Background: Exercise-Induced Bronchospasm (EIB) is an inflammatory condition characterized by severe airway constriction following the mobilization of inflammatory cells and interleukin-6 (IL-6). When severe, EIB can ...Background: Exercise-Induced Bronchospasm (EIB) is an inflammatory condition characterized by severe airway constriction following the mobilization of inflammatory cells and interleukin-6 (IL-6). When severe, EIB can require the use of pressurized salbutamol to treat athletes. This study investigated the nature of the systemic changes in inflammatory cells and post-exercise IL-6 concentrations after salbutamol treatment in EIB-susceptible distance runners. Materials and Methods: This was an experimental study that enrolled 12 long-distance runners. In Session A, the participants completed a treadmill exercise test, and those who had a maximum expiratory volume per second (FEV1) that was decreased by at least 10% compared to their base value were placed in the EIB-susceptible group (EIB+) (n = 6). Those whose FEV1 did not meet this criterion were placed in the nonresponsive (EIB?) group (n = 6). Before the Session B exercise, athletes in the BIE+ group inhaled two puffs of salbutamol (EIB+ Salb), while their EIB? counterparts received no treatment. Spirometry was performed before and after the exercise using a Spirobank G portable spirometer. Blood samples were taken before, immediately after and 2 hours after the stress test. Results: The mean post-exercise FEV1 values were not significantly different (p > 0.05) between the EIB+ Salb group and the EIB? group. The systemic changes in inflammatory cells and IL-6 concentrations in the EIB+ runners after salbutamol treatment were similar to those observed in their EIB? counterparts. Conclusion: Salbutamol pretreatment improved the systemic immune status of EIB-susceptible athletes.展开更多
Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of ...Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts(CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and noncellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a contextdependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.展开更多
BACKGROUND:Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE: To observe changes in white blood cells (WBC) and poly...BACKGROUND:Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE: To observe changes in white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING: A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences between August 2007 and May 2008. PARTICIPANTS: Sixty-three patients, admitted within 24 hours after craniocerebral injury and who received no surgery, were included in the study. The cohort consisted of 41 males and 22 females, aged 9–72 years, with an average age of 42 years. Ten healthy volunteers, selected from the Department of Neurosurgery, were designated as the control group. METHODS: WBC and PMN from the peripheral blood were measured 0, 24, 48, 72, and 168 hours after admission to hospital. The Glasgow coma scale, area of cerebral hemorrhage, and degree of brain edema were simultaneously determined. The Glasgow outcome scale was evaluated six months after injury. The relationship between changes in WBC and PMN were analyzed. Sixty-three patients were divided into 0, 24, 48, 72, and 168 hours groups, with admission time to hospital as the determining factor. As controls, WBC and PMN of peripheral blood were also detected in 10 healthy volunteers. MAIN OUTCOME MEASURES: The main outcome measures were WBC and PMN counts in the peripheral blood at 0, 24, 48, 72, and 168 hours after admission to hospital, the mutual relationship between GCS, WBC and PMN, and changes in brain hemorrhage volume and edema size. RESULTS: WBC peaked at 24 hours after injury, and PMN peaked at 48 hours after injury (P 〈 0.01). These measures negatively correlated to the Glasgow coma scale (r = -0.657, -0.541, respectively, P 〈 0.05). In patients with Glasgow coma sale 〈 8, WBC and PMN were significantly higher than in the patients with GCS ≥ 8 (P 〈 0.05). Cerebral hemorrhage reached a peak at 24 hours after injury, and the degree of brain edema was maximal at 168 hours after injury. WBC and PMN counts were positively correlated to cerebral hemorrhage volume and brain edema size (P 〈 0.05). CONCLUSION: WBC and PMN counts significantly increased after craniocerebral injury and exhibited a correlation with the GCS score, volume of hemorrhage and edema, and Glasgow outcome scale.展开更多
Subepidermal autoimmune bullous diseases (SABD) are some autoimmune skin diseases that can present in a variety of forms and can be a challenging disease to treat. An overview of the different forms of SABD are disc...Subepidermal autoimmune bullous diseases (SABD) are some autoimmune skin diseases that can present in a variety of forms and can be a challenging disease to treat. An overview of the different forms of SABD are discussed including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), cicatricial pemphigoid (CP), bullous systemic lupus erythematosus (BSLE), and Anti-p200 pemphigoid. Emphasis on recent advancement is presented. In recent years, improved knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in some SABD. Defects of such structures cause the subepidermal bullous diseases and have also led to the discovery of new diseases (e.g. anti-p200-pemphigoid). Recent studies have outlined the important role of autoantibodies, mast cell lymphocytes and their cytokines in pathogenesis of SABD.展开更多
Objective: To find out possible associations between wound inflammatory cell response and the patients’ survival. Background: Several articles have written about the effects of single inflammatory cell types on wound...Objective: To find out possible associations between wound inflammatory cell response and the patients’ survival. Background: Several articles have written about the effects of single inflammatory cell types on wound healing but little is known about the interaction of these cells on survival. The methods used in this study have made possible this kind of exploration. Methods: One hundred patients, aged from 41 to 78 years, underwent open heart surgery in the years 1998-1999 and were studied by using the Cellstick device for harvesting wound inflammatory cells during the first 24 hours after surgery. The results of the differential count were computerized by using artificial neural network for obtaining wound inflammatory cell node (WICN). The patients were followed up for sixteen years or to the death. WICN values were compared with the patients’ survival. Results: WICN reflects survival better than any single type of wound inflammatory cells alone (HR = 3.1;p = 0.081 for low/high WICN at 10 year survival). From several clinical characteristics diabetes only predicted shorter survival time (HR = 5.5;p = 0.014 for 10 year survival) better than WICN. Conclusion: These results support the view that regularly timed cell-to-cell ratios in wound inflammation, most often seen as high WICN, reflect beneficial survival. Instead, aberrant counts of inflammatory cells in the wounds lead to low WICN and often to the patients’ shorter survival.展开更多
Chronic obstructive pulmonary disease </span><span style="font-family:""><span style="font-family:Verdana;">(COPD) is a major chronic respiratory disease worldwide. Inflammat...Chronic obstructive pulmonary disease </span><span style="font-family:""><span style="font-family:Verdana;">(COPD) is a major chronic respiratory disease worldwide. Inflammatory cells reflect the </span><span style="font-family:Verdana;">inflammatory situation both in peripheral blood and induced sputum. </span></span><span style="font-family:""><span style="font-family:Verdana;">Their correlation has not been reported. </span><span style="font-family:Verdana;">The correlation between neutrophils (Neu), eosinophils (Eos), and lymphocyte (Lym) in induced sputum and that in peripheral blood of COPD </span><span style="font-family:Verdana;">patients was evaluated </span><span><span style="font-family:Verdana;">to explore the </span><span style="font-family:Verdana;">consistency of inflammatory cells in peripheral blood and induced sputum. Peripheral blood and induced sputum were collected from 437 </span><span style="font-family:Verdana;">patients with acute exacerbation of COPD</span></span><span style="font-family:Verdana;"> (AECOPD) who were hospitalized in the Department of respiratory and critical care medicine, Inner Mongolia People’s Hospital. </span><span style="font-family:Verdana;">The correlation analysis was performed by Spearman correlation analysis. </span><span style="font-family:Verdana;">The r</span><span style="font-family:Verdana;">atios of Neu, Eos, and Lym in induced sputum were (79.15 ± 22.60)%, (5.23 ± 12.74)%, and (1.69 ± 2.66)%. The ratios of </span><span style="font-family:Verdana;">Neu, Eos, and Lym in </span><span style="font-family:Verdana;">peripheral blood were (63.29 ± 11.44)%, (2.99 ± 3.60)%, and (25.16 ± 10.19)%. The results showed that the ratios of Neu and Eos in induced sputum were significantly correlated with the proportion of </span><span style="font-family:Verdana;">corresponding cells in peripheral blood (P < 0.05). </span><span style="font-family:Verdana;">There was no correlation between the ratio of Lym and Leu in induced sputum and corresponding cells in </span><span style="font-family:Verdana;">peripheral blood (P > 0.05). In patients with AECOPD, the tendency of Neu and Eos in induced sputum was </span><span style="font-family:Verdana;">consistent with the corresponding cells in peripheral blood. Neu and Eos in </span><span style="font-family:Verdana;">induced sputum and peripheral blood reflected the degree of inflammation to guide the individualized medication of patients.展开更多
<strong>Introduction: </strong>Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts an...<strong>Introduction: </strong>Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) from our routine practice for the predictor of prognosis of breast cancer after resection. <strong>Patients and</strong> <strong>Methods: </strong>There were 574 breast cancer patients accepted surgical resection and registered in Cancer Registry Center of our hospital. Patient’s basic profiles, peripheral neutophil, lymphocyte and platelet count were measured for study. The scales of NLR and PLR were derived from the lower and higher normal range in cell count from neutrophil, lymphocyte and platelet respectively. Therefore, the scales for NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively for analysis. <strong>Results: </strong>Poor 5-yr survival rate was found if higher cell counts of neutrophil and platelet (p ≤ 0.05). Three scales of NLR were ≤1.62, 1.63 - 2.57, ≥2.58, and their 5-year survival rates were 94%, 91% and 84% respectively (p = 0.019). In the subgroup of HER-2 (negative), and 3-Negative breast patients had a higher NLR of poor prognosis. But higher PLR was found less in 3-Negative and non in 3-Positive patients (p = 0.039). The PLR was ≤224, 225 - 253, ≥254 and their 5-year survival rates were 92%, 87%, and 64% respectively (p = 0.001);Multivariate Cox regression model for predictor of breast cancer patients who have 3.39 (PLR ≥ 254) and 2.45 (NLR ≥ 2.58 ) times risk (p = 0.02 and p = 0.002) of poor prognosis respectively. <strong>Conclusion: </strong>Peripheral inflammatory cell counts are easily to take in our clinical practice and have a potential role as predictors of prognosis. We have to pay attention to the trends of peripheral inflammatory cell count and their ratio in our clinical practice where possible.展开更多
AIM: To find out the effect of Cat's whiskers (Cleome gynandra L., Capparidaceae) flavonoid (CWF) for the scavenging of free radicals in some inflammatory cells. METHODS: Mouse erythrocyte's hemoglobin, perito...AIM: To find out the effect of Cat's whiskers (Cleome gynandra L., Capparidaceae) flavonoid (CWF) for the scavenging of free radicals in some inflammatory cells. METHODS: Mouse erythrocyte's hemoglobin, peritoneal macrophage, and peripheral blood lymphocytes were oxidized either by some of toxic chemicals (nitrite, carbon tetrachloride) or by enzymatic stimulation (glu- coseoxidase) to produce oxidative damage to cells. The protective effect of the CWF was examined, and the biochemical mechanism of action was also investigated in terms of the scavenging of free radicals. RESULTS: CWF (1 20 μg mL 1 ) decreased glucoseoxidase and nitrite induce oxidative damage in a concentration dependent manner in an in vitro model and inhibited the lysis of RBC [(28.64 ± 13.03)% and (70.31 ± 1.80)%] when mice were treated with CWF (25 and 50 mg kg 1 ). To assess the antioxidant potential of CWF in the lymphocytes and macrophages in living animals, the effect of CWF was measured on the elevated level of superoxide anions production in the cells. CWF scavenged the superoxide anion (O 2 ) production and inhibited the O 2 induced destruction of protein and lipid biomolecules. CONCLUSION: The study has established that the CWF mediates its antioxidant activity in some chronic inflammatory cells via its free radical scavenging activity.展开更多
Inflammatory bowel disease (IBD) affects a part of the young population and has a strong impact upon quality of life. The underlying etiology is not known, and the existing treatments are not curative. Furthermore, a ...Inflammatory bowel disease (IBD) affects a part of the young population and has a strong impact upon quality of life. The underlying etiology is not known, and the existing treatments are not curative. Furthermore, a significant percentage of patients are refractory to therapy. In recent years there have been great advances in our knowledge of stem cells and their therapeutic applications. In this context, autologous hematopoietic stem cell transplantation (HSCT) has been used in application to severe refractory Crohn’s disease (CD), with encouraging results. Allogenic HSCT would correct the genetic defects of the immune system, but is currently not accepted for the treatment of IBD because of its considerable risks. Mesenchymal stem cells (MSCs) have immune regulatory and regenerative properties, and low immunogenicity (both autologous and allogenic MSCs). Based on these properties, MSCs have been used via the systemic route in IBD with promising results, though it is still too soon to draw firm conclusions. Their local administration in perianal CD is the field where most progress has been made in recent years, with encouraging results. The next few years will be decisive for defining the role of such therapy in the management of IBD.展开更多
Bone formation is important for the reconstruction of bone-related structures in areas that have been damaged by inflammation.Inflammatory conditions such as those that occur in patients with rheumatoid arthritis, cys...Bone formation is important for the reconstruction of bone-related structures in areas that have been damaged by inflammation.Inflammatory conditions such as those that occur in patients with rheumatoid arthritis, cystic fibrosis, and periodontitis have been shown to inhibit osteoblastic differentiation. This study focussed on dental follicle stem cells(DFSCs), which are found in developing tooth germ and participate in the reconstruction of alveolar bone and periodontal tissue in periodontal disease. After bacterial infection of inflamed dental tissue, the destruction of bone was observed. Currently, little is known about the relationship between the inflammatory environment and bone formation. Osteogenic differentiation of inflamed DFSCs resulted in decreased alkaline phosphatase(ALP) activity and alizarin red S staining compared to normal DFSCs. Additionally, in vivo transplantation of inflamed and normal DFSCs demonstrated severe impairment of osteogenesis by inflamed DFSCs. Protein profile analysis via liquid chromatography coupled with tandem mass spectrometry was performed to analyse the differences in protein expression in inflamed and normal tissue. Comparison of inflamed and normal DFSCs showed significant changes in the level of expression of transforming growth factor(TGF)-β2. Porphyromonas gingivalis(P.g.)-derived lipopolysaccharide(LPS) was used to create in vitro inflammatory conditions similar to periodontitis. The osteogenic differentiation of LPS-treated DFSCs was suppressed, and the cells displayed low levels of TGF-β1 and high levels of TGF-β2. DFSCs treated with TGF-β2 inhibitors showed significant increases in alizarin red S staining and ALP activity. TGF-β1 expression was also increased after inhibition of TGF-β2. By examining inflamed DFSCs and LPS-triggered DFSCs, these studies showed both clinically and experimentally that the increase in TGF-β2 levels that occurs under inflammatory conditions inhibits bone formation.展开更多
AIM:To investigate the effect of anti-vascular epithelial growth factor(VEGF)agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mecha...AIM:To investigate the effect of anti-vascular epithelial growth factor(VEGF)agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS:Human retinal pigment epithelial(RPE)cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following:1)control group:no treatment; 2)bevacizumab group:bevacizumab at 0.25 mg/mL was added to the media; 3)hypoxia group:CoCl_2 at 200 μmol/L was added to the media; 4)hypoxia+bevacizumab group:CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin(IL)-1β,IL-6,IL-8 and tumor necrosis factor(TNF)-α were evaluated using real-time polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at 6,12,24 and 48 h. RESULTS:Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h(P〈0.05). Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h(P〈0.05). IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION:Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.展开更多
Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an in...Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1(HMGB1), is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products(RAGE), but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.展开更多
To explore changes of toll-like receptor (TLR) 2,4 in peripheral blood mononuclear cells (PBMC) in acute abdomen patients with systemic inflammatory response syndrome (SIRS) and their significance.Methods A clinical s...To explore changes of toll-like receptor (TLR) 2,4 in peripheral blood mononuclear cells (PBMC) in acute abdomen patients with systemic inflammatory response syndrome (SIRS) and their significance.Methods A clinical study was done on 103 patients of which 65 were with SIRS.The mRNA expression of TLR2,4 were detected by RT-PCR;the expression of TNF-α and IL-6 were observed by ELISA;the correlation between TLR2,4 mRNA,the level of TNF-α and IL-6,and the clinical course was evaluated.Results TLR2 mRNA ,TNF-α and IL-6 were upregulated markedly on the first day of hospitalization,then decreased gradually;TLR2 mRNA maintained on high level till the 5th day.The expression of TLR2,4 mRNA was positive correlated with the level of TNF-α and IL-6,and the length of stay.TLR2,4 mRNA expression increased in patients with multiple organ failure.Conclusion In actue abdomen patients with SIRS,the expression of TLR2,4 of PBMC increased markedly,indicating its improtant role in the pathogenesis of SIRS.4 refs,2 figs,2 tabs.展开更多
Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas...Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea- tures of 36 cases of inflammatory demyelinating pseudotumer in the spinal cord were retrospec- tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensofimotor disorder. Among them, six cases were misdiagnosed as having intrame- dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologically confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were common. Magnetic resonance imaging revealed edema and space-occupying lesions to varying degrees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like reinforcement (open-loop sign). Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re- sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement (open-ring sign) on magnetic resonance imaging is the predominant property of inflammatory de- myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional patho- logical properties.展开更多
BACKGROUD Follicular dendritic cell(FDC)sarcomas are rare neoplasms that occur predominantly in the lymph nodes.They can also occur extranodally.Extranodal FDC sarcomas most commonly present as solitary masses.Inflamm...BACKGROUD Follicular dendritic cell(FDC)sarcomas are rare neoplasms that occur predominantly in the lymph nodes.They can also occur extranodally.Extranodal FDC sarcomas most commonly present as solitary masses.Inflammatory pseudotumor(IPT)-like FDC sarcomas,a subcategory of FDC sarcomas,are rarer than other sarcoma subtypes.They are composed of spindle or ovoid neoplastic cells and exhibit an admixture of plasma cells and prominent lymphoplasmacytic infiltration.Paraneoplastic pemphigus(PNP),also known as paraneoplastic autoimmune multiorgan syndrome,is a rare autoimmune bullous disease that is associated with underlying neoplasms.PNP has a high mortality,and its early diagnosis is usually difficult.CASE SUMMARY We describe a 27-year-old woman who presented with stomatitis,conjunctivitis,and skin blisters and erosions as her first symptoms of PNP with an intraabdominal IPT-like FDC sarcoma.The patient underwent surgical tumor resection and received tapering oral corticosteroid treatment.She showed no recurrence at the 1-year follow-up.CONCLUSION IPT-like FDC sarcomas are rare underlying neoplasms that have an uncommon association with PNP.PNP-associated FDC sarcomas predominantly occur in intra-abdominal sites and suggest a poor prognosis.Surgical resection is an essential and effective treatment for PNP and primary and recurrent FDC sarcomas.展开更多
Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells h...Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastro-enterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immunemediated conditions,further studies are needed to fully understand the biology of stem cellsand carefully assess their put ativeonco- genicproperties.Moreover,there searchonstemcellsarousesferventethical,socialandpoliticaldebate.TheItalianSocietyofGastroenterologysponsoredaworkshoponstemcellsheldinVeronaduringtheⅩⅥCongressoftheFederationofItalianSocietiesofDigestiveDiseases(March 6-9,2010).Here,we report on the issues discussed,including liver and intestinal diseases that may benefit from stemcell therapy,the biology of hepatic and intestinal tissue repair,and stem cell usage inclinical trials.展开更多
Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as ...Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.展开更多
Dear Editor,I am Dr.Austin Bach from Larkin Community Hospital in South Miami,Florida,USA.I am writing to you to present three cases of inflammatory optic neuritis that was followed to resolution using pattern electro...Dear Editor,I am Dr.Austin Bach from Larkin Community Hospital in South Miami,Florida,USA.I am writing to you to present three cases of inflammatory optic neuritis that was followed to resolution using pattern electroretinography(PERG).展开更多
Non-alcoholic fatty liver disease(NAFLD)or metabolic(dysfunction)-associated fatty liver disease is the leading cause of chronic liver diseases defined as a disease spectrum comprising hepatic steatosis,non-alcoholic ...Non-alcoholic fatty liver disease(NAFLD)or metabolic(dysfunction)-associated fatty liver disease is the leading cause of chronic liver diseases defined as a disease spectrum comprising hepatic steatosis,non-alcoholic steatohepatitis(NASH),liver fibrosis,cirrhosis,and hepatic carcinoma.NASH,characterized by hepatocyte injury,steatosis,inflammation,and fibrosis,is associated with NAFLD prognosis.Ductular reaction(DR)is a common compensatory reaction associated with liver injury,which involves the hepatic progenitor cells(HPCs),hepatic stellate cells,myofibroblasts,inflammatory cells(such as macrophages),and their secreted substances.Recently,several studies have shown that the extent of DR parallels the stage of NASH and fibrosis.This review summarizes previous research on the correlation between DR and NASH,the potential interplay mechanism driving HPC differentiation,and NASH progression.展开更多
Background:Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis(UC).Here,we developed a novel diagnostic criterion for assessing...Background:Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis(UC).Here,we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods:We conducted a retrospective cohort study in UC patients,whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022.We identified an inflammatory cell enumeration index(ICEI)for assessing histological healing based on the proportions of eosinophils,CD177^(+)neutrophils,and CD40L^(+)T cells in the colonic lamina propria under high power field(HPF),and the outcomes(risks of symptomatic relapses)of achieving histological remission vs.persistent histological inflammation using Kaplan-Meier curves.Intrareader reliability and inter-reader reliability were evaluated by each reader.The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness.The ICEI was further validated in a new cohort of UC patients from other nine university hospitals.Results:We developed an ICEI for clinical diagnosis of histological healing,i.e.,Y=1.701X_(1)+0.758X_(2)+1.347X_(3)-7.745(X_(1),X_(2),and X_(3)represent the proportions of CD177^(+)neutrophils,eosinophils,and CD40L^(+)T cells,respectively,in the colonic lamina propria under HPF).The receiver operating characteristics curve(ROC)analysis revealed that Y<-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve(AUC)was 0.942(95%confidence interval[CI]:0.905-0.979)with a sensitivity of 92.5%and a specificity of 83.6%(P<0.001).The intraclass correlation coefficient(ICC)for the intrareader reliability was 0.855(95%CI:0.781-0.909),and ICEI had good inter-reader reliability of 0.832(95%CI:0.748-0.894).During an 18-month follow-up,patients with histological healing had a substantially better outcome compared with those with unachieved histological healing(P<0.001)using ICEI.During a 12-month follow-up from other nine hospitals,patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing.Conclusions:ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy.Therefore,ICEI provides a promising,simplified approach to monitor histological healing and to predict the prognosis of UC.Registration:Chinese Clinical Trial Registry,No.ChiCTR2300077792.展开更多
文摘Background: Exercise-Induced Bronchospasm (EIB) is an inflammatory condition characterized by severe airway constriction following the mobilization of inflammatory cells and interleukin-6 (IL-6). When severe, EIB can require the use of pressurized salbutamol to treat athletes. This study investigated the nature of the systemic changes in inflammatory cells and post-exercise IL-6 concentrations after salbutamol treatment in EIB-susceptible distance runners. Materials and Methods: This was an experimental study that enrolled 12 long-distance runners. In Session A, the participants completed a treadmill exercise test, and those who had a maximum expiratory volume per second (FEV1) that was decreased by at least 10% compared to their base value were placed in the EIB-susceptible group (EIB+) (n = 6). Those whose FEV1 did not meet this criterion were placed in the nonresponsive (EIB?) group (n = 6). Before the Session B exercise, athletes in the BIE+ group inhaled two puffs of salbutamol (EIB+ Salb), while their EIB? counterparts received no treatment. Spirometry was performed before and after the exercise using a Spirobank G portable spirometer. Blood samples were taken before, immediately after and 2 hours after the stress test. Results: The mean post-exercise FEV1 values were not significantly different (p > 0.05) between the EIB+ Salb group and the EIB? group. The systemic changes in inflammatory cells and IL-6 concentrations in the EIB+ runners after salbutamol treatment were similar to those observed in their EIB? counterparts. Conclusion: Salbutamol pretreatment improved the systemic immune status of EIB-susceptible athletes.
基金Supported by University of Southern DenmarkOdense University Hospital Research Fund
文摘Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts(CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and noncellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a contextdependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.
文摘BACKGROUND:Recent studies have indicated that reactive encephalitis plays an important role in secondary tissue damage after craniocerebral injury. OBJECTIVE: To observe changes in white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in peripheral blood, and to determine their role in secondary brain insult in patients with craniocerebral injury. DESIGN, TIME AND SETTING: A case-control study at the Department of Neurosurgery of the Affiliated Hospital North Sichuan University of Medical Sciences between August 2007 and May 2008. PARTICIPANTS: Sixty-three patients, admitted within 24 hours after craniocerebral injury and who received no surgery, were included in the study. The cohort consisted of 41 males and 22 females, aged 9–72 years, with an average age of 42 years. Ten healthy volunteers, selected from the Department of Neurosurgery, were designated as the control group. METHODS: WBC and PMN from the peripheral blood were measured 0, 24, 48, 72, and 168 hours after admission to hospital. The Glasgow coma scale, area of cerebral hemorrhage, and degree of brain edema were simultaneously determined. The Glasgow outcome scale was evaluated six months after injury. The relationship between changes in WBC and PMN were analyzed. Sixty-three patients were divided into 0, 24, 48, 72, and 168 hours groups, with admission time to hospital as the determining factor. As controls, WBC and PMN of peripheral blood were also detected in 10 healthy volunteers. MAIN OUTCOME MEASURES: The main outcome measures were WBC and PMN counts in the peripheral blood at 0, 24, 48, 72, and 168 hours after admission to hospital, the mutual relationship between GCS, WBC and PMN, and changes in brain hemorrhage volume and edema size. RESULTS: WBC peaked at 24 hours after injury, and PMN peaked at 48 hours after injury (P 〈 0.01). These measures negatively correlated to the Glasgow coma scale (r = -0.657, -0.541, respectively, P 〈 0.05). In patients with Glasgow coma sale 〈 8, WBC and PMN were significantly higher than in the patients with GCS ≥ 8 (P 〈 0.05). Cerebral hemorrhage reached a peak at 24 hours after injury, and the degree of brain edema was maximal at 168 hours after injury. WBC and PMN counts were positively correlated to cerebral hemorrhage volume and brain edema size (P 〈 0.05). CONCLUSION: WBC and PMN counts significantly increased after craniocerebral injury and exhibited a correlation with the GCS score, volume of hemorrhage and edema, and Glasgow outcome scale.
文摘Subepidermal autoimmune bullous diseases (SABD) are some autoimmune skin diseases that can present in a variety of forms and can be a challenging disease to treat. An overview of the different forms of SABD are discussed including bullous pemphigoid (BP), epidermolysis bullosa acquisita (EBA), cicatricial pemphigoid (CP), bullous systemic lupus erythematosus (BSLE), and Anti-p200 pemphigoid. Emphasis on recent advancement is presented. In recent years, improved knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in some SABD. Defects of such structures cause the subepidermal bullous diseases and have also led to the discovery of new diseases (e.g. anti-p200-pemphigoid). Recent studies have outlined the important role of autoantibodies, mast cell lymphocytes and their cytokines in pathogenesis of SABD.
文摘Objective: To find out possible associations between wound inflammatory cell response and the patients’ survival. Background: Several articles have written about the effects of single inflammatory cell types on wound healing but little is known about the interaction of these cells on survival. The methods used in this study have made possible this kind of exploration. Methods: One hundred patients, aged from 41 to 78 years, underwent open heart surgery in the years 1998-1999 and were studied by using the Cellstick device for harvesting wound inflammatory cells during the first 24 hours after surgery. The results of the differential count were computerized by using artificial neural network for obtaining wound inflammatory cell node (WICN). The patients were followed up for sixteen years or to the death. WICN values were compared with the patients’ survival. Results: WICN reflects survival better than any single type of wound inflammatory cells alone (HR = 3.1;p = 0.081 for low/high WICN at 10 year survival). From several clinical characteristics diabetes only predicted shorter survival time (HR = 5.5;p = 0.014 for 10 year survival) better than WICN. Conclusion: These results support the view that regularly timed cell-to-cell ratios in wound inflammation, most often seen as high WICN, reflect beneficial survival. Instead, aberrant counts of inflammatory cells in the wounds lead to low WICN and often to the patients’ shorter survival.
文摘Chronic obstructive pulmonary disease </span><span style="font-family:""><span style="font-family:Verdana;">(COPD) is a major chronic respiratory disease worldwide. Inflammatory cells reflect the </span><span style="font-family:Verdana;">inflammatory situation both in peripheral blood and induced sputum. </span></span><span style="font-family:""><span style="font-family:Verdana;">Their correlation has not been reported. </span><span style="font-family:Verdana;">The correlation between neutrophils (Neu), eosinophils (Eos), and lymphocyte (Lym) in induced sputum and that in peripheral blood of COPD </span><span style="font-family:Verdana;">patients was evaluated </span><span><span style="font-family:Verdana;">to explore the </span><span style="font-family:Verdana;">consistency of inflammatory cells in peripheral blood and induced sputum. Peripheral blood and induced sputum were collected from 437 </span><span style="font-family:Verdana;">patients with acute exacerbation of COPD</span></span><span style="font-family:Verdana;"> (AECOPD) who were hospitalized in the Department of respiratory and critical care medicine, Inner Mongolia People’s Hospital. </span><span style="font-family:Verdana;">The correlation analysis was performed by Spearman correlation analysis. </span><span style="font-family:Verdana;">The r</span><span style="font-family:Verdana;">atios of Neu, Eos, and Lym in induced sputum were (79.15 ± 22.60)%, (5.23 ± 12.74)%, and (1.69 ± 2.66)%. The ratios of </span><span style="font-family:Verdana;">Neu, Eos, and Lym in </span><span style="font-family:Verdana;">peripheral blood were (63.29 ± 11.44)%, (2.99 ± 3.60)%, and (25.16 ± 10.19)%. The results showed that the ratios of Neu and Eos in induced sputum were significantly correlated with the proportion of </span><span style="font-family:Verdana;">corresponding cells in peripheral blood (P < 0.05). </span><span style="font-family:Verdana;">There was no correlation between the ratio of Lym and Leu in induced sputum and corresponding cells in </span><span style="font-family:Verdana;">peripheral blood (P > 0.05). In patients with AECOPD, the tendency of Neu and Eos in induced sputum was </span><span style="font-family:Verdana;">consistent with the corresponding cells in peripheral blood. Neu and Eos in </span><span style="font-family:Verdana;">induced sputum and peripheral blood reflected the degree of inflammation to guide the individualized medication of patients.
文摘<strong>Introduction: </strong>Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) from our routine practice for the predictor of prognosis of breast cancer after resection. <strong>Patients and</strong> <strong>Methods: </strong>There were 574 breast cancer patients accepted surgical resection and registered in Cancer Registry Center of our hospital. Patient’s basic profiles, peripheral neutophil, lymphocyte and platelet count were measured for study. The scales of NLR and PLR were derived from the lower and higher normal range in cell count from neutrophil, lymphocyte and platelet respectively. Therefore, the scales for NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively for analysis. <strong>Results: </strong>Poor 5-yr survival rate was found if higher cell counts of neutrophil and platelet (p ≤ 0.05). Three scales of NLR were ≤1.62, 1.63 - 2.57, ≥2.58, and their 5-year survival rates were 94%, 91% and 84% respectively (p = 0.019). In the subgroup of HER-2 (negative), and 3-Negative breast patients had a higher NLR of poor prognosis. But higher PLR was found less in 3-Negative and non in 3-Positive patients (p = 0.039). The PLR was ≤224, 225 - 253, ≥254 and their 5-year survival rates were 92%, 87%, and 64% respectively (p = 0.001);Multivariate Cox regression model for predictor of breast cancer patients who have 3.39 (PLR ≥ 254) and 2.45 (NLR ≥ 2.58 ) times risk (p = 0.02 and p = 0.002) of poor prognosis respectively. <strong>Conclusion: </strong>Peripheral inflammatory cell counts are easily to take in our clinical practice and have a potential role as predictors of prognosis. We have to pay attention to the trends of peripheral inflammatory cell count and their ratio in our clinical practice where possible.
基金provided by the University Grant Commission,New Delhi
文摘AIM: To find out the effect of Cat's whiskers (Cleome gynandra L., Capparidaceae) flavonoid (CWF) for the scavenging of free radicals in some inflammatory cells. METHODS: Mouse erythrocyte's hemoglobin, peritoneal macrophage, and peripheral blood lymphocytes were oxidized either by some of toxic chemicals (nitrite, carbon tetrachloride) or by enzymatic stimulation (glu- coseoxidase) to produce oxidative damage to cells. The protective effect of the CWF was examined, and the biochemical mechanism of action was also investigated in terms of the scavenging of free radicals. RESULTS: CWF (1 20 μg mL 1 ) decreased glucoseoxidase and nitrite induce oxidative damage in a concentration dependent manner in an in vitro model and inhibited the lysis of RBC [(28.64 ± 13.03)% and (70.31 ± 1.80)%] when mice were treated with CWF (25 and 50 mg kg 1 ). To assess the antioxidant potential of CWF in the lymphocytes and macrophages in living animals, the effect of CWF was measured on the elevated level of superoxide anions production in the cells. CWF scavenged the superoxide anion (O 2 ) production and inhibited the O 2 induced destruction of protein and lipid biomolecules. CONCLUSION: The study has established that the CWF mediates its antioxidant activity in some chronic inflammatory cells via its free radical scavenging activity.
文摘Inflammatory bowel disease (IBD) affects a part of the young population and has a strong impact upon quality of life. The underlying etiology is not known, and the existing treatments are not curative. Furthermore, a significant percentage of patients are refractory to therapy. In recent years there have been great advances in our knowledge of stem cells and their therapeutic applications. In this context, autologous hematopoietic stem cell transplantation (HSCT) has been used in application to severe refractory Crohn’s disease (CD), with encouraging results. Allogenic HSCT would correct the genetic defects of the immune system, but is currently not accepted for the treatment of IBD because of its considerable risks. Mesenchymal stem cells (MSCs) have immune regulatory and regenerative properties, and low immunogenicity (both autologous and allogenic MSCs). Based on these properties, MSCs have been used via the systemic route in IBD with promising results, though it is still too soon to draw firm conclusions. Their local administration in perianal CD is the field where most progress has been made in recent years, with encouraging results. The next few years will be decisive for defining the role of such therapy in the management of IBD.
基金supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)funded by the Ministry of Health & Welfare, Republic of Korea [grant number HI12C0763]
文摘Bone formation is important for the reconstruction of bone-related structures in areas that have been damaged by inflammation.Inflammatory conditions such as those that occur in patients with rheumatoid arthritis, cystic fibrosis, and periodontitis have been shown to inhibit osteoblastic differentiation. This study focussed on dental follicle stem cells(DFSCs), which are found in developing tooth germ and participate in the reconstruction of alveolar bone and periodontal tissue in periodontal disease. After bacterial infection of inflamed dental tissue, the destruction of bone was observed. Currently, little is known about the relationship between the inflammatory environment and bone formation. Osteogenic differentiation of inflamed DFSCs resulted in decreased alkaline phosphatase(ALP) activity and alizarin red S staining compared to normal DFSCs. Additionally, in vivo transplantation of inflamed and normal DFSCs demonstrated severe impairment of osteogenesis by inflamed DFSCs. Protein profile analysis via liquid chromatography coupled with tandem mass spectrometry was performed to analyse the differences in protein expression in inflamed and normal tissue. Comparison of inflamed and normal DFSCs showed significant changes in the level of expression of transforming growth factor(TGF)-β2. Porphyromonas gingivalis(P.g.)-derived lipopolysaccharide(LPS) was used to create in vitro inflammatory conditions similar to periodontitis. The osteogenic differentiation of LPS-treated DFSCs was suppressed, and the cells displayed low levels of TGF-β1 and high levels of TGF-β2. DFSCs treated with TGF-β2 inhibitors showed significant increases in alizarin red S staining and ALP activity. TGF-β1 expression was also increased after inhibition of TGF-β2. By examining inflamed DFSCs and LPS-triggered DFSCs, these studies showed both clinically and experimentally that the increase in TGF-β2 levels that occurs under inflammatory conditions inhibits bone formation.
基金Supported by Shandong Provincial Natural Science Foundation,China(No.ZR2014HM029)
文摘AIM:To investigate the effect of anti-vascular epithelial growth factor(VEGF)agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS:Human retinal pigment epithelial(RPE)cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following:1)control group:no treatment; 2)bevacizumab group:bevacizumab at 0.25 mg/mL was added to the media; 3)hypoxia group:CoCl_2 at 200 μmol/L was added to the media; 4)hypoxia+bevacizumab group:CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin(IL)-1β,IL-6,IL-8 and tumor necrosis factor(TNF)-α were evaluated using real-time polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at 6,12,24 and 48 h. RESULTS:Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h(P〈0.05). Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h(P〈0.05). IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION:Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.
基金supported by the National Natural Science Foundation of China,No.31471011a grant from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542202+1 种基金the Natural Science Foundation of Jiangsu Province of China,No.BK20131203a grant from the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)of China
文摘Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1(HMGB1), is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products(RAGE), but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.
文摘To explore changes of toll-like receptor (TLR) 2,4 in peripheral blood mononuclear cells (PBMC) in acute abdomen patients with systemic inflammatory response syndrome (SIRS) and their significance.Methods A clinical study was done on 103 patients of which 65 were with SIRS.The mRNA expression of TLR2,4 were detected by RT-PCR;the expression of TNF-α and IL-6 were observed by ELISA;the correlation between TLR2,4 mRNA,the level of TNF-α and IL-6,and the clinical course was evaluated.Results TLR2 mRNA ,TNF-α and IL-6 were upregulated markedly on the first day of hospitalization,then decreased gradually;TLR2 mRNA maintained on high level till the 5th day.The expression of TLR2,4 mRNA was positive correlated with the level of TNF-α and IL-6,and the length of stay.TLR2,4 mRNA expression increased in patients with multiple organ failure.Conclusion In actue abdomen patients with SIRS,the expression of TLR2,4 of PBMC increased markedly,indicating its improtant role in the pathogenesis of SIRS.4 refs,2 figs,2 tabs.
文摘Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea- tures of 36 cases of inflammatory demyelinating pseudotumer in the spinal cord were retrospec- tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensofimotor disorder. Among them, six cases were misdiagnosed as having intrame- dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologically confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were common. Magnetic resonance imaging revealed edema and space-occupying lesions to varying degrees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like reinforcement (open-loop sign). Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re- sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement (open-ring sign) on magnetic resonance imaging is the predominant property of inflammatory de- myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional patho- logical properties.
文摘BACKGROUD Follicular dendritic cell(FDC)sarcomas are rare neoplasms that occur predominantly in the lymph nodes.They can also occur extranodally.Extranodal FDC sarcomas most commonly present as solitary masses.Inflammatory pseudotumor(IPT)-like FDC sarcomas,a subcategory of FDC sarcomas,are rarer than other sarcoma subtypes.They are composed of spindle or ovoid neoplastic cells and exhibit an admixture of plasma cells and prominent lymphoplasmacytic infiltration.Paraneoplastic pemphigus(PNP),also known as paraneoplastic autoimmune multiorgan syndrome,is a rare autoimmune bullous disease that is associated with underlying neoplasms.PNP has a high mortality,and its early diagnosis is usually difficult.CASE SUMMARY We describe a 27-year-old woman who presented with stomatitis,conjunctivitis,and skin blisters and erosions as her first symptoms of PNP with an intraabdominal IPT-like FDC sarcoma.The patient underwent surgical tumor resection and received tapering oral corticosteroid treatment.She showed no recurrence at the 1-year follow-up.CONCLUSION IPT-like FDC sarcomas are rare underlying neoplasms that have an uncommon association with PNP.PNP-associated FDC sarcomas predominantly occur in intra-abdominal sites and suggest a poor prognosis.Surgical resection is an essential and effective treatment for PNP and primary and recurrent FDC sarcomas.
文摘Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastro-enterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immunemediated conditions,further studies are needed to fully understand the biology of stem cellsand carefully assess their put ativeonco- genicproperties.Moreover,there searchonstemcellsarousesferventethical,socialandpoliticaldebate.TheItalianSocietyofGastroenterologysponsoredaworkshoponstemcellsheldinVeronaduringtheⅩⅥCongressoftheFederationofItalianSocietiesofDigestiveDiseases(March 6-9,2010).Here,we report on the issues discussed,including liver and intestinal diseases that may benefit from stemcell therapy,the biology of hepatic and intestinal tissue repair,and stem cell usage inclinical trials.
基金supported by the National Natural Science Foundation of China,No. 82171062 (to JFZ)。
文摘Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the firstline treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor-α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.
文摘Dear Editor,I am Dr.Austin Bach from Larkin Community Hospital in South Miami,Florida,USA.I am writing to you to present three cases of inflammatory optic neuritis that was followed to resolution using pattern electroretinography(PERG).
基金the National Natural Science Foundation of China,No.81970511&82270620.
文摘Non-alcoholic fatty liver disease(NAFLD)or metabolic(dysfunction)-associated fatty liver disease is the leading cause of chronic liver diseases defined as a disease spectrum comprising hepatic steatosis,non-alcoholic steatohepatitis(NASH),liver fibrosis,cirrhosis,and hepatic carcinoma.NASH,characterized by hepatocyte injury,steatosis,inflammation,and fibrosis,is associated with NAFLD prognosis.Ductular reaction(DR)is a common compensatory reaction associated with liver injury,which involves the hepatic progenitor cells(HPCs),hepatic stellate cells,myofibroblasts,inflammatory cells(such as macrophages),and their secreted substances.Recently,several studies have shown that the extent of DR parallels the stage of NASH and fibrosis.This review summarizes previous research on the correlation between DR and NASH,the potential interplay mechanism driving HPC differentiation,and NASH progression.
基金National Natural Science Foundation of China(Nos.82370532,and 82341219)
文摘Background:Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis(UC).Here,we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods:We conducted a retrospective cohort study in UC patients,whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022.We identified an inflammatory cell enumeration index(ICEI)for assessing histological healing based on the proportions of eosinophils,CD177^(+)neutrophils,and CD40L^(+)T cells in the colonic lamina propria under high power field(HPF),and the outcomes(risks of symptomatic relapses)of achieving histological remission vs.persistent histological inflammation using Kaplan-Meier curves.Intrareader reliability and inter-reader reliability were evaluated by each reader.The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness.The ICEI was further validated in a new cohort of UC patients from other nine university hospitals.Results:We developed an ICEI for clinical diagnosis of histological healing,i.e.,Y=1.701X_(1)+0.758X_(2)+1.347X_(3)-7.745(X_(1),X_(2),and X_(3)represent the proportions of CD177^(+)neutrophils,eosinophils,and CD40L^(+)T cells,respectively,in the colonic lamina propria under HPF).The receiver operating characteristics curve(ROC)analysis revealed that Y<-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve(AUC)was 0.942(95%confidence interval[CI]:0.905-0.979)with a sensitivity of 92.5%and a specificity of 83.6%(P<0.001).The intraclass correlation coefficient(ICC)for the intrareader reliability was 0.855(95%CI:0.781-0.909),and ICEI had good inter-reader reliability of 0.832(95%CI:0.748-0.894).During an 18-month follow-up,patients with histological healing had a substantially better outcome compared with those with unachieved histological healing(P<0.001)using ICEI.During a 12-month follow-up from other nine hospitals,patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing.Conclusions:ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy.Therefore,ICEI provides a promising,simplified approach to monitor histological healing and to predict the prognosis of UC.Registration:Chinese Clinical Trial Registry,No.ChiCTR2300077792.