Effect of transcutaneous electrical nerve stimulation at acupoints on patients with type 2 diabetes mellitus: a randomized controlled trial.

OBJECTIVE: To examine whether transcutaneous electric nerve stimulation at acupoints (Acu-TENS) improved the biochemical and physical indices of patients with type 2 diabetes mellitus (T2DM). METHODS: Ninety subjects with T2DM were divided randomly into a control group (n = 30), aerobic exercise group (n = 30), or Acu-TENS group (n = 30). In addition to conventional diabetes drug treatment, patients in the Acu-TENS group received acupoint stimulation, the aerobic exercise group engaged in walking exercises, and the control group was given sham electrical stimulation. All groups were treated for 30 min for each session and five times a week for 2 months. The indices of glycosylated hemoglobin, 2 h postprandial glucose, fasting serum insulin, triglyceride, total cholesterol, and body mass index were assessed at pre-treatment, post-treatment, and follow-up, which was 2 months after treatment. RESULTS: The indices of the control group were not changed (P > 0.05) at the three time points. At the pre-treatment measurement, there were significant differences (P > 0.05) in indices among the three groups. At post-treatment, each index of the two groups was lower than that of the control group (P < 0.05), and improved in comparison with the pre-treatment measurement (P < 0.05). In follow-up, each index of the aerobic exercise group and Acu-TENS group increased, but was still decreased compared with the pre-treatment value (P < 0.05), excluding body mass index. CONCLUSION: Acu-TENS could improve the state of patients with T2DM and be used as a therapy in clinical application.

Transcriptome profiling of abdominal aortic tissues reveals alterations in mRNAs of Takayasu arteritis.

Takayasu arteritis (TA) is a chronic granulomatous vasculitis involving in the main branches of aorta. Previous studies mainly used peripheral blood and some vascular tissues but seldom studies have sequenced vascular tissues. Here in this study, we aimed to explore the alterations of mRNA in TA by performing bulk RNA sequencing. A total of 14 abdominal aortic tissues including 8 from renal transplantation and 6 from patient with TA undergoing bypass surgeries. Bulk RNA sequencing were performed and after the quality control, a total of 1897 transcripts were observed to be significantly differently (p < 0.05 and Log2FC > 1) expressed between the TA and control group, among which 1,361 transcripts were in TA group and 536 in the Control group. Reactome Pathway Enrichment Comparison analysis revealed interleukin-10 signaling and signaling by interleukins were highly expressed in TA group. Besides, extracellular matrix organization was also observed in this group. WGCNA and PPI obtained 26 core genes which were highly correlated with the clinical phenotype. We then also perform deconvolution of the bulk RNA-seq data by using the scRNA-seq dataset and noticed the high proportion of smooth muscle cells in our dataset. Additionally, immunohistochemical staining confirmed our bioinformatic analysis that TA aortic tissues express high levels of IL-1R1 and IL-1R2. Briefly, this study revealed critical roles of interleukins in TA pathogenesis, and SMCs may also participate in the reconstruction in vessel wall at late stage of TA.

Ginkgo biloba leaf extract (EGb-761) elicits neuroprotection against cerebral ischemia/reperfusion injury by enhancement of autophagy flux in neurons in the penumbra.

OBJECTIVES: Ginkgo biloba leaf extract (EGb-761) injection has been widely used as adjuvant therapy for cerebral stroke in China. However, its underlying pharmacological mechanism is not completely understood. The present study aimed to investigate whether the therapeutic effects of EGb-761 are exerted by modulating autophagy flux. MATERIALS AND METHODS: Ischemic cerebral stroke was prepared in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) followed by reperfusion. The MCAO/reperfusion rats were then treated with EGb-761 injection once daily for 7 days. Thereafter, the brain tissues in the ischemic penumbra were obtained to detect the key proteins in the autophagic/lysosomal pathway with Beclin1, LC3, (SQSTM1)/p62, ubiquitin, LAMP-1, cathepsin B, and cathepsin D antibodies by western blot and immunofluorescence. Meanwhile, the infarct volume, neurological deficits, and neuronal apoptosis were assessed to evaluate the therapeutic outcomes. RESULTS: The results illustrated that EGb-761 treatment was not only able to promote the autophagic activities of Beclin1 and LC3-II in neurons, but also could enhance the autophagic clearance, as indicated by reinforced lysosomal activities of LAMP-1, cathepsin B, and cathepsin D, as well as alleviating autophagic accumulation of ubiquitin and insoluble p62 in the MCAO+EGb-761 group, compared with those in the MCAO+saline group. Meanwhile, cerebral ischemia-induced neurological deficits, infarct volume, and neuronal apoptosis were significantly attenuated by 7 days of EGb-761 therapy. CONCLUSION: Our data suggest that EGb-761 injection can elicit a neuroprotective efficacy against MCAO/reperfusion injury, and this neuroprotection may be exerted by enhancement of autophagy flux in neurons in the ischemic penumbra.

Single-Cell RNA Sequencing Revealed CD14+ Monocytes Increased in Patients With Takayasu's Arteritis Requiring Surgical Management.

Objectives: Takayasu Arteritis (TA) is a highly specific vascular inflammation and poses threat to patients' health. Although some patients have accepted medical treatment, their culprit lesions require surgical management (TARSM). This study aimed at dissecting the transcriptomes of peripheral blood mononuclear cells (PBMCs) in these patients and to explore potential clinical markers for TA development and progression. Methods: Peripheral blood were collected from four TA patients requiring surgical management and four age-sex matched healthy donors. Single cell RNA sequencing (scRNA-seq) was adopted to explore the transcriptomic diversity and function of their PBMCs. ELISA, qPCR, and FACS were conducted to validate the results of the analysis. Results: A total of 29918 qualified cells were included for downstream analysis. Nine major cell types were confirmed, including CD14+ monocytes, CD8+ T cells, NK cells, CD4+ T cells, B cells, CD16+ monocytes, megakaryocytes, dendritic cells and plasmacytoid dendritic cells. CD14+ monocytes (50.0 vs. 39.3%, p < 0.05) increased in TA patients, as validated by FACS results. TXNIP, AREG, THBS1, and CD163 increased in TA patients. ILs like IL-6, IL-6STP1, IL-6ST, IL-15, and IL-15RA increased in TA group. Conclusion: Transcriptome heterogeneities of PBMCs in TA patients requiring surgical management were revealed in the present study. In the patients with TA, CD14+ monocytes and gene expressions involved in oxidative stress were increased, indicating a new treatment and research direction in this field.

Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold nanoparticles (cmHsp70.1-AuNPs) for tumor-specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities but not on corresponding normal cells, predestining this target for a tumor-selective in vivo imaging. In vitro microscopic analysis revealed the presence of cmHsp70.1-AuNPs in the cytosol of tumor cell lines after internalization via the endo-lysosomal pathway. In preclinical models, the biodistribution as well as the intratumoral enrichment of AuNPs were examined 24 h after i.v. injection in tumor-bearing mice. In parallel to spectral CT analysis, histological analysis confirmed the presence of AuNPs within tumor cells. In contrast to control AuNPs, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively inside tumor cells in different tumor mouse models. Furthermore, a machine-learning approach was developed to analyze AuNP accumulations in tumor tissues and organs. In summary, utilizing mHsp70 on tumor cells as a target for the guidance of cmHsp70.1-AuNPs facilitates an enrichment and uniform distribution of nanoparticles in mHsp70-expressing tumor cells that enables various microscopic imaging techniques and spectral-CT-based tumor delineation in vivo.

[Effect of lentivirus-mediated hIL-24 gene on proliferation, migration and invasion of keloid fibroblasts].

OBJECTIVE: To investigate the effect of hIL-24 gene on proliferation, migration and invasion activity of human keloid fibroblasts (KFs). METHODS: hIL-24 gene was cloned into lentivirus vector, then the lentivirus particles expressing hlL-24 were infected into KF cells. Real-time PCR and Western blot were performed to examine the expression of hIL-24 in lentivirus infected cells. The growth ability was detected by MTT assay. The cell cycle was analyzed by flow cytometry, The invasion and migration were detected by matrigel invasion assay and wound healing assay. RESULTS: Comparing to controls group and KF-NC group, the expression levels of hIL-24 mRNA and protein were both significantly up-regulated after 4 days of hIL-24 lentivims infection. Comparing with the KF-NC group, MTT assay showed that the A490 of KF-hlL-24 group was down-regulated after lentivims infection ( P < 0. 05 ). Comparing with the KF-NC group, Cell cycle test revealed hlL-24 gene could block KF cells in G1 [(75. 40 ±2. 10)% ] , the proportion of KF cells was decreased in S phase [(4. 96 ± 1. 60)% ] and G2 phase [(0.01 ± 0.01)% ]. After KF cells were infected(P <0.01). Transfection of hlL-24 lentivirus inhibited the migration and invasion activity of KF cells. CONCLUSION: Lentivirus-mediated hlL-24 gene efficiently inhibits proliferation, cell cycle progression, migration and invasion activity of KF cells.