Parkinson’s Disease Motor Subtypes Show Different Responses to Long-Term Subthalamic Nucleus Stimulation

Background and purpose: Subthalamic nucleus deep brain stimulation (STN DBS) is well established for the treatment of advanced Parkinson’s disease (PD), substantially improving motor symptoms, quality of life, and reducing the long-term need for dopaminergic medication. However, whether chronic STN DBS produces different effects on PD motor subtypes is unknown. This retrospective study aimed to evaluate the long-term effects of STN DBS on the PD motor subtypes.Methods: Eighty patients undergoing STN DBS were included. The Unified Parkinson’s Disease Rating Scale (UPDRS) analysis was performed in “On” and “Off” medication/“On” and “Off” stimulation conditions. The patients were classified as akinetic-rigid type (ART), tremor-dominant type (TDT), and mixed type (MT) based on the preoperative UPDRS III subscores in the “Off” medication state. Preoperative and postoperative comparisons were performed.Results: After 4.9 years, STN DBS produced significant improvement in the UPDRS III total scores and subscores of tremor, rigidity, and bradykinesia in the “Off” medication state in the ART group, less improvement in the MT group, and the least improvement in the TDT group. The UPDRS II and III total scores and other subscores failed to improve during the “On” medication state. However, all groups improved substantially, and the improvement in tremor was sustained for both the “On” and “Off” medication states after years. Long-term STN DBS failed to improve swallowing and speech in all the subtypes.Conclusion: The data confirms that PD is heterogeneous. Long-term STN DBS produced the best effects on bradykinesia/rigidity in the “Off” medication state and on tremor in the “On” and “Off” medication states. There were differences in the response by each group, but some of the differences could be explained by the fact that more severe symptoms at baseline tend to have greater improvement. The findings support the idea that ART mainly involves the basal ganglia-thalamo-cortical pathway, whereas TDT involves a different circuit, likely the cerebellar-thalamo-cortical pathway

Molecular mechanism of ethylene stimulation of latex yield in rubber tree (Hevea brasiliensis) revealed by de novo sequencing and transcriptome analysis

Differential expression of unigenes involved in hormone signaling in E8 and E24 compared to C samples of Hevea brasiliensis. Ethylene signalling pathway: ETR1: ETHYLENE RESPONSE 1; CTR1: CONSTITUTIVE TRIPLE RESPONSE 1; EIN2: ETHYLENE INSENSITIVE 2; EIN3: ETHYLENE INSENSITIVE 3; ERF1/2: ETHYLENE RESPONSE FACTOR 1/2; EBF1/2: EIN3 binding F-Box protein 1/2; BR signaling pathway: BRI1: Brassinosteroid-Insensitive 1; BAK1: BRI1-associated kinase 1; BKI1: BRI1 KINASE INHIBITOR 1; BSK: BR SIGNALING KINASE; BSU1: bri1 SUPPRESSOR 1; BIN2: BRASSINOSTEROID-INSENSITIVE 2; BZR1/2: BRASSINAZOLE RESISTANT 1/2; TCH: TOUCH genes; CYCD3: CYCLIN D3; GA signaling pathway: GID1: GIBBERELLIN INSENSITIVE DWARF 1; GID2: GIBBERELLIN INSENSITIVE DWARF 2; DELLAs: DELLA growth inhibitors; TF: transcriptional factor; Auxin signaling pathway: AUX1: AUXIN1; TIR1: TRANSPORT INHIBITOR RESPONSE 1; IAA: INDOLE ACETIC ACID; ARF: AUXIN RESPONSE FACTOR; SAUR: Small Auxin-Up RNA; G10H: geraniol 10-hydroxylase gene; Cytokinin signaling pathway: CRE1: CYTOKININ RESPONSE 1; AHP: histidine phosphotransfer protein; B-ARR: type-B response regulator (ARR); A-ARR: type-A response regulator (ARR); SA signalling pathway: NPR1: Non-expressor of pathogenesis-related genes 1; TGA: the bZIP transcription factors; PR1: pathogenesis related protein 1; JA signaling pathway: JAR1: JASMONATES RESISTANT 1; JA-Ile: jasmonoyl isoleucine; JAZ: Jasmonate ZIM-domain-containing protein; MYC2: a basic helix-loop-helix (bHLH) transcription factor; ORCA3: Octadecanoid-derivative Responsive Catharanthus AP2-domain gene; ABA signalling pathway: PYR1/PYLs: Pyrabactin Resistance Protein1/PYR-Like proteins; PP2Cs: protein phosphatases which fall under the category of type 2C; SnRK2: SNF1 (Sucrose-Nonfermenting Kinase1)-related protein kinase 2: ABF: ABA responsive element (ABRE) binding factors. Cells with gray border lines in the upper rows represent differentially expressed unigenes in E8 compared to C and cells with green border lines in the lower rows represent differentially expressed unigenes in E24 compared to C. Relative levels of expression are showed by a color gradient from low (blue) to high (red). (JPG 249 kb

Ispitivanje antioksidativne aktivnosti in vitro polipeptida meduze (Rhopilema esculentum)

Jellyfish gelatin was hydrolyzed by different proteases to obtain antioxidative polypeptides. The gelatin hydrolysate obtained by progressive hydrolysis using trypsin and Properase E exhibited the highest hydrolysis degree and antioxidant activity. Three series of gelatin polypeptides (SCP1, SCP2 and SCP3) were obtained by ultrafiltrating the gelatin hydrolysate through molecular mass cut-off membranes of 10, 6 and 2 kDa, respectively. Amino acid composition analysis showed that SCP3 had the highest total hydrophobic amino acid content. The in vitro antioxidant tests demonstrated that SCP2 had the strongest hydroxyl radical and hydrogen peroxide scavenging activities and metal chelating ability, while SCP3 showed the highest reducing power, antioxidant activity in linoleic acid emulsion system and superoxide anion radical scavenging activity. The results support the feasibility of jellyfish gelatin as a natural antioxidant polypeptide provider, and enzymatic hydrolysis and ultrafiltration could be potent future processing technologies to utilize the abundant jellyfish resource.Hidrolizom želatine iz meduze pomoću različitih proteaza dobiveni su polipeptidi antioksidativnih svojstava. Najveći stupanj hidrolize i najbolja antioksidativna svojstva imao je hidrolizat dobiven progresivnom hidrolizom pomoću tripsina i Properase E. Ultrafiltracijom hidrolizata kroz membrane (10, 6 i 2 kDa) dobivene su tri serije polipeptida želatine: SCP1, SCP2 i SCP3. Analizom aminokiselinskoga sastava ustanovljeno je da SCP3 ima najveći ukupni udio hidrofobnih aminokiselina. Antioksidativni testovi in vitro pokazali su da SCP2 ima najveću sposobnost uklanjanja hidroksilnih radikala i vodikova peroksida te keliranja metala, a SCP3 najveću redukcijsku moć, najbolju antioksidativnu aktivnost u emulzijskom sustavu linoleinske kiseline te sposobnost uklanjanja superoksidnih aniona. Rezultati potvrđuju da se želatina iz meduze može upotrijebiti kao izvor prirodnih antioksidativnih polipeptida, a enzimska hidroliza i ultrafiltracija kao postupci prerade za njezino iskorištavanje

Ispitivanje antioksidativne aktivnosti in vitro polipeptida meduze (Rhopilema esculentum)

Jellyfish gelatin was hydrolyzed by different proteases to obtain antioxidative polypeptides. The gelatin hydrolysate obtained by progressive hydrolysis using trypsin and Properase E exhibited the highest hydrolysis degree and antioxidant activity. Three series of gelatin polypeptides (SCP1, SCP2 and SCP3) were obtained by ultrafiltrating the gelatin hydrolysate through molecular mass cut-off membranes of 10, 6 and 2 kDa, respectively. Amino acid composition analysis showed that SCP3 had the highest total hydrophobic amino acid content. The in vitro antioxidant tests demonstrated that SCP2 had the strongest hydroxyl radical and hydrogen peroxide scavenging activities and metal chelating ability, while SCP3 showed the highest reducing power, antioxidant activity in linoleic acid emulsion system and superoxide anion radical scavenging activity. The results support the feasibility of jellyfish gelatin as a natural antioxidant polypeptide provider, and enzymatic hydrolysis and ultrafiltration could be potent future processing technologies to utilize the abundant jellyfish resource.Hidrolizom želatine iz meduze pomoću različitih proteaza dobiveni su polipeptidi antioksidativnih svojstava. Najveći stupanj hidrolize i najbolja antioksidativna svojstva imao je hidrolizat dobiven progresivnom hidrolizom pomoću tripsina i Properase E. Ultrafiltracijom hidrolizata kroz membrane (10, 6 i 2 kDa) dobivene su tri serije polipeptida želatine: SCP1, SCP2 i SCP3. Analizom aminokiselinskoga sastava ustanovljeno je da SCP3 ima najveći ukupni udio hidrofobnih aminokiselina. Antioksidativni testovi in vitro pokazali su da SCP2 ima najveću sposobnost uklanjanja hidroksilnih radikala i vodikova peroksida te keliranja metala, a SCP3 najveću redukcijsku moć, najbolju antioksidativnu aktivnost u emulzijskom sustavu linoleinske kiseline te sposobnost uklanjanja superoksidnih aniona. Rezultati potvrđuju da se želatina iz meduze može upotrijebiti kao izvor prirodnih antioksidativnih polipeptida, a enzimska hidroliza i ultrafiltracija kao postupci prerade za njezino iskorištavanje

Serum miR-224 Reflects Stage of Hepatocellular Carcinoma and Predicts Survival

Background. In our previous study, we conducted a systematic screening of miRNA to identify potential serum biomarkers for predicting venous metastasis and survival in patients with hepatocellular carcinoma (HCC). miR-224 was one of the differentially expressed miRNAs. This study aimed to confirm whether serum miR-224 level is associated with the presence of venous metastasis and survival. Methods. TaqMan miRNA probe was used to perform qRT-PCR assays to evaluate the expression of serum miR-224 in a cohort of 182 HCC patients. Results. Patients with high miR-224 serum level showed poor survival compared to that with low miR-224 serum level (HR 1.985; 95% CI, 1.08, 3.65, = 0.027). The serum miR-224 levels were significantly higher in the BCLC stage C patients compared with the stage B patients ( = 0.005). In further analysis, significant difference of serum miR-224 expression level was observed when patients grouped by the status of PVTT but not the status of extra-liver metastasis ( = 0.013 and = 0.091). Serum levels of miR-224 showed significant relation with parameters of liver damage and serum AFP. Conclusion. Serum miR-224 might be BCLC stage dependent. It can reflect the status of tumor and liver damage. It was an independent predictor for the survival of HCC patients

Differences in subthalamic oscillatory activity in the two hemispheres associated with severity of Parkinson’s disease

BackgroundIt is well known that motor features of Parkinson’s disease (PD) commonly begin on one side of the body and extend to the other side with disease progression. The onset side generally remains more severely affected over the course of the disease. However, the pathophysiology underlying the asymmetry of motor manifestations remains unclear. The purpose of the present study is to examine whether alterations in neuronal activity in the subthalamic nucleus (STN) associate with PD severity.MethodsMicroelectrode recording was performed in the STN during targeting for 30 patients in the treatment of deep brain stimulation. The mean spontaneous firing rate (MSFR), power density spectral analysis, and correlations were calculated. Characteristics of subthalamic oscillatory activity were compared between two hemispheres. UPDRS III scores during “Off” and “On” states were obtained for the body side of initial symptoms (BSIS) and the body side of extended symptoms (BSES).ResultsThere were significant differences of MSFR (41.3 ± 11.0 Hz vs 35.2 ± 10.0 Hz) and percentage of ß frequency oscillatory neurons (51.3% vs 34.9%) between BSIS and BSES. The percentage of ß frequency oscillatory neurons correlated with the bradykinesia/rigidity scores for both sides (p < 0.05). In contrast, the percentage of tremor frequency oscillatory neurons was significantly higher in the BSES than that in the BSIS. In particular, these neurons only correlated with the tremor scores of the BSES (p < 0.05).ConclusionThe results suggest that increased neuronal firing rate and ß frequency oscillatory neurons in the STN are associated with contralateral side motor severity and its progression. Tremor frequency oscillatory neurons are less observed in the STN of the BSIS suggesting that ß oscillatory activity dominates and tremor frequency oscillatory activity reciprocally declines

Characterization of the denaturation and renaturation of human plasma vitronectin II. Investigation into the mechanism of formation of multimers

Unfolding and refolding of plasma vitronectin appear irreversible under near physiological conditions, with rearrangements of disulfides and self-association to a multimeric form observed as prominent structural alterations which accompany denaturation. A mechanism for the folding reactions of vitronectin has been proposed (Zhuang, P., Blackburn, M. NPeterson, C. B. (1996) J. Biol. Chem. 270, 14323-14332) in which vitronectin acquires a partially folded intermediate structure which is highly prone to oligomerize into a multimeric form. Strongly oxidizing conditions adopted for refolding from urea were effective at preventing disulfide rearrangement which disrupts distal disulfides near the C terminus of the protein. Prohibiting disulfide rearrangement under these conditions, however, was not sufficient to achieve reversibility in folding. In contrast, variations in the ionic strength of the refolding medium affect the partitioning of species so that refolded monomers are obtained at high ionic strength, and self-association is precluded. The effects of ionic strength on the partially folded intermediate in the vitronectin folding pathway appear to favor intramolecular hydrophobic collapse to form a stable hydrophobic core for the monomer versus intermolecular hydrophobic interactions which stabilize multimeric vitronectin. Although both ionic and hydrophobic interactions presumably contribute to subunit interfaces within the multimer, the basic heparin-binding region near the C terminus of the protein does not provide binding interactions which are important for self-association of vitronectin

The inhibitory effect against collagen-induced arthritis by Schistosoma japonicum infection is infection stage-dependent

<p>Abstract</p> <p>Background</p> <p>A long-term existing schistosome infection can aid in maintaining immuno-homeostasis, thus providing protection against various types of autoimmune diseases to the infected host. Such benefits have often been associated with acute or egg stage infection and with the egg-induced Th2 response. However, since schistosome infection undergoes different stages, each associated with a specific induction of Th responses, the requirements for the ability of the different stages of schistosome infection to protect against autoimmune disease has not been elucidated. The present study was designed to study whether different stages of schistosome infection offer unique protection in collagen-induced arthritis and its mechanisms.</p> <p>Results</p> <p>Arthritis susceptible strain DBA/1 male mice were infected with <it>Schistosoma japonicum </it>for either 2 weeks resulting in early stage infection or for 7 weeks resulting in acute or egg stage infection. Following <it>Schistosoma japonicum </it>infection, collagen II was administered to induce collagen-induced arthritis, an animal model for human rheumatoid arthritis. Infection by <it>Schistosoma japonicum </it>significantly reduced the severity and the incidence of experimental autoimmune collagen-induced arthritis. However, this beneficial effect can only be provided by a pre-established acute stage of infection but not by a pre-established early stage of the infection. The protection against collagen-induced arthritis correlated with reduced levels of anti-collagen II IgG, especially the subclass of IgG2a. Moreover, in protected mice increased levels of IL-4 were present at the time of collagen II injection together with sustained higher IL-4 levels during the course of arthritis development. In contrast, in unprotected mice minimal levels of IL-4 were present at the initial stage of collagen II challenge together with lack of IL-4 induction following <it>Schistosoma japonicum </it>infection.</p> <p>Conclusion</p> <p>The protective effect against collagen-induced arthritis provided by <it>Schistosoma japonicum </it>infection is infection stage-dependent. Furthermore, the ability of schistosomiasis to negatively regulate the onset of collagen-induced arthritis is associated with a dominant as well as long-lasting Th2 response at the initiation and development of autoimmune joint and systemic inflammation.</p

The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro

<p>Abstract</p> <p>Background</p> <p>Despite of the recent success of EGFR inhibitory agents, the primary drug-resistant becomes a major challenge for EGFR inhibitor therapies. PTEN gene is an important positive regulatory factor for response to EGFR inhibitor therapy. Low-expression of PTEN is clearly one of the important reasons why tumor cells resisted to tyrosine kinase inhibitors.</p> <p>Methods</p> <p>To investigate the drug-resistance reversal to gefitinb and the mechanism in PTEN low expression cells which radiated with X-rays in vitro, We demonstrated that H-157 lung cancer cells (low-expression of PTEN but phospho-EGFR overexpressed tumor cells) exposed to X-rays. The PTEN expressions and radiosensitizing effects of tyrosine kinase inhibitor before and after irradiation were observed. The cell-survival rates were evaluated by colony-forming assays. The cell apoptosis was investigated using FCM. The expressions of phospho-EGFR and PTEN were determined by Western blot analysis.</p> <p>Results</p> <p>The results showed that the PTEN expressions were significantly enhanced by X-rays. Moreover, the cell growth curve and survival curve were down-regulated in the gefitinib-treated groups after irradiation. Meanwhile, the radiation-induced apoptosis of tumor cells was increased by inhibition of the EGFR through up-regulation of PTEN.</p> <p>Conclusion</p> <p>These results suggested that PTEN gene is an important regulator on TKI inhibition, and the resistance to tyrosine kinase inhibitors might be reversed by irradiation in PTEN low expression cancer cells.</p