Comparative effectiveness and safety of intravenous methylprednisolone and tacrolimus monotherapy in ocular myasthenia gravis with unsatisfactory prednisone responses: a retrospective study.

BACKGROUND: Oral prednisone has been recognized as the first-line therapy for the treatment of ocular myasthenia gravis (OMG). However, its long-term use is complicated by numerous adverse effects and is ineffective for some OMG patients in reaching remission. This study aimed to evaluate the effectiveness and safety of intravenous methylprednisolone (IVMP) and tacrolimus monotherapy for OMG patients with unsatisfactory responses to conventional prednisone therapy. METHODS: We retrospectively reviewed 57 OMG patients who had not achieved satisfactory improvement after prednisone therapy and thereby received IVMP or tacrolimus monotherapy for at least 6 months. Ocular symptoms were evaluated by the ocular-quantitative MG (QMG) score at each time point. A ≥ 2-point fall in ocular QMG score was defined as the cut-off point to indicate clinical improvement. Logistic regression analysis was performed to identify factors associated with the efficacy of IVMP at discharge. Adverse events were recorded. RESULTS: Both IVMP and tacrolimus monotherapy demonstrated significant clinical efficacy, with no statistical differences observed at the study endpoint. The proportions of patients who reached the cut-off point for efficacy evaluation were higher in the IVMP group than in the tacrolimus group (1, 3, and 6 months: 51.7% (15/29) vs 12.0% (3/25), p = 0.002; 69.0% (20/29) vs 40.0% (10/25), p = 0.033; 69.0% (20/29) vs 46.4% (13/28), p = 0.085, respectively). Multivariate logistics analysis showed that high ocular QMG scores at baseline indicated favourable responses to IVMP treatment (OR = 1.781; 95% CI 1.066-2.975; p = 0.028). All the adverse events were transient and tolerable. CONCLUSION: Our findings suggest that both IVMP and tacrolimus monotherapy hold promise as viable treatment options for OMG patients with unsatisfactory responses to oral prednisone. The study supports the safety and effectiveness of both therapies, with IVMP exhibiting faster improvement and favourable efficacy in patients with high ocular QMG scores.

CaCO 3 Nanoparticles Delivering MicroRNA-200c Suppress Oral Squamous Cell Carcinoma.

MicroRNA (miR)-200c suppresses the initiation and progression of oral squamous cell carcinoma (OSCC), the most prevalent head and neck cancer with high recurrence, metastasis, and mortality rates. However, miR-200c -based gene therapy to inhibit OSCC growth and metastasis has yet to be reported. To develop an miR-based gene therapy to improve the outcomes of OSCC treatment, this study investigates the feasibility of plasmid DNA encoding miR-200c delivered via non-viral CaCO 3 -based nanoparticles to inhibit OSCC tumor growth. CaCO 3 -based nanoparticles with various ratios of CaCO 3 and protamine sulfate (PS) were utilized to transfect pDNA encoding miR-200c into OSCC cells and the efficiency of these nanoparticles was evaluated. The proliferation, migration, and associated oncogene production, as well as in vivo tumor growth for OSCC cells overexpressing miR-200c were also quantified. It was observed that, while CaCO 3 -based nanoparticles improve transfection efficiencies of pDNA miR-200c , the ratio of CaCO 3 to PS significantly influences the transfection efficiency. Overexpression of miR-200c significantly reduced proliferation, migration, and oncogene expression of OSCC cells, as well as the tumor size of cell line-derived xenografts (CDX) in mice. In addition, a local administration of pDNA miR-200c using CaCO 3 delivery significantly enhanced miR-200c transfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO 3 /pDNA miR-200c may potentially be used to reduce oral cancer recurrence and metastasis and improve clinical outcomes in OSCC treatment. (227 words).

Simulation-aided infrared thermography with decomposition-based noise reduction for detecting defects in ancient polyptychs.

In recent years, the conservation and protection of ancient cultural heritage have received increasing attention, and non-destructive testing (NDT), which can minimize the damage done to the test subject, plays an integral role therein. For instance, NDT through active infrared thermal imaging can be applied to ancient polyptychs, which can realize accurate detection of damage and defects existing on the surface and interior of the polyptychs. In this study, infrared thermography is used for non-invasive investigation and evaluation of two polyptych samples with different pigments and artificial defects, but both reproduced based on a painting by Pietro Lorenzetti (1280/85-1348) using the typical tempera technique of the century. It is noted that, to avoid as far as possible secondary damages done to the ancient cultural heritages, repeated damage-detection experiments are rarely carried out on the test subjects. To that end, numerical simulation is used to reveal the heat transfer properties and temperature distributions, as to perform procedural verification and reduce the number of experiments that need to be conducted on actual samples. Technique-wise, to improve the observability of the experimental results, a total variation regularized low-rank tensor decomposition algorithm is implemented to reduce the background noise and improve the contrast of the images. Furthermore, the efficacy of image processing is quantified through the structural-similarity evaluation.

Immune infiltration patterns and identification of new diagnostic biomarkers GDF10, NCKAP5, and RTKN2 in non-small cell lung cancer.

This study aimed to identify potential biomarkers for non-small cell lung cancer (NSCLC) and analyze the role of immune cell infiltration in NSCLC. R software was used to screen differentially expressed genes (DEGs) from NSCLC datasets obtained from the Gene Expression Omnibus (GEO) database, and functional correlation analysis was performed. The machine learning algorithms were used to screen the potential biomarkers of NSCLC. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. The protein and mRNA expression levels of potential biomarkers were verified based on the Human Protein Atlas (HPA) database and qRT-PCR. CIBERSORT was used to evaluate the infiltration of immune cells in NSCLC tissues, and the correlation between potential biomarkers and infiltrated immune cell was analyzed. Finally, specific siRNAs were utilized to reduce the GDF10, NCKAP5, and RTKN2 expression in A549 and H1975 cells. The proliferation ability of A549 and H1975 cells was detected by MTT assay. A total of 848 upregulated DEGs and 1308 downregulated DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the DEGs were mainly related to cell division. Disease ontology (DO) enrichment analysis showed that the diseases with these DEGs were mainly lung diseases, including NSCLC. In addition,three potential biomarkers were identified: GDF10, NCKAP5, and RTKN2. Immune cell infiltration analysis showed that resting NK cells, activated dendritic cells, and Tregs may be involved in the pathogenesis of NSCLC. Meanwhile, GDF10, NCKAP5, and RTKN2 were negatively correlated with Tregs and naïve B cells but were positively correlated with activated dendritic cells and resting NK cells. Immunohistochemical staining showed that the expression of GDF10, NCKAP5, and RTKN2 in the lung tissue of patients with NSCLC was lower than that of normal lung tissue. qRT-PCR also confirmed that the mRNA expression of three biomarkers in NSCLC cell lines A549 and H1975 were significantly lower than those in human normal lung epithelial cells BEAS-2B. An MTT assay showed that GDF10, NCKAP5, and RTKN2 knockdown significantly promoted the proliferation of A549 and H1975 cells. The in vitro experiments showed that GDF10, NCKAP5, and RTKN2 played the inhibitory effects on NSCLC cell lines proliferation. Hence, GDF10, NCKAP5, and RTKN2 can be used as diagnostic biomarkers for NSCLC.

Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. METHODS: A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. CONCLUSIONS: In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

Immunological classification of glioblastoma and its prognostic implications.

OBJECTIVES: The progress of immunotherapy for glioblastoma (GBM) is currently slow. To improve immunotherapy, we need a deeper understanding of the immune microenvironment of GBM. Here, we aimed to establish a classification system based on immune expression profile in GBM. METHODS: Immune gene expression profiles of 152 patients with GBM from The Cancer Genome Atlas (TCGA) were used to identify subtypes by consensus clustering, and the classification system was reproduced in the two validation datasets (CGGA and GSE16011). Clinical information, molecular characteristics, immune infiltration, and genomic variation were integrated to characterize the subtypes. RESULTS: Two distinct immune subtypes in GBM were successfully identified and validated. The Im2 subtype was closely related to IDH-wildtype and combined +7/-10, while the Im1 subtype was associated with IDH mutation. Survival curve analysis showed that the Im2 subtype was associated with significantly shorter survival than the Im1 subtype. Im2 showed a high immune score and stromal score, low tumor purity, enrichment of macrophages, and high immune checkpoint and HLA gene expression. Im1 was characterized by low immune score and stromal score, high tumor purity, enrichment of lymphocytes, and low immune checkpoint and HLA gene expression. Finally, we developed an immune-related signature in GBM with better prognosis prediction. CONCLUSIONS: Our study confirmed the immune heterogeneity of GBM and might provide valuable classification for immunotherapy.

Iron-doped novel Co-based metal-organic frameworks for preparation of bifunctional catalysts with an amorphous structure for OER/HER in alkaline solution.

A novel two-dimensional Co-MOF material {[Co(dptz)2(oba)2]·(DMF)2}n is prepared using mixed organic ligands, which exhibits both OER (oxygen evolution reaction) and HER (hydrogen evolution reaction) catalytic performance. The integration of an Fe dopant and amorphous interface into Co-MOF to improving the electrocatalytic performance of pristine MOFs (metal-organic frameworks) is demonstrated and the origin of the remarkable electrocatalytic performance of the catalyst is elucidated. The comprehensive characterization data of Fe@Co-MOFs illustrate that there is a crystallinity transition during the doping of Co-MOF, which increases the electron transfer rate of the material and ensures increased exposure of the ligand unsaturated active site on the surface, and modulates the electronic structure of the Co center in a synergistic manner. As a result, the optimized catalytic Fe@Co-MOF-3 with an amorphous structure exhibits outstanding electrocatalytic performance for the OER, with only 248 mV at a current density of 50 mA cm-2 and excellent stability after 11 h of testing in alkaline solution. Not only that, the HER was achieved with a low overpotential of 150 mV at 10 mA cm-2. The present work indicates that the as-synthesized Co-MOF and Fe@Co-MOFs offer prospects in developing electrocatalysts for water splitting.

Primary cutaneous adenoid cystic carcinoma: a clinicopathologic, immunohistochemical, and fluorescence in-situ hybridisation study of 13 cases.

AIMS: This study aimed to investigate the clinical, histological, immunohistochemical and chromosomal features of primary cutaneous adenoid cystic carcinoma (PCACC). METHODS AND RESULTS: We retrospectively analysed 13 cases identified on their clinicopathological features and performed fluorescence in-situ hybridisation (FISH) on six available cases. Head and neck (46.2%) were most commonly involved. The median age was 53 years, with a male predilection. Histologically, tumours were classified as grades 1 (eight), 2 (four) and 3 with high-grade transformation (HGT) (one). The HGT component was demonstrated as poorly differentiated carcinoma with multifocal necrosis and myoepithelial differentiation. Patients with one of the following factors: longest diameter of the lesion (≥ 1 cm), involvement of subcutaneous fat tissue and widely infiltrative border had a relatively higher rate of local recurrence, distant metastasis and death. Five of six cases were confirmed to have MYB translocation, while nuclear staining for MYB proto-oncogene, transcription factor (MYB) protein was found in four cases. During the follow-up (median = 64 months), two patients experienced local recurrences. One patient, who was classified as grade III PCACC with HGT, developed multiple metastases and died of disease. Another patient was alive with multiple metastases. CONCLUSIONS: This is the largest single-institution study, to our knowledge, of PCACC in an Asian population. We describe the first case of scalp PCACC with HGT, which is the only death case in our series. PCACC tends to recur locally and has metastatic potential. PCACC with HGT has a poor prognosis.

Preferentially expressed antigen in melanoma immunohistochemistry as an adjunct for differential diagnosis in acral lentiginous melanoma and acral nevi.

Preferentially expressed antigen in melanoma (PRAME) has shown promising utility in distinguishing benign melanocytic lesions from melanomas, but knowledge of its expression pattern in acral lentiginous melanoma (ALM) and acral nevi (ANs) is limited. Immunohistochemical expression of PRAME was examined in 75 ALMs and 34 ANs. The clinical and histopathologic characteristics of patients with ALM were collected. PRAME was immunoreactive in 89.3% (67/75) of ALMs, but entirely negative in 94.1% (32/34) of ANs. When staining at least 50% of lesional melanocytes was determined as positivity, the sensitivity and specificity of PRAME for distinguishing ALM from ANs were 69.3% and 100%, respectively. Seventy-one cases of ALMs had tumor cells in the epidermis; 71.8% (51/71) of them showed positive for PRAME. By contrast, 61 ALMs had tumor cells in the dermis; 65.6% (40/61) exhibited positive expression. Twenty-nine of 39 (74.4%) epithelioid cell ALMs were observed to be positive for PRAME. By comparison, 63.8% (23/36) of ALMs with spindle tumor cells were positive for PRAME. However, PRAME positive expression was not associated with any clinical and histopathologic characteristics of patients with ALM, including Breslow thickness, ulcer, cytomorphology, lymph node metastasis, or tumor-infiltrated lymphocytes (TILs). Nevertheless, we observed that 82.6% (19/23) of ALMs with lymph node involvement at diagnosis expressed PRAME, compared with 57.6% (20/35) of those without. In summary, PRAME immunohistochemistry can serve as a helpful adjunct in the differential diagnosis of ALMs and ANs with good sensitivity and high specificity. Additionally, PRAME tends to have a higher positive rate in epidermal melanocytes than in the dermis and is inclined to express in epithelioid cells than in spindle cells of ALMs.

Universal extracellular vesicles and PD-L1+ extracellular vesicles detected by single molecule array technology as circulating biomarkers for diffuse large B cell lymphoma.

Plasma extracellular vesicles (EVs) have been reported to be a promising source of diagnostic and prognostic biomarkers in various cancers. However, further research in this area is needed due to the limitations of circulating extracellular vesicles detection methods. Using the Single Molecule array (SiMoa) technology, we developed two extracellular vesicle detection assays, CD9-CD63 and PD-L1-CD63, to determine circulating universal EVs and PD-L1 positive EVs, respectively. A total of 164 diffuse large B-cell lymphoma (DLBCL) patients were retrospectively included in this study. Compared with healthy volunteers (n = 25), elevated CD9-CD63 and PD-L1-CD63 signals were detected in the plasma of DLBCL patients (n = 164). High CD9-CD63 signals was associated with molecular subtype, extranodal site and treatment response in DLBCL. A high PD-L1-CD63 signal was also associated with certain clinical features, including extranodal site and treatment response. CD9-CD63 and PD-L1-CD63 signals were found to be important prognostic factors for both progression-free and overall survival. Furthermore, PD-L1-positive EVs were found in all patients, though PD-L1 protein expression was positive in only 35.4% (17/48) of tumor biopsies. No correlation was found between circulating PD-L1+ EVs and soluble PD-L1 (sPD-L1) levels. Our results show that plasma universal EV and PD-L1-positive EV levels are significantly elevated in DLBCL and might serve as biomarkers for predicting survival outcomes in DLBCL patients.

Prevalence and determinants of potentially inappropriate medications prescribing in elderly patients in Chinese communities.

BACKGROUND: To assess the prevalence and associated risk of potentially inappropriate medications (PIMs) prescribing in community-dwelling elderly patients in China and to examine the most frequently used PIMs. This will provide a reference for the formulation of medication manuals for the community-dwelling elderly and further standardize the use of medications in elderly patients. METHODS: We conducted a cross-sectional retrospective study from April 1, 2020 to April 30, 2020. Data from elderly patients aged ≥65 years were collected from the Hengjie (N=2,294), Loujiang (N=3,972), and Tongxing communities (N=1,969) in Suzhou. The frequency of PIMs was detected using the 2019 Beers criteria and the 2017 Chinese criteria. Chi-square (for categorical variables), ANOVA (for continuous variables as applicable), and logistic regression were used to describe and identify potential predictors of PIMs. RESULTS: A total of 8,235 elderly patients were examined. Using the Chinese criteria, the prevalence of PIMs was 37.07%, which was slightly higher than that found using the 2019 Beers criteria (32.16%). The most prescribed PIMs were estazolam (21.53%) and insulin (4.60%) based on the Chinese criteria. Logistic regression analysis showed that advanced age, polypharmacy, and comorbid disease of patients were associated with a high risk of PIMs. Furthermore, the educational background and professional title of physicians were also associated with PIMs. CONCLUSIONS: Given the high prevalence of PIMs in the Chinese community-dwelling elderly population, the implementation of evidence-based interventions to promote rational clinical drug use could improve their quality of life.

Aptamers used for biosensors and targeted therapy.

Aptamers are single-stranded nucleic acid sequences that can bind to target molecules with high selectivity and affinity. Most aptamers are screened in vitro by a combinatorial biology technique called systematic evolution of ligands by exponential enrichment (SELEX). Since aptamers were discovered in the 1990s, they have attracted considerable attention and have been widely used in many fields owing to their unique advantages. In this review, we present an overview of the advancements made in aptamers used for biosensors and targeted therapy. For the former, we will discuss multiple aptamer-based biosensors with different principles detected by various signaling methods. For the latter, we will focus on aptamer-based targeted therapy using aptamers as both biotechnological tools for targeted drug delivery and as targeted therapeutic agents. Finally, challenges and new perspectives associated with these two regions were further discussed. We hope that this review will help researchers interested in aptamer-related biosensing and targeted therapy research.

Nevus cell aggregates massively occupying parenchyma of an external iliac lymph node: A case report and review of the literature.

We report a case of nevus cell aggregates (NCAs) in an external iliac lymph node from a patient with a compound congenital nevus in the corresponding drainage skin. Melanocytes in parenchyma were in band, nest-like or nodular fashion, and partly continuous with those in capsule and trabeculae. The largest nodule in parenchyma measured 6.5 mm. Melanocytes mostly exhibited benign appearance identical to cutaneous nevus. A few regions abundant in cells displayed atypical features, including increased nucleo-cytoplasmic ratio, small nucleoli, and occasional mitotic figures. Immunohistochemistry showed that melanocytes stained positive for p16, but negative for HMB-45 and nestin. Ki-67 labeling was less than 1% and reticulin mainly surrounded individual melanocytes. Besides, Vysis melanoma fluorescence in situ hybridization (FISH) plus another 2 probes targeting 9p21(CDKN2A) and 8q24(MYC) showed normal results. The patient is alive without malignant tumor after 52-month follow up. Our case provides a new evidence for the existence of intraparenchymal NCAs in deep lymph node and indicates that melanocytes with some atypical features can occur in nodal nevi. Nevus cells in parenchyma connected to those in capsule and trabeculae are a significant clue to distinguish nodal nevi from metastatic melanomas. Additionally, immunohistochemistry and FISH assay are useful in differential diagnosis.

The association between smoking and unfavorable outcomes in acute ischemic stroke patients with mechanical thrombectomy.

INTRODUCTION: Little is known about the relationship between smoking and clinical outcomes in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). The outcomes could depend on different stroke subtypes. The aim of this study was to investigate whether smoking affected differently the outcomes in patients with different stroke subtypes who received MT. METHODS: AIS patients who underwent MT were prospectively enrolled from three hospitals between January 2014 and December 2018. Smokers were defined as current users of cigarettes. The stroke subtypes were classified according to TOAST criteria. Outcome measurements included treatment effects, intracerebral hemorrhage (ICH), and functional outcomes at 3 months. The effects of smoking on outcomes were assessed by logistic regression analysis. RESULTS: A total of 128 AIS patients with MT were enrolled, including 64 smokers and 64 non-smokers. Logistic regression analysis indicated that smoking was related to higher risk of In-hospital ICH (OR=4.31; 95% CI: 1.10-16.96; p=0.036) in patients with cardioembolism subtype. Furthermore, smoking was also associated with lower rates of mild stroke at discharge (OR=0.07; 95% CI: 0.02-0.31; p<0.001) and functional independence (OR=0.13; 95% CI: 0.03-0.56; p=0.006) in patients with cardioembolism subtype. CONCLUSIONS: In AIS patients undergoing MT, smoking could be related to a higher risk of In-hospital ICH and lower rates of mild stroke at discharge and functional independence if their stroke subtype is cardioembolism.

Adoptive Cell Therapy: A Novel and Potential Immunotherapy for Glioblastoma.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with very poor prognosis and few advances in its treatment. Recently, fast-growing cancer immunotherapy provides a glimmer of hope for GBM treatment. Adoptive cell therapy (ACT) aims at infusing immune cells with direct anti-tumor activity, including tumor-infiltrating lymphocyte (TIL) transfer and genetically engineered T cells transfer. For example, complete regressions in patients with melanoma and refractory lymphoma have been shown by using naturally tumor-reactive T cells and genetically engineered T cells expressing the chimeric anti-CD19 receptor, respectively. Recently, the administration of ACT showed therapeutic potentials for GBM treatment as well. In this review, we summarize the success of ACT in the treatment of cancer and provide approaches to overcome some challenges of ACT to allow its adoption for GBM treatment.

Local Delivery of ß-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury.

BACKGROUND/AIMS: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract ß-elemene in vitro and in a rat model of SCI. METHODS: CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen's method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression. RESULTS: ß-elemene (20 µg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. ß-elemene reduced CoCl2-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that ß-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that ß-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, ß-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1ß. CONCLUSION: ß-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, ß-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of ß-elemene in SCI patients.

Hyperglycemia via activation of thromboxane A2 receptor impairs the integrity and function of blood-brain barrier in microvascular endothelial cells.

Diabetes is one of high risk factors for cardio- and cerebra-vascular diseases, including stroke, atherosclerosis and hypertension. This study was conducted to elucidate whether and how thromboxane receptor (TPr) activation contributes to blood-brain barrier (BBB) dysfunction in diabetes. Human brain microvascular endothelial cells (HBMECs) were cultured. The levels of phosphorylated endothelial nitric oxide synthase (eNOS) at Ser1177 (p-eNOS) and Akt at Ser473 (p-Akt) were assayed by western blot. Exposure of HBMECs to either high glucose (HG) or thromboxane A2 (TxA2) mimetic U46619, significantly reduced p-eNOS and p-Akt. These effects were abolished by pharmacological or genetic inhibitors of TPr. HG/U46619-induced suppressions of eNOS and Akt phosphorylation were accompanied by upregulation of PTEN and Ser380/Thr382/383 PTEN phosphorylation. PTEN-specific siRNA restored Akt-eNOS signaling in the face of TPr activation or HG. The small GTPase, Rho, was also activated by HG stimulation, and pretreatment of HBMECs with Y27632, a Rho-associated kinase (ROCK) inhibitor, rescued HG-impaired Akt-eNOS signaling. In STZ-injected rats, we found that hyperglycemia dramatically increased the levels of PTEN and PTEN-Ser380/Thr382/383 phosphorylation, reduced both levels of p-eNOS and p-Akt, and disrupted BBB function assayed by Evans blue staining, which were abolished by SQ29548 treatment. We conclude that hyperglycemia activates thromboxane A2 receptor to impair the integrity and function of blood-brain barrier via the ROCK-PTEN-Akt-eNOS pathway.

Electrospinning of poly(glycerol sebacate)-based nanofibers for nerve tissue engineering.

Nerve tissue engineering (TE) requires biomimetic scaffolds providing essential chemical and topographical cues for nerve regeneration. Poly(glycerol sebacate) (PGS) is a biodegradable and elastic polymer that has gained great interest as a TE scaffolding biomaterial. However, uncured PGS is difficult to be electrospun into nanofibers. PGS would, therefore, require the addition of electrospinning agents. In this study, we modified PGS by using atom transfer radical polymerization (ATRP) to synthesize PGS-based copolymers with methyl methacrylate (MMA). The synthesized PGS-PMMA copolymer showed a molecular weight of 82kDa and a glass transition temperature of 115°C. More importantly, the PGS-PMMA could be easily electrospun into nanofiber with a fiber diameter of 167±33nm. Blending gelatin into PGS-PMMA nanofibers was found to increase its hydrophilicity and biocompatibility. Rat PC12 cells were seeded onto the PGS-PMMA/gelatin nanofibers to investigate their potential for nerve regeneration. It was found that gelatin-containing PGS-based nanofibers promoted cell proliferation. The elongated cell morphology observed on such nanofibers indicated that the scaffolds could induce the neurite outgrowth of the nerve stem cells. Overall, our study suggested that the synthesis of PGS-based copolymers might be a promising approach to enhance their processability, and therefore advancing bioscaffold engineering for various TE applications.

Comparative proteomic analyses of Asian cotton ovules with attached fibers in the early stages of fiber elongation process.

BACKGROUND: Plenty of proteomic studies were performed to characterize the allotetraploid upland cotton fiber elongation process, whereas little is known about the elongating diploid cotton fiber proteome. METHODS: In this study, we used a two-dimensional electrophoresis-based comparative proteomic approach to profile dynamic proteomes of diploid Asian cotton ovules with attached fibers in the early stages of fiber elongation process. One-way ANOVA and Student-Newman-Keuls test were used to find the differentially displayed protein (DDP) spots. RESULTS: A total of 55 protein spots were found having different abundance ranging from 1 to 9 days post-anthesis (DPA) in a two-day interval. These 55 DDP spots were all successfully identified using high-resolution mass spectrometric analyses. Gene ontology analyses revealed that proteoforms involved in energy/carbohydrate metabolism, redox homeostasis, and protein metabolism are the most abundant. In addition, orthologues of the 13 DDP spots were also found in differential proteome of allotetraploid elongating cotton fibers, suggesting their possible essential roles in fiber elongation process. CONCLUSIONS: Our results not only revealed the dynamic proteome change of diploid Asian cotton fiber and ovule during early stages of fiber elongation process but also provided valuable resource for future studies on the molecular mechanism how the polyploidization improves the trait of fiber length.

Synergistic effect of topography, surface chemistry and conductivity of the electrospun nanofibrous scaffold on cellular response of PC12 cells.

Electrospun nanofibrous nerve implants is a promising therapy for peripheral nerve injury, and its performance can be tailored by chemical cues, topographical features as well as electrical properties. In this paper, a surface modified, electrically conductive, aligned nanofibrous scaffold composed of poly (lactic acid) (PLA) and polypyrrole (Ppy), referred to as o-PLAPpy_A, was fabricated for nerve regeneration. The morphology, surface chemistry and hydrophilicity of nanofibers were characterized by Scanning Electron Microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle, respectively. The effects of these nanofibers on neuronal differentiation using PC12 cells were evaluated. A hydrophilic surface was created by Poly-ornithine coating, which was able to provide a better environment for cell attachment, and furthermore aligned fibers were proved to be able to guide PC12 cells grow along the fiber direction and be beneficial for neurite outgrowth. The cellular response of PC12 cells to pulsed electrical stimulation was evaluated by NF 200 and alpha tubulin expression, indicating that electrical stimulation with a voltage of 40mV could enhance the neurite outgrowth. The PC12 cells stimulated with electrical shock showed greater level of neurite outgrowth and smaller cell body size. Moreover, the PC12 cells under electrical stimulation showed better viability. In summary, the o-PLAPpy_A nanofibrous scaffold supported the attachment, proliferation and differentiation of PC12 cells in the absence of electrical stimulation, which could be potential candidate for nerve regeneration applications.