The oncometabolite 2-hydroxyglutarate inhibits microglial activation via the AMPK/mTOR/NF-κB pathway.

Microglia, the brain-resident macrophage, is known as the innate immune cell type in the central nervous system. Microglia is also the major cellular component of tumor mass of gliomas that plays a key role in glioma development. Mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2) frequently occur in gliomas, which leads to accumulation of oncometabolic product 2-hydroxyglutarate (2HG).

Glucose-Sensitive CFTR Suppresses Glucagon Secretion by Potentiating KATP Channels in Pancreatic Islet α Cells.

The secretion of glucagon by islet α cells is normally suppressed by high blood glucose, but this suppressibility is impaired in patients with diabetes or cystic fibrosis (CF), a disease caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), a cyclic adenosine monophosphate-activated Cl- channel. However, precisely how glucose regulates glucagon release remains controversial. Here we report that elevated glucagon secretion, together with increased glucose-induced membrane depolarization and Ca2+ response, is found in CFTR mutant (DF508) mice/islets compared with the wild-type.

Defective CFTR leads to aberrant β-catenin activation and kidney fibrosis.

Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys.

Epigenetic Modification of the CCL5/CCR1/ERK Axis Enhances Glioma Targeting in Dedifferentiation-Reprogrammed BMSCs.

The success of stem cell-mediated gene therapy in cancer treatment largely depends on the specific homing ability of stem cells. We have previously demonstrated that after in vitro induction of neuronal differentiation and dedifferentiation, bone marrow stromal cells (BMSCs) revert to a primitive stem cell population (De-neu-BMSCs) distinct from naive BMSCs. We report here that De-neu-BMSCs express significantly higher levels of chemokines, and display enhanced homing abilities to glioma, the effect of which is mediated by the activated CCL5/CCR1/ERK axis.

Defective CFTR-regulated granulosa cell proliferation in polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the most frequent causes of female infertility, featured by abnormal hormone profile, chronic oligo/anovulation, and presence of multiple cystic follicles in the ovary. However, the mechanism underlying the abnormal folliculogenesis remains obscure. We have previously demonstrated that CFTR, a cAMP-dependent Cl(-) and HCO3 (-) conducting anion channel, is expressed in the granulosa cells and its expression is downregulated in PCOS rat models and human patients.

Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR.

The cause of insulin insufficiency remains unknown in many diabetic cases. Up to 50% adult patients with cystic fibrosis (CF), a disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), develop CF-related diabetes (CFRD) with most patients exhibiting insulin insufficiency. Here we show that CFTR is a regulator of glucose-dependent electrical acitivities and insulin secretion in β-cells.

Formation of aerobic granular sludge under adverse conditions: low DO and high ammonia.

In this study, two adverse environments: low dissolved oxygen (DO) and high ammonia concentration, were employed to investigate the morphology, interspecies quorum sensing, extracellular polymers (EPS) characterization and microbial communities in the formation of aerobic granular sludge. Results showed that low DO could promote filamentous bacterial outgrowth. Under high ammonia concentration aerobic granular sludge (AGS) could still be cultivated, although it was looser and lighter than the control group.

[Effect of fertilization levels on soil microorganism amount and soil enzyme activities].

Field experiments were conducted in Shangluo pharmaceutical base in Shaanxi province to study the effect of nitrogen, phosphorus and potassium in different fertilization levels on Platycodon grandiflorum soil microorganism and activities of soil enzyme, using three-factor D-saturation optimal design with random block design. The results showed that N0P2K2, N2P2K0, N3P1K3 and N3P3K1 increased the amount of bacteria in 0-20 cm of soil compared with N0P0K0 by 144.34%, 39.

Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer.

How mutations or dysfunction of CFTR may increase the risk of malignancies in various tissues remains an open question. Here we report the interaction between CFTR and an adherens junction molecule, AF-6/afadin, and its involvement in the development of colon cancer. We have found that CFTR and AF-6/afadin are co-localized at the cell-cell contacts and physically interact with each other in colon cancer cell lines.

Downregulation of CFTR promotes epithelial-to-mesenchymal transition and is associated with poor prognosis of breast cancer.

The epithelial-to-mesenchymal transition (EMT), a process involving the breakdown of cell-cell junctions and loss of epithelial polarity, is closely related to cancer development and metastatic progression. While the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-) and HCO3(-) conducting anion channel expressed in a wide variety of epithelial cells, has been implicated in the regulation of epithelial polarity, the exact role of CFTR in the pathogenesis of cancer and its possible involvement in EMT process have not been elucidated. Here we report that interfering with CFTR function either by its specific inhibitor or lentiviral miRNA-mediated knockdown mimics TGF-β1-induced EMT and enhances cell migration and invasion in MCF-7.

[Effect of Astragalus membranaceus var. mongholicus seed extracts on seed germination and seedling growth of different Codonopsis pilosula caltiver].

Objective: To reveal the allelopathy effect of Astragalus membranaceus var. mongholicus seeds and provide information for the intercrop production.

Method: The A.

Flavonoid Myricetin Modulates GABA(A) Receptor Activity through Activation of Ca(2+) Channels and CaMK-II Pathway.

The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN) by increasing the decay time and frequency of the inhibitory currents mediated by GABA(A) receptor.

[Responses of Scutellaria baicalensis Georgi yield and root baicalin content to the fertilization rates of nitrogen, phosphorus, and potassium].

A field experiment with three-factor (N, P, and K) and quadratic saturation D-optimal design was conducted to evaluate the effects of the fertilization rates of N, P, and K on the yield and root baicalin content of Scutellaria baicalensis Georgi at harvesting time. A ternary quadratic polynomial mathematical model was built, in which, the N, P, and K fertilization rates were independent variables, and the yield and root baicalin content were the target functions. Through the analysis of the model, the optimum fertilization pattern was obtained.

[A primary application and evaluation of temporomandibular joint replacement with stock prosthesis].

Purpose: To evaluate the effect of total joint replacement in treatment of temporomandibular joint(TMJ) osteoarthropathy with stock prostheses.

Methods: Six female patients involving 10 joints (2 unilateral and 4 bilateral), with an average age of 59 years old, were involved in this study. Three patients (5 joints) were diagnosed as internal derangement in V stage depending on MRI, 3D-CT findings and clinical characteristics.

STK31 maintains the undifferentiated state of colon cancer cells.

The expression of serine/threonine kinase (STK) family is frequently altered in human cancers. However, the functions of these kinases in cancer development remain elusive. Here, we report that STK31 is robustly and heterogeneously expressed in colon cancer tissues and plays a critical role in determining the differentiation state of colon cancer cells.

Cryptorchidism-induced CFTR down-regulation results in disruption of testicular tight junctions through up-regulation of NF-κB/COX-2/PGE2.

Study Question: Does elevated temperature-induced cystic fibrosis transmembrane conductance regulator (CFTR) down-regulation in Sertoli cells in cryptorchid testis disrupt testicular tight junctions (TJs) through the nuclear factor kappa B (NF-κB)/cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway?

Summary Answer: Our results suggest that CFTR may be involved in regulating testicular TJs and the blood-testis barrier (BTB) through its negative regulation of the NF-κB/COX-2/PGE(2) pathway in Sertoli cells, a defect of which may result in the spermatogenesis defect in cryptorchidism.

What Is Known Already: Cryptorchidism, or undescended testes, is known to result in defective spermatogenesis. Although an elevated testicular temperature is regarded as an important factor affecting spermatogenesis in cryptorchidism, the exact mechanism remains elusive.

Activation of the epithelial Na+ channel triggers prostaglandin E₂ release and production required for embryo implantation.

Embryo implantation remains a poorly understood process. We demonstrate here that activation of the epithelial Na⁺ channel (ENaC) in mouse endometrial epithelial cells by an embryo-released serine protease, trypsin, triggers Ca²⁺ influx that leads to prostaglandin E₂ (PGE₂) release, phosphorylation of the transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. We detected maximum ENaC activation, as indicated by ENaC cleavage, at the time of implantation in mice.

CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development.

Although HCO(3)(-) is known to be required for early embryo development, its exact role remains elusive. Here we report that HCO(3)(-) acts as an environmental cue in regulating miR-125b expression through CFTR-mediated influx during preimplantation embryo development. The results show that the effect of HCO(3)(-) on preimplantation embryo development can be suppressed by interfering the function of a HCO(3)(-)-conducting channel, CFTR, by a specific inhibitor or gene knockout.

Lymphocyte CFTR promotes epithelial bicarbonate secretion for bacterial killing.

The expression of cystic fibrosis transmembrane conductance regulator (CFTR) in lymphocytes has been reported for nearly two decades; however, its physiological role remains elusive. Here, we report that co-culture of lymphocytes with lung epithelial cell line, Calu-3, promotes epithelial HCO(3)- production/secretion with up-regulated expression of carbonic anhydrase 2 and 4 (CA-2, CA-4) and enhanced bacterial killing capability. The lymphocyte-enhanced epithelial HCO(3)- secretion and bacterial killing activity was abolished when Calu3 cells were co-cultured with lymphocytes from CFTR knockout mice, or significantly reduced by interfering with E-cadherin, a putative binding partner of CFTR.

The neck linker of kinesin 1 seems optimally designed to approach the largest stepping velocity: a simulation study of an ideal model.

The neck linker is widely believed to play a critical role in the hand-over-hand walking of conventional kinesin 1. Experiments have shown that change of the neck linker length will significantly change the stepping velocity of the motor. In this paper, we studied this length effect based on a highly simplified chemically powered ratchet model.

Impaired CFTR-dependent amplification of FSH-stimulated estrogen production in cystic fibrosis and PCOS.

Context: Estrogens play important roles in a wide range of physiological and pathological processes, and their biosynthesis is profoundly influenced by FSH that regulates the rate-limiting enzyme aromatase-converting estrogens from androgens. Abnormal estrogen levels are often seen in diseases such as ovarian disorders in polycystic ovarian syndrome (PCOS), an endocrine disorder affecting 5-10% of women of reproductive age, and cystic fibrosis (CF), a common genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR).

Objectives: We undertook the present study to investigate the mechanism underlying these ovarian disorders, which is not well understood.

Preauricular transcondylar approach for basal cell adenoma of parotid coexist with ganglion cyst of the ipsilateral temporomandibular joint.

The concurrence of 2 independent neoplasias in the ipsilateral parotid and the temporomandibular joint (TMJ) region was infrequently reported. In this article, we present a unique case characterized by the coexistence of a rare salivary gland tumor, basal cell adenoma, of the parotid gland with a ganglion cyst in the ipsilateral TMJ region. A special surgical procedure was also presented here using a modified preauricular incision and transcondylar approach for extracapsular dissection of both lesions.

Synovial chondromatosis in the inferior compartment of the temporomandibular joint: different stages with different treatments.

Purpose: To discuss a new classification and the treatment principles of synovial chondromatosis (SC) in the inferior compartment of the temporomandibular joint (TMJ).

Patients And Methods: Five cases of SC in the inferior compartment were treated in an open manner between January 2008 and May 2011. Each case had different clinical and radiologic aspects and was treated with different surgical therapies.

Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia.

Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice.