Thioredoxin-1 decreases alpha-synuclein induced by MPTP through promoting autophagy-lysosome pathway.

Parkinson's disease (PD) is characterized by the formation of Lewy body in dopaminergic neurons in the substantia nigra pars compacta (SNpc). Alpha-synuclein (α-syn) is a major component of Lewy body. Autophagy eliminates damaged organelles and abnormal aggregated proteins. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays roles in protecting dopaminergic neurons against neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the relationship between Trx-1 and α-syn in PD is still unknown. In the present study, the movement disorder and dopaminergic neurotoxicity in MPTP-treated mice were improved by Trx-1 overexpression and were aggravated by Trx-1 knockdown in the SNpc in mice. The expression of α-syn was increased in the SNpc of MPTP-treated mice, which was inhibited by Trx-1 overexpression and was exacerbated in Trx-1 knockdown mice. Autophagosomes was increased under electron microscope after MPTP treatment, which were recovered in Trx-1 overexpressing mice and were further increased in Trx-1 knockdown in the SNpc in mice. The expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced putative kinase 1 (PINK1), Parkin, LC3 II and p62 were increased by MPTP, which were blocked in Trx-1 overexpressing mice and were further increased in Trx-1 knockdown mice. Cathepsin D was decreased by MPTP, which was restored in Trx-1 overexpressing mice and was further decreased in Trx-1 knockdown mice. The mRFP-GFP-LC3 green fluorescent dots were increased by 1-methyl-4-phenylpyridinium (MPP+) and further increased in Trx-1 siRNA transfected PC12 cells, while mRFP-GFP-LC3 red fluorescent dots were increased in Trx-1 overexpressing cells. These results indicate that Trx-1 may eliminate α-syn in PD mice through potentiating autophagy-lysosome pathway.

Thioredoxin-1 regulates calcium homeostasis in MPP+ /MPTP-induced Parkinson's disease models.

Disturbance in calcium (Ca2+ ) homeostasis has been involved in a variety of neuropathological conditions including Parkinson's disease (PD). The Ca2+ channel, transient receptor potential channel 1 (TRPC1), plays a protective role in regulating entry of Ca2+ activated by store depletion of Ca2+ in endoplasmic reticulum (ER). We have showed that thioredoxin-1 (Trx-1) plays a role in suppressing ER stress in PD. However, whether Trx-1 regulates TRPC1 expression in PD is still unknown. In the present study, we demonstrated that treatment of 1-methyl-4-phenylpyridinum ion (MPP+ ) significantly reduced the expression of TRPC1 in PC12 cells, which was restored by Trx-1 overexpression, and further decreased significantly by Trx-1 siRNA. Moreover, we found that Ca2+ entered into the cells was decreased by MPP+ in PC 12 cells, which was restored by Trx-1 overexpression, and further decreased by Trx-1 siRNA. MPP+ significantly increased calcium-dependent cysteine protease calpain1 expression in PC12 cells, which was suppressed by Trx-1 overexpression. Calpain1 expression was increased by Trx-1 siRNA or SKF96365, an inhibitor of TRPC1. Moreover, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased TRPC1 expression in the substantia nigra pars compacta region (SNpc), which was restored in mice overexpressing Trx-1, and further decreased in mice of knockdown Trx-1. Inversely, the expression of calpain1 was increased by MPTP, which was suppressed in mice overexpressing Trx-1, and further increased in mice of knockdown Trx-1. In conclusion, Trx-1 regulates the Ca2+ entry through regulating TRPC1 expression after treatment of MPP+ /MPTP.

Assessment of the contralateral facial artery pedicle nasolabial island flap for buccal defect repair.

The facial artery pedicle nasolabial island flap (FAPNIF) is widely used for oral and maxillofacial reconstruction. However, its use in reconstruction after malignant tumour resection is limited by the possibility of ipsilateral cervical lymph node metastasis along the facial artery. Through fine dissection, it was found that the contralateral FAPNIF can be used to repair the defect after buccal carcinoma resection. The aim of this study was to evaluate the clinical outcomes of the contralateral FAPNIF for buccal defect repair. From 2013 to 2016, 30 patients underwent the repair of a buccal defect with a contralateral FAPNIF after tumour resection. Clinical outcomes and complications were recorded and quality of life was evaluated preoperatively and at 3, 6, and 12 months postoperative. The flaps survived in all 30 cases. Mean mouth opening was 2.50±0.14cm at 1 month, 3.22±0.25cm at 6 months, and 3.35±0.23cm at 12 months postoperative. With regard to patient quality of life, adverse effects included impaired aesthetics, pain, and difficulty eating; these usually subsided within 1year after surgery. The contralateral FAPNIF is easily harvested and is a safe and effective option for the repair of medium-sized buccal defects after the resection of carcinoma.

Brain-derived neurotrophic factor induces thioredoxin-1 expression through TrkB/Akt/CREB pathway in SH-SY5Y cells.

Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that are vital to the survival and proliferation of neuron. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays various roles in regulating transcript factors and inhibiting apoptosis. It has been reported that Trx-1 is required for nerve growth factor-mediated signal transduction and neurite outgrowth, and is involved in synaptic protein expression induced by BDNF. However, the molecular mechanism on BDNF inducing Trx-1 expression has not been fully verified. The present study investigated the expression of Trx-1 after treatment with BDNF in SH-SY5Y cells. We first demonstrated that cell viability and the expression of Trx-1 were increased by BDNF in SH-SY5Y cells, which were inhibited by the tyrosine kinase B (TrkB) inhibitor, K252a, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. Moreover, BDNF increased the activity of cAMP response element-binding protein (CREB) through TrkB/PI3-K/Akt pathway. Whereas the expression of Trx-1 induced by BDNF was suppressed by CREB siRNA. Thus, our data suggest that BDNF induces the expression of Trx-1 through the TrkB/Akt/CREB pathway.

Morphine reverses the effects of 1-methyl-4-phenylpyridinium in PC12 cells through activating PI3K/Akt.

AIM OF THE STUDY: Parkinson's disease (PD) is a neurodegenerative disorder. It is caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion in the substantia nigra pars compacta (SNpc). Morphine elevates the level of dopamine in the mesolimbic dopamine system and plays a role in alleviating PD symptoms. However, the molecular mechanism is still unclear. The aim of the study is to investigate the mechanism on morphine alleviating PD symptoms. MATERIALS AND METHODS: The viability of PC12 cells was measured by using MTT assay. The expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot. RESULTS: In present study, we found that morphine increased the cell viability in PC12 cells. 1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression, which were reversed by morphine. MPP+ decreased the expressions of Trx-1, CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor. CONCLUSIONS: These results suggest that morphine reverses effects induced by MPP þ through activating PI3K/Akt pathway.

Trx-1 ameliorates learning and memory deficits in MPTP-induced Parkinson's disease model in mice.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characteristic motor symptoms and cognitive impairment. Thioredoxin-1 (Trx-1) is a redox protein and protects neurons from various injuries. Our previous study has shown that Trx-1 overexpression attenuates movement disorder in PD. However, whether Trx-1 ameliorates cognitive deficits in PD is still unknown. In the present study, we investigated the effects of Trx-1 on learning and memory in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in mice. We demonstrated that deficits in learning and memory were induced by MPTP in mice through the elevated plus-maze test. We found that the retention transfer latency time was shorten, escape latency was decreased and the number of platform crossings was increased in the Morris water maze (MWM) in Trx-1 transgenic (TG) mice when compared with wild type mice. The expressions of tyrosine hydroxylase (TH) and dopamine D1 receptor (D1R) were decreased by MPTP, which were restored in Trx-1 TG mice. The expression of N-methyl-D-aspartate receptor 2B subunit (NR2B), the levels of phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cAMP-response element binding protein (CREB) in the hippocampus were decreased by MPTP, which were reversed in Trx-1 TG mice. These results suggest that Trx-1 ameliorates learning and memory deficits in MPTP-induced PD model in mice via modulating the D1R and the NMDAR-ERK1/2-CREB pathway. Trx-1 may be a therapy target for learning and memory deficits in PD.

Use of medial upper arm free flap in oral cavity reconstruction: a preliminary study.

The medial upper arm has previously been proposed as a potential free flap donor site, but the clinical application of such flaps in head and neck reconstruction has not been popular. The preliminary results of the clinical application of medial upper arm free flaps in oral cavity reconstruction are reported here. Five patients with oral cancer underwent surgical resection and neck dissection, with simultaneous reconstruction using a medial upper arm free flap. Functional outcomes were investigated using the University of Washington Quality of Life Questionnaire. Sensory-motor functions of the upper arm donor site were recorded before and after surgery. Four flaps were successfully transferred. One flap was abandoned during surgery because of a lack of perforators, and a forearm flap was used instead. All patients survived without loco-regional recurrence or distant metastasis. Functional outcomes, especially swallowing and speech, were satisfactory. The donor site scar was well hidden, with no functional impairment. This initial experience shows that the medial upper arm free flap represents an alternative perforator flap for oral cavity microsurgical reconstruction. The well-hidden scar and better texture match compared with other flaps make it suitable for oral cavity reconstruction.

[Acceptability and related factors on male circumcision among young men with Yi ethnicity in one county of Sichuan province.].

OBJECTIVE: To explore the acceptability of male circumcision (MC) as an HIV prevention method and its related factors among young men of Yi ethnicity in Liangshan prefecture. METHODS: 446 young men were selected in Butuo county, under stratified sampling method. Using a self-designed questionnaire, face to face interviews were taken to collect HIV-related risk behaviors, knowledge and acceptability of MC. RESULTS: After an introduction on MC by interviewers, 40.6% of the interviewees expressed their willingness in taking this surgery. The main reason for acceptance was that they felt this surgery might reduce the risk of HIV infection (90.1%). For those who refused to take this surgery, most of them thought it was too sensitive and embarrassing (52.5%) and were afraid that it might affect their procreation ability. Data from logistic regression analysis indicated that the acceptability of MC was associated with the following factors as:age, income, experience of commercial sexual behavior. They also felt that messages related to male MC surgery could reduce the risk of being infected with HIV/STDs or induce pain when having sexual intercourse, or it might cause partial infection after surgery, or they might be mocked at if taking the surgery. CONCLUSION: It is the prerequisite in helping young people of Yi ethnicity to have a good understanding on MC as for Yi people, embarrassment attitudes towards sex appears to be one of the big obstacles against the popularization of this surgery. The operation should be provided by trained and professional doctors, with standardized procedure, in good sanitary conditions and free for service.