Living Biobanks of Organoids: Valuable Resource for Translational Research.

The emergence of organoids is considered a revolutionary model, changing the landscape of traditional translational research. These three-dimensional miniatures of human organs or tissues, cultivated from stem cells or biospecimens obtained from patients, faithfully replicate the structural and functional characteristics of specific target organs or tissues. In this extensive review, we explore the profound impact of organoids and assess the current state of living organoid biobanks, which are essential repositories for cryopreserving organoids derived from a variety of diseases. These resources hold significant value for translational research. We delve into the diverse origins of organoids, the underlying technologies, and their roles in recapitulating human development, disease modeling, as well as their potential applications in the pharmaceutical field. With a particular emphasis on biobanking organoids for prospective applications, we discuss how these advancements expedite the transition from bench to bedside translational research, thereby fostering personalized medicine and enriching our comprehension of human health.

Leukoaraiosis: Epidemiology, Imaging, Risk Factors, and Management of Age-Related Cerebral White Matter Hyperintensities.

Leukoaraiosis (LA) manifests as cerebral white matter hyperintensities on T2-weighted magnetic resonance imaging scans and corresponds to white matter lesions or abnormalities in brain tissue. Clinically, it is generally detected in the early 40s and is highly prevalent globally in individuals aged >60 years. From the imaging perspective, LA can present as several heterogeneous forms, including punctate and patchy lesions in deep or subcortical white matter; lesions with periventricular caps, a pencil-thin lining, and smooth halo; as well as irregular lesions, which are not always benign. Given its potential of having deleterious effects on normal brain function and the resulting increase in public health burden, considerable effort has been focused on investigating the associations between various risk factors and LA risk, and developing its associated clinical interventions. However, study results have been inconsistent, most likely due to potential differences in study designs, neuroimaging methods, and sample sizes as well as the inherent neuroimaging heterogeneity and multi-factorial nature of LA. In this article, we provided an overview of LA and summarized the current knowledge regarding its epidemiology, neuroimaging classification, pathological characteristics, risk factors, and potential intervention strategies.

Volume electron microscopy reveals age-related ultrastructural differences of globular bush cell axons in mouse central auditory system.

In mammals, thick axonal calibers wrapped with heavy myelin sheaths are prevalent in the auditory nervous system. These features are crucial for fast traveling of nerve impulses with minimal attenuation required for sound signal transmission. In particular, the long-range projections from the cochlear nucleus - the axons of globular bush cells (GBCs) - to the medial nucleus of the trapezoid body (MNTB) are tonotopically organized. However, it remains controversial in gerbils and mice whether structural and functional adaptations are present among the GBC axons targeting different MNTB frequency regions. By means of high-throughput volume electron microscopy, we compared the GBC axons in full-tonotopy-ranged MNTB slices from the C57BL/6 mice at different ages. Our quantification reveals distinct caliber diameter and myelin profile of the GBC axons with endings at lateral and medial MNTB, arguing for modulation of functionally heterogeneous axon subgroups. In addition, we reported axon-specific differences in axon caliber, node of Ranvier, and myelin sheath among juvenile, adult, and old mice, indicating the age-related changes of GBC axon morphology over time. These findings provide structural insight into the maturation and degeneration of GBC axons with frequency tuning across the lifespan of mice.

Cuprotosis Patterns Are Associated with Tumor Mutation Burden and Immune Landscape in Lung Adenocarcinoma.

Background: The association involving cuprotosis, molecular subtype, and specific immune cell groups in the tumor microenvironment has been focused on by more recent studies. In lung adenocarcinoma (LUAD), the potential functions of cuprotosis remain elusive. Methods: The cuprotosis regulations and tumor immune profile of 567 LUAD patients and the correlation between the cuprotosis patterns and the immune landscape were comprehensively evaluated. The cuprotosisScore was calculated using principal component analysis (PCA). The prognostic significance of the cuprotosisScore was evaluated by Cox regression statistics analysis. Results: Five cuprotosisClusters (named mc1, 2, 3, 4, 5)-characterized by differences in expression of immunomodulatory genes, mRNA, or lncRNA expression, and prognosis were identified. We established cuprotosisScore to quantify the cuprotosis pattern of individual LUAD patients. As is shown in further analyses, the cuprotosisScore was a relatively potential independent prognostic factor of LUAD involved in mc1. Finally, the prognostic value of the cuprotosisScore and its association with tumor immune microenvironment (iTME) of LUAD in five cuprotosisClusters were verified. Conclusions: We demonstrated the correlation between cuprotosis modification, the molecular subtype, and tumor immune landscape in LUAD. The cuprotosisCluster with high cuprotosisScore and high tumor mutation burden (TMB) was identified with a good prognosis and immune functions. The comprehensive evaluation of cuprotosis patterns in individual LUAD patients enhances the understanding of iTME and gives a new insight toward improved immune treatment strategies for LUAD patients.

Potassium channel-related genes are a novel prognostic signature for the tumor microenvironment of renal clear cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) accounts for 80% of renal cell carcinomas (RCCs), and its morbidity and prognosis are unfavorable. Surgical resection is the first-line treatment for ccRCC, but the oncogenesis of ccRCC is very complex. With the development of high-throughput sequencing technology, it is necessary to analyze the transcriptome to determine more effective treatment methods. The tumor microenvironment (TME) is composed of tumor cells, various immune-infiltrating cells, fibroblasts, many cytokines, and catalysts. It is a complex system with a dynamic balance that plays an essential role in tumor growth, invasion, and metastasis. Previous studies have confirmed that potassium channels can affect the immune system, especially T lymphocytes that require potassium channel activation. However, the effect of potassium channels on the TME of ccRCC remains to be studied. Therefore, this study aims to construct a prognostic signature for ccRCC patients based on potassium ion channel-related genes (PCRGs), assess patient risk scores, and divide patients into high- and low-risk groups based on the cutoff value. In addition, we investigated whether there were differences in immune cell infiltration, immune activator expression, somatic mutations, and chemotherapeutic responses between the high- and low-risk groups. Our results demonstrate that the PCRG signature can accurately assess patient prognosis and the tumor microenvironment and predict chemotherapeutic responses. In summary, the PCRG signature could serve as an auxiliary tool for the precision treatment of ccRCC.

MRGBP promotes colorectal cancer metastasis via DKK1/Wnt/ß-catenin and NF-kB/p65 pathways mediated EMT.

MRG domain binding protein (MRGBP) has been proposed to participate in the development of multiple tumors. However, the role of MRGBP in colorectal cancer (CRC) still remains largely unknown. Here, we found that MRGBP expression is significantly elevated in CRC, and that higher MRGBP expression correlates with poorer survival in CRC patients. Experiments in vivo and in vitro indicated that MRGBP promotes CRC cells proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and xenograft tumor growth. Mechanically, for one thing, we discovered that MRGBP suppresses DKK1 expression, thus further activating the Wnt/ß-catenin pathway in CRC cells. For another, MRGBP also enhances acetylation of NF-kB/p65 pathway. Treatment with Wnt/ß-catenin and NF-kB pathways inhibitors further confirmed the mediation of these two pathways in MRGBP-promoted CRC cell processes. In conclusion, these findings together suggest that MRGBP promotes CRC progression via DKK1/Wnt/ß-catenin and NF-kB/p65 pathways mediated EMT, identifying MRGBP as a promising prognostic and therapeutic target for CRC.

Removal and recovery of phosphorus from secondary effluent using layered double hydroxide-biochar composites.

Removal of phosphorus (P) from wastewater and its recovery as a fertilizer are solutions to both P pollution control and resource recycling for agriculture. In this study, various layered double hydroxide biochar composites (LDH/BCs), namely, Zn-Al-LDH/BC, Mg-Al-LDH/BC, and Mg-Fe-LDH/BC, were synthesized to remove P from secondary effluents and then applied as fertilizers. Batch experiments showed that LDH/BCs could adsorb P in fast kinetics, with adsorption capacities ranging 35.19-55.76 mg P/g. A dynamic experiment was performed under different column heights and flow rates, and the results fitted well with Thomas model (R2 > 0.90). These LDH/BCs effectively removed P in the continuous mode, even when treating secondary effluents. Furthermore, when the used LDH/BCs applied as fertilizers, the adsorbed Mg-Al-LDH/BC and Mg-Fe-LDH/BC stimulated crop growth; however, Zn-Al-LDH/BC did not. These differences were attributed to not only the availability of P, but also the stimulation or inhibition of photosynthetic pigment synthesis in crops by adsorbents. Overall, we synthesized LDH/BCs, which effectively removed and recovered P from secondary effluents, and investigated the factors influencing the effects of LDH/BCs on crops. We suggest that both P availability and physiological influences of adsorbents on crops should be considered when using adsorbents as fertilizers.

Cone-beam computed tomography three-dimensional reconstruction aids treatment of three root canals with severe curvature in maxillary first premolar: a case report.

The maxillary first premolar commonly has one or two root canals; the presence of three canals is rare. These root canals are easily missed during treatment, resulting in failure of root canal therapy. The present report describes a case in which three root canals in the maxillary first premolar were diagnosed by cone-beam computed tomography. The herein-described patient was successfully treated using three-dimensional reconstruction technology to determine the form and direction of curvature of the root canals.

Angiotensin(1-7) activates MAS-1 and upregulates CFTR to promote insulin secretion in pancreatic ß-cells: the association with type 2 diabetes.

Objective: The beneficial effect of angiotensin(1-7) (Ang(1-7)), via the activation of its receptor, MAS-1, has been noted in diabetes treatment; however, how Ang(1-7) or MAS-1 affects insulin secretion remains elusive and whether the endogenous level of Ang(1-7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl- channel, in the regulation of insulin secretion. Here, we tested the possible involvement of CFTR in mediating Ang(1-7)'s effect on insulin secretion and measured the level of Ang(1-7), MAS-1 as well as CFTR in the blood of individuals with or without type 2 diabetes. Methods: Ang(1-7)/MAS-1/CFTR pathway was determined by specific inhibitors, gene manipulation, Western blotting as well as insulin ELISA in a pancreatic ß-cell line, RINm5F. Human blood samples were collected from 333 individuals with (n = 197) and without (n = 136) type 2 diabetes. Ang(1-7), MAS-1 and CFTR levels in the human blood were determined by ELISA. Results: In RINm5F cells, Ang(1-7) induced intracellular cAMP increase, cAMP-response element binding protein (CREB) activation, enhanced CFTR expression and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not Ang(1-7), were significantly higher in individuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in type-2 diabetic but not non-diabetic subjects. Conclusion: These results suggested that MAS-1 and CFTR as key players in mediating Ang(1-7)-promoted insulin secretion in pancreatic ß-cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.

Volume electron microscopy reveals age-related circuit remodeling in the auditory brainstem.

The medial nucleus of the trapezoid body (MNTB) is an integral component of the auditory brainstem circuitry involved in sound localization. The giant presynaptic nerve terminal with multiple active zones, the calyx of Held (CH), is a hallmark of this nucleus, which mediates fast and synchronized glutamatergic synaptic transmission. To delineate how these synaptic structures adapt to reduced auditory afferents due to aging, we acquired and reconstructed circuitry-level volumes of mouse MNTB at different ages (3 weeks, 6, 18, and 24 months) using serial block-face electron microscopy. We used C57BL/6J, the most widely inbred mouse strain used for transgenic lines, which displays a type of age-related hearing loss. We found that MNTB neurons reduce in density with age. Surprisingly we observed an average of approximately 10% of poly-innervated MNTB neurons along the mouse lifespan, with prevalence in the low frequency region. Moreover, a tonotopy-dependent heterogeneity in CH morphology was observed in young but not in older mice. In conclusion, our data support the notion that age-related hearing impairments can be in part a direct consequence of several structural alterations and circuit remodeling in the brainstem.

Prevalence and Persistence of Ceftiofur-Resistant Escherichia coli in A Chicken Layer Breeding Program.

We determined the longitudinal persistence of ceftiofur-resistant Escherichia coli from a chicken breeding farm in China. A total of 150 samples were collected from 5 breeding periods in a flock of layer hens, and the prevalence of ceftiofur-resistant E. coli fluctuated across the 5 chicken breeding stages: eggs, 3.33%; growing period, 100%; early laying period, 36.7%; peak laying period, 66.7% and late laying period, 80%. The most prevalent ceftiofur resistance genes were blaCTX-M-55, blaCMY and blaNDM, and ST101 was the most prevalent and persistent sequence type across the breeding periods. Our results indicated that this breeder flock was heavily contaminated by ST101 ceftiofur-resistant E. coli and that its presence should be intensively monitored on chicken farms.

MIER3 induces epithelial-mesenchymal transition and promotes breast cancer cell aggressiveness via forming a co-repressor complex with HDAC1/HDAC2/Snail.

Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in women. MIER3 (Mesoderm induction early response 1, family member3) is considered as a potential oncogene for breast cancer. However, the role of MIER3 in breast cancer remain largely unknown. The expression of MIER3 was detected and the relationship between its expression and clinicopathological characteristics was also analyzed. The effect of MIER3 on proliferation and migration of breast cancer cells was detected in vitro and in vivo. Western blot, IF, and Co-IP were employed to detect the relationship between MIER3, HDAC1, HDAC2, and Snail. ChIP assay was performed to determine the binding of MIER3/HDAC1/HDAC2/Snail complex to the promoter of E-cadherin. In this study, we found that MIER3 was upregulated in breast cancer tissue and closely associated with poor prognosis of patients. MIER3 could promote the proliferation, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further studies showed that MIER3 interacted with HDAC1/HDAC2 and Snail to form a repressive complex which could bind to E-cadherin promoter and was related to its deacetylation. Our study concluded that MIER3 was involved in forming a co-repressor complex with HDAC1/HDAC2/Snail to promote EMT by silencing E-cadherin.

Cytoarchitecture and innervation of the mouse cochlear amplifier revealed by large-scale volume electron microscopy.

In mammalian cochlea, sound-induced vibration is amplified by a three-row lattice of Y-shaped microstructures consisting of electromotile outer hair cell and supporting Deiters cell. This highly organized structure is thought to be essential for hearing of low-level sounds. Prior studies reported differences in geometry and synaptic innervation of the outer hair cells between rows, but how these fine features are achieved at subcellular level still remains unclear. Using serial block-face electron microscopy, we acquired few-hundred-micron-sized cytoarchitecture of mouse organ of Corti at nanometer resolution. Structural quantifications were performed on the Y-shapes as well as afferent and efferent projections to outer hair cells (OHCs). Several new features, which support the previously observed inter-row heterogeneity, are described. Our result provides structural bases for the gradient of mechanical properties and diverse centrifugal regulation of OHC rows.

Integrated analysis of microRNA and mRNA expression profiling identifies BAIAP3 as a novel target of dysregulated hsa-miR-1972 in age-related white matter lesions.

White matter lesions known as leukoaraiosis (LA) are cerebral white matter hyperintensities observed in elderly individuals. Currently, no reliable molecular biomarkers are available for monitoring their progression over time. To identify biomarkers for the onset and progression of LA, we analyzed whole blood-based, microRNA expression profiles of leukoaraiosis, validated those exhibiting significant microRNA changes in clinical subjects by means of quantitative real-time polymerase chain reactions and determined the function of miRNA in cell lines by means of microRNA mimic transfection assays. A total of seven microRNAs were found to be significantly down-regulated in leukoaraiosis. Among the microRNAs, hsa-miR-1972 was downregulated during the early onset phase of leukoaraiosis, as confirmed in independent patients, and it was found to target leukoaraiosis-dependent BAIAP3, decreasing its expression in 293T cell lines. Functional enrichment analysis revealed that significantly dysregulated miRNAs-mRNAs changes associated with the onset of leukoaraiosis were involved in neurogenesis, neuronal development, and differentiation. Taken together, the study identified a set of candidate microRNA biomarkers that may usefully monitor the onset and progression of leukoaraiosis. Given the enrichment of leukoaraiosis-associated microRNAs and mRNAs in neuron part and membrane system, BAIAP3 could potentially represent a novel target of hsa-miR-1972 in leukoaraiosis through which microRNAs are involved in the pathogenesis of white matter lesions.

[Effect of different pretreatment methods on dentin microleakage and bonding effect in caries].

PURPOSE：To evaluate the effect of different pretreatment methods on dentin microleakage and bonding effect of caries, so as to provide reference for clinical practice. METHODS: Sixty isolated caries were collected from Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanchang University from January 2020 to December 2020, and 120 dental samples were obtained by grinding them into two halves along the long axis of the precursor teeth. According to different pretreatment methods, they were divided into group A (2%NaClO), group B (2% chlorhexidine) and group C (75% ethanol). The bond strength, microtensile test and microleakage of the three groups of teeth were compared. SPSS 24.0 software package was used for statistical analysis of the data. RESULTS: The bond strength of the three groups from high to low was group A, group B and group C(P＜0.05); the fracture type of the three groups was compared, mixed damage of group A was lower than that of group B and group C； microleakage of the three groups was compared, and microleakage of group A was better than that of group B and group C(P＜0.05). CONCLUSIONS: Pre-treatment with 2%NaClO can reduce dentin microleakage and significantly improve the bonding strength of teeth, which is conducive to the promotion and application in the treatment of dental diseases.

Moderate Hydrogen Peroxide Postconditioning Ameliorates Ischemia/Reperfusion Injury in Cardiomyocytes via STAT3-Induced Calcium, ROS, and ATP Homeostasis.

INTRODUCTION: Moderate hydrogen peroxide postconditioning (H2O2PoC) activates signal transducer and activator of transcription 3 (STAT3) to alleviate mitochondrial calcium overload during cardiac ischemia/reperfusion (I/R). However, the initial time window of STAT3-induced calcium hemostasis, the production of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in H2O2PoC, and its regulated mechanism remain unknown. This study aimed to investigate H2O2PoC-induced homeostasis of calcium, ROS and ATP, and the role of STAT3 in the regulation. METHODS: Isolated rat cardiomyocytes were exposed to H2O2PoC and Janus kinase 2 (JAK2)/STAT3 inhibitor AG490 during I/R. Ca2+ transients, cell contraction, intracellular calcium concentration, ROS production, ATP contents, phosphorylation of STAT3, gene and protein expression of manganese superoxide dismutase (MnSOD), metallothionein 1 (MT1) and metallothionein 2 (MT2), as well as activities of mitochondrial complex I and complex II were detected. RESULTS: Moderate H2O2PoC improved post-ischemic Ca2+ transients and cell contraction recovery as well as alleviated cytosolic and mitochondrial calcium overload, which were abrogated by AG490 in rat cardiomyocytes. Moderate H2O2PoC increased ROS production and rate of ROS production at early reperfusion in rat I/R cardiomyocytes, and this phenomenon was also abrogated by AG490. Notably, the expression of phosphorylated nuclear STAT3; gene and protein expression of MnSOD, MT1, and MT2; and activities of mitochondrial complex I and complex II were upregulated by moderate H2O2PoC but downregulated by AG490. CONCLUSION: These findings indicated that the cardioprotection of moderate H2O2PoC against cardiac I/R could be associated with activated STAT3 at early reperfusion to maintain calcium, ROS, and ATP homeostasis in rat cardiomyocytes.

CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways.

Metastasis is a major cause of death in patients with colorectal cancer (CRC). Cysteine-rich protein 2 (CSRP2) has been recently implicated in the progression and metastasis of a variety of cancers. However, the biological functions and underlying mechanisms of CSRP2 in the regulation of CRC progression are largely unknown. Methods: Immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were used to detect the expression of CSRP2 in CRC tissues and paracancerous tissues. CSRP2 function in CRC was determined by a series of functional tests in vivo and in vitro. WB and immunofluorescence were used to determine the relation between CSRP2 and epithelial-mesenchymal transition (EMT). Co-immunoprecipitation and scanning electron microscopy were used to study the molecular mechanism of CSRP2 in CRC. Results: The CSRP2 expression level in CRC tissues was lower than in adjacent normal tissues and indicated poor prognosis in CRC patients. Functionally, CSRP2 could suppress the proliferation, migration, and invasion of CRC cells in vitro and inhibit CRC tumorigenesis and metastasis in vivo. Mechanistic investigations revealed a physical interaction between CSRP2 and p130Cas. CSRP2 could inhibit the activation of Rac1 by preventing the phosphorylation of p130Cas, thus activating the Hippo signaling pathway, and simultaneously inhibiting the ERK and PAK/LIMK/cortactin signaling pathways, thereby inhibiting the EMT and metastasis of CRC. Rescue experiments showed that blocking the p130Cas and Rac1 activation could inhibit EMT induced by CSRP2 silencing. Conclusion: Our results suggest that the CSRP2/p130Cas/Rac1 axis can inhibit CRC aggressiveness and metastasis through the Hippo, ERK, and PAK signaling pathways. Therefore, CSRP2 may be a potential therapeutic target for CRC.

[LncRNA NEAT1 regulates proliferation, migration and invasion of tongue squamous cell carcinoma cells by regulating miR-339-5p/ITGA3 axis].

PURPOSE: To investigate the molecular mechanism of LncRNA NEAT1 regulating proliferation, migration and invasion of tongue squamous cell carcinoma cells by regulating miR-339-5p/ITGA3 axis. METHODS: qRT-PCR and Western blot were used to detect the expression of NEAT1, miR-339-5p, ITGA3 mRNA and ITGA3 protein in 25 cases of human tongue squamous cell carcinoma, its corresponding adjacent tissues, human normal oral mucosal cell line HOK and human tongue squamous cell carcinoma cell lines TSCCA, CAL27, SCC15 and HN13. CAL27 cell lines that inhibited NEAT1 and overexpressed miR-339-5p were constructed, respectively. Cell viability was detected by MTT assay, cell numbers of migration and invasion were detected by Transwell assay, and the expression of Cyclin D1 and MMP-9 proteins were detected by Western blotting. The dual luciferase reporter gene was used to verify the targeting relationship of NEAT1, miR-339-5p and ITGA3, and the regulatory relationship was detected by Western blotting and qRT-PCR. SPSS 17.0 software package was used for statistical analysis of the data. RESULTS: Compared with normal human oral mucosal cell line HOK, the expression of NEAT1 and ITGA3 was up-regulated, while the expression of miR-339-5p was down-regulated in human tongue squamous cell carcinoma cell lines. Inhibition of NEAT1 or over-expression of miR-339-5p significantly inhibited proliferation, migration and invasion of CAL27 cells, and significantly inhibited expression of Cyclin D1 and MMP-9 proteins. Dual luciferase reporter gene assay confirmed that NEAT1 directly interacted with miR-339-5p and suppressed its expression. miR-339-5p negatively regulated ITGA3 expression. Inhibition of NEAT1 reversed the inhibitory effect of the inhibition of miR-339-5p on proliferation, migration and invasion of CAL27 cells. CONCLUSIONS: LncRNA NEAT1 promotes proliferation, migration and invasion of tongue squamous cell carcinoma cells by down-regulating miR-339-5p/ITGA3 axis.

CFTR promotes malignant glioma development via up-regulation of Akt/Bcl2-mediated anti-apoptosis pathway.

Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl- channel, is extensively expressed in the epithelial cells of various tissues and organs. Accumulating evidence indicates that aberrant expression or mutation of CFTR is related to carcinoma development. Malignant gliomas are the most common and aggressive intracranial tumours; however, the role of CFTR in the development of malignant gliomas is unclear. Here, we report that CFTR is expressed in malignant glioma cell lines. Suppression of CFTR channel function or knockdown of CFTR suppresses glioma cell viability whereas overexpression of CFTR promotes it. Additionally, overexpression of CFTR suppresses apoptosis and promotes glioma progression in both subcutaneous and orthotopic xenograft models. Cystic fibrosis transmembrane conductance regulator activates Akt/Bcl2 pathway, and suppression of PI3K/Akt pathway abolishes CFTR overexpression-induced up-regulation of Bcl2 (MK-2206 and LY294002) and cell viability (MK-2206). More importantly, the protein expression level of CFTR is significantly increased in glioblastoma patient samples. Altogether, our study has revealed a mechanism by which CFTR promotes glioma progression via up-regulation of Akt/Bcl2-mediated anti-apoptotic pathway, which warrants future studies into the potential of using CFTR as a therapeutic target for glioma treatment.