Fabrication of Nb2 O5 /Carbon Submicrostructures for Advanced Lithium-Ion Battery Anodes.

Nb2 O5 possesses superior fast Li+ storage capability for LIB anodes, benefiting from its fast pseudocapacitive behavior and low volumetric change within the cycling processes. However, the poor electric conductivity for Nb2 O5 restricts its reaction kinetics and rate property. Herein, Nb2 O5 /carbon (C) submicrostructures are fabricated by solvothermal method followed by calcination process. The Nb2 O5 /C submicrostructures exhibit outstanding rate behavior and cyclic performance (332 (194) mAh g-1 after 1000 cycles at 1 (5) A g-1 ). The superior electrochemical property is attributed to the distinctive structure for Nb2 O5 /C submicrostructures, in which Nb2 O5 nanoparticles uniformly distributed within Nb2 O5 /C composite can protect Nb2 O5 nanoparticles from agglomeration, and the porous carbon matrix can enhance electron/ion conductivity. This work furnishes a novel strategy for fabricating Nb2 O5 /C submicrostructures with superior Li+ storage performance, which can be potentially used to design other metal oxide/C submicrostructures for second battery anode.

[Clinical analysis of chronic sternal osteomyelitis with sinus tract after cardiovascular surgery].

Objective: To explore the diagnosis, therapy and prevention method of chronic sternal osteomyelitis with sinus tract after cardiovascular surgery. Methods: A total of 53 patients with chronic sternal sinus tract after cardiovascular surgery between January 2000 and January 2016. After definite diagnosis by contrast fistulography and CT scanning, all the patients received combined modality therapy including debridement, musculocutaneous flap transplantation and intermediate thickness free skin graft transplantation if necessary. Results: One patient died of false aneurysm due to the sternal sinus tract infection, there were no peri-operative death for all the left 52 patients. Forty-five patients had primary healing and 7 patients had secondary healing. All the patients became total recovery within 3-12 weeks after operation and maintained well during the 5-18 months' follow-up. Conclusions: For the patients with chronic sternal osteomyelitis, operative therapy should be performed as soon as possible once the diagnosis is confirmed. Combined modality therapy including debridement, musculocutaneous flap transplantation and intermediate thickness free skin graft transplantation is confirmed to be effective and secure.

Apparent diffusion coefficients of normal uterus in premenopausal women with 3 T MRI.

AIM: To investigate the apparent diffusion coefficient (ADC) values of the normal uterine cervical zonal structures (cervical epithelium, the junctional zone, and myometrium) during different phases of the menstrual cycle among premenopausal women in different age groups. MATERIALS AND METHODS: Seventy healthy women, who were divided into three age groups (group A, 24 women in their twenties; group B, 23 women in their thirties; group C, 23 women in their forties), underwent 3 T magnetic resonance imaging (MRI) with T2-weighted and diffusion-weighted imaging (DWI) during the mid-proliferative and the mid-secretory phases. RESULTS: The ADC values of each cervical zonal structure were significantly different from one another (p < 0.001). The ADC values of the epithelium and junctional zones were both lower during the mid-secretory phase than those during the mid-proliferative phase in each age group (p < 0.05). There were no significant differences in the ADC values of any of the cervical zones among the three age groups for a given phase (p > 0.05). CONCLUSION: ADC values of normal cervical epithelium and the junctional zone change with different phases of the menstrual cycle, which should be taken into consideration when early cervical disease is detected, when monitoring treatment response, and differentiating early tumour recurrence.

Quetiapine ameliorates anxiety-like behavior and cognitive impairments in stressed rats: implications for the treatment of posttraumatic stress disorder.

The purpose of this study was to determine preventive and protective effects of chronic orally administration with quetiapine (QUE) against anxiety-like behavior and cognitive impairments in rats exposed to the enhanced single prolonged stress (ESPS), an animal model that is used to study post-traumatic stress disorder (PTSD), and to detect changes in the expression of cortical phosphorylated p44/42 extracellular-regulated protein kinase (pERK1/2). Before or after exposure to ESPS paradigm, consisting of 2-h constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, rats were given orally QUE (10 mg/kg daily) for 14 days. Animals were then tested in the open field (OF), elevated plus-maze (EPM), and Morris water maze (MWM). Brains were removed for immunohistochemical staining of pERK1/2. ESPS exposure resulted in pronounced anxiety-like behavior compared to unexposed animals. ESPS-exposed animals also displayed marked learning and spatial memory impairments. However, QUE treatment (both before and after ESPS exposure) significantly ameliorated anxiety-like behavior, learning and spatial memory impairments. ESPS also markedly reduced the expression of pERK1/2 in the prefrontal cortex, medial amygdala nucleus, and cingulate gyrus. Both before and after ESPS exposure QUE treatments significantly elevated the reduced pERK1/2 expression in the three brain regions. QUE has preventive and protective effects against stress-associated symptoms and the changes in pERK1/2 functions may be associated with the pathophysiology of traumatic stress and the therapeutic efficacy of anti-PTSD therapy.

STRAP reduces endoplasmic reticulum stress and apoptosis in cardiomyocytes and attenuates myocardial ischemia-reperfusion injury by activating PI3K/PDK1/Akt signaling pathway.

OBJECTIVE: Myocardial ischemia-reperfusion injury (MIRI) is a common problem in heart-related diseases. The aim of this study was to explore the protective effects of STRAP on cardiomyocytes in the MIRI process and its mechanisms. MATERIALS AND METHODS: We used SD rats to construct a MIRI model and increased the expression of STRAP in myocardial tissue by Entranster to detect the effect of STRAP on rat myocardial tissue. In addition, we cultured rat cardiomyocyte cell line H9c2 cells and constructed a hypoxia-reoxygenation model to detect the protective effect of STRAP on H9c2 cells. LY294002, an inhibitor of the PI3K/PDK1/Akt signaling pathway, was used to validate the mechanism by which STRAP protects cardiomyocytes. RESULTS: Overexpression of STRAP significantly reduced the activity of MDA in myocardial tissue and increased the activity of SOD. STRAP also substantially lowered CK and LDH levels in rat serum and increased Na+-K+-ATPase and Ca2+-Mg2+-ATPase activity. In addition, overexpression of STRAP considerably reduced endoplasmic reticulum stress (ERS) and apoptosis levels in H9c2 cells. However, LY294002 attenuated the protective effect of STRAP on cardiomyocytes. CONCLUSIONS: STRAP reduces ERS and apoptosis in cardiomyocytes by activating the PI3K/PDK1/Akt signaling pathway, thereby reducing myocardial MIRI.

[Analysis of causes and treatment methods of complication of early acute kidney injury in four severely burned patients].

Objective: To analyze the causes of complication of early acute kidney injury (AKI) in four severely burned patients, and to explore the related treatment methods. Methods: The clinical data of 4 patients with severe burn complicated with early AKI admitted to Guangzhou Red Cross Hospital Affiliated to Medical College of Jinan University (hereinafter referred to as our hospital) from June 2014 to December 2017 were retrospectively analyzed. All the patients were male, aged 23-33 (30±5) years old, with depth of burns ranged from deep partial-thickness to full-thickness, complicated with myofascial compartment syndrome of extremities and varying degrees of striated muscle injury, and treated in other hospitals before transfer to our hospital. The patients were numbered from small to large according to the total burn area. The total burn area of patients No. 1, 2, 3, and 4 was 10%, 80%, 90%, and 95% total body surface area respectively, their occurrence time of early AKI was 48, 11, 29, and 48 hours after injury respectively, and their time of arriving our hospital was 60, 11, 29, and 144 hours after injury respectively. Hypovolemic shock occurred in patients No. 2 and 3 at admission to our hospital. All the patients received continuous renal replacement therapy (CRRT) after admission to our hospital. Under the support of hemodynamic monitoring and organ function monitoring, the limbs complicated with myofascial compartment syndrome were incised, thorough decompression exploration was performed, and necrotic muscle tissue was removed or amputation was performed. After escharectomy and decompression of limbs, fresh granulation wounds were formed by temporarily covering wounds with Jieya dressing skin or pig skin, multiple debridements, and vacuum sealing drainage. Fresh granulation wounds and other wounds underwent staged eschar excision and shaving were covered with autologous Meek skin graft, particulate skin graft, reticular skin graft and small skin graft respectively. The treatment outcome, CRRT time, operation times, time of recovery of serum creatinine and myoglobin, length of hospital stay, and follow-up were recorded. Results: All the 4 patients were cured after transfer to our hospital. Among them, totally 5 limbs of patients No. 1 and No. 4 underwent amputation because of complication of myofascial compartment syndrome and a large amount of necrotic muscle which could not be preserved. Patients No. 1, 2, 3, and 4 were treated with CRRT for 19, 35, 14, and 25 days respectively and performed with operation for 5, 6, 10, 8 times respectively. Serum creatinine of patients No. 1, 2, 3, and 4 returned to normal on 22, 35, 37, and 48 days after transfer respectively, and their serum myoglobin returned to normal on 18, 28, 25, and 30 days after transfer respectively. Patients No. 1, 2, 3, and 4 were hospitalized for 52, 105, 148, and 156 days and discharged after basic wound healing. Follow-up for 1 to 36 months showed no abnormal renal function in 4 patients. Conclusions: The early AKI in patients No. 1 and 4 was caused by rhabdomyolysis after severe burn complicated with myofascial compartment syndrome, while that of the other 2 cases were also related to hypovolemic shock and poor renal perfusion. The success rate of early AKI treatment in severely burned patients can be effectively improved by removing the causes of diseases at the same time of CRRT and actively treating burn wounds under the support of organ function and hemodynamic monitoring.

CIRBP protects H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.

Myocardial ischemia is a major cause of death and remains a disease with extremely deficient clinical therapies and a major problem worldwide. Cold inducible RNA-binding protein (CIRBP) is reported to be involved in multiple pathological processes, including myocardial ischemia. However, the molecular mechanisms of myocardial ischemia remain elusive. Here, we first overexpressed CIRBP by transfection of pc-CIRBP (pcDNA3.1 containing coding sequenced for CIRBP) and silenced CIRBP by transfection of small interfering RNA targeting CIRBP (siCIRBP). pcDNA3.1 and the negative control of siCIRBP (siNC) were transfected into H9C2 cells to act as controls. We then constructed a cell model of myocardial ischemia through culturing cells in serum-free medium with hypoxia in H9C2 cells. Subsequently, AlamarBlue assay, flow cytometry and western blot analysis were used, respectively, to assess cell viability, reactive oxygen species (ROS) level and apoptosis, and expression levels of IκBα, p65 and Bcl-3. We demonstrated that CIRBP overexpression promoted cell proliferation (P<0.001), inhibited cell apoptosis (P<0.05), reduced ROS level (P<0.001), down-regulated phosphorylated levels of IκBα and p65 (P<0.01 or P<0.001), and up-regulated expression of Bcl-3 (P<0.001) in H9C2 cells with myocardial ischemia. The influence of CIRBP knockdown yielded opposite results. Our study revealed that CIRBP could protect H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.

[Effects of silencing Smad ubiquitination regulatory factor 2 on the function of human hypertrophic scar-derived fibroblasts].

Objective: To explore the effects of silencing Smad ubiquitination regulatory factor 2 (Smurf2) on the secretion of transforming growth factor beta 1 (TGF-ß(1)), alpha-smooth muscle actin (α-SMA), and collagen type Ⅰ by human hypertrophic scar-derived fibroblasts. Methods: The human normal skin-derived fibroblasts and hypertrophic scar-derived fibroblasts were cultured with explant culture technique from the normal skin and hypertrophic scar tissue, which was obtained from 9 patients with hypertrophic scars after burn. Two kinds of fibroblasts of the third passage were both divided into 6 groups according to the random number table, with 9 wells in each group. Fibroblasts in blank control group were cultured for 72 h without transfection of any small interfering RNA (siRNA), fibroblasts in negative control group were for cultured for 72 h after transfected with non-target siRNA, fibroblasts in Smurf2 siRNA group were cultured for 72 h after transfected with 100 nmol/L Smurf2 siRNA, fibroblasts in blank control+ TGF-ß(1) group were cultured for 72 h without transfection of any siRNA and then treated with 10 ng/mL TGF-ß(1) for 6 h, fibroblasts in negative control+ TGF-ß(1) group were cultured for 72 h after transfected with non-target siRNA and then treated with 10 ng/mL TGF-ß(1) for 6 h, fibroblasts in Smurf2 siRNA+ TGF-ß(1) group were cultured for 72 h after transfected with Smurf2 siRNA and then treated with 10 ng/mL TGF-ß(1) for 6 h. (1) The protein and mRNA expression levels of Smurf2 of the two kinds of cells in blank control group, negative control group, and Smurf2 siRNA group were assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively. (2) The content of TGF-ß(1) in the cell culture supernatant of the two kinds of cells in blank control group and Smurf2 siRNA group was determined by enzyme-linked immunosorbent assay (ELISA). (3) The protein expression levels of α-SMA of the two kinds of cells in the 6 groups were assessed by Western blotting. The content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in the 6 groups was determined by ELISA. (4) The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in the 6 groups were assessed by RT-PCR. The sample numbers of each group in the above experiments were all 9. Data were processed with analysis of variance of factorial design and Bonferroni test. Results: (1) The protein and mRNA expression levels of Smurf2 of the two kinds of cells in Smurf2 siRNA group were significantly lower than those in blank control group and negative control group (with P values below 0.05). The protein and mRNA expression levels of Smurf2 of the two kinds of cells in blank control group and negative control group were close (with P values above 0.05). (2) The content of TGF-ß(1) in the cell culture supernatant of hypertrophic scar-derived fibroblasts in blank control group and Smurf2 siRNA group was respectively (4.34±0.56) and (2.14±0.28) pg/mL, which was significantly higher than (1.52±0.20) and (1.41±0.18) pg/mL of normal skin-derived fibroblasts respectively (with P values below 0.05). In hypertrophic scar-derived fibroblasts, the content of TGF-ß(1) in the cell culture supernatant in Smurf2 siRNA group was significantly lower than that in blank control group (P<0.05). In normal skin-derived fibroblasts, the content of TGF-ß(1) in the cell culture supernatant in Smurf2 siRNA group was close to that in blank control group (P>0.05). (3) The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in blank control+ TGF-ß(1) group were significantly higher than those in blank control group (with P values below 0.05). The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in negative control+ TGF-ß(1) group were significantly higher than those in negative control group (with P values below 0.05). The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in Smurf2 siRNA group were close to those in blank control group and negative control group (with P values above 0.05). The protein expression levels of α-SMA and content of collagen type Ⅰ in the cell culture supernatant of the two kinds of cells in Smurf2 siRNA+ TGF-ß(1) group were significantly lower than those in blank control+ TGF-ß(1) group and negative control+ TGF-ß(1) group (with P values below 0.05). (4) The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in blank control+ TGF-ß(1) group were significantly higher than those in blank control group (with P values below 0.05). The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in negative control+ TGF-ß(1) group were significantly higher than those in negative control group (with P values below 0.05). The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in Smurf2 siRNA group were close to those in blank control group and negative control group (with P values above 0.05). The mRNA expression levels of α-SMA and collagen type Ⅰ of the two kinds of cells in Smurf2 siRNA+ TGF-ß(1) group were significantly lower than those in blank control+ TGF-ß(1) group and negative control+ TGF-ß(1) group (with P values below 0.05). Conclusions: Silencing Smurf2 in human hypertrophic scar-derived fibroblasts can reduce the autocrine of TGF-ß(1) and inhibit the TGF-ß(1)-induced α-SMA expression and collagen type Ⅰ synthesis.

[The expression of SnoN in human hypertrophic scar fibroblasts and the mechanism of its participation in hypertrophic scar formation].

Objective: To investigate the expression of SnoN in human hypertrophic scar fibroblasts and the mechanism of its participation in hypertrophic scar formation. Methods: Eight patients with hypertrophic scar after burn in need of surgery were admitted in our unit from January to October 2013, and then hypertrophic scar tissue and normal skin tissue of full-thickness skin donor site resected by surgery of the patients were collected. Hypertrophic scar fibroblasts and normal skin fibroblasts of patients were isolated with method of explant culture and then sub-cultured. Cells of the third to fifth passage were used in the following experiments. (1) The protein expressions of SnoN of hypertrophic scar fibroblasts and normal skin fibroblasts were assessed with Western blotting. (2) The mRNA expressions of SnoN of another batch of hypertrophic scar fibroblasts and normal skin fibroblasts were determined with reverse transcription polymerase chain reaction. (3) Another batch of hypertrophic scar fibroblasts and normal skin fibroblasts were treated with 10 ng/mL transforming growth factor beta1 (TGF-ß(1)) for 30 min, 1 h, 2 h, and 6 h, respectively, and then the protein expressions and mRNA expressions of SnoN of untreated cells and treated cells were detected as above. Data were processed with one way analysis of variance and independent sample t test. Results: (1) The protein expression of SnoN of hypertrophic scar fibroblasts was 0.020±0.003, significantly lower than that of normal skin fibroblasts (0.032±0.005, t=7.19, P<0.05). (2) The mRNA expression of SnoN of hypertrophic scar fibroblasts was 0.407±0.157, with no significant difference from that of normal skin fibroblasts (0.339±0.095, t=-1.29, P>0.05). (3) The protein expression of SnoN of normal skin fibroblasts was increased in a time-dependent fashion with the TGF-ß(1) stimulation, and the protein expressions of SnoN of cells treated with TGF-ß(1) for 30 min, 1 h, 2 h, and 6 h were significantly higher than those of untreated cells (with t values from 2.27 to 27.89, P values below 0.05). The protein expression of SnoN of hypertrophic scar fibroblasts was decreased in a time-dependent fashion with the TGF-ß(1) stimulation, and the protein expressions of SnoN of cells treated with TGF-ß(1) for 30 min, 1 h, 2 h, and 6 h were obviously lower than those of untreated cells (with t values from 10.80 to 13.85, P values below 0.05). (4) The mRNA expressions of SnoN of normal skin fibroblasts and hypertrophic scar fibroblasts were both increased in a time-dependent fashion with the TGF-ß(1) stimulation, and the mRNA expressions of SnoN of the two types of cells treated with TGF-ß(1) for 30 min, 1 h, 2 h, and 6 h were both significantly higher than those of untreated cells (with t values from 18.16 to 58.22, P values below 0.05). Conclusions: The protein expression of SnoN in hypertrophic scar fibroblasts is reduced, which weakens its inhibitory effect on TGF-ß(1) signal, thus amplifying the TGF-ß(1) signal, and it may participate in the formation of hypertrophic scar.

Evaluation of glucose metabolic disorder: insulin resistance and insulin receptors in critically ill children.

OBJECTIVE: To explore the pathogenesis of glucose metabolic disorder and insulin resistance in critically ill children under severe stress. METHODS: To test glucose, lactate, glucagon, insulin, c-peptide, cortisol levels in 50 critically ill children. While we measured 125I-insulin binding to erythrocytes of 13 critically ill children who had hyperglycemia and hyperinsulinemia. Glucose and lactate were measured biochemically. Insulin, c-peptide, cortisol and glucagon were determined by RIA. Erythrocytes insulin receptor was detected by insulin radioreceptor assay. RESULTS: Glucose, lactate, insulin, c-peptide, glucagon, cortisol, insulin/glucose, insulin/glucagon ratio in patients were higher than those in normal controls (P < 0.05). As compared with normal controls, the maximum 125I-insulin bound and insulin receptor number per cell were significantly lower (P < 0.01). But there was no difference of mean value in receptor affinity (P > 0.05). CONCLUSIONS: Hyperglycemia is common in critically ill children during stress, which may be attributed to hormones disturbance and tissure insulin resistance. Insulin receptor defect due to comprehensive factors was one of the important causes for insulin resistance. The blood glucose level can be used as an predicting index in ICU.

Role of regulated upon activation normal T-cell expressed and secreted in a model of retransplantation acute rejection mediated by alloreactive memory CD4+ T cells.

BACKGROUND: It is unknown what role Regulated Upon Activation Normal T-Cell Exposed and Secreted may play in retransplantation or T-cell memory-transfer models. The experiment observed the influence of the chemokine RANTES in a mouse model of acute cardiac allograft rejection induced by adoptive transfer of alloreactive CD4(+) memory T (Tm) cells. METHODS: Alloreactive CD4(+) Tm cells from spleens of skin-grafted C57BL/6 were adoptively transferred to naïve C57BL/6 recipients prior to heterotopic heart transplantation. We measured the median survival time of cardiac grafts and performed some tests. RESULTS: Spleens from skin-grafted C57BL/6 contained 26.83% CD4(+) Tm cells. The median graft survival time of heterotopic heart transplantations (n = 6) was 5.17 ± 0.17 days for hosts receiving CD4(+) Tm cells compared with 7.76 ± 0.21 days among controls (n = 6; P < .001). The mean rejection activity in histological sections of cardiac allografts at day 5 postgrafting was 3.92 ± 0.08 in the CD4(+) Tm cell recipient group (n = 6) compared with 2.67 ± 0.14 in the controls (n = 6; P < .001). Gene expression of Ccl5, interferon (IFN)-γ and interleukin2 was significantly higher among CD4(+) Tm recipients compared with controls. Serum concentrations of RANTES and IFN-γ were higher in the heterotopic heart transplantation group receiving CD4(+) Tm compared with controls. CONCLUSIONS: Alloreactive CD4(+) Tm cells contribute to increased expression and secretion of RANTES, and to the Tm and other inflammatory cells migration into the graft.

CIRBP protects H9C2 cells against myocardial ischemia through inhibition of NF-kappaB pathway

Myocardial ischemia is a major cause of death and remains a disease with extremely deficient clinical therapies and a major problem worldwide. Cold inducible RNA-binding protein (CIRBP) is reported to be involved in multiple pathological processes, including myocardial ischemia. However, the molecular mechanisms of myocardial ischemia remain elusive. Here, we first overexpressed CIRBP by transfection of pc-CIRBP (pcDNA3.1 containing coding sequenced for CIRBP) and silenced CIRBP by transfection of small interfering RNA targeting CIRBP (siCIRBP). pcDNA3.1 and the negative control of siCIRBP (siNC) were transfected into H9C2 cells to act as controls. We then constructed a cell model of myocardial ischemia through culturing cells in serum-free medium with hypoxia in H9C2 cells. Subsequently, AlamarBlue assay, flow cytometry and western blot analysis were used, respectively, to assess cell viability, reactive oxygen species (ROS) level and apoptosis, and expression levels of IκBα, p65 and Bcl-3. We demonstrated that CIRBP overexpression promoted cell proliferation (P<0.001), inhibited cell apoptosis (P<0.05), reduced ROS level (P<0.001), down-regulated phosphorylated levels of IκBα and p65 (P<0.01 or P<0.001), and up-regulated expression of Bcl-3 (P<0.001) in H9C2 cells with myocardial ischemia. The influence of CIRBP knockdown yielded opposite results. Our study revealed that CIRBP could protect H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.

Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.

Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced pluripotent stem cells (iPS cells) derived from somatic cells may represent a powerful tool for studying the pathogenesis of PD and provide a source for replacement therapies in this neurodegenerative disease. Yamanaka et al. [2006, 2007] first succeeded in generating iPS cells by reprogramming fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc in both mouse and human. Animal studies have further shown that iPS cells from fibroblasts could be induced into dopamine neurons and transplantation of these cells within the central nervous system improved motor symptoms in the 6-OHDA model of PD. More interestingly, neural stem cells or fibroblasts from patients can be efficiently reprogrammed and subsequently differentiated into dopamine neurons. Derivation of patient-specific iPS cells and subsequent differentiation into dopamine neurons would provide a disease-specific in vitro model for disease pathology, drug screening and personalized stem cell therapy for PD. This review summarizes current methods and modifications in producing iPS cells from somatic cells as well as safety concerns of reprogramming procedures. Novel reprogramming strategies that deter abnormal permanent genetic and epigenetic alterations are essential for propagating clinically-qualified iPS cells. Future investigations into cell transforming and reprogramming processes are needed to generate the disease-specific iPS cells for personalized regeneration medicine of PD patients by disclosing detailed reprogramming mechanisms.

Membrane current-based mechanisms for excitability transitions in neurons of the rat mesencephalic trigeminal nuclei.

Since Hodgkin's first description of three classes of excitability in crustacean nerve axons (1948), theoretical studies have used mathematical models to demonstrate that small changes in the parameters describing ionic currents could result in transitions between classes of membrane excitability. However, these transitions have rarely been investigated experimentally. Here, we show that states of excitability in rat mesencephalic V (Mes V) neurons can be classified into three groups, with manipulations of the 4-aminopyridine sensitive K(+) current (I(4-AP)) or persistent Na(+) current (I(NaP)) leading to the corresponding transitions. However, alterations in the hyperpolarization-activated cation current (I(h)), tetraethylammonium (TEA)-sensitive K(+) current, or Cd(2+)-sensitive Ca(2+) current were ineffective in causing these transitions. These results provide experimental evidence for the excitability transitions predicted by Hodgkin and characterize their ionic mechanisms in Mes V neurons.