Zimmermanfranks9296

Up to now, little is known about the detailed immune profiles of COVID-19 patients from admission to discharge. In this study we retrospectively reviewed the clinical and laboratory characteristics of 18 COVID-19 patients from January 30, 2020 to February 21, 2020. These patients were divided into two groups; group 1 had a severe acute respiratory syndrome coronavirus 2 nucleic acid-positive duration for more than 15 days (n = 6) and group 2 had a nucleic acid-positive duration for less than 15 days (n = 12). Group 1 patients had lower level of peripheral blood lymphocytes (0.40 vs. 0.78 ×109/L, p = 0.024) and serum potassium (3.36 vs. 3.79 mmol/L, p = 0.043) on admission but longer hospitalization days (23.17 vs. 15.75 days, p less then 0.001) compared to Group 2 patients. Moreover, baseline level of lymphocytes (r = -0.62, p = 0.006) was negatively correlated with the nucleic acid-positive duration. Additionally, lymphocytes (420.83 vs. 1100.56 /μL), T cells (232.50 vs. 706.78 /μL), CD4+ T cells (114.67 vs. 410.44 /μL), and CD8+ T cells (94.83 vs. 257.44 /μL) in the peripheral blood analyzed by flow cytometry were significantly different between Group 1and Group 2. Furthermore, there was also a negative correlation between lymphocytes (r = -0.54, p = 0.038) or T cells (r = -0.55, p = 0.034) at diagnosis and the nucleic acid-positive duration, separately. In conclusion, the patients with nucleic acid-positive ≥ 15 days had significantly decreased lymphocytes, T cell and its subsets compared to those who remained positive for less than 15 days.Postmenopausal osteoporosis is characterized by excess osteoclastogenesis which leads to net bone loss and brittle fractures. Studies have demonstrated that estrogen deficiency-associated bone loss is microbiota-dependent and could be prevented by probiotics and prebiotics. In this study, we report that orally administered lactulose (20 g/kg, 6 weeks) orally administered significantly inhibited osteoclastogenesis, bone resorption, and prevented ovariectomy (OVX)-induced bone loss in mice. Lactulose increased intestinal Claudin 2, 3 and 15, compared to the OVX group, and lowered pro-osteoclastogenic cytokines levels including tumor necrosis factor-α, interleukin(IL)-6, receptor activator of nuclear factor kappa-Β ligand (RANKL), and IL-17 as well as increased the anti-inflammatory cytokine IL-10 in the intestine, peripheral blood, and bone marrow. Lactulose significantly preserved the number of Foxp3+ Treg cells in the intestines compared with that in OVX mice. Lactulose altered the composition of intestinal microbiota measured by 16s rDNA sequencing and increased intestinal and serum short-chain fatty acids (SCFAs) levels including acetate, propionate and butyrate which were decreased in OVX mice as measured by gas chromatography. Oral administration of lactulose for 2 weeks significantly lowered the level of bone resorption marker C-telopeptide of type 1 collagen-1 in healthy male young volunteers (aging 20-25 years). In conclusion, lactulose inhibited osteoclastogenesis and bone resorption by altering the intestinal microbiota and increasing SCFAs. Lactulose could serve as an ideal therapeutic agent for postmenopausal osteoporosis.Neuroimaging-driven brain age estimation has introduced a robust (reliable and heritable) biomarker for detecting and monitoring neurodegenerative diseases. Here, we computed and compared brain age in Alzheimer's disease (AD) and Parkinson's disease (PD) patients using an advanced machine learning procedure involving T1-weighted MRI scans and gray matter (GM) and white matter (WM) models. Brain age estimation frameworks were built using 839 healthy individuals and then the brain estimated age difference (Brain-EAD chronological age subtracted from brain estimated age) was assessed in a large sample of PD patients (n = 160) and AD patients (n = 129), respectively. The mean Brain-EADs for GM were +9.29 ± 6.43 years for AD patients versus +1.50 ± 6.03 years for PD patients. For WM, the mean Brain-EADs were +8.85 ± 6.62 years for AD patients versus +2.47 ± 5.85 years for PD patients. In addition, PD patients showed a significantly higher WM Brain-EAD than GM Brain-EAD. In a direct comparison between PD and AD patients, we observed significantly higher Brain-EAD values in AD patients for both GM and WM. A comparison of the Brain-EAD between PD and AD patients revealed that AD patients may have a significantly "older-appearing" brain than PD patients.The complex pathology of chronic thoracic spinal cord compression involves vascular and neuroarchitectural repair processes that are still largely unknown. In this study, we used synchrotron radiation microtomography (SRμCT) to quantitatively characterize the 3D temporal-spatial changes in the vascular and neuronal network after chronic thoracic spinal cord compression in order to obtain further insights into the pathogenesis of this disease and to elucidate its underlying mechanisms. Direct 3D characterization of the spinal cord microvasculature and neural microstructure of the thoracic spinal cord was successfully reconstructed. The significant reduction in vasculature and degeneration of neurons in the thoracic spinal cord visualized via SRμCT after chronic compression were consistent with the changes detected by immunofluorescence staining. The 3D morphological measurements revealed significant reductions of neurovascular parameters in the thoracic spinal cord after 1 month of compression and became even worse after 6 months without relief of compression. In addition, the distinct 3D morphological twist and the decrease in branches of the central sulcal artery after chronic compression vividly displayed that these could be the potential triggers leading to blood flow reduction and neural deficits of the thoracic spinal cord. Our findings propose a novel methodology for the 3D analysis of neurovascular repair in chronic spinal cord compression, both qualitatively and quantitatively. The results indicated that compression simultaneously caused vascular dysfunction and neuronal network impairment, which should be acknowledged as concurrent events after chronic thoracic spinal cord injury. Combining neuroprotection with vasoprotection may provide promising therapeutic targets for chronic thoracic spinal cord compression.Dipeptidyl peptidase 4 (DPP-4) inhibitors exert pleiotropic effects beyond glycemic control. We investigated the renoprotective effects of DPP-4 inhibitors on aging mice mediated by the renin-angiotensin system (RAS). C57BL/6 mice were divided into three groups the two-month-old mice (YM group), the eighteen-month-old mice (AM group) and the eighteen-month-old, linagliptin-treated mice (AM + LIN group). Renal function was improved, based on serum creatinine and cystatin-C levels (p less then 0.05 compared with the AM group for both parameters). Fibrotic areas and the levels of proteins related to fibrosis improved in the AM + LIN group (p less then 0.001 compared with the AM group for all parameters). In the AM + LIN group, the DPP-4-positive area and activity and expressions of DPP-4 were decreased (p less then 0.05 compared with the AM group for all parameters). The levels of proteins related to the RAS, including prorenin receptor, angiotensin-converting enzyme, angiotensin II and angiotensin 1 receptor, were decreased in the AM + LIN group (p less then 0.05, p less then 0.01, p less then 0.05, and p less then 0.01 compared with the AM group, respectively). NADPH oxidase 2 and NADPH oxidase 4 levels decreased in the AM + LIN group (p less then 0.001 compared with the AM group for both proteins), whereas the levels of endothelial nitric oxide synthase (eNOS) phosphorylated at serine1177 and superoxide dismutase 1 were increased (p less then 0.01 compared with the AM group for both proteins). DPP-4 inhibitors may exert renoprotective effects via prorenin receptor/angiotensin-converting enzyme/angiotensin II/angiotensin 1 receptor axis.Aging-related adipose tissue dysfunction contributes to the progression of chronic metabolic diseases. We investigated the role of age-dependent expression of a neurotrophin, brain-derived neurotrophic factor (BDNF) in adipose tissue. Pro-BDNF expression was elevated in epididymal white adipose tissue (eWAT) with advanced age, which was associated with the reduction in sympathetic innervation. Interestingly, BDNF expression was enriched in PDGFRα+ adipocyte progenitors isolated from eWAT, with age-dependent increase in expression. In vitro pro-BDNF treatment caused apoptosis in adipocytes differentiated from C3H10T1/2 cells, and siRNA knockdown of sortilin mitigated these effects. Tamoxifen-inducible PDGFRα+ cell-specific deletion of BDNF (BDNFPdgfra KO) reduced pro-BDNF expression in eWAT, prevented age-associated declines in sympathetic innervation and mitochondrial content in eWAT, and improved insulin sensitivity. Moreover, BDNFPdgfra KO mice showed reduced expression of aging-induced inflammation and senescence markers in eWAT. Collectively, these results identified the upregulation of pro-BDNF expression in adipocyte progenitors as a feature of visceral white adipose tissue aging and suggested that inhibition of BDNF expression in adipocyte progenitors is potentially beneficial to prevent aging-related adipose tissue dysfunction.Parkinson's disease (PD), the second most common neurodegenerative disorder, is neuropathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the presence of Lewy bodies in surviving neurons. selleck compound α-synuclein (α-syn) is the major component of Lewy bodies and its deposition in neurons is critical pathological event in the pathogenesis of PD. Herein, we reported that Oxyphylla A, a novel lead compound from the fruit of Alpinia oxyphylla, significantly promoted α-syn degradation in a cellular PD model. When exploring the molecular pathways, we found that Oxyphylla A promoted α-syn degradation in a ubiquitin proteasome system (UPS)-dependent and autophagy-independent manner. We further confirmed that Oxyphylla A enhanced UPS activity by upregulating 20S subunit PSMB8 expression. A mechanism study revealed that Oxyphylla A activated the PKA/Akt/mTOR pathway to trigger PSMB8 expression and enhance UPS activity. Finally, we illustrated that Oxyphylla A alleviated the accumulation of both Triton-soluble and Triton-insoluble forms of α-syn and protected against α-syn-induced neurotoxicity in A53T α-syn transgenic mice. These findings suggest that the activation of UPS, via small molecular UPS enhancers including Oxyphylla A, may be a therapeutic strategy for intervention against PD and related diseases.The receptor for advanced glycation end-products (RAGE) is expressed on human brain endothelial cells (HBEC) and is implicated in neuronal cell death after ischemia. We report that endogenous secretory RAGE (esRAGE) is a splicing variant form of RAGE that functions as a decoy against ischemia-induced neuronal cell damage. This study demonstrated that esRAGE was associated with heparan sulphate proteoglycans on HBEC. The parabiotic experiments between human esRAGE overexpressing transgenic (Tg), RAGE knockout (KO), and wild-type (WT) mice revealed a significant neuronal cell damage in the CA1 region of the WT side of parabiotic WT→WT mice, but not of Tg→WT mice, 7 days after bilateral common carotid artery occlusion. Human esRAGE was detected around the CA1 neurons in the WT side of the parabiotic Tg→WT pair, but not in the KO side of the Tg→KO pair. To elucidate the dynamic transfer of esRAGE into the brain, we used the blood-brain barrier (BBB) system (PharmaCo-Cell) with or without RAGE knockdown in endothelial cells.