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• Fgl2 could inhibit the expression of TLR9 in autoimmune myelitis. • Fgl2 had important value in the clinical treatment of autoimmune myelitis and even multiple sclerosis. • Number of TLR9-positive cells in rat brain and spinal cord tissue were all better than autoimmune myelitis group. Toll-like receptor 9 (TLR9) can participate in the signal transduction of activated immune cells and induce myelitis and other autoimmune diseases. The effector molecule fibrin-like protein 2 (Fgl2) plays a role in regulating the body's autoimmune signaling pathway. They both have the conditions for the treatment of this disease target. The objective of this work was to investigate the effect of Fgl2 on the expression of DNA receptor TLR9 in autoimmune myelitis. 140 rats were randomly divided into a normal control group, an autoimmune myelitis group, a low-dose Fgl2 group, a middle-dose Fgl2 group, a higher-dose Fgl2 group, a high-dose Fgl2 group, and a methylprednisolone group. Different injection methods were used in each group. The changes of rat behavior and disease were recorded, and brain and spinal cord tissue slices were made for observation. The results showed that in the high dose Fgl2 group, the incidence of disease was 15 %, the nerve injury score was 1.0 ± 0.15, the body weight change was −5.8 ± 1.24 g, the number of spinal cord tissue injury was 1.82 ± 0.44, the number of TLR9 positive cells in the brain tissue was 7.53 ± 1.84, and the number of TLR9 positive cells in spinal cord tissue was 5.02 ± 1.81. These indexes were lower than those in other Fgl2 groups and significantly lower than those in autoimmune myelitis group (P < 0.05). The average incubation period of the disease was 13.66 ± 0.41 days, which was significantly higher than that of the autoimmune myelitis group (P < 0.05). It can be observed that TLR9 signaling pathway played an important role in the occurrence and development of autoimmune myelitis. With the increase of Fgl2 dose, the number of TLR9 positive cells decreased gradually. Fgl2 treatment can reduce the expression of inflammatory factors and the severity of dysfunction in autoimmune myelitis, inhibit the expression of TLR9, and improve the condition of autoimmune myelitis. [ABSTRACT FROM AUTHOR]

A correction for the article "A Novel Human Acute Encephalitis Caused by Pseudorabies Virus Variant Strain" is presented, which is published in the previous issue of the periodical.

Background: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Peripheral insulin resistance increases the risk for memory impairment and the development of AD. Objective: This study aims to assess changes in cognitive functions and the level of hyperphosphorylated tau proteins in central insulin-resistant rats. Methods: An in vivo central insulin-resistant (CIR) animal model was generated through intracerebroventricular injection of streptozotocin (STZ) into insulin-resistant (IR) rats that were induced by feeding a high-glucose/-protein/-fat diet. The Morris water maze test was used to assess changes in cognitive functions, pathological changes in the cornu ammonis 1 (CA1) region of the hippocampus were detected by immunohistochemistry, and the phosphorylation levels of tau proteins at specific sites were determined by Western blot analysis. Results: The escape latency time in the Morris water maze test was significantly prolonged; the number of phosphorylated tau proteins in the CA1 region of the hippocampus was significantly increased; and the phosphorylation levels of tau proteins at Ser199, Thr205, Thr212, Thr217 and Ser396 were significantly elevated in the CIR group compared with the IR and control groups. Conclusion: This study provides direct evidence that CIR plays an important role in AD pathogenesis by facilitating tau hyperphosphorylation. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Numb has been shown to play diverse roles in the central nervous system of adult mammals, and accumulating evidence indicates a role for Numb in apoptosis. In this study, we characterize the role of Numb in ischemia-induced apoptosis, and investigate the underlying pathway involved in this process. In vivo, exposure of pheochromocytoma (PC12) cells to glucose deprivation (GD) resulted in caspase-3-dependent apoptosis. Numb expression was upregulated by GD in a time-dependent manner, while Notch expression was down regulated. Knocking down endogenous Numb expression via siRNA protected PC12 cells from GD-induced apoptosis, whereas Numb overexpression sensitized PC12 cells to GD-induced apoptosis. In vivo, significantly increased Numb expression levels, together with activation of apoptosis, can be observed in the ischemic penumbra following cerebral ischemia. Taken together, our data show that Numb promotes ischemia-induced apoptosis. Based on these results, we conclude that inhibition of Numb could be a novel therapeutic approach for inhibiting apoptosis in the ischemic penumbra. [ABSTRACT FROM AUTHOR]

Abstract: Erythroid differentiation is a tightly regulated multi-step process that has not been fully elucidated. We previously reported that a siRNA screened from random siRNA library, siRNA clone-67, induced erythroid differentiation in human erythroleukemia K-562cell line. Here we identified that human CCDC12 (coiled-coil domain containing 12) is a target of siRNA clone-67, by target capture with biotinylated siRNA. Over-expression of CCDC12 in K-562cell up-regulated the expression of CD235, ɛ-globin and γ-globin, accelerated cell growth, and slightly down-regulated the expression of GATA-2. Knockdown of CCDC12 slowed down the cell growth. These data indicate that CCDC12 is a new participant that promotes early erythroid differentiation. [Copyright &y& Elsevier]

Cancers are characterized by poor differentiation. Differentiation therapy is a strategy to alleviate malignant phenotypes by inducing cancer cell differentiation. Here we carried out a combinatorial high-throughput screen with a random siRNA library on human erythroleukemia K-562 cell differentiation. Two siRNAs screened from the library were validated to be able to induce erythroid differentiation to varying degrees, determined by CD235 and globin up-regulation, GATA-2 down-regulation, and cell growth inhibition. The screen we performed here is the first trial of screening cancer differentiation-inducing agents from a random siRNA library, demonstrating that a random siRNA library can be considered as a new resource in efforts to seek new therapeutic agents for cancers. As a random siRNA library has a broad coverage for the entire genome, including known/unknown genes and protein coding/non-coding sequences, screening using a random siRNA library can be expected to greatly augment the repertoire of therapeutic siRNAs for cancers. [ABSTRACT FROM AUTHOR]

Mutations in I DPM3 i lead to deficient -dystroglycan, so it is classified into dystroglycanopathies, which represent a group of muscular dystrophies with a wide spectrum ranging from mild limb-girdle muscular dystrophy to severe congenital muscular dystrophy with brain and eye abnormalities.[1] Till date, only three mutations of I DPM3 i (NM 153471), c.254T>A (p.Leu85Ser), c.41T>C (p.Leu14Pro) and a deletion, have been reported in five patients.[[1]] Mild and progressive limb-girdle muscular dystrophy was present in four patients, and isolated hyperCKemia was reported in one patient. Our patient showed hyperCKemia with developmental delay, epilepsy, intellectual impairment, and brain abnormality, indicating involvement of CNS. [Extracted from the article]

This research aims to analyze CCD inpatients' mobility patterns in central China and explore the influences of nonclinical factors on their decisions of medical travel. Using patients' information (n = 105,120) collected from Henan, a central province of China, as well as county-level health care, transportation, and socioeconomic data, we analyzed spatial-temporal variations of CCD inpatients' mobility from 2013 to 2017. The multiple regression, geographically weighted regression, and path analysis were integrated to reveal how health care level (availability), insurance coverage (affordability), transportation/accessibility, local economic development, and regional factors have influenced CCD inpatients' medical travel. Our findings indicate that CCD patients' mobility has greatly increased in central China, with a growth rate of 28.9% from 2013 to 2017. The spatial pattern of medical travel was uneven among four economic zones but relatively balanced between urban rural areas. Over 51% of CCD inpatients traveled from the most disadvantaged zone to the capital city for treatment. The mobility pattern has been mainly determined by local medical resources, health insurance coverage, and transportation/accessibility. Furthermore, despite little direct effects, local economic development and regional factors have greatly influenced medical travel through indirectly affecting the local health care sector and transportation development. • Domestic medical travel has growing quickly in China with new health care reforms. • More CCD patients traveled from disadvantaged areas to big cities for better healthcare. • The key push factor of domestic medical travel is insufficient local medical resources. • Advanced transportation/accessibility encourages patients' mobility. • Local economic development and regional factors also play fundamental roles. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration. [ABSTRACT FROM AUTHOR]

The low-temperature cracking performance of asphalt is considered one of the main deteriorations in asphalt pavements. However, there have been few studies on the low-temperature cracking performance of asphalt under heat and light together. Hence, the ductility test, bending beam rheometer (BBR) test, and asphalt composition analysis test are combined to investigate the low-temperature cracking performance under heat and light together based on the climatic conditions of China. The styrene–butadiene–styrene block copolymer (SBS)-modified asphalt binders were prepared with different modifier types and base asphalt in this research. The results show that the low-temperature cracking resistance of asphalt reduces under heat and light together. It is obviously reduced at the early stage, and it becomes worse with the increase of the aging time, temperature, and ultraviolet (UV) intensity. The asphalt composition has a significant impact on its low-temperature cracking performance, and the SBS modifier can improve the low-temperature cracking resistance of asphalt. The rational selection of base asphalt and modifier can improve the low-temperature cracking performance of asphalt. Under heat and light together, whether base asphalt or modified asphalt, the change trends of their ductility and component content are similar. Therefore, to improve the anti-cracking ability of the asphalt pavement, it is suggested to use the ductility of asphalt aged by heat and light together for 15 days as the evaluation index of the low-temperature cracking performance of asphalt, and asphalt should be selected according to the temperature and UV intensity of the asphalt pavement use area. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment. Methods: In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury. Results: We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling. Conclusion: MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury. [ABSTRACT FROM AUTHOR]

Chitinase-3-like 1 (CHI3L1) and osteopontin (OPN) are known biomarkers of neuroinflammation. Herein, we explored the relationship between these inflammatory markers with the disease severity and prognosis in anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis. We recruited 36 anti-NMDAR encephalitis patients and 20 controls. Compared to the levels in the controls, the cerebrospinal fluid (CSF) and serum levels of CHI3L1 and OPN were significantly increased in patients with anti-NMDAR encephalitis, and the CSF levels were found to be correlated with the initial and 6-month follow-up modified Rankin Scale (mRS) scores and abnormal brain MRI (suggestive of encephalitis). In addition, the CSF levels of CHI3L1 were associated with age, the CSF white blood cell (WBC) count and the CSF/serum albumin index (CSF-AI). CHI3L1 and OPN might serve as promising biomarkers for anti-NMDAR encephalitis. Unlabelled Image • Compared with controls, CSF CHI3L1 and OPN levels were significantly higher in anti-NMDAR encephalitis. • CSF CHI3L1 and OPN levels were correlated with mRS scores in anti-NMDAR encephalitis. • CSF CHI3L1 levels were also correlated with age, CSF WBC count, brain MRI, CSF-AI. • CSF CHI3L1 and OPN might be promising biomarkers for anti-NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

We describe a probably novel mutation in exon 5 of the presenilin 2 gene (Pro123Leu) in a Chinese familial early-onset Alzheimer's disease, which clinically manifests as progressive memory loss, cognitive impairment, parkinsonism, and myoclonic jerks. Clinical and neuroimaging examination, target region capture, and high-throughput sequencing were performed in a family of 4 generations. Cerebral perfusion and glucose metabolism were evaluated using arterial spin labeling perfusion magnetic resonance imaging and 18 F-fludeoxyglucose positron emission tomography, respectively. Target region capture sequencing yielded a novel missense mutation at codon 123 (P123L) which is a heterozygous C to T point mutation at position 368 (c.368C>T) in exon 5 of the presenilin 2 leading to a proline-to-leucine substitution. The results were also identified by Sanger sequencing in 7 family members but not in the other 9 unaffected family members and 100 control subjects. This mutation is probably pathogenic and is the first of its kind reported in an early-onset familial AD associated with atypical symptom presentation. [ABSTRACT FROM AUTHOR]