Neuroinflammation, especially innate immunocyte-mediated neuroinflammation, has been reported to participate in pathogenesis of Alzheimer's disease (AD). However, the involvement of adaptive immune ...cells, such as CD4(+) T lymphocytes, in pathogenesis of AD is not well clarified. Herein, we focus on T helper 17 (Th17) cells, a subpopulation of CD4(+) T cells with high proinflammation, and show the implication of the cells in neurodegeneration of AD. Amyloid β1-42 (Aβ1-42) was bilaterally injected into hippocampus of rats to induce AD. On days 7 and 14 following the Aβ1-42 administration, escape latency of the rats in Morris water maze was increased, expression of amyloid precursor protein was upregulated, but expression of protein phosphatase 2A was downregulated in the hippocampus, and Nissl stain showed neuronal loss and gliosis in CA1 region. Infusion of FITC-linked albumin in blood circulation and combination with immunostaining of hippocampal sections for RORγ, a specific transcriptional factor of Th17 cells, demonstrated blood-brain barrier (BBB) disruption and Th17 cells' infiltration into brain parenchyma of AD rats. Expression of Th17 proinflammatory cytokines, interleukin (IL)-17 and IL-22, was increased in the hippocampus, and concentrations of the two cytokines were elevated in both the cerebrospinal fluid and the serum in AD occurrence and development. Compared with intact or saline-treated control rats, AD animals indicated an upregulated expression of Fas and FasL in the hippocampus. Further, the immunofluorescent histochemistry on AD hippocampal sections with NeuN, RORγ, Fas and FasL displayed that Fas was principally expressed by neurons and FasL was predominantly expressed by Th17 cells, and that neuronal apoptosis shown by TUNEL and NeuN double-labeled cells increased. These results suggest that Th17 cells, which were infiltrated into AD brain parenchyma, participate in neuroinflammation and neurodegeneration of AD by release of proinflammatory cytokines and by direct action on neurons via Fas/FasL apoptotic pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuroinflammation has been reported to be associated with Alzheimer's disease (AD) pathogenesis. Neuroinflammation is generally considered as an outcome of glial activation; however, we recently ...demonstrated that T helper (Th)17 cells, a subpopulation of proinflammatory CD4+ T cells, are also involved in AD pathogenesis. Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, can be immunosuppressive, but its effects on lymphocyte-mediated neuroinflammation in AD pathogenesis have not been well addressed. In the current study we administered TGF-β1 via intracerebroventricle (ICV) and intranasal (IN) routes in AD model rats to investigate its antiinflammatory and neuroprotective effects. The AD rat model was prepared by bilateral hippocampal injection of amyloid-β (Aβ)1-42. TGF-β1 was administered via ICV one hour prior to Aβ1-42 injection or via both nares seven days after Aβ1-42 injection. ICV administration of TGF-β1 before Aβ1-42 injection remarkably ameliorated Aβ1-42-induced neurodegeneration and prevented Aβ1-42-induced increases in glia-derived proinflammatory mediators (TNF-α, IL-1β and iNOS), as well as T cell-derived proinflammatory cytokines (IFN-γ, IL-2, IL-17 and IL-22), in the hypothalamus, serum or cerebrospinal fluid (CSF) in a concentration-dependent manner. TGF-β1 pretreatment also prevented Aβ1-42-induced decreases in the neurotrophic factors, IGF-1, GDNF and BDNF, and in the antiinflammatory cytokine, IL-10. Similarly, IN administration of TGF-β1 after Aβ1-42 injection reduced neurodegeneration, elevation of proinflammatory mediators and cytokines, and reduction of neurotrophic and antiinflammatory factors, in the hypothalamus, serum or CSF. These findings suggest that TGF-β1 suppresses glial and T cell-mediated neuroinflammation and thereby alleviates AD-related neurodegeneration. The effectiveness of IN administered TGF-β1 in reducing Aβ1-42 neurotoxicity suggests a possible therapeutic approach in patients with AD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bone defects are a common clinical issue, but therapeutic efficiency can be challenging in cases of more considerable traumas or elderly patients with degenerated physiological metabolism. To address ...this issue, a more suitable cell‐biomaterial construct promoting bone regeneration has been extensively investigated, with the chitosan scaffold being considered a potential candidate. In this study, chitosan was crosslinked with different doses of glucose (CTS‐10~50%Glc) using a modified Maillard reaction condition to develop a more appropriate cell‐biomaterial construct. Mouse MC3T3‐E1 pre‐osteoblasts were seeded onto the scaffolds to examine their osteoinductive capability. The results showed that CTS‐Glc scaffolds with higher glucose contents effectively improved the adhesion and survival of mouse MC3T3‐E1 pre‐osteoblasts and promoted their differentiation and mineralization. It was further demonstrated that the membrane integrin α5 subunit of pre‐osteoblasts is the primary adhesion molecule that communicates with CTS‐Glc scaffolds. After that, Akt signaling was activated, and then bone morphogenetic protein 4 was secreted to initiate the osteoinduction of pre‐osteoblasts. The prepared CTS‐Glc scaffold, with enhanced osteoinduction capability and detailed mechanism elucidations, offers a promising candidate material for advancing bone tissue engineering and clinical regenerative medicine. As a result, this study presents a potential tool for future clinical treatment of bone defects.
The theory of inflammation is one of the important theories in the pathogenesis of diabetic nephropathy (DN). We herein aimed to explore whether loganin affected macrophage infiltration and ...activation upon diabetic nephropathy (DN) by a spontaneous DN mice and a co-culture system of glomerular mesangial cells (GMCs) and macrophage cells (RAW264.7) which was induced by advanced glycation end products (AGEs).
Loganin showed remarkable capacity on protecting renal from damage by mitigating diabetic symptoms, improving the histomorphology of the kidney, decreasing the expression of extracellular matrix such as FN, COL-IV and TGF-β, reversing the production of IL-12 and IL-10 and decreasing the number of infiltrating macrophages in the kidney. Moreover, loganin showed markedly effects by suppressing iNOS and CD16/32 expressions (M1 markers), increasing Arg-1 and CD206 expressions (M2 markers), which were the phenotypic transformation of macrophage. These effects may be attributed to the inhibition of the receptor for AGEs (RAGE) /monocyte chemotactic protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2) signaling pathway, with significantly down-regulated expressions of RAGE, MCP-1 and CCR2 by loganin. Loganin further decreased MCP-1 secretion when RAGE was silenced, which means other target was involved in regulating the MCP-1 expression. While loganin combinated with the inhibitor of CCR2 exerted stronger anti-inhibition effects of iNOS expression, suggesting that CCR2 was the target of loganin in regulating the activation of macrophages.
Loganin could ameliorate DN kidney damage by inhibiting macrophage infiltration and activation via the MCP-1/CCR2 signaling pathway in DN.
The aim of the present large population-based cohort study is to explore the risk factors of age-related mortality in liver transplant recipients in Taiwan. Basic information and data on medical ...comorbidities for 2938 patients who received liver transplants between July 1, 1998, and December 31, 2012, were extracted from the National Health Insurance Research Database on the basis of ICD-9-codes. Mortality risks were analyzed after adjusting for preoperative comorbidities and compared among age cohorts. All patients were followed up until the study endpoint or death. This study finally included 2588 adults and 350 children 2068 (70.4%) male and 870 (29.6%) female patients. The median age at transplantation was 52 (interquartile range, 43-58) years. Recipients were categorized into the following age cohorts: <20 (n = 350, 11.9%), 20-39 (n = 254, 8.6%), 40-59 (n = 1860, 63.3%), and ≥60 (n = 474, 16.1%) years. In the total population, 428 deaths occurred after liver transplantation, and the median follow-up period was 2.85 years (interquartile range, 1.2-5.5 years). Dialysis patients showed the highest risk of mortality irrespective of age. Further, the risk of death increased with an increase in the age at transplantation. Older liver transplant recipients (≥60 years), especially dialysis patients, have a higher mortality rate, possibly because they have more medical comorbidities. Our findings should make clinicians aware of the need for better risk stratification among elderly liver transplantation candidates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Based on previous studies about microflora regulation and immunity enhancement activities of polysaccharides from
Nannf. var.
(Nannf.) L. T. Shen (CPP), there is little study on intestinal mucosal ...immunity, which is a possible medium for contacting microflora and immunity. In the present study, the BALB/c mice were divided into five groups (eight mice in each group), including a normal group (Con), a model control group (Model), and model groups that were administered CPP (50, 100, 200 mg/kg/d) orally each day for seven days after intraperitoneal injection of 60 mg/kg BW/d cyclophosphamide (CP) for three days. CPP recovered the spleen index and restored the levels of IFN-γ, IL-2, IL-10, as well as serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA), the number of
and acetic acid content in cecum. These results indicated that CPP plays an important role in the protection against immunosuppression, especially mucosa immune damage, and the inhibition of pathogenic bacteria colonization, which could be considered a potential natural source of immunoregulator.
Aconitum septentrionale is known to contain toxic diterpene alkaloids, while other bioactive compounds in the plant remain unclear. The aim of this study was to explore the phenolic compounds and ...polysaccharides from the water extract of A. septentrionale roots. Fifteen phenolic compounds were isolated and identified by NMR and MS, including fourteen known and one new dianthramide glucoside (2‐2‐(β‐D‐glucopyranosyloxy)‐5‐hydroxybenzoylamino‐4,5‐dihydroxybenzoic acid methyl ester, 14). One neutral (complex of glucans with minor amounts of mannans) and two acidic polysaccharide fractions (complexes of pectic polysaccharides and glucans) were also obtained. Hydroxytyrosol (1), hydroxytyrosol‐1‐O‐β‐glucoside (2) and bracteanolide A (7) inhibited the release of nitric oxide by dendritic cells. Magnoflorine (8) and 2‐2‐(β‐D‐glucopyranosyloxy)‐5‐hydroxybenzoylamino‐5‐hydroxybenzoic acid methyl ester (12) inhibited 15‐lipoxygenase, and bracteanolide A (7) was a moderate inhibitor of xanthine oxidase. This study is the first to describe the diversity of phenolics and polysaccharides from A. septentrionale and their anti‐inflammatory and anti‐oxidant activities.
Given the high cost and poisoning issues of Pt, developing Pd-based catalysts as substitutes is highly essential. Although substantial progress has been made, the synthesis of Pd-based ...electrocatalysts with both high activity and stability in the oxygen reduction reaction (ORR) remains a challenge. In this work, we prepared Pd-Ag nanowires with up to micro-sized length and a diameter of ∼17 nm
via
a facile modified polyol method. The obtained Pd-Ag nanowires (NWs) exhibit interlaced features and are rich in grain boundary defects. Due to the continuous grain boundaries in the one-dimensional (1D) structure and the optimized composition, the synthesized Pd
1
Ag
1
NWs show half-wave potential of 0.897 V and mass activity of 0.103 A mg
−1
in alkaline media toward ORR, higher than those of both state-of-the-art Pt/C and other Pd-Ag counterparts. Significantly, after stability tests over 5000 cycles, Pd
1
Ag
1
NWs shows a 2 mV positive shift, much better than that of Pt/C, exhibiting striking stability for ORR. This work may provide an avenue to construct advanced catalysts by surface defect engineering.
Pd-Ag interlaced nanowires with grain boundary defect engineering exhibit enhanced activity and superior stability for oxygen reduction reaction in alkaline media.
Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration ...and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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