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Objective: To investigate the effects of different acupuncture on the content of glial cell derived neurotrophic factor (GDNF) in substantia nigra, stomach and colon of rats with Parkinson's gastrointestinal dysfunction. Methods: The gastrointestinal dysfunction model of PD was established by injecting rotenone solution and detecting with apmorphine induction test. According to random number table method, 60 rats were divided into 6 groups: blank group, sham-operated group, model group, western medicine group, Tiaoshen Changzhi group and ordinary acupuncture group. The rats were treated for 2 weeks. The changes of body weight were observed, fecal moisture content, gastric content residual rate and intestinal propelling rate were detected, and GDNF content in substantia nigra, stomach and colon were detected by immunohistochemistry and ELISA. Results: Body weight and fecal water content: the western medicine group and the two acupuncture groups were significantly increased compared with the model group (P<0.01). The improvement degree in the western medicine group was better than that in the Tiaoshen Changzhi group (P<0.05), and the improvement degree in the Tiaoshen Changzhi group was better than in the ordinary acupuncture group (P<0.05). In terms of intestinal propulsion rate and gastric contents residual rate, there were significant differences between the western medicine group and the two acupuncture groups and model group (P<0.01). The improvement of the western medicine group was better than that of Tiaoshen Changzhi group (P<0.05), the Tiaoshen Changzhi group was better than the ordinary group (P<0.05). The changes of GDNF in substantia nigra, stomach and colon of midbrain were as follows: the contents of GDNF in blank group and sham group were higher than the model group (P<0.01). Compared with the model group, the content of the western medicine group and the two acupuncture groups increased (P<0.01). The efficacy of the western medicine group was better than that of the Tiaoshen Changzhi group (P<0.05), and the Tiaoshen Changzhi group was better than that of the conventional acupuncture group (P<0.05). Conclusion: Acupuncture treatment increased the content of GDNF in substantia nigra, stomach and colon of rats with PD gastrointestinal dysfunction, and the Tiaoshen Changzhi group was better than the conventional group and close to the western medicine group. One of the mechanisms of Tiaoshen Changzhi acupuncture in the treatment of gastrointestinal dysfunction of PD may be due to the enhancement of GDNF in the brain, stomach and colon. [ABSTRACT FROM AUTHOR]

The regeneration of nerve tissue after spinal cord injury is a complex and poorly understood process. Medication and surgery are not very effective treatments for patients with spinal cord injuries. Gene therapy is a popular approach for the treatment of such patients. The delivery of therapeutic genes is carried out in a variety of ways, such as direct injection of therapeutic vectors at the site of injury, retrograde delivery of vectors, and ex vivo therapy using various cells. Recombinant adenoviruses are often used as vectors for gene transfer. This review discusses the advantages, limitations and prospects of adenovectors in spinal cord injury therapy.

The regeneration of nerve tissue after spinal cord injury is a complex and poorly understood process. Medication and surgery are not very effective treatments for patients with spinal cord injuries. Gene therapy is a popular approach for the treatment of such patients. The delivery of therapeutic genes is carried out in a variety of ways, such as direct injection of therapeutic vectors at the site of injury, retrograde delivery of vectors, and ex vivo therapy using various cells. Recombinant adenoviruses are often used as vectors for gene transfer. This review discusses the advantages, limitations and prospects of adenovectors in spinal cord injury therapy. [ABSTRACT FROM AUTHOR]

Background This study aims to investigate glial cell derived neurotrophic factor (GDNF) levels in newborns’ umbilical cord blood and cerebrospinal fluid across various perinatal growth parameters and clinical conditions. Methods Cord blood from 20 newborns and 58 residual CSF samples (stored after completion of clinical testing) were collected. GDNF levels were determined using GDNF ELISA kits from R&D Systems in triplicates with appropriate controls to eliminate background. Results Cord blood GDNF levels were significantly higher (p = 0.004) in preterm newborns (n = 6) (115.05 ± 57.17, pg/ml) when compared to term newborns (n = 14) (19.67 ± 10.67, pg/ml). GDNF levels in CSF trended (p = 0.07) higher in term newborns (n = 10) (19.56 ± 9.11, pg/ml) when compared to preterm newborns at term or post term corrected gestational ages (n = 5) (14.49 ± 3.53, pg/ml). Conclusions GDNF levels in preterm newborns were higher in cord blood and lower in CSF as compared to term newborns. It is important to further study circulating and CSF-GDNF levels in newborns at different gestational ages and clinical conditions. [ABSTRACT FROM AUTHOR]

We analyzed the effect of glial cell derived neurotrophic factor (GDNF) on changes in functional bioelectric and calcium activity in dissociated hippocampal cell cultures under conditions of modeled acute normobaric hypoxia in vitro. GDNF (1 ng/ml) partially neutralized the negative effects of hypoxia on cell survival and parameters of functional network activity. GDNF exhibited a pronounced anti-hypoxic effect. [ABSTRACT FROM AUTHOR]

Highlights: [•] Estradiol regulates reactive astrogliosis and the inflammatory response of astrocytes. [•] Estradiol regulates neuroglobin expression in astrocytes. [•] Estradiol regulates the synthesis of neurotrophic factors in astrocytes. [•] Estradiol controls edema by regulating aquaporin 4 expression in astrocytes. [•] Estradiol controls excitotoxicity by regulating glutamate transport by astrocytes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the therapeutic effect of transplanted Glial cell derived neurotrophic factor (GDNF) modified marrow stromal cells (MSCs) on an experimental ischemic brain injury based on the behavioral, morphological and immunohistochemical observations. Methods: The MSCs from newborn rats were cultured in vitro. The cerebral ischemia and reperfusion model was established in rats by using the suture method. 3 days after model establishment, the animals were injected with prepared MSCs via their caudal veins. The animals were then divided into a sham-operation group, ischemia group, MSCs transplantation group or GDNF+MSCs transplantation group and were scored for their neurobehavioral manifestations at 3, 14 and 28 days after the transplantation was performed. At this time, the survival condition of intracerebral transplanted cells was measured by laser confocal microscopy while the effect of transplantation on the GDBF expression in the ischemic brain tissue was evaluated. Results: The MSCs cells transfected with GDNF gene were characterized by green fluorescence. 3 days after the transplantation, the animals that underwent the cell transplantation showed significantly better behavioral data than the controls. 14 days after transplantation, the animals transplanted with GDNF gene modified MSCs were better than those transplanted with common MSCs. As compared with common MSCs transplantation, GDNF+MSCs transplantation was significantly more effective in reducing apoptotic cell volume and enhancing Bcl-2 expression, which was favorable for the ischemic brain injury. Conclusions: Transplanted GDNF modified MSCs can improve the nervous function and have a protective effect on the ischemic brain injury through reducing apoptotic cell volume and enhancing the expression of antiapoptotic gene Bcl-2.

Abstract: Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field. [Copyright &y& Elsevier]

Abstract: Patients with glioblastoma are commonly treated with chemotherapy. But a significant proportion of patients develop disease progression after an initial response to chemotherapy. Presently, there is no standard of care for such patients. The bone morphogenetic protein 4 (BMP4) has been reported to play a tumor-suppressing role in glioblastoma, but its role in glioblastoma multidrug resistance (MDR) is not clear. We reported that BMP4 can reverse MDR of glioblastoma through the inhibition of B-cell lymphoma 2(BCL-2) and glial cell derived neurotrophic factor (GDNF). We showed that the expression level of BMP4 was lower in glioblastoma compared to normal brain tissue, and also showed that BMP4 expression decreased in multidrug resistance cell line U251/TMZ compared to U251 cells. Our research demonstrated that over-expression of BMP4 can reverse the multidrug resistance. BCL-2 and GDNF were inhibited when BMP4 was over-expressed, and this data were consistent with the negative relationship in human samples; analysis of 40 patient's glioblastoma and brain samples revealed a significant negative correlation between BMP4 and BCL-2, GDNF. When BCL-2 and GDNF were knocked down, the effect of BMP4 in regulating MDR was partially lost. This novel result showed, for the first time, that BMP4 can reverse MDR in glioblastoma, which involved negative inhibition of BCL-2 and GDNF. [Copyright &y& Elsevier]

Abstract: The protective effect of an iridoid catalpol extracted and purified from the traditional Chinese medicinal herb Rehmannia glutinosa on the neuronal degeneration of nigral-striatal dopaminergic pathway was studied in a chronic 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP)/probenecid C57BL/6 mouse model and in 1-methyl-4-phenylpyridimium (MPP+) intoxicated cultured mesencephalic neurons. Rotarod performance revealed that the locomotor ability of mice was significantly impaired after completion of model production and maintained thereafter for at least 4 weeks. Catalpol orally administered for 8 weeks (starting from the second week of model production) dose dependently improved the locomotor ability. HPLC revealed that catalpol significantly elevated striatal dopamine levels without changing the metabolite/dopamine ratios. Nor did it bind to dopamine receptors. Therefore it is unlikely that catalpol resembles any of the known compounds for treating Parkinsonism. Instead, catalpol dose dependently raised the tyrosine hydroxylase (TH) neuron number in substantia nigra pars compacta (SNpc), the striatal dopamine transporter (DAT) density and the striatal glial cell derived neurotrophic factor (GDNF) protein level. Linear regression revealed that both the TH neuron number and DAT density were positively correlated to the GDNF level. In the cultured mesencephalic neurons, MPP+ decreased the dopaminergic neuron number and shortened the neurite length, whereas catalpol showed protective effect dose dependently. Furthermore, the expression of GDNF mRNA was up-regulated by catalpol to a peak nearly double of normal control in neurons intoxicated with MPP+ for 24 h but not in normal neurons. The GDNF receptor tyrosine kinase RET inhibitor 4-amino-5-(4-methyphenyl)-7-(t-butyl)-pyrazolo-[3,4-d]pyrimidine (PP1) abolished the protective effect of catalpol either partially (TH positive neuron number) or completely (neurite length). Taken together, catalpol improves locomotor ability by attenuating the neuronal degeneration of nigral-striatal dopaminergic pathway, and this attenuation is at least partially through elevating the striatal GDNF expression. [Copyright &y& Elsevier]

Background: Nerve injury-related erectile dysfunction (ED) is one of the types that respond poorly to conventional ED treatments. Our previous experiments have demonstrated the paracrine of various neurotrophic factors (NTFs) by stem cells or other treatment modalities as a potential mechanism in the recovery of nerve injury-related ED. Glial cell derived neurotrophic factor (GDNF) is one of the essential NTFs for the regeneration of nerve fibers, especially for parasympathetic nerves. The aim of this study is to explore if local continuous GDNF administration is beneficial for the functional and histological recovery of nerve injury induced ED., Methods: Eight-week-old male Sprague-Dawley rats were used for this study. Rats were randomly grouped into 5: Sham surgery (Sham), bilateral cavernous nerve injury (BCNI) and placebo treatment, BCNI and 0.1 µg/100 µL GDNF treatment (BCNI+GDNF 0.1), BCNI and 1 µg/100 µL GDNF treatment (BCNI+GDNF 1), BCNI and 10 µg/100 µL GDNF treatment (BCNI+GDNF 10). GDNF was administered using an osmotic pump technique which would deliver GDNF locally and continuously for 28 days without the need for external connections or frequent handling of animals. Recovery of sexual function, nerve fibers regeneration, and expression of neurotrophic receptors were examined and compared among groups after the treatment., Results: Local continuous GDNF release treatment increased the average number of intromissions in the sexual behavior test and intracavernous pressure (ICP) in the erectile function test in a dose dependent manner. Osmotic pump implantation induced increased local GDNF concentration and mild inflammatory response. Gene expression of GDNF receptors in major pelvic ganglion (MPG) and nerve regeneration along the urethra were partially promoted by GDNF. These changes were associated with increased nerve fibers especially the parasympathetic nerve fibers in dorsal nerve of penis (DNP) in GDNF treated groups., Conclusions: In conclusion, our project illustrated the promising effects of local continuous GDNF administration for the functional and histological recovery of nerve injury-induced ED., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1110). The authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)