Overlapping syndrome of recurrent anti-N-methyl-D-aspartate receptor encephalitis and anti-myelin oligodendrocyte glycoprotein demyelinating diseases: A case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (NMDARe) is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease, whereas it has been relatively rare. We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease. CASE SUMMARY: A 29-year-old man was initially admitted with headache, fever, intermittent abnormal behavior, decreased intelligence, limb twitching and loss of consciousness on July 16, 2018. On admission, examination reported no abnormality. During his presentation, he experienced aggravated symptoms, and the re-examination of cranial magnetic resonance imaging (MRI) indicated punctate abnormal signals in the left parietal lobe. External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody (Ab) (-), cerebrospinal fluid NMDAR-Ab (+) 1:10 and Epstein-Barr virus capsid antigen antibody IgG (+). Due to the imaging findings, anti-NMDARe was our primary consideration. The patient was treated with methylprednisolone and gamma globulin pulse therapy, mannitol injection dehydration to reduce intracranial pressure, sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms. The patient was admitted to the hospital for the second time for "abnormal mental behavior and increased limb movements" on December 14, 2018. Re-examination of electroencephalography and cranial MRI showed no abnormality. The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive. Considering comprehensive recurrent anti-NMDARe, the patient was treated with propylene-hormone pulse combined with immunosuppressive agents (mycophenolate mofetil), and the symptoms were relieved. The patient was admitted for "hoarseness and double vision" for the third time on August 23, 2019. Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe, and synoptophore examination indicated concomitant esotropia. The patient's visual acuity further decreased, and the re-examination of cranial MRI + enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata, left pons arm, left cerebellum and right midbrain, thalamus. The patient was diagnosed with an accompanying demyelinating disease. Serum anti-myelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive. The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome. The patient was successfully treated with methylprednisolone, gamma globulin pulse therapy and rituximab treatment. The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion. CONCLUSION: We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.

[Bone damage in osteoporotic fractures].

Osteoporotic fracture is fundamentally different from traumatic fracture. It is a pathological fracture based on the skeletal system in the state of osteoporosis, and the essence of its lesion is the decline of bone strength. Bone strength is influenced by a variety of factors, including the material properties and tissue structure of the bone, as well as muscle load. The pathological changes of osteoporotic fracture both of the damage of bone mass and bone quality. After the occurrence of osteoporotic fracture, even successful surgical treatment cannot prevent the further aggravation of osteoporotic bone damage. In this paper, the material properties and tissue structure damage of osteoporotic fractures are elaborated, and it is emphasized to clarify and pay attention to these bone lesions and their risks. Anti-osteoporosis treatment is of great importance to improve the clinical efficacy of osteoporosis and fracture intervention and prevent the occurrence of re-fractures.

Metabolic disposition of [14 C]-abivertinib, an epidermal growth factor receptor tyrosine kinase inhibitor: Role of glutathione conjugation.

AIMS: To determine the absorption, distribution, metabolism and excretion of abivertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seven patients with advanced NSCLC were given a single 200 mg/83 µCi oral suspension of [14 C]-abivertinib. Blood, urine and faeces were collected. Mass balance of radioactivity, the pharmacokinetics of abivertinib, and the total radioactivity were determined. Metabolite profiling and characterisation were performed. RESULTS: The mean recovery was 82.16%, with 2.38 and 79.78% of the radioactive dose excreted in urine and faeces, respectively. The unchanged abivertinib was the major radioactive component detected in plasma within the first 24 hours after dosing, accounting for 59.17% of the total drug-related radioactivity. Abivertinib in urine accounted for only 0.96% of the administered dose, whereas in faeces it accounted for 33.36%. Eight metabolites were detected and characterised in plasma, among which MII-7, a product of cysteine glycine conjugate, was the only circulating metabolite, accounting for approximate 10.6% of the total drug-related exposure. MII-2 (an abivertinib cysteine-glycine adduct) and M7 (a reduced product of abivertinib) were the 2 major metabolites in the excreta, accounting for 20.0 and 12.4%, respectively, of the drug-related radioactivity in faeces. CONCLUSION: Following a single oral administration, the unchanged abivertinib was the predominant drug-related material in plasma, urine and faeces. The drug-related materials were primarily eliminated via the faecal route. Direct glutathione conjugation of abivertinib played a significant role in the metabolic clearance and metabolite exposure of abivertinib.

Standardization of BCR-ABL1 quantification on the international scale in China using locally developed secondary reference panels.

For patients with chronic myeloid leukemia, reverse transcription quantitative polymerase chain reaction is widely used in laboratories to quantify BCR-ABL1 fusion gene transcripts for disease management. Many efforts have been made to standardize the BCR-ABL1 testing assay, including the primary and secondary reference reagents, but the secondary standards have not been developed and used in the standardization program in China. With the use of armored RNA technology, armored RNA of BCR-ABL1 and control genes was manufactured to prepare the secondary reference material anchored to the World Health Organization primary reference calibrators for standardization of BCR-ABL1 testing assays. The secondary reference was sent to 30 laboratories in China for validation. Data from an external quality assessment after the standardization process were collected and analyzed as well. The assigned %BCR-ABL1/ABL1IS values of the four levels of the secondary material panels were 0.0118, 0.1345, 1.3808, and 19.4266, respectively. In validation trials, 70.0% (21/30) of laboratories obtained valid conversion factors for the BCR-ABL1 assay. All valid conversion factors from 11 international scale laboratories were equivalent to their respective previous values. External quality assessment data indicated that the accuracy and precision between laboratories were improved. Moreover, the quantity of the panels is abundant to be used as quality control samples for monitoring the shift of data. In this study, we established a secondary genetic reference panel for BCR-ABL1 quantification. This study will play a role in facilitating the worldwide dissemination of the international scale, especially in promoting the standardization of molecular monitoring in China.

External quality assessment of p210 BCR-ABL1 transcript quantification by RT-qPCR: Findings and recommendations.

INTRODUCTION: External quality assessment (EQA) is an essential tool for quality assurance of analytical testing processes of p210 BCR-ABL1 transcripts by RT-qPCR. As an EQA provider, the National Center for Clinical Laboratories organized an EQA scheme of p210 BCR-ABL1 testing in China for the first time to identify existing problems and ensure the reliability of p210 BCR-ABL1 testing. METHODS: Using armored RNA technology, we first constructed pACYC-MS2-p210 and CG recombinant plasmids and expressed p210 and CG armored RNAs, with packaging segments of p210 BCR-ABL1 fusion gene (FG) and four common control gene (CG) transcripts. Using these armored RNAs, we prepared lyophilized p210 quality control (QC) sample panels and evaluated detection performance of participating laboratories in China. RESULTS: Of the 66 participating laboratories, great variation was found with coefficient of variation (CV%) of raw p210 BCR-ABL1 results basically ranging from 60.0% to 100.0%. In 24 International Scale (IS) laboratories, the CV% of results decreased from 82.4% to 61.6%, and the percentage of laboratories within 2-, 3-, and 5-fold of the median values increased from 78.2%, 87.0%, and 92.1% to 80.1%, 89.4%, and 97.2%, respectively, after conversion with a laboratory-specific conversion factor (CF); however, poorly converted results were also observed in laboratories resulting from changed components of RT-qPCR procedures. False-negative and false-positive results were also found in the EQA. CONCLUSIONS: Various problems were found for p210 BCR-ABL1 detection in the EQA. By solving the existing problems, the performance of p210 BCR-ABL1 detection can be improved, ensuring robust laboratory diagnostic capacities in China.

Evaluation of frailty status among older people living in urban communities by Edmonton Frail Scale in Wuhu, China: a cross-sectional study.

BACKGROUND: Few studies have explored the factors that are associated with frailty among older people. OBJECTIVE: To investigate the frailty status and examine the sociodemographic factors that are associated with of older peoples' frailty status in China. DESIGN: Cross-sectional study. METHODS: We used convenience sampling to recruit the participants (aged 60 and above) from four communities in an urban area of Wuhu, Anhui, China. Participants completed a questionnaire which included the Edmonton Frail Scale (EFS) and sociodemographic factorsWe used convenience sampling to recruit the participants (aged 60 and above) from four communities in an urban area of Wuhu, Anhui, China. Participants completed a questionnaire which included the Edmonton Frail Scale (EFS) and sociodemographic factors. RESULTS: Of 306 participants, the percentage of participants with a robust score (0-4) on the EFS was 71.9%, 14.1% had an apparently vulnerable score (5-6), and 14.0% had a frail score (7-17). Age, chronic disease status and marital status were significantly associated with frailty. CONCLUSIONS: There are a high percentage of frail older Chinese adults in the urban area. The present study findings could provide better understanding of the factors associated with frailty status of this population.

Development and evaluation of armored RNA-based standards for quantification of BCR-ABL1p210/p190 fusion gene transcripts.

BACKGROUND: Standards play an important role in detection of the BCR-ABL1 fusion gene (FG) transcript. However, the standards widely used in laboratories are mainly based on plasmids or cDNA, which cannot accurately reflect the process of RNA extraction and cDNA synthesis. Therefore, we aimed to develop armored RNA-based standards for p210 and p190 BCR-ABL1FG transcripts' quantification. METHODS: Using overlapping polymerase chain reaction (PCR) technology, we first linked a segment of the p210 or p190 BCR-ABL1FG transcript with four control genes (CGs; ABL1, BCR, GUSB, and B2M) to form p210FG-CG and p190FG-CG. Subsequently, using armored RNA technology, we prepared p210FG-CG- and p190FG-CG-armored RNAs and the p210FG-CG and p190FG-CG standards, the values of which were assigned by digital PCR (dPCR). RESULTS: The p210FG-CG and p190FG-CG standards were stable and homogeneous, and were significantly linear with r2  > 0.98. A field trial including 52 laboratories across China showed that the coefficient of variation (CV%) of BCR-ABL1 values among samples was in the range of 58.6%-129.6% for p210 samples and 73.2%-194.0% for p190 samples when using local standards. By contrast, when using the p210FG-CG and p190FG-CG standards, the CV% of BCR-ABL1 values was decreased to 35.6%-124.9% and 36.6%-170.6% for p210 and p190 samples, respectively. In addition, 33.3% (3/9) of the p210 and p190 samples had CV% values <50.0%, whereas 44.4% (4/9) and 77.8% (7/9) of the samples had lower CV% values when using the p210FG-CG and p190FG-CG standards. CONCLUSION: The overall variability of detection of BCR-ABL1 transcripts decreased significantly when using the p210FG-CG or p190FG-CG standards, especially the p190FG-CG standard.

Preparation of MS2-based nanoparticles as control and standard materials for the molecular detection of dengue virus serotypes.

To quantify dengue virus (DENV) and evaluate the performance of clinical laboratories using quantitative real-time polymerase chain reaction (qRT-PCR) assays, we constructed high-efficiency expression systems to produce DENV-1 to 4 nanoparticles and assessed their suitability as standard and control materials in 20 laboratories across China. Targeted gene sequences of DENV-1 to 4 were synthesized and inserted into pACYC-Duet 1-MS2 recombinant plasmids to generate corresponding nanoparticle expression systems. After collection, verification, and quantification by digital PCR (dPCR), DENV-1 to 4 nanoparticles were prepared as control and standard materials. Five positive and three negative samples of each DENV serotype in every panel were used for assessing the performance of the participating laboratories across China, as well as standard materials for the quantitative detection of DENV using qRT-PCR assays. The accuracy, sensitivity, and specificity of qRT-PCR used by the 20 evaluated laboratories were 89.6 (569/635), 85.1 (336/395), and 97.1% (233/240), respectively. Overall, sixteen (80.0%) laboratories were qualified in detecting DENV, among which five (25.0%) were designated as "competent", eleven (55.0%) were defined as "acceptable", and four (20%) were considered to be "improvable". The results generated from the DENV standard samples were significantly positively correlated with those generated by dPCR (r2=0.8698, P<0.001). In summary, DENV nanoparticles could potentially be used as controls for improving the performance of laboratories and as standards for the quantitative detection of DENV.

Paliperidone increases spontaneous and evoked firing of mesocortical dopaminergic neurons by activating a hyperpolarization-activated inward current.

Mesocortical dopaminergic (DA) subtype neurons specifically project to the prefrontal cortex, which is closely related with schizophrenia. Mesocortical DA neurons have unique physiological characteristics that are different from those of mesostriatal and mesolimbic DA neurons. Paliperidone, an atypical antipsychotic, is currently used to treat schizophrenia and has better therapeutic effects than typical antipsychotics. However, the underlying physiological mechanism remains unclear. To explore the effects of paliperidone on mesocortical DA neuron activity, here, we retrogradely labeled these cells with fluorescent microsphere retrobeads, and the electrophysiological changes were recorded in whole-cell recordings in rat midbrain slices with or without paliperidone. The data showed that paliperidone (20µmol/L) increased the spontaneous firing rates of labeled mesocortical neurons (P<0.05). Moreover, paliperidone also increased the frequency of evoked action potentials by current injection stimulation (P<0.05), whereas the accompanying amplitude decreased. Furthermore, to explore the mechanisms of paliperidone's effect, Ih currents were detected, and the results showed that hyperpolarizing voltage pulses evoked instantaneous Ih inward currents and paliperidone increased the maximum Ih current. In addition, paliperidone decreased the spontaneous inhibitory postsynaptic currents. Thus, paliperidone increased the spontaneous and evoked firing of mesocortical neurons, possibly by activating the Ih inward current and reducing the inhibitory synaptic transmission, which provides an underlying mechanism of paliperidone's application in schizophrenia.

Resveratrol Protects PC12 Cell against 6-OHDA Damage via CXCR4 Signaling Pathway.

Resveratrol, herbal nonflavonoid polyphenolic compound naturally derived from grapes, has long been acknowledged to possess extensive biological and pharmacological properties including antioxidant and anti-inflammatory ones and may exert a neuroprotective effect on neuronal damage in neurodegenerative diseases. However, the underlying molecular mechanisms remain undefined. In the present study, we intended to investigate the neuroprotective effects of resveratrol against 6-OHDA-induced neurotoxicity of PC12 cells and further explore the possible mechanisms involved. For this purpose, PC12 cells were exposed to 6-OHDA in the presence of resveratrol (0, 12.5, 25, and 50 µM). The results showed that resveratrol increased cell viability, alleviated the MMP reduction, and reduced the number of apoptotic cells as measured by MTT assay, JC-1 staining, and Hoechst/PI double staining (all p < 0.01). Immunofluorescent staining and Western blotting revealed that resveratrol averts 6-OHDA induced CXCR4 upregulation (p < 0.01). Our results demonstrated that resveratrol could effectively protect PC12 cells from 6-OHDA-induced oxidative stress and apoptosis via CXCR4 signaling pathway.

TNF causes changes in glomerular endothelial permeability and morphology through a Rho and myosin light chain kinase-dependent mechanism.

A key function of the endothelium is to serve as a regulated barrier between tissue compartments. We have previously shown that tumor necrosis factor (TNF) plays a crucial role in lipopolysaccharide (LPS)-induced acute kidney injury, in part by causing injury to the renal endothelium through its receptor TNFR1. Here, we report that TNF increased permeability to albumin in primary culture mouse renal endothelial cells, as well as human glomerular endothelial cells. This process occurred in association with changes in the actin cytoskeleton and was associated with gaps between previously confluent cells in culture and decreases in the tight junction protein occludin. This process was dependent on myosin light chain activation, as seen by its prevention with Rho-associated kinase and myosin light chain kinase (MLCK) inhibitors. Surprisingly, permeability was not blocked by inhibition of apoptosis with caspase inhibitors. Additionally, we found that the renal glycocalyx, which plays an important role in barrier function, was also degraded by TNF in a Rho and MLCK dependent fashion. TNF treatment caused a decrease in the size of endothelial fenestrae, dependent on Rho and MLCK, although the relevance of this to changes in permeability is uncertain. In summary, TNF-induced barrier dysfunction in renal endothelial cells is crucially dependent upon the Rho/MLCK signaling pathway.

Assessment of physiological factors for the establishment of serum insulin reference intervals in healthy Chinese Han adults: A community-based large cross-sectional study.

The aim of this study was to investigate physiological factors that affect serum insulin levels and to establish insulin reference intervals for healthy Chinese Han adults. A total of 4401 subjects with normal glucose tolerance (NGT) were screened from 10,027 individuals in an epidemiological study. Based on the exclusion criteria, 2414 apparently healthy adults (healthy) were selected as reference individuals. Serum insulin levels of the reference individuals were measured at fasting, 30 min and 120 min after oral glucose tolerance test (OGTT). Significant correlations were found between serum insulin levels and physiological factors in healthy subjects, including body mass index (BMI), weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), etc. (p < 0.05). No increase or decrease was found in age-dependent insulin levels by ANOVA (p > 0.05). There was also no substantial difference in fasting serum insulin levels between males and females (p > 0.05). However, we detected notable differences in serum insulin levels between males and females at 30 min (p < 0.01), which became more pronounced at 120 min (p < 0.001). According to our data, BMI/gender-related insulin reference intervals were defined by calculating 2.5th and 97.5th percentiles. The insulin reference intervals, determined after assessing the relationship between physiological factors and serum insulin levels in Chinese adults, will provide valuable information for physicians in their interpretation of insulin levels.

Complement in Lupus Nephritis: New Perspectives.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder caused by loss of tolerance to self-antigens, the production of autoantibodies and deposition of complement-fixing immune complexes (ICs) in injured tissues. SLE is characterized by a wide range of clinical manifestations and targeted organs, with lupus nephritis being one of the most serious complications. The complement system consists of three pathways and is tightly controlled by a set of regulatory proteins to prevent injudicious complement activation on host tissue. The involvement of the complement system in the pathogenesis of SLE is well accepted; yet, its exact role is still not clear. SUMMARY: Complement plays dual roles in the pathogenesis of SLE. On the one hand, the complement system appears to have protective features in that hereditary homozygous deficiencies of classical pathway components, such as C1q and C4, are associated with an increased risk for SLE. On the other hand, IC-mediated activation of complement in affected tissues is clearly evident in both experimental and human SLE along with pathological features that are logical consequences of complement activation. Studies in genetically altered mice have shown that lack of complement inhibitors, such as complement factor H (CFH) or decay-accelerating factor (DAF) accelerates the development of experimental lupus nephritis, while treatment with recombinant protein inhibitors, such as Crry-Ig, CR2-Crry, CR2-DAF and CR2-CFH, ameliorates the disease development. Complement-targeted drugs, including soluble complement receptor 1 (TP10), C1 esterase inhibitor and a monoclonal anti-C5 antibody (eculizumab), have been shown to inhibit complement safely, and are now being investigated in a variety of clinical conditions. KEY MESSAGES: SLE is an autoimmune disorder which targets multiple systems. Complement is centrally involved and plays dual roles in the pathogenesis of SLE. Studies from experimental lupus models and clinical trials support the use of complement-targeted therapy in the treatment of SLE.

Loss of CD11b exacerbates murine complement-mediated tubulointerstitial nephritis.

Acute complement activation occurs in the tubulointerstitium (TI) of kidneys transplanted from Crry(-/-)C3(-/-) mice into complement-sufficient wildtype mice, followed by marked inflammatory cell infiltration, tubular damage and interstitial fibrosis. We postulated iC3b-CD11b interactions were critical in this TI nephritis model. We transplanted Crry(-/-)C3(-/-) mouse kidneys into CD11b(-/-) and wildtype C57BL/6 mice. Surprisingly, there was greater inflammation in Crry(-/-)C3(-/-) kidneys in CD11b(-/-) recipients compared to those in wildtype hosts. Kidneys in CD11b(-/-) recipients had large numbers of CD11b-Ly6ChiCCR2hiF4/80+ cells consistent with inflammatory (M1) macrophages recruited from circulating monocytes of the host CD11b(-/-) animal. There was also an expanded population of CD11b(+)CD11c(+)Ly6C(-)F4/80(hi) cells. Since these cells were CD11b(+), they must have originated from the transplanted kidney; their surface protein expression and appearance within the kidney were consistent with the intrinsic renal mononuclear cellular population. These cells were markedly expanded relative to all relevant controls, including the contralateral donor kidney and Crry(-/-)C3(-/-) mouse kidneys in CD11b(+/+) wildtype recipients. Direct evidence for their in situ proliferation was the presence of nuclear Ki67 and PCNA in CD11b(+)F4/80(+) cells. Thus, in this experimental model in which there is unrestricted C3 activation, CD11b(+) monocytes limit their own infiltration into the kidney and prevent proliferation of endogenous mononuclear cells. This suggests a role for outside-in iC3b-CD11b signals in limiting intrinsic organ inflammation.

K-shell photoabsorption edge of strongly coupled matter driven by laser-converted radiation.

The first observation of the K-shell photoabsorption edge of strongly coupled matter with an ion-ion coupling parameter of about 65 generated by intense x-ray radiation-driven shocks is reported. The soft x-ray radiation generated by laser interaction with a "dog bone" high-Z hohlraum is used to ablate two thick CH layers, which cover a KCl sample, to create symmetrical inward shocks. While the two shocks impact at the central KCl sample, a highly compressed KCl is obtained with a density of 3-5 times solid density and a temperature of about 2-4 eV. The photoabsorption spectra of chlorine near the K-shell edge are measured with a crystal spectrometer using a short x-ray backlighter. The redshift of the K edge up to 11.7 eV and broadening of 15.2 eV are obtained for the maximum compression. A comparison of the measured redshifts and broadenings with dense plasma calculations are made, and it indicates potential improvements in the theoretical description.

Using protein granularity to extract the protein sequence features.

The feature extraction of protein sequences is a challenging problem. It might need a lot of theoretical and practical knowledge from many fields. The difficulty would increase when investigators extract the features solely from protein sequences. In this paper, we present a method of protein granularity. The concepts of protein granularity, granularity order, granularity bound, granularity limit, and granularity increment are given respectively. The protein granularity can dig out the useful information solely from protein sequences. We provide an approach to construct the feature vectors. The feature vectors include the amino acid composition information, the sequence-order information, the same amino acid 'neighbor' information, and the sequence length information. Hence, the feature vectors can better represent protein sequences. Our feature extraction method does obviously consider the protein sequence length effects. An experiment of the protein structure class prediction was carried out. The prediction achieved 96.6% overall accuracy, and the success rate for each subset is all-α 92.3%, all-ß 100%, α/ß 100%, α+ß 93.5%, respectively. The last three success rates for subsets are equal to the best success rates in the published literatures. The overall accuracy of PG-SVM prediction is the second best result only having one protein prediction error difference with the first best result. The theoretical and experimental results demonstrate the application of protein granularity succeeds in the feature extraction of protein sequences.

Resveratrol inhibits ß-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway.

Alzheimer's disease (AD) is characterized by the accumulation of ß-amyloid peptide (Aß) and loss of neurons. Recently, a growing body of evidences have indicated that as a herbal compound naturally derived from grapes, resveratrol modulates the pathophysiology of AD, however, with a largely unclear mechanism. Therefore, we aimed to investigate the protection of resveratrol against the neurotoxicity of ß-amyloid peptide 25-35 (Aß(25-35)) and further explore its underlying mechanism in the present study. PC12 cells were injuried by Aß(25-35), and resveratrol at different concentrations was added into the culture medium. We observed that resveratrol increased cell viability through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) colorimetric assays. Flow cytometry indicated the reduction of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the intercellular Ca(2+) homeostasis and attenuated Aß(25-35) neurotoxicity. Additionally, Aß(25-35)-suppressed silent information regulator 1 (SIRT1) activity was significantly reversed by resveratrol, resulting in the downregulation of Rho-associated kinase 1 (ROCK1). Our results clearly revealed that resveratrol significantly protected PC12 cells and inhibited the ß-amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role in the pathomechanism of AD.

Diagnostic value of cystatin C and glomerular filtration rate formulae in Chinese nonelderly and elderly populations.

BACKGROUND: Serum cystatin C has been recognized as a surrogate marker for serum creatinine (SCr). However, whether cystatin C and cystatin C-based glomerular filtration rate (GFR) formulae offer any diagnostic value in nonelderly and elderly subjects has rarely been investigated. METHODS: Reference GFR (rGFR) values were established using the 99mTc-DTPA renal dynamic imaging method. Nine GFR formulae were used to predict estimated GFR (eGFR). RESULTS: A total of 534 Chinese participants were enrolled. Cystatin C had a better diagnostic value than SCr. The superiority of cystatin C was more distinctly observed in the elderly. Combined cystatin C and SCr gave similar diagnostic values to cystatin C alone (p>0.05). Compared with single markers, GFR prediction formulae improved accuracy. Each formula had its own characteristics and applicability. Most formulae predicted with higher accuracy in the elderly than they did in the nonelderly. In chronic kidney disease (CKD) stage 1, the CKD-EPI formula had the least bias and the highest accuracy for the nonelderly, while the Hojs and Ma formulae performed best for the elderly. In the CKD stage 2-3, the Macisaac formula gave the most accurate eGFR. In the CKD stage 4-5, it was the CG formula that gave the closest estimate to the rGFR. CONCLUSIONS: Cystatin C could be superior to SCr, particularly in the elderly; however, cystatin C formulae and SCr formulae may possess their own applicability in different CKD stages and age groups. At present, it is not possible to say that cystatin C formulae are superior to SCr formulae.

Striatal extracts promote the dopaminergic differentiation of GFP-bone mesenchymal stem cells.

Bone mesenchymal stem cells (BMSCs) are an attractive donor graft source because of the potential of self-renewal and multi-direction differentiation. However, it is a great challenge to induce BMSCs to specifically differentiate to dopamine (DA) neurons for the treatment of Parkinson's disease. Because the striatum is the target tissue for the projection of DA neurons in the midbrain, we investigated whether its extracts could promote the dopaminergic differentiation of BMSCs. BMSCs were isolated from green fluorescent protein (GFP) transgenic mice. Flow cytometry was used to identify the expression of CD29 and CD11b in cultured BMSCs; and immunochemical staining was employed to determine the differentiation of BMSCs. Our results showed that striatal extracts could induce differentiation of BMSCs into both neurons and glia, especially the DA neurons. When transplanted to the rat striatum, GFP-BMSCs could differentiate into tyrosine hydroxylase positive neurons and demonstrate potential migration in the brain. Taking together, our results suggest that striatal extracts can specifically promote the dopaminergic differentiation of GFP-BMSCs, thereby providing a feasible strategy for the treatment of Parkinson's disease.

Are cystatin C-based equations superior to creatinine-based equations for estimating GFR in Chinese elderly population?

PURPOSE: Cystatin C has been proposed as a surrogate marker of kidney function. The elderly population accounts for the largest proportion of chronic kidney disease (CKD) patients. The aim of this study was to assess the diagnostic value of serum cystatin C and compare the applicability of cystatin C-based equations with serum creatinine (Scr)-based equations for estimating glomerular filtration rate (GFR). METHODS: The estimated GFR (eGFR) values from six cystatin C-based equations (Tan, MacIsaac, Ma, Stevens1-3) and three Scr-based equations (CG, MDRD, CKD-EPI) were compared with the reference GFR (rGFR) values from 99mTc-DTPA renal dynamic imaging method. RESULTS: A total of 110 elderly Chinese (60-92 year, 71.05±7.62 year) were enrolled. Cystatin C had better diagnostic value than Scr (relationship coefficient with rGFR: cystatin C -0.847 vs. Scr -0.729, P<0.01; sensitivity: cystatin C 0.90 vs. Scr 0.55, P<0.01; AUCROC: cystatin C 0.857 vs. Scr 0.757, P<0.01). All the equations predicted GFR more accurately for rGFR≥60 ml/min/1.73 m2 than for rGFR<60 ml/min/1.73 m2. Most equations had acceptable accuracy. The cystatin C-based equations deviated from rGFR by -12.78 ml/min/1.73 m2 to -2.12 ml/min/1.73 m2, with accuracy varying from 64.6 to 82.7%. The Scr-based equations deviated from rGFR by -5.37 ml/min/1.73 m2 to -0.68 ml/min/1.73 m2, with accuracy varying from 77.3 to 79.1%. The CKD-EPI, MacIsaac and Ma equations predicted no bias with rGFR (P>0.05), with higher accuracy and lower deviation in the total group. The MacIsaac, CKD-EPI and Stevens3 equations could be optimal for those with normal and mildly impaired kidney function, whereas the Ma equation for those with CKD. CONCLUSION: Cystatin C is a promising kidney function marker. However, not all cystatin C-based equations could be superior to the Scr-equations.