Gut microbiota interacts with host immune system in ways that influence the development of disease. Advances in respiratory immune system also broaden our knowledge of the interaction between host and microbiome in the lung. Increasing evidence indicated the intimate relationship between the gastrointestinal tract and respiratory tract. Exacerbations of chronic gut and lung disease have been shown to share key conceptual features with the disorder and dysregulation of the microbial ecosystem. In this review, we discuss the impact of gut and lung microbiota on disease exacerbation and progression, and the recent understanding of the immunological link between the gut and the lung, the gut-lung axis.
Hmgb1, an evolutionarily conserved chromosomal protein, was recently re-discovered to be an innate immune-mediator contributing to both innate and adaptive immune responses. Here, we show a pivotal role for Hmgb1 in acute allograft rejection in a murine cardiac transplantation model. Extracellular Hmgb1 was found to be a potent stimulator for adaptive immune responses. Hmgb1 can be either passively released from damaged cells after organ harvest and ischemia/reperfusion insults, or actively secreted by allograft infiltrated immune cells. After transplantation, allografts show a significant temporal upregulation of Hmgb1 expression accompanied by inflammatory infiltration, a consequence of graft destruction. These data suggest the involvement of Hmgb1 in acute allograft rejection. In line with these observations, treatment of recipients with rA-box, a specific blockade for endogenous Hmgb1, significantly prolonged cardiac allograft survival as compared to those recipients treated with either rGST or control vehicle. The enhanced graft survival is associated with reduced allograft expression of TNFa , IFNc and Hmgb1 and impaired Th1 immune response.
Introduction Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. Aim To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. Methods Twenty-eight male rats were induced to develop hyperlipidemia with a high fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for one week, labeled with 5-ethynyl-2′-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate-buffered saline (PBS). At 3 and 14 days post-transplantation, 4 rats in the HR+ADSC group were sacrificed for tracking of the transplanted cells. At one month post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function and penile histology. Main Outcome Measures Erectile function was assessed by intracavernous pressure measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. Results Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean intracavernous pressure/mean arterial pressure ratio was significantly lower in HR+PBS than in NR+PBS or HR+ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR+PBS than in HR+ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. Conclusions Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED.
Purpose It has been previously demonstrated that adipose tissue-derived stem cell (ADSC) can differentiate into muscle and neuron-like cells in vitro. In this study, we investigate the utility of ADSC in the treatment of overactive bladder (OAB) in obese hyperlipidemic rats (OHR). Materials and Methods Hyperlipidemia was induced in healthy rats by administration of a high fat diet. The resulting OHR were then treated with bladder injection of saline or ADSC or tail vein injection of ADSC. Bladder function was assessed by 24-h voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining followed by image analysis. Results Serum total cholesterol and low-density lipoprotein levels were significantly higher in OHR than in normal rats (p < 0.01). Micturition intervals were shorter in the saline-treated OHR relative to normal rats, OHR that received ADSC via tail vein, and OHR that received ADSC by bladder injection (143 ± 28.7 vs 407 ± 77.9 vs 281 ± 43.9 vs 368 ± 66.7 seconds respectively, p = 0.0084). Smooth muscle content of the bladder wall was significantly lower in OHR than in normal animals (p = 0.0061) while there was no significant difference between OHR groups. Nerve content and blood vessel density were lower in control than in ADSC-treated OHR. Conclusions Hyperlipidemia is associated with increased urinary frequency and diminished bladder blood vessel and nerve density in rats. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for OAB.
The emerging coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic, and brings formidable challenges to public health, society and the economy worldwide. Currently, the antibody responses against SARS‐CoV‐2 remains largely unknown. We herein estimated the longevity of specific antibodies against SARS‐CoV‐2, and reported that antibodies waned over substantially in COVID‐19 patients after recovery. This article is protected by copyright. All rights reserved.
Background-Thymidine analog bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) has been widely used to label cells in culture and in tissue. The labeled cells can also be tracked when transplanted into a suitable host. In the present study we tested a new thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for labeling and tracking of mesenchymal stem cells (MSC), specifically adipose tissue-derived stem cells (ADSC).
Kim-1 is a potential novel urinary biomarker in the early detection of AKI within 24 hours after kidney insult. It might be especially beneficial in the diagnosis of ischemic ATN.
Introduction Epimedium species (aka horny goat weed) have been utilized for the treatment of erectile dysfunction in Traditional Chinese Medicine for many years. Icariin (ICA) is the active moiety of Epimedium species. Aim To evaluate the penile hemodynamic and tissue effects of ICA in cavernous nerve injured rats. We also studied the in vitro effects of ICA on cultured pelvic ganglia. Methods Rats were subjected to cavernous nerve injury and subsequently treated for 4 weeks with daily gavage feedings of a placebo solution of normal saline and Dimethyl sulfoxide (DMSO) vs. ICA dissolved in DMSO at doses of 1, 5, and 10 mg/kg. A separate group underwent a single dose of ICA 10 mg/kg 2 hours prior to functional testing. Functional testing with cavernous nerve stimulation and real-time assessment of intracavernous pressure (ICP) was performed at 4 weeks. After functional testing, penile tissue was procured for immunohistochemistry and molecular studies. In separate experiments, pelvic ganglia were excised from healthy rats and cultured in the presence of ICA, sildenafil, or placebo culture media. Main Outcome Measure Ratio of ICP and area under the curve (AUC) to mean arterial pressure (MAP) during cavernous nerve stimulation of subject rodents. We also assayed tissue expression of neuronal nitric oxide synthase (nNOS), eNOS: endothelial nitric oxide synthase (eNOS), calponin, and apoptosis via immunohistochemistry and Western blot. Serum testosterone and luteinizing hormone (LH) were assayed using enzyme-linked immunosorbant assay (ELISA). Differential length of neurite outgrowth was assessed in cultured pelvic ganglia. Results Rats treated with low-dose ICA demonstrated significantly higher ICP/MAP and AUC/MAP ratios compared with control and single-dose ICA animals. Immunohistochemistry and Western blot were revealing of significantly greater positivity for nNOS and calponin in penile tissues of all rats treated with ICA. ICA led to significantly greater neurite length in cultured specimens of pelvic ganglia. Conclusion ICA may have neurotrophic effects in addition to known phosphodiesterase type 5 inhibiting effects.
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