A folding motif formed with an expanded genetic alphabet.

Adding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5 °C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ-:dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ-:dZ pairs join parallel strands in a four-stranded compact down-up-down-up fold. These have two possible structures: one with intercalated dZ-:dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC+-reversed pairing at pH ≤ 6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.

Functional Selection of Tau Oligomerization-Inhibiting Aptamers.

Pathological hyperphosphorylation and aggregation of microtubule-associated Tau protein contribute to Alzheimer's Disease (AD) and other related tauopathies. Currently, no cure exists for Alzheimer's Disease. Aptamers offer significant potential as next-generation therapeutics in biotechnology and the treatment of neurological disorders. Traditional aptamer selection methods for Tau protein focus on binding affinity rather than interference with pathological Tau. In this study, we developed a new selection strategy to enrich DNA aptamers that bind to surviving monomeric Tau protein under conditions that would typically promote Tau aggregation. Employing this approach, we identified a set of aptamer candidates. Notably, BW1c demonstrates a high binding affinity (Kd=6.6 nM) to Tau protein and effectively inhibits arachidonic acid (AA)-induced Tau protein oligomerization and aggregation. Additionally, it inhibits GSK3ß-mediated Tau hyperphosphorylation in cell-free systems and okadaic acid-mediated Tau hyperphosphorylation in cellular milieu. Lastly, retro-orbital injection of BW1c tau aptamer shows the ability to cross the blood brain barrier and gain access to neuronal cell body. Through further refinement and development, these Tau aptamers may pave the way for a first-in-class neurotherapeutic to mitigate tauopathy-associated neurodegenerative disorders.

Preoperative prediction of lymphovascular space invasion in endometrioid adenocarcinoma: an MRI-based radiomics nomogram with consideration of the peritumoral region.

BACKGROUND: Lymphovascular space invasion (LVSI) of endometrial cancer (EC) is a postoperative histological index, which is associated with lymph node metastases. A preoperative acknowledgement of LVSI status might aid in treatment decision-making. PURPOSE: To explore the utility of multiparameter magnetic resonance imaging (MRI) and radiomic features obtained from intratumoral and peritumoral regions for predicting LVSI in endometrioid adenocarcinoma (EEA). MATERIAL AND METHODS: A total of 334 EEA tumors were retrospectively analyzed. Axial T2-weighted (T2W) imaging and apparent diffusion coefficient (ADC) mapping were conducted. Intratumoral and peritumoral regions were manually annotated as the volumes of interest (VOIs). A support vector machine was applied to train the prediction models. Multivariate logistic regression analysis was used to develop a nomogram based on clinical and tumor morphological parameters and the radiomics score (RadScore). The predictive performance of the nomogram was assessed by the area under the receiver operator characteristic curve (AUC) in the training and validation cohorts. RESULTS: Among the features obtained from different imaging modalities (T2W imaging and ADC mapping) and VOIs, the RadScore had the best performance in predicting LVSI classification (AUCtrain = 0.919, and AUCvalidation = 0.902). The nomogram based on age, CA125, maximum anteroposterior tumor diameter on sagittal T2W images, tumor area ratio, and RadScore was established to predict LVSI had AUC values in the training and validation cohorts of 0.962 (sensitivity 94.0%, specificity 86.0%) and 0.965 (sensitivity 90.0%, specificity 85.3%), respectively. CONCLUSION: The intratumoral and peritumoral imaging features were complementary, and the MRI-based radiomics nomogram might serve as a non-invasive biomarker to preoperatively predict LVSI in patients with EEA.

Targeting HSF1 for cancer treatment: mechanisms and inhibitor development.

Heat Shock Factor 1 (HSF1) is a master regulator of heat shock responsive signaling. In addition to playing critical roles in cellular heat shock response, emerging evidence suggests that HSF1 also regulates a non-heat shock responsive transcriptional network to handle metabolic, chemical, and genetic stress. The function of HSF1 in cellular transformation and cancer development has been extensively studied in recent years. Due to important roles for HSF1 for coping with various stressful cellular states, research on HSF1 has been very active. New functions and molecular mechanisms underlying these functions have been continuously discovered, providing new targets for novel cancer treatment strategies. In this article, we review the essential roles and mechanisms of HSF1 action in cancer cells, focusing more on recently discovered functions and their underlying mechanisms to reflect the new advances in cancer biology. In addition, we emphasize new advances with regard to HSF1 inhibitors for cancer drug development.

New frontiers in immune checkpoint B7-H3 (CD276) research and drug development.

B7-H3 (CD276), a member of the B7 family of proteins, is a key player in cancer progression. This immune checkpoint molecule is selectively expressed in both tumor cells and immune cells within the tumor microenvironment. In addition to its immune checkpoint function, B7-H3 has been linked to tumor cell proliferation, metastasis, and therapeutic resistance. Furthermore, its drastic difference in protein expression levels between normal and tumor tissues suggests that targeting B7-H3 with drugs would lead to cancer-specific toxicity, minimizing harm to healthy cells. These properties make B7-H3 a promising target for cancer therapy.Recently, important advances in B7-H3 research and drug development have been reported, and these new findings, including its involvement in cellular metabolic reprograming, cancer stem cell enrichment, senescence and obesity, have expanded our knowledge and understanding of this molecule, which is important in guiding future strategies for targeting B7-H3. In this review, we briefly discuss the biology and function of B7-H3 in cancer development. We emphasize more on the latest findings and their underlying mechanisms to reflect the new advances in B7-H3 research. In addition, we discuss the new improvements of B-H3 inhibitors in cancer drug development.

FBXO11 regulates bone development.

FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this study, we reported a novel mechanism of how bone development is regulated by FBXO11. FBXO11 gene knockdown by lentiviral transduction in mouse pre-osteoblast MC3T3-E1 cells leads to reduced osteogenic differentiation, while overexpressing FBXO11 accelerates their osteogenic differentiation in vitro. Furthermore, we generated two osteoblastic-specific FBXO11 conditional knockout mouse models, Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO mice. In both conditional FBXO11KO mouse models, we found FBXO11 deficiency inhibits normal bone growth, in which the osteogenic activity in FBXO11cKO mice is reduced, while osteoclastic activity is not significantly changed. Mechanistically, we found FBXO11 deficiency leads to Snail1 protein accumulation in osteoblasts, leading to suppression of osteogenic activity and inhibition of bone matrix mineralization. FBXO11 knockdown in MC3T3-E1 cells reduced Snail1 protein ubiquitination and increased Snail1 protein accumulation in the cells, which eventually inhibited osteogenic differentiation. In conclusion, FBXO11 deficiency in osteoblasts inhibits bone formation through Snail1 accumulation, inhibiting osteogenic activity and bone mineralization.

MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer.

The mammalian STE 20-like protein kinase 4 (MST4) gene is highly expressed in several cancer types, but little is known about the role of MST4 in breast cancer, and the function of MST4 during epithelial-mesenchymal transition (EMT) has not been fully elucidated. Here we report that overexpression of MST4 in breast cancer results in enhanced cell growth, migration, and invasion, whereas inhibition of MST4 expression significantly attenuates these properties. Further study shows that MST4 promotes EMT by activating Akt and its downstream signaling molecules such as E-cadherin/N-cadherin, Snail, and Slug. MST4 also activates AKT and its downstream pro-survival pathway. Furthermore, by analyzing breast cancer patient tissue microarray and silicon datasets, we found that MST4 expression is much higher in breast tumor tissue compared to normal tissue, and significantly correlates with cancer stage, lymph node metastasis and a poor overall survival rate (p < 0.05). Taken together, our findings demonstrate the oncogenic potential of MST4 in breast cancer, highlighting its role in cancer cell proliferation, migration/invasion, survival, and EMT, suggesting a possibility that MST4 may serve as a novel therapeutic target for breast cancer.

Construction of a Landscape Design and Greenery Maintenance Scheduling System Based on Multimodal Intelligent Computing and Deep Neural Networks.

Digitalization brings challenges and new opportunities to the development of landscape gardening, "smart gardening," which is a product of landscape gardening in response to the development of the digital era. Based on the multimodal intelligent computing method and deep neural network machine learning algorithm, this paper adopts "digital landscape design logic" to analyze and research smart gardens and digital design. The digital landscape design process and methods are discussed based on design logic, design basis, environment analysis, and results presentation, and the greenery maintenance scheduling system is constructed. The paper focuses on the digital implementation of the environmental analysis of the site and uses Rhino software and Grasshopper visual programming language to build parametric logic, establish parametric analysis models, and conduct a comprehensive analysis of the current environment. The main theme of the whole paper is a logical approach to digital landscape design for smart gardens, using digital technology tools from the perspective of smart garden thinking, combining quantitative analysis and qualitative design, and intervening in digital landscape garden planning and design to explore the application of digital technology and tools.

Epithelial-Mesenchymal Transition Suppresses AMPK and Sensitizes Cancer Cells to Pyroptosis under Energy Stress.

Epithelial-mesenchymal transition (EMT) is implicated in tumor metastasis and therapeutic resistance. It remains a challenge to target cancer cells that have undergone EMT. The Snail family of key EMT-inducing transcription factors directly binds to and transcriptionally represses not only epithelial genes but also a myriad of additional genomic targets that may carry out significant biological functions. Therefore, we reasoned that EMT inherently causes various concomitant phenotypes, some of which may create targetable vulnerabilities for cancer treatment. In the present study, we found that Snail transcription factors bind to the promoters of multiple genes encoding subunits of the AMP-activated protein kinase (AMPK) complex, and expression of AMPK genes was markedly downregulated by EMT. Accordingly, high AMPK expression in tumors correlated with epithelial cell markers and low AMPK expression in tumors was strongly associated with adverse prognosis. AMPK is the principal sensor of cellular energy status. In response to energy stress, AMPK is activated and critically reprograms cellular metabolism to restore energy homeostasis and maintain cell survival. We showed that activation of AMPK by energy stress was severely impaired by EMT. Consequently, EMT cancer cells became hypersensitive to a variety of energy stress conditions and primarily underwent pyroptosis, a regulated form of necrotic cell death. Collectively, the study suggests that EMT impedes the activation of AMPK signaling induced by energy stress and sensitizes cancer cells to pyroptotic cell death under energy stress conditions. Therefore, while EMT promotes malignant progression, it concurrently induces collateral vulnerabilities that may be therapeutically exploited.

Renal Denervation Attenuates Adverse Remodeling and Intramyocardial Inflammation in Acute Myocardial Infarction With Ischemia-Reperfusion Injury.

Background: Inhibition of sympathetic activity and renin-angiotensin system with renal denervation (RDN) was proved to be effective in managing refractory hypertension, and improving left ventricular (LV) performance in chronic heart failure. The inhibition of sustained sympathetic activation prevents or delays the development of cardiac fibrosis and dysfunction that occurs after myocardial infarction and ischemia-reperfusion (I/R) injury. The translational efficiency of RDN remains to be defined in preclinical animal studies. Objectives: This study investigated the therapeutic role of RDN in adverse remodeling and intramyocardial inflammation in myocardial ischemia-reperfusion (MI/R) injury. Methods: Herein, 15 minipigs were subjected to 90-min percutaneous occlusion of the left anterior descending artery followed by reperfusion. Eight animals received simultaneous RDN using catheter-based radiofrequency ablation (MI/R-RDN). Cardiac function and infarct volume were measured in vivo, followed by histological and biochemical analyses. Results: The infarct volume in I/R-RDN pigs reduced at 30 days postreperfusion, compared to I/R-Sham animals. The levels of catecholamine and cytokines in the serum, kidney cortex, the border, and infarcted regions of the heart were significantly reduced in I/R-RDN group. Moreover, the gene expression of collagen and the protein expression of adrenergic receptor beta 1 in heart were also decreased in I/R-RDN mice. Additionally, RDN therapy alleviated myocardial oxidative stress. Conclusion: RDN is an effective therapeutic strategy for counteracting postreperfusion myocardial injury and dysfunction, and the application of RDN holds promising prospects in clinical practice.

Effect of naturally derived surgical hemostatic materials on the proliferation of A549 human lung adenocarcinoma cells.

Hemostatic materials are generally applied in surgical operations for cancer, but their effects on the growth and recurrence of tumors are unclear. Herein, three commonly used naturally derived hemostatic materials, gelatin sponge, Surgicel (oxidized regenerated cellulose), and biopaper (mixture of sodium hyaluronate and carboxymethyl chitosan), were cocultured with A549 human lung adenocarcinoma cells in vitro. Furthermore, the performance of hemostatic materials and the tumorigenicity of the materials with A549 â€‹cells were observed after subcutaneous implantation into BALB/c mice. The in vitro results showed that biopaper was dissolved quickly, with the highest cell numbers at 2 and 4 days of culture. Gelatin sponges retained their structure and elicited the least cell infiltration during the 2- to 10-day culture. Surgicel partially dissolved and supported cell growth over time. The in vivo results showed that biopaper degraded rapidly and elicited an acute Th1 lymphocyte reaction at 3 days after implantation, which was decreased at 7 days after implantation. The gelatin sponge resisted degradation and evoked a hybrid M1/M2 macrophage reaction at 7-21 days after implantation, and a protumor M2d subset was confirmed. Surgicel resisted early degradation and caused obvious antitumor M2a macrophage reactions. Mice subjected to subcutaneous implantation of A549 â€‹cells and hemostatic materials in the gelatin sponge group had the largest tumor volumes and the shortest overall survival (OS), while the Surgicel and the biopaper group had the smallest volumes and the longest OS. Therefore, although gelatin sponges exhibited cytotoxicity to A549 â€‹cells in vitro, they promoted the growth of A549 â€‹cells in vivo, which was related to chronic M2d macrophage reaction. Surgicel and biopaper inhibited A549 â€‹cell growth in vivo, which is associated with chronic M2a macrophage reaction or acute Th1 lymphocyte reaction.

Zinc oxide nanoparticles dissolution and toxicity enhancement by polystyrene microplastics under sunlight irradiation.

Zinc oxide nanoparticles (ZnO NPs) dissolution is a critical process for the transformation and toxicity of ZnO NPs in aquatic environments. However, the effect of microplastics (MPs) on dissolution and toxicity of ZnO NPs under sunlight irradiation is still lacking. Herein, the dramatic increase in sunlight-induced ZnO NPs dissolution by polystyrene (PS) MPs was proven, which was attributed to the increase in h+-dependent and proton-dependent ZnO NPs dissolution by PS MPs, yielding 1O2 generation inhibition and acid release, respectively. The sizes, functional groups and aging status of PS MPs and pH were characteristic ZnO NPs dissolution through modifying 1O2, •OH and O2•- generation and acid release. Furthermore, the ZnO NPs dissolution affected by PS MPs also occurred in three realistic water samples, which were mainly governed by dissolved organic matter (DOM) and CO32-, rather than Cl- or SO42-. The PS MPs (1 µg/mL) dramatically altered the Zn2+:ZnO ratio in ZnO NPs suspension after 96 h of sunlight irradiation and presented vehicle effects on Zn2+, which in turn significantly increased the ion-related toxicity of ZnO NPs to Daphnia magna. Based on the PS MPs enhanced dissolution and toxicity of ZnO NPs, the effects of PS MPs on the environmental risk assessment of ZnO NPs should be seriously considered in freshwater environments under sunlight irradiation.

Rapid, accurate, and novel diagnostic technique for respiratory pathogens: Clinical application of loop-mediated isothermal amplification assay in older patients with pneumonia, a multicenter prospective observational study.

Background: Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method using only one type of enzyme that can amplify DNA with high specificity, efficiency and rapidity under isothermal conditions. Chips for Complicated Infection Detection (CCID) is based on LAMP. This study translate CCID into clinical application and evaluate its diagnostic value for pneumonia. Methods: Eighty one older patients with pneumonia were prospectively enrolled from January 1 to July 23, 2021, and 57 sputum/airway secretion and 35 bronchoalveolar lavage fluid samples were collected and analyzed by CCID and conventional microbiological tests (CMTs). Samples were collected, transported, monitored, and managed by a multidisciplinary team using a sample management information system. Results: CCID turnaround time was 50 min, and the detection limit was 500 copies/reaction. The percentage of positive samples was significantly higher using CCID than CMTs, especially for Klebsiella pneumoniae (odds ratio [OR], 9.0; 95% confidence interval [CI], 1.1-70.5; p < 0.05), Enterococcus faecalis (OR, ∞; p < 0.01), Stenotrophomonas maltophilia (OR, ∞; p < 0.01), fungi (OR, 26.0; 95% CI, 3.6-190.0; p < 0.01), and viruses (CCID only; p < 0.01). In addition, the percentage of positive results was significantly higher using CCID than CMTs in patients who used antibiotics for more than 3 days (91.9% vs. 64.9%; p < 0.01). Analyzing clinical impact, 55 cases (59.8%) benefited from CCID. Conclusion: CCID allows the rapid and accurate detection of pneumonia in older patients. Moreover, this technique is less affected by previous antibiotic treatment and can improve patient care.

Anti-inflammatory mechanisms and research progress of colchicine in atherosclerotic therapy.

Inflammatory responses play a vital role in the onset and development of atherosclerosis, and throughout the entire process of the chronic disease. The inflammatory responses in atherosclerosis are mainly mediated by the NLRP3 inflammasome and its downstream inflammatory factors. As a powerful anti-inflammatory medicine, colchicine has a history of more than 200 years in clinical application and is the first-choice treatment for immune diseases such as gout and familial Mediterranean fever. In atherosclerosis, colchicine can inhibit the assembly and activation of NLRP3 inflammasome via various mechanisms to effectively reduce the expression of inflammatory factors, thereby reducing the inflammation. Recent clinical trials show that a low dose of colchicine (0.5 mg per day) has a certain protective effect in stable angina patients or those with acute myocardial infarction after PCI. This article summarizes and discusses the mechanisms of colchicine in the treatment of atherosclerosis and the latest research progress.

Dependency of human and murine LKB1-inactivated lung cancer on aberrant CRTC-CREB activation.

Lung cancer with loss-of-function of the LKB1 tumor suppressor is a common aggressive subgroup with no effective therapies. LKB1-deficiency induces constitutive activation of cAMP/CREB-mediated transcription by a family of three CREB-regulated transcription coactivators (CRTC1-3). However, the significance and mechanism of CRTC activation in promoting the aggressive phenotype of LKB1-null cancer remain poorly characterized. Here, we observed overlapping CRTC expression patterns and mild growth phenotypes of individual CRTC-knockouts in lung cancer, suggesting functional redundancy of CRTC1-3. We consequently designed a dominant-negative mutant (dnCRTC) to block all three CRTCs to bind and co-activate CREB. Expression of dnCRTC efficiently inhibited the aberrantly activated cAMP/CREB-mediated oncogenic transcriptional program induced by LKB1-deficiency, and specifically blocked the growth of human and murine LKB1-inactivated lung cancer. Collectively, this study provides direct proof for an essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer and proposes the CRTC-CREB interaction interface as a novel therapeutic target.

The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma.

No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown. Here, we show that doxycycline-induced CRTC1-MAML2 knockdown blocked the growth of established MEC xenografts, validating CRTC1-MAML2 as a therapeutic target. We further generated a conditional transgenic mouse model and observed that Cre-induced CRTC1-MAML2 expression caused 100% penetrant formation of salivary gland tumors resembling histological and molecular characteristics of human MEC. Molecular analysis of MEC tumors revealed altered p16-CDK4/6-RB pathway activity as a potential cooperating event in promoting CRTC1-MAML2-induced tumorigenesis. Cotargeting of aberrant p16-CDK4/6-RB signaling and CRTC1-MAML2 fusion-activated AREG/EGFR signaling with the respective CDK4/6 inhibitor Palbociclib and EGFR inhibitor Erlotinib produced enhanced antitumor responses in vitro and in vivo. Collectively, this study provides direct evidence for CRTC1-MAML2 as a key driver for MEC development and maintenance and identifies a potentially novel combination therapy with FDA-approved EGFR and CDK4/6 inhibitors as a potential viable strategy for patients with MEC.

Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC) is the most common type of salivary gland cancers and patients with advanced, metastatic, and recurrent MECs have limited therapeutic options and poor treatment outcomes. MEC is commonly associated with a chromosomal translocation t(11;19) (q14-21;p12-13) that encodes the CRTC1-MAML2 oncogenic fusion. The CRTC1-MAML2 fusion is required for MEC growth in part through inducing autocrine AREG-EGFR signaling. Growing evidence suggests that MEC malignancy is maintained by cancer stem-like cells. In this study, we aimed to determine critical signaling for maintaining MEC stem-like cells and the effect of combined targeting of stem cell signaling and CRTC1-MAML2-induced EGFR signaling on blocking MEC growth. First, we evaluated the significance of Notch signaling in regulating MEC stem-like cells. Aberrantly activated Notch signaling was detected in human fusion-positive MEC cells. The inhibition of Notch signaling with genetic or pharmacological inhibitors reduced oncosphere formation and ALDH-bright population in vitro and blocked the growth of MEC xenografts in vivo. Next, we investigated the effect of co-targeting Notch signaling and EGFR signaling, and observed enhanced inhibition on MEC growth in vivo. Collectively, this study identified a critical role of Notch signaling in maintaining MEC stem-like cells and tumor growth, and revealed a novel approach of co-targeting Notch and EGFR signaling as a potential effective anti-MEC treatment.

Enhancing the Nucleolytic Resistance and Bioactivity of Functional Nucleic Acids by Diverse Nanostructures through in Situ Polymerization-Induced Self-assembly.

Functional nucleic acids (FNAs) are garnering tremendous interest owing to their high modularity and unique bioactivity. Three-dimensional FNAs have been developed to overcome the issues of nuclease degradation and limited cell uptake. We have developed a new facile approach to the synthesis of multiple three-dimensional FNA nanostructures by harnessing photo-polymerization-induced self-assembly. Sgc8 aptamer and CpG oligonucleotide were modified as macro chain-transfer reagents to mediate in situ polymerization and self-assembly. Diverse structures, including micelles, rods, and short worms, afford these two FNAs afford these two FNAs with higher nuclease resistance in serum serum, greater cellular uptake efficiency, and increased bioactivity.

LATS kinase-mediated CTCF phosphorylation and selective loss of genomic binding.

Chromatin topological organization is instrumental in gene transcription. Gene-enhancer interactions are accommodated in the same CTCF-mediated insulated neighborhoods. However, it remains poorly understood whether and how the 3D genome architecture is dynamically restructured by external signals. Here, we report that LATS kinases phosphorylated CTCF in the zinc finger (ZF) linkers and disabled its DNA-binding activity. Cellular stress induced LATS nuclear translocation and CTCF ZF linker phosphorylation, and altered the landscape of CTCF genomic binding partly by dissociating it selectively from a small subset of its genomic binding sites. These sites were highly enriched for the boundaries of chromatin domains containing LATS signaling target genes. The stress-induced CTCF phosphorylation and locus-specific dissociation from DNA were LATS-dependent. Loss of CTCF binding disrupted local chromatin domains and down-regulated genes located within them. The study suggests that external signals may rapidly modulate the 3D genome by affecting CTCF genomic binding through ZF linker phosphorylation.

In vivo construction of lymphoid node by implantation of adipose-derived stromal cells with hydroxypropyl methyl cellulose hydrogel in BALB/c nude mice.

Adipose-derived stromal cells have multilineage potential to differentiate into several specialized tissue types. Herein, we investigated whether ADSCs could differentiate into lymphoid node in vivo. Human ADSCs from routine liposuction were cultured in differentiation medium and were supplemented with transforming growth factor ß1 (TGF)-ß1 and basic fibroblast growth factor (bFGF). The induced hADSCs mixed with 13% (w/v) hydroxypropyl methylcellulose (HPMC) were injected into BALB/c nude mice subcutaneously. Eight weeks later, nodules were found under the injected sites. Histology, immunohistochemistry, and species identification analysis confirmed that the nodules were lymphoid nodes that were derived from the injected hADSCs. Our experiment demonstrated that the hADSCs could differentiate into lymphocyte-like cells and form lymphoid nodes in vivo. TGF-ß1 and bFGF might play important roles in the differentiation of hADSCs into lymphocyte-like cells. Our study might present an alternative approach for engineering immune organs and thus offer potential treatment for immunodeficiency diseases.