Rituximab maintenance treatment outcomes in patients with relapsing neuromyelitis optica spectrum disorder: a monocentric retrospective analysis.

Some patients with neuromyelitis optica spectrum disorder (NMOSD) experience relapse after rituximab (RTX) treatment. In this retrospective study, we analyzed the recurrence-related clinical features, laboratory investigation results, and dosing protocol of 30 female patients with relapsing NMOSD with immunoglobulin G autoantibodies against aquaporin-4 and relapses during repeated 0.5 g RTX infusions as maintenance treatment. The median follow-up period was 6.62 years. Thirty-five episodes were observed, with myelitis being the most frequent. The median expanded disability status scale change score was 0.50. The recurrence rate decreased by 44.23%/year with RTX infusion. Approximately 85.71% of the patients showed relapse without RTX infusion within 10 months. Overall, RTX may be effective for relapsing NMOSD cases.

Carane-3,4-diol Derivatives as Potential Water-Based Herbicides.

Twelve novel carane-3,4-diol derivatives were designed, synthesized, and evaluated for their herbicidal activities against Lolium multiflorum Lam. and Brassica campestris for the first time. The relationships between the chemical structural factors, including types, the number or the carbon chain length of functional groups, associated with the lipophilicity and the herbicidal activity of the tested compounds were also discussed. The results showed that most of newly synthesized compounds had a dose-dependent, herbicidal activity against the root and shoot growths of Lolium multiflorum Lam. and Brassica campestris. Compared to carane-3,4-diol, most of the target derivatives possessed improved lipophilicity and certain solubilities in representative solvents with different polarities. Particularly, ester derivatives 3a-3b and 3e can be dissolved or dispersed in water, but also displayed higher herbicidal activity against Lolium multiflorum Lam. and Brassica campestris than other ester derivatives. The 50 % inhibitory concentration (IC50) value of compound 3e against shoot growth of Brassica campestris (0.485 mmol/L) was superior to that of commercial herbicide glyphosate (1.14 mmol/L), indicating that the potential application as a water-based herbicide for Brassica campestris control.

Manganese (II) chloride leads to dopaminergic neurotoxicity by promoting mitophagy through BNIP3-mediated oxidative stress in SH-SY5Y cells.

BACKGROUND: Manganese overexposure can induce neurotoxicity, lead to manganism and result in clinical manifestations similar to those of parkinsonism. However, the underlying molecular mechanism is still unclear. This study demonstrated that MnCl2 induces mitophagy and leads to neurotoxicity by promoting BNIP3-mediated reactive oxygen species (ROS) generation. METHODS: Human neuroblastoma SH-SY5Y cells were used throughout our experiments. Cell viability was detected by cell proliferation/toxicity test kits. Mitochondrial membrane potential was measured by flow cytometry. ROS generation was detected using a microplate reader. Protein levels were evaluated by Western blot. Transmission electron microscopy was used to evaluate mitochondrial morphology. Co-immunoprecipitation was used to verify the interaction between BNIP3 and LC3. RESULTS: MnCl2 led to loss of mitochondrial membrane potential and apoptosis of SH-SY5Y cells by enhancing expression of BNIP3 and conversion of LC3-I to LC3-II. Moreover, MnCl2 reduced expression of the mitochondrial marker protein TOMM20 and promoted interaction between BNIP3 and LC3. The results also indicated that a decrease in BNIP3 expression reduced the mitochondrial membrane potential loss, attenuated apoptosis and reduced mitochondrial autophagosome formation in SH-SY5Y cells after MnCl2 treatment. Finally, we found that manganese-induced ROS generation could be reversed by the antioxidant N-acetyl cysteine (NAC) or silencing BNIP3 expression. CONCLUSIONS: BNIP3 mediates MnCl2-induced mitophagy and neurotoxicity in dopaminergic SH-SY5Y cells through ROS. Thus, BNIP3 contributes to manganese-induced neurotoxicity by functioning as a mitophagy receptor protein.

Petroleum hydrocarbon-contaminated soil bioremediation assisted by isolated bacterial consortium and sophorolipid.

Pollution in soil by petroleum hydrocarbon has become a global environmental problem. The bioremediation of petroleum hydrocarbon-contaminated soil was enhanced with the combination of an isolated indigenous bacterial consortium and biosurfactant. The biodegradation efficiency of total petroleum hydrocarbon (TPH) was increased from 12.2% in the contaminated soil to 44.5% and 57.7% in isolated consortium and isolated consortium & 1.5 g sophorolipid (SL)/kg dry soil, respectively. The half-life of TPH degradation process was decreased from 32.5 d in the isolated consortium reactor to 20.4 d in the isolated consortium & 1.5 g SL/kg dry soil. The addition of biosurfactant into contaminated soils improved the TPH desorption from solid matrix to the aqueous solution and the subsequent solubilization, which ultimately improved the bioavailability of TPH in contaminated soils. Biosurfactant also served as carbon sources which contributed to the stimulation of cell growth and microbial activity and accelerated the biodegradation process via co-metabolism. The enzyme activities and quantities of functional genes were demonstrated to be incremented in SL reactors. The biosurfactant improved the TPH bioavailability, stimulated the microbial activities and participated in the co-metabolism. The combination of bioaugmentation and SL benefitted the bioremediation of petroleum hydrocarbon-contaminated soil.

Promotion of mitochondrial biogenesis via the regulation of PARIS and PGC-1α by parkin as a mechanism of neuroprotection by carnosic acid.

BACKGROUND: Impairment of mitochondrial biogenesis is associated with the pathological progression of Parkinson's disease (PD). Parkin-interacting substrate (PARIS) can be ubiquitinated by parkin and prevents the repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α). PURPOSE: This study investigated whether the neuroprotective mechanism of carnosic acid (CA) from rosemary is mediated via the regulation of PARIS and PGC-1α by parkin. METHODS: The Western blotting and RT-PCR were used to determine protein and mRNA, respectively. To investigate the protein-protein interaction of between PARIS and ubiquitin, the immunoprecipitation assay (IP assay) was utilized. Silencing of endogenous parkin or PGC-1α was performed by using transient transfection of small interfering RNA (siRNA). RESULTS: SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA) increased PARIS protein, decreased PGC-1α protein, and reduced protein and mRNA of mitochondrial biogenesis-related genes. CA pretreatment reversed the effects of 6-OHDA. By IP assay, the interaction of PARIS with ubiquitin protein caused by CA was stronger than that caused by 6-OHDA. Moreover, knockdown of parkin attenuated the ability of CA to reverse the 6-OHDA-induced increase in PARIS and decrease in PGC-1α expression. PGC-1α siRNA was used to investigate how CA influenced the effect of 6-OHDA on the modulation of mitochondrial biogenesis and apoptosis. In the presence of PGC-1α siRNA, CA could no longer significantly reverse the reduction of mitochondrial biogenesis or the induction of cleavage of apoptotic-related proteins by 6-OHDA. CONCLUSION: The cytoprotective of CA is related to the enhancement of mitochondrial biogenesis by inhibiting PARIS and inducing PGC-1α by parkin. The activation of PGC-1α-mediated mitochondrial biogenesis by CA prevents the degeneration of dopaminergic neurons, CA may have therapeutic application in PD.

Genome-wide identification of m6A-associated single-nucleotide polymorphisms in Parkinson's disease.

N6-methyladenosine (m6A)-associated single nucleotide polymorphisms (SNPs) play a vital role in several neurological diseases. However, little is known about the relationship between m6A modification and Parkinson's disease (PD). We investigated potential functional variants of m6A-SNPs from large-scale genome-wide association studies (GWAS) in PD patients. The candidate m6A-SNPs were further assessed by expression quantitative trait loci (eQTL) analysis and differential gene expression analysis. We identified 12 m6A-SNPs that were significantly associated with PD risk. Further, eQTL and expression analyses identified five of these m6A-SNPs (rs75072999 of GAK, rs1378602, rs4924839 and rs8071834 of ALKBH5, and rs1033500 of C6orf10) that were associated with altered gene expression in PD. Our results suggest that m6A-SNPs could play a role in PD risk. Future studies are needed to confirm these PD-associated m6A-SNPs and elucidate their mechanisms.

Association of GLP-1 receptor gene polymorphisms with sporadic Parkinson's disease in Chinese Han population.

The Glucagon Like Peptide 1 Receptor (GLP1R) plays a critical role in selective death of dopaminergic neurons and development of Parkinson's disease (PD). However, little is known about genetic associations of GLP1R gene polymorphisms with PD susceptibility. Therefore, this study aimed to verify whether GLP1R polymorphisms contribute to PD risk in a Chinese Han population. We recruited 518 individuals comprising 259 sporadic PD patients and 259 healthy controls. All of the participants were genotyped for two possibly functional polymorphisms located in GLP1R (rs3765467 and rs6923761) using the Sequenom MassARRAY platform. The frequency of the rs3765467 GG genotype was significantly higher in the PD group compared with that in the control group (OR = 1.444, 95 % CI: 1.015-2.055, p =  0.041). Subgroup analysis revealed that male patients and late-onset patients with the rs3765467 GG genotype suffered an increased risk of PD compared with healthy controls (p =  0.021 and p =  0.012, respectively). However, the genotype and allele frequencies for rs6923761 were not significantly different between PD and healthy subjects. Our results indicate that the GLP1R rs3765467 GG genotype is a potential risk factor for PD, especially for male and late-onset PD patients in the Chinese Han population.

Application of alkyl polyglycosides for enhanced bioremediation of petroleum hydrocarbon-contaminated soil using Sphingomonas changbaiensis and Pseudomonas stutzeri.

Bioremediation is considered a cost-effective and environmentally sound method for degradation of petroleum hydrocarbons in contaminated soils. This study investigated the effects of biosurfactant alkyl polyglycosides (APG) on enhanced biodegradation of petroleum hydrocarbon-contaminated soils using Sphingomonas changbaiensis and Pseudomonas stutzeri and explored the mechanism responsible for the enhanced petroleum hydrocarbon degradation. To accomplish this, the following treatments were evaluated: (1) bioaugmentation with Sphingomonas changbaiensis; (2) bioaugmentation with Pseudomonas stutzeri; (3) a combination of Sphingomonas changbaiensis and APG; and (4) a combination of Pseudomonas stutzeri and APG. The results showed that the degradation rates of total petroleum hydrocarbons (TPH) in contaminated soil samples bioaugmented with S. changbaiensis and P. stutzeri for 30 days were 39.2 ± 1.9% and 47.2 ± 1.2%, respectively. The addition of biosurfactant APG enhanced the bioremediation processes and improved the biodegradation rates. The biodegradation rate at 1.5 g/kg APG in soil samples bioaugmented with S. changbaiensis was 52.1 ± 2.0%, while the rate at 1.5 g/kg APG in soil samples bioaugmented with P. stutzeri was 59.0 ± 1.8%. The half-life decreased from 39.7 d to 24.5 d and from 29.6 to 20.1 d when the dosage of APG was 1.5 g/kg in contaminated soil samples bioaugmented with S. changbaiensis and P. stutzeri, respectively. Mechanism studies showed that the addition of APG can increase the TPH solubility, promote the sorption of TPH onto microbial cells and subsequent trans-membrane transport by APG-induced structural changes, stimulate microbial activities and participate in the co-metabolism. Therefore, the combination of bioaugmentation and APG is an effective method for remediation of petroleum hydrocarbon-contaminated soil.

[Comparative analysis and comprehensive evaluation for growth and photosynthetic characteristics of different lily species and varieties].

The biological characteristics,agronomic traits,yield traits,stress resistance,quality and photosynthetic characteristics among six lily varieties were compared in order to screen out the excellent lily varieties suitable for spread planting in Hunan province. Lilium longiflorum had the longest growth period,246 days,among these six lily varieties,while others were about 170 days. The leaves of L.longiflorum,self-selected variety,L. lancifolium and L. dauricum had higher chlorophyll content. No obvious difference was found in net photosynthetic rate,stomatal conductance,transpiration rate and intercellular CO2 concentration among all varieties. The self-selected variety had the highest theoretical and actual yield,2 543. 03,1 608. 65 kg per Mu(1 Mu≈666. 7 m2),respectively,but contents of polysaccharides and flavones in bulbs were lower. All of these six lily varieties can sowing,seedling emergence,growth,flowering,mature harvest in Hunan province. L. dauricum and L. lancifolium would be provided for edible lily. L. brownie and the self-selected variety are highly susceptible varieties. L. dauricum and L. lancifolium are suitable to plant widely in disease-prone regions,due to their strong resistance. L. brownie and L. lancifolium are preferred varieties for medicinal and food using for their good quality and higher contents of polysaccharides and flavones. L. davidii had lower theoretical and actual yield,so planting extension of it should be taken into account.

Effect of endoplasmic reticulum stress involved in manganese­induced neurotoxicity in rats.

The aim of the present study was to probe the mechanism of apoptosis induced by endoplasmic reticulum stress (ERS) in manganese­induced rats. A total of 60 Sprague­Dawley rats were randomly divided into a Vehicle group, LoMag group, HiMag group, and HiMag + 4­phenylbutyrate (PBA) group. Manganese content was measured by Inductively Coupled Plasma­Atomic Emission Spectrometry. Pathogenic morphology, the cellular structure of the striatum and ER were observed by hematoxylin and eosin staining and electron microscopy. The TUNEL method was used to examine neuronal apoptosis in the rat striatum. The expression levels of glucose­regulated protein 78KD (GRP78), C/EBP homologous protein (CHOP), c­Jun N­terminal kinase (JNK) and caspase­12 were analyzed by western blot analysis. The results revealed that striatal manganese concentrations in the LoMag and HiMag groups were higher than that in the Vehicle group (P<0.01). Rat striatal neuronal structure and apoptotic rates in the LoMag and HiMag groups were higher than those in the Vehicle group (P<0.05). 4­PBA treatment effectively reduced the apoptotic cell number (P<0.05). In addition, ER swelling and vacuolization in the HiMag + PBA group was reduced compared with that in the HiMag group. In addition, the protein expression levels of GRP78, CHOP, JNK and caspase­12 in the LoMag and HiMag groups were higher than those in the Vehicle group (P<0.05). However, the expression of these four proteins was reduced by 4­PBA treatment (P<0.05). In conclusion, 4­PBA significantly reduced the damage and apoptosis induced by manganese exposure in rats.

C-Reactive Protein and Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: C-reactive protein (CRP) has been identified as a common inflammation-related cytokine. Although publications indicate that CRP is associated with the pathogenesis of neurological disorders and deemed to be a "risk factor" for Parkinson's disease (PD), the evidence exists still indefinitely. Here, we performed a systematic review with meta-analysis synthesizing all the eligible studies on serum, plasma, and cerebrospinal fluid (CSF) CRP levels and PD risk to investigate the potential relevance. Methods: A systematical search up to October 2018 was performed via PubMed, Embase, Science Direct, ISI Web of Science as well as three Chinese medical databases: China National Knowledge Infrastructure database (CNKI), VIP database and WanFang database. Risk was assessed by standardized mean difference (SMD) with 95% confidence interval (CI) to investigate the involvement of CRP levels in PD patients. Results: Twenty-three eligible case-control studies involving 4,598 individuals (2,646 PD patients and 1,932 healthy controls) were incorporated into this meta-analysis. Results have indicated significant increase of CRP levels in PD subjects when compared with control groups in serum (SMD = 1.115, 95% CI 0.619-1.61, P < 0.001), CSF (SMD = 1.127, 95% CI 0.133-2.120, P = 0.026) as well as whole blood (SMD = 1.071, 95% CI 0.715-1.426, P < 0.001). Conclusions: This meta-analysis revealed that PD is associated with an increase of CRP levels. CRP might be a risk factor for PD or PD leads to an inflammatory response.

Upregulated Expression of Long Non-Coding RNA, LINC00460, Suppresses Proliferation of Colorectal Cancer.

Through bioinformatics analysis, a novel lncRNA, LINC00460, was implicated in the development of multiple cancers. However, the precise expression pattern, clinical significance and biological function of LINC00460 in colorectal cancer (CRC) remain unknown. Network databases were used to investigate the correlation between LINC00460 and CRC. In situ hybridization was performed to verify the precise expression pattern and clinical significance of LINC00460 in a CRC tissue microarray, which included 92 pairs of CRC and adjacent normal tissues. The effect of LINC00460 on proliferation was evaluated by MTT, colony formation assays and flow cytometry employing SW620 and HCT116 cell lines. Cell migration and matrigel invasion assays were performed to investigate whether LINC00460 is involved in the metastasis of CRC. The expression of LINC00460 was significantly upregulated in CRC tissues and cells, associated with early stage CRC and low disease-free survival. The downregulated of LINC00460 expression increased cell proliferation by regulating the cell cycles of SW620 and HCT116 cells. LINC00460 knockdown did not affect cell migration or invasion in vitro. These findings suggest that LINC00460 may be an interesting target for the development of CRC.

IGFBP7 is associated to prognosis and could suppress cell survival in cholangiocarcinoma.

Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein and its expression was restrained in varied solid tumours, but there was no report about biological role of IGFBP7 in cholangiocarcinoma (CCA). Here, we found that high expression of IGFBP7 correlated to a better overall survival in CCA patients. To investigate the hypothetic antineoplastic activity of IGFBP7 in CCA, we induced overexpression of IGFBP7 in QBC939 and RBE cells, as well as knockdown in HCCC9810 cells. And the biological functions triggered by level changes of IGFBP7 were assessed, including proliferation, cell cycle distribution, apoptosis and invasion evaluation. Cell growth assessment showed that enhanced IGFBP7 expression significantly retarded proliferation rates of QBC939 and RBE cells while an enhancement was observed in IGFBP7-inhibited HCCC9810 cells. The inhibition of cell viability was induced via G2/M phase arrest and apoptosis. Both QBC939 and RBE cells possess highly invasive ability, and IGFBP7 overexpression attenuated their serious invasiveness by reversing their mesenchymal phenotype to endothelial signature. We next investigated the potential mechanism involving in IGFBP7-induced tumour suppression and found that increased expression of IGFBP7 resulted in decrease of IGF-IR, IRS-1 and phosphor-AKT protein levels, accompanied with elevation of phorsphor-p38MAPK. These results suggest that IGFBP7 might be related to CCA carcinogenesis and metastasis, which further implicates that IGFBP7 might become a prospective benchmark for CCA diagnosis and therapy.

Isolation and characterization of a novel 2-methyl-4-chlorophenoxyacetic acid-degrading Enterobacter sp. strain SE08.

A bacterial strain (SE08) capable of utilizing 2-methyl-4-chlorophenoxy acetic acid (MCPA) as the sole carbon and energy source for growth was isolated by continuous enrichment culturing in minimal salt medium (MSM) from a long term MCPA exposed soil. This bacterial strain was identified as Enterobacter sp. based on morphological, physiological and biochemical tests, as well as 16S rRNA sequence analysis. Its ability to degrade MCPA was determined using high performance liquid chromatography. The strain SE08 can tolerate unusually high MCPA concentrations (125-2000mg/L). The influences of culturing factors (initial concentration, pH, and temperature) on the bacterial growth and substrate degradation were studied. The results showed that the optimal MCPA degradation occurred at an MCPA concentration of 500mg/L, 30°C and pH 6.0. Under these conditions, 68.5 percent of MCPA in MSM was degraded by SE08, and the OD600nm reached 0.64 after culturing for 72h. The degradation of MCPA could be enhanced by addition of both carbon and nitrogen sources. At an initial MCPA concentration of 500mg/L, when 5g/L glucose and 2.5g/L yeast extract were added into the MSM media, the MCPA degradation was significantly increased to 83.8 percent, and OD600nm was increased to 1.09 after incubation at 30°C and pH 6.0 for 72h. This is the first study showing that an Enterobacter sp. strain is capable of degrading MCPA, which might provide a new approach for the remediation of MCPA contaminated soil and contribute to the limited knowledge about the function of Enterobacter species.