Dihydrotestosterone reduces neuroinflammation in spinal cord injury through NF-κB and MAPK pathway.

Neuroinflammation induced by microglia following spinal cord injury (SCI) leads to secondary neurologic injury. Androgens including testosterone and dihydrotestosterone (DHT) show as endogenous neuroprotective factors against multiple neurologic diseases, while their therapeutic role in SCI-induced neuroinflammation and underlying mechanism remains elusive. In the study, we aimed to investigate the role of DHT against microglia-induced neuroinflammation in SCI and evaluate its protective treatment. BV2 cells were activated by neuroinflammation via LPS in vitro. Adult male C57BL/6 mice were used to establish the SCI model. BV2 cells and SCI mice were administrated DHT. Microglia activation, pro-inflammatory factors, p38 and p65 phosphorylation, glial scar, fibrotic scar, histology, and locomotor function recovery were measured, respectively. We demonstrated that DHT administration attenuates neuroinflammation in microglia through inhibition of p38 and p65 pathways. Moreover, DHT reduces microglia and astrocyte accumulation, cord fibrosis and histologic damage. Besides, DHT ameliorates locomotor functional recovery after SCI. DHT is verified to play a neuroprotective role in SCI, which fights against neuroinflammation by inhibition of p38 and p65 pathways. Therefore, Mel is defined as a promising factor in protecting neural tissue after SCI.

Regeneration of Pancreatic Cells Using Optimized Nanoparticles and l-Glutamic Acid-Gelatin Scaffolds with Controlled Topography and Grafted Activin A/BMP4.

Regeneration of insulin-producing cells (IPCs) from induced pluripotent stem cells (iPSCs) under controlled conditions has a lot of promise to emulate the pancreatic mechanism in vivo as a foundation of cell-based diabetic therapy. l-Glutamic acid-gelatin scaffolds with orderly pore sizes of 160 and 200 µm were grafted with activin A and bone morphogenic proteins 4 (BMP4) to differentiate iPSCs into definitive endoderm (DE) cells, which were then guided with fibroblast growth factor 7 (FGF7)-grafted retinoic acid (RA)-loaded solid lipid nanoparticles (FR-SLNs) to harvest IPCs. Response surface methodology was adopted to optimize the l-glutamic acid-to-gelatin ratio of scaffolds and to optimize surfactant concentration and lipid proportion in FR-SLNs. Experimental results of immunofluorescence, flow cytometry, and western blots revealed that activin A (100 ng/mL)-BMP4 (50 ng/mL)-l-glutamic acid (5%)-gelatin (95%) scaffolds provoked the largest number of SOX17-positive DE cells from iPSCs. Treatment with FGF7 (50 ng/mL)-RA (600 ng/mL)-SLNs elicited the highest number of PDX1-positive ß-cells from differentiated DE cells. To imitate the natural pancreas, the scaffolds with controlled topography were appropriate for IPC production with sufficient insulin secretion. Hence, the current scheme using FR-SLNs and activin A-BMP4-l-glutamic acid-gelatin scaffolds in the two-stage differentiation of iPSCs can be promising for replacing impaired ß-cells in diabetic management.

An Effective Treatment of Perimenopausal Syndrome by Combining Two Traditional Prescriptions of Chinese Botanical Drugs.

Ethnopharmacological relevance: Two types of traditional Chinese formulas of botanical drugs are prescribed for treating perimenopausal syndrome (PMS), a disorder in middle-aged women during their transition to menopause. One is for treating PMS as kidney deficiency (KD) due to senescence and declining reproductive functions, and the other is for treating it as liver qi stagnation (LQS) in association with stress and anxiety. Despite the time-tested prescriptions, an objective attestation to the effectiveness of the traditional Chinese treatment of PMS is still to be established and the associated molecular mechanism is still to be investigated. Materials and methods: A model for PMS was generated from perimenopausal rats with chronic restraint stress (CRS). The effectiveness of traditional Chinese formulas of botanical drugs and a combination of two of the formulas was evaluated based on 1H NMR plasma metabolomic, as well as behavioral and physiological, indicators. To investigate whether the formulas contained ligands that could compensate for the declining level of estrogen, the primary cause of PMS, the ligand-based NMR technique of saturation transfer difference (STD) was employed to detect possible interacting molecules to estrogen receptors in the decoction. Results: Each prescription of the classical Chinese formula moderately attenuated the metabolomic state of the disease model. The best treatment strategy however was to combine two traditional Chinese formulas, each for a different etiology, to adjust the metabolomic state of the disease model to that of rats at a much younger age. In addition, this attenuation of the metabolomics of the disease model was by neither upregulating the estrogen level nor supplementing an estrogenic compound. Conclusion: Treatment of PMS with a traditional Chinese formula of botanical drugs targeting one of the two causes separately could ameliorate the disorder moderately. However, the best outcome was to treat the two causes simultaneously with a decoction that combined ingredients from two traditional prescriptions. The data also implicated a new paradigm for phytotherapy of PMS as the prescribed decoctions contained no interacting compound to modulate the activity of estrogen receptors, in contrast to the treatment strategy of hormone replacement therapy.

The Metabolomic Rationale for Treating Perimenopausal Syndrome as Kidney Deficiency.

BACKGROUND: Traditional Chinese medicine (TCM) typically attributes the etiopathogenesis of perimenopausal syndrome (PMS) to kidney deficiency in the TCM stratification system for diagnosis. However, the molecular basis of this classical attribution remains to be investigated. Aim of the Study. By unraveling the responses to TCM treatment for kidney deficiency, the metabolomic link between PMS and kidney deficiency can be evaluated for in-depth understanding of the mechanism of TCM treatment and development of better treatment protocols. MATERIALS AND METHODS: With naturally aged rats as a model for PMS, the metabolomic response to TCM treatment for kidney deficiency was investigated by 1H NMR. RESULTS: 1H NMR metabolomic evidence of plasma samples demonstrates that treatments with two classical TCM prescriptions for kidney deficiency, decoctions of Yougui and Zuogui, result in modulating the metabolic state of the disease model towards that of rats of younger age. CONCLUSION: The data support the notion that kidney deficiency is responsible, in part at least, for PMS, and the relevant prescriptions are helpful in dampening the changes in the body's metabolic states to alleviate symptoms of the disorder.

Bone marrow rejuvenation accelerates re-endothelialization and attenuates intimal hyperplasia after vascular injury in aging mice.

BACKGROUND: Aging-associated functional impairment of endothelial progenitor cells (EPCs) contributes to delayed re-endothelialization after vascular injury and exaggerated intimal hyperplasia (IH). This study tested if bone marrow (BM) rejuvenation accelerates post-injury re-endothelialization in aging mice. METHODS AND RESULTS: Using BM transplantation (BMT(Gfp→Wild)), young(Gfp) to young(Wild) (YTY), old(Gfp) to old(Wild) (OTO), young(Gfp) to old(Wild) (YTO), and old(Gfp) to young(Wild) (OTY) groups were created. After vascular injury, IH was significantly greater in the old group than the young group (P<0.001). BM rejuvenation (YTO) significantly accelerated re-endothelialization and attenuated IH. Compared with the OTO group, the YTY and YTO groups had earlier and greater EPC-derived re-endothelialization (P<0.001). The number of Sca-1(+)KDR(+) EPCs mobilized in the circulation induced by vascular injury was higher in young, YTO, and YTY mice than in old mice (P<0.05). Sca-1(+) BM cells from the young, YTO, and YTY groups had better migration and adhesion capacities than those from the old group (P<0.05). The increase in blood vascular endothelial growth factor (VEGF) levels after vascular injury was higher in young than in old mice. PI3K, Akt, and FAK pathways played a pivotal role in VEGF-associated EPC migration. Specifically, EPCs from young and YTO mice, compared with old mice, demonstrated stronger FAK phosphorylation after VEGF stimulation. CONCLUSIONS: EPCs play a critical role in vascular repair in aging mice. BM rejuvenation accelerates re-endothelialization by improving EPC function.

Surface markers of heterogeneous peripheral blood-derived smooth muscle progenitor cells.

OBJECTIVE: Smooth muscle progenitor cells (SMPCs) were intriguingly shown to act as a double-edged sword in the pathogenesis of atherosclerosis. To fully clarify the roles of SMPCs in atherosclerosis, a distinct panel of SMPC surface markers is mandatory to be developed. METHODS AND RESULTS: Microarray gene expression analyses were used to discover potential surface markers of SMPCs. In vitro and in vivo experiments documented that platelet-derived growth factor receptor-ß, carboxypeptidase M, carbonic anhydrase 12, receptor activity-modifying protein 1, and low-density lipoprotein receptor-related protein were the 5 specific surface markers regulating various SMPC functions, including migration, extracellular matrix formation, resistance to hypoxia, and anti-inflammation. In severe combined immunodeficiency/nonobese diabetic mice after femoral arterial wire injury, injected human peripheral blood mononuclear cells contributed to substantial amount of neointimal α-smooth muscle actin-positive cells, coexpressing platelet-derived growth factor receptor-ß, carboxypeptidase M, carbonic anhydrase 12, receptor activity-modifying protein 1, and low-density lipoprotein receptor-related protein. Based on these markers, a novel quantification assay was developed to enumerate circulating early SMPC. Early SMPC numbers were higher in patients with unstable angina compared with those with normal coronary angiograms. In patients with acute ST-elevation myocardial infarction, different patterns of serial early SMPC changes were noted, related to different clinical presentations. CONCLUSIONS: Surface markers of heterogeneous SMPCs exhibit various functions associated with atherosclerotic pathophysiology. Quantification of surface marker-defined SMPCs provides a platform for studying SMPCs in cardiovascular diseases.

Analysis of the correlation between the facial temperature and the stenosis of carotid arteries.

Death caused by stroke above the age of 60 years placed second in the world, and is the fifth leading cause in people aged 15 to 59 years old. Several methods for early detection of stroke are magnetic resonance angiography, and carotid duplex, both diagnoses are cost and time consuming. This research is aimed to provide a noninvasive, cost effective, and rapid technique for diagnosing carotid artery stenosis by using thermography. In this study, 64 images from 32 people were used to analysis the correlation between the temperature of the face and the stenosis of carotid arteries by automatically selecting and calculating the mean and standard deviation of the facial temperature. We find that external carotid artery affects the facial temperature significantly.