Snail in ovarian cancer metastasis.Moreover, in epithelial ovarian cancer cells and xenograft mice, FSH was showed to promote epithelial mesenchymal transition (EMT) progress and metastasis of ovarian cancer via prolonging the half-life of Snail mRNA in a N6-methyladenine methylation (m6A) dependent manner, which was mechanistically through the CREB/ALKBH5 signaling pathway.Conclusions: These findings indicated that FSH induces EMT progression and ovarian cancer metastasis via CREB/ALKBH5/Snail pathway.Thus, this study provided new insight into the therapeutic strategy of ovarian cancer patients with high level of FSH.
Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer
Authors: Aushia Tanzih Al Haq, Pao-Pao Yang, Christopher Jin, Jou-Ho Shih, Li-Mei Chen, Hong-Yu Tseng, Yen-An Chen, Yueh-Shan Weng, Lu-Hai Wang, Michael P. Snyder, Hsin-Ling Hsu
Journal: Theranostics (2024)

Rationale: Multiple copies in T-cell malignancy 1 (MCT-1) is a prognostic biomarker for aggressive breast cancers.Overexpressed MCT-1 stimulates the IL-6/IL-6R/gp130/STAT3 axis, which promotes epithelial-to-mesenchymal transition and cancer stemness.Because cancer stemness largely contributes to the tumor metastasis and recurrence, we aimed to identify whether the blockade of MCT-1 and IL-6R can render these effects and to understand the underlying mechanisms that govern the process.Methods: We assessed primary tumor invasion, postsurgical local recurrence and distant metastasis in orthotopic syngeneic mice given the indicated immunotherapy and MCT-1 silencing (shMCT-1).Results: We found that shMCT-1 suppresses the transcriptomes of the inflammatory response and metastatic signaling in TNBC cells and inhibits tumor recurrence, metastasis and mortality in xenograft mice.IL-6R immunotherapy and shMCT-1 combined further decreased intratumoral M2 macrophages and T regulatory cells (Tregs) and avoided postsurgical TNBC expansion.shMCT-1 also enhances IL-6R-based immunotherapy effectively in preventing postsurgical TNBC metastasis, recurrence and mortality.Anti-IL-6R improved helper T, cytotoxic T and natural killer (NK) cells in the lymphatic system and decreased Tregs in the recurrent and metastatic tumors.Combined IL-6R and PD-L1 immunotherapies abridged TNBC cell stemness and M2 macrophage activity to a greater extent than monotherapy.Sequential immunotherapy of PD-L1 and IL-6R demonstrated the best survival outcome and lowest postoperative recurrence and metastasis compared with synchronized therapy, particularly in the shMCT-1 context.Multiple positive feedforward loops of the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 axis were identified in TNBC cells, which boosted metastatic niches and immunosuppressive microenvironments.Clinically, MCT-1 high /PD-L1 high /CXCL7 high and CXCL7 high /IL-6 high /IL-6R high expression patterns predict worse prognosis and poorer survival of breast cancer patients.Conclusion: Systemic targeting the MCT-1/IL-6/IL-6R/CXCL7/PD-L1 interconnections enhances immune surveillance that inhibits the aggressiveness of TNBC.
An advanced comprehensive muti-cell-type-specific model for predicting anti-PD-1 therapeutic effect in melanoma
Authors: Wei Sun, Yu Zhu, Zijian Zou, Lu Wang, Jingqin Zhong, Kangjie Shen, Xinyi Lin, Zixu Gao, Wanlin Liu, Yinlam Li, Yu Xu, Ming Ren, Tu Hu, Chuanyuan Wei, Jianying Gu, Yong Chen
Journal: Theranostics (2024)

Immune checkpoint inhibitors targeting the programmed cell death (PD)-1/PD-L1 pathway have promise in patients with advanced melanoma. However, drug resistance usually results in limited patient benefits. Recent single-cell RNA sequencing studies have elucidated that MM patients display distinctive transcriptional features of tumor cells, immune cells and interstitial cells, including loss of antigen presentation function of tumor cells, exhaustion of CD8+T and extracellular matrix secreted by fibroblasts to prevents immune infiltration, which leads to a poor response to immune checkpoint inhibitors (ICIs). However, cell subgroups beneficial to anti-tumor immunity and the model developed by them remain to be further identified.
Comparing Continuous Glucose Monitoring and Blood Glucose Monitoring in Adults With Inadequately Controlled, Insulin-Treated Type 2 Diabetes (Steno2tech Study): A 12-Month, Single-Center, Randomized Controlled Trial
Authors: Nanna Lind, Merete B. Christensen, Dorte L. Hansen, Kirsten Nørgaard
Journal: Diabetes Care (2024)

OBJECTIVE To compare the 12-month effects of continuous glucose monitoring (CGM) versus blood glucose monitoring (BGM) in adults with insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS This is a single-center, parallel, open-label, randomized controlled trial including adults with inadequately controlled, insulin-treated type 2 diabetes from the outpatient clinic at Steno Diabetes Center Copenhagen, Denmark. Inclusion criteria were ≥18 years of age, insulin-treated type 2 diabetes, and HbA1c ≥7.5% (58 mmol/mol). Participants were randomly assigned (1:1) to 12 months of either CGM or BGM. All participants received a diabetes self-management education course and were followed by their usual health care providers. Primary outcome was between-group differences in change in time in range (TIR) 3.9–10.0 mmol/L, assessed at baseline, after 6 and 12 months by blinded CGM. The prespecified secondary outcomes were differences in change in several other glycemic, metabolic, and participant-reported outcomes. RESULTS The 76 participants had a median baseline HbA1c of 8.3 (7.8, 9.1)% (67 [62–76] mmol/mol), and 61.8% were male. Compared with BGM, CGM usage was associated with significantly greater improvements in TIR (between-group difference 15.2%, 95% CI 4.6; 25.9), HbA1c (−0.9%, −1.4; −0.3 [−9.4 mmol/mol, −15.2; −3.5]), total daily insulin dose (−10.6 units/day, −19.9; −1.3), weight (−3.3 kg, −5.5; −1.1), and BMI (−1.1 kg/m2, −1.8; −0.3) and greater self-rated diabetes-related health, well-being, satisfaction, and health behavior. CONCLUSIONS In adults with inadequately controlled insulin-treated type 2 diabetes, the 12-month impact of CGM was superior to BGM in improving glucose control and other crucial health parameters. The findings support the use of CGM in the insulin-treated subgroup of type 2 diabetes.
One in 8 People Worldwide Are Obese
Authors: Samantha Anderer
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal