BACKGROUND The bidirectional link between periodontitis and diabetes mellitus(DM)has been established.Periodontitis causes systemic inflammatory burden through inflammatory mediators.The currently utilized tools[clini...BACKGROUND The bidirectional link between periodontitis and diabetes mellitus(DM)has been established.Periodontitis causes systemic inflammatory burden through inflammatory mediators.The currently utilized tools[clinical attachment loss(CAL)and probing pocket depth(PPD)]are linear measurements,that do not exactly quantify the inflammatory burden of periodontitis.Periodontal inflamed surface area(PISA)quantifies the surface area of bleeding pocket epithelium and estimates the inflammatory burden.Studies relating to the periodontal status of diabetic patients with and without microvascular complications are scarce.This study assessed the proportion of periodontitis and correlation of PISA with glycemic status in controlled,uncontrolled type 2 DM(T2DM)with and without microvascular complications.AIM To assess the proportion of periodontitis and correlation of PISA with glycemic status in controlled,and uncontrolled T2DM with and without microvascular complications.METHODS This study comprised 180 T2DM patients.Based on glycated hemoglobin(HbA1c)levels,they were grouped into:(1)Controlled T2DMgroup:(HbA1c≤7%);(2)Uncontrolled T2DM group:(HbA1c>7%)without microvascular complications;and(3)Uncontrolled T2DM group:(HbA1c>7%)with microvascular complications.Each group comprised 60 patients.All patients were assessed for periodontal parameters(Bleeding on Probing,PPD,CAL,Oral hygiene index simplified and PISA),and systemic parameters(HbA1c,fasting plasma glucose and post prandial plasma glucose).RESULTS The proportion of periodontitis among controlled T2DM group,uncontrolled T2DM group without microvascular complications,uncontrolled T2DM group with micro-vascular complications was 75%,93.4%and 96.6%respectively.Extent and severity of periodontitis were high in the uncontrolled T2DM group.A significant positive correlation was found between PISA and HbA1c among all patients(r=0.393,P<0.001).The dose–response relationship between PISA and HbA1c was observed.An increase of PISA with 168 mm^(2) was associated with a 1.0%increase of HbA1c.CONCLUSION High proportion and severity of periodontitis,and increased inflamed surface area in uncontrolled T2DM may have contributed to the poor glycemic control and microvascular complications.展开更多
In recent years, it has been shown that inflammatory biomarkers can be used as an effective signal for disease diagnoses. The early detection of these signals provides useful information that could prevent the occurre...In recent years, it has been shown that inflammatory biomarkers can be used as an effective signal for disease diagnoses. The early detection of these signals provides useful information that could prevent the occurrence of severe diseases. Here, we employed surface-enhanced Raman scattering(SERS) probe gold nanorods(GNRs) as a tool for the early detection of inflammatory molecules in inflamed cells. A murine macrophage cell line(Raw264.7) stimulated with lipopolysaccharide(LPS) was used as a model in this study. The prepared SERS probe GNRs containing 4-mercaptobenzoic acid as a Raman reporter to generate SERS signals were used for detection of intracellular adhesion molecule-1(ICAM-1) in macrophages after treatment with LPS for varying lengths of time. Our results show that SERS probe GNRs could detect significant differences in the expression of ICAM-1 molecules in LPS-treated macrophages compared to those in untreated macrophages after only 1 h of LPS treatment. In contrast, when using fluorescent labeling or enzyme-linked immunosorbent assays(ELISA) to detect ICAM-1, significant differences between inflamed and un-inflamed macrophages were not seen until the cells had been treated with LPS for 5 h. These results indicate that our SERS probe GNRs provide a higher sensitivity for detecting biomarker molecules in inflamed macrophages than the conventional fluorescence and ELISA techniques, and could therefore be useful as a potential diagnostic tool for managing disease risk.展开更多
BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus(T2DM)is well established.Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentu...BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus(T2DM)is well established.Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentuating diabetic complications.An inflammatory link exists between diabetic retinopathy(DR)and periodontitis,but the studies regarding this association and the role of lipoprotein(a)[Lp(a)]and interleukin-6(IL-6)in these conditions are scarce in the literature.AIM To determine the correlation of periodontal inflamed surface area(PISA)with glycated Hb(HbA1c),serum IL-6 and Lp(a)in T2DM subjects with retinopathy.METHODS This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR.All subjects were assessed for periodontal parameters[bleeding on probing(BOP),probing pocket depth,clinical attachment loss(CAL),oral hygiene index-simplified,plaque index(PI)and PISA],and systemic parameters[HbA1c,fasting plasma glucose and postprandial plasma glucose,fasting lipid profile,serum IL-6 and serum Lp(a)].RESULTS The proportion of periodontitis in T2DM with and without DR was 47.5%and 27.5%respectively.Severity of periodontitis,CAL,PISA,IL-6 and Lp(a)were higher in T2DM with DR group compared to T2DM without DR group.Significant difference was observed in the mean percentage of sites with BOP between T2DM with DR(69%)and T2DM without DR(41%),but there was no significant difference in PI(P>0.05).HbA1c was positively correlated with CAL(r=0.351,P=0.001),and PISA(r=0.393,P≤0.001)in study subjects.A positive correlation was found between PISA and IL-6(r=0.651,P<0.0001);PISA and Lp(a)(r=0.59,P<0.001);CAL and IL-6(r=0.527,P<0.0001)and CAL and Lp(a)(r=0.631,P<0.001)among study subjects.CONCLUSION Despite both groups having poor glycemic control and comparable plaque scores,the periodontal parameters were higher in DR as compared to T2DM without DR.Since a bidirectional link exists between periodontitis and DM,the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.展开更多
Egypt is a river of tension in the wake of the anti-President Morsi demonstrators demanding his removal for abuse of power,leading to the army ousting the country＇s first democratically elected president in a July 3 ...Egypt is a river of tension in the wake of the anti-President Morsi demonstrators demanding his removal for abuse of power,leading to the army ousting the country＇s first democratically elected president in a July 3 military coup.The preceding violent days in early August saw Islamist President Morsi＇s supporters clashing with the country＇s police force in ongoing clashes that have already seen more than 1.000 lives lost,most of them Islamists and their supporters.The court decision to release former President Hosni Mubarak from prison may also inflame public anger.展开更多
Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanism...Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc.By constructing a rat model of TMJ arthritis,we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund’s complete adjuvant.By mimicking inflammatory conditions with interleukin-1 beta in vitro,we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment.In contrast,three-dimensional(3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils,inappropriate arrangement,and decreased Young’s modulus.Mechanistically,inflammation-related activation of the nuclear factor kappa-B(NF-κB)pathway occurs during the progression of TMJ arthritis.NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro,and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo.Therefore,the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs,offering a potential therapeutic target for disc displacement.展开更多
The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(...The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model;moreover, NLRP3 inflammasome activation(NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus(NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species(mt ROS)production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mt ROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.展开更多
AIM: To verify the impact of induction therapy with infliximab(IFX) on mucosal healing in children with ulcerative colitis(UC).METHODS: The study included all UC pediatric patients treated with IFX at our center over ...AIM: To verify the impact of induction therapy with infliximab(IFX) on mucosal healing in children with ulcerative colitis(UC).METHODS: The study included all UC pediatric patients treated with IFX at our center over the last10 years. The data were collected from patients' medical charts and analyzed retrospectively. A total of 16 patients with UC underwent colonoscopy with sample collection before and after three IFX injections.Pediatric Ulcerative Colitis Activity Index(PUCAI)was used to assess the clinical condition; endoscopic features were classified according to the Baron scale;and histological changes were evaluated according to the protocol of The British Society of Gastroenterology and Geboes Index. Clinical response was defined as a ≥ 20-point reduction in PUCAI index, and clinical remission as PUCAI index < 10 points. Endoscopic mucosal remission was defined as completely normal(score 0) on the Baron scale. Histological remission was defined as grade 0 in the Geboes Index. To assess correlation between variables, Spearman's rank correlation coefficient was used.RESULTS: Clinical remission(PUCAI < 10) at week 8 was achieved in 68.75% of investigated subjects. Endoscopic mucosal remission at week 8(Baron 0) was observed in 12.5% of patients. Histological remission(Geboes 0)after induction therapy with IFX was noticed in 18.75%cases. A general histological improvement, expressedby normal surface and crypt architecture, number of crypts, and lamina propria cellularity, was observed in six(37.5%) patients; there was no improvement in nine(56.25%) individuals, and worsening was observed in one(3.75%) case. Changes were not related to UC location. A reduction of inflammatory process was observed in 10(62.5%) patients; there were no changes in four(25%) individuals, and the inflammation became more severe in two(12.5 %) cases. Simultaneous clinical, endoscopic and histological improvement of parameters assessing disease activity at week 8 was noticed in six(37.5%) patients. 55.5% of investigated patients with normal mucosa seen on endoscopy showed no inflammation on histology. A Baron score of 2 and 3showed a good correlation with histology results(78.2%of patients with a Geboes Index ≥ 3).CONCLUSION: IFX has a positive histological effect in more than one-third of UC patients. IFX reduces intestinal inflammation and improves clinical condition.展开更多
300 cases of chronic atrophic gastritis were classified into 3 types of qi-dificiency of spleen and stomach, yang-deficiency of spleen and stomach, and yin-deficiency of spleen and stomach according to syndrom differe...300 cases of chronic atrophic gastritis were classified into 3 types of qi-dificiency of spleen and stomach, yang-deficiency of spleen and stomach, and yin-deficiency of spleen and stomach according to syndrom differentiation of traditional Chinese medicine. The biopsy specimens of gastric mucosa were examined histopathologically and for the presence of pyloric spirobaeteria. The results showed that the type of yin-deficiency was the most seri-ous in the degree of pathologic changes, or the glandular atrophy and the interstitial inflam-matory cellular infiltration, while the rate of pyloric spirobacteria presence was comparable in all types.展开更多
Key points:With aging,there is increased nucleotide-binding oligomerization domain-(NOD-)like receptor(NLR) protein-3(NLRP3) activation in neural and ocular tissues.Activation of the NLRP3 inflammasome appears to be a...Key points:With aging,there is increased nucleotide-binding oligomerization domain-(NOD-)like receptor(NLR) protein-3(NLRP3) activation in neural and ocular tissues.Activation of the NLRP3 inflammasome appears to be a common denominator in the pathogenesis of age-related diseases of the eye and brain.Pharmacological inhibition of the NLRP3 inflammasome may be a potent therapy for preventing the development and progression of age-related eye and brain diseases.展开更多
Recent studies showed that inflammation is a critical cause for initiation and/or development of many cancers. In prostate cancer(PC), the inflammatory cells usually populate an immune-competent organ. This inflammato...Recent studies showed that inflammation is a critical cause for initiation and/or development of many cancers. In prostate cancer(PC), the inflammatory cells usually populate an immune-competent organ. This inflammatory organ can be involved in the initiation and progression of PC. Here, we mainly focus on the role of inflammation in the PC and progression of castration-resistant PC(CRPC). Moreover, we summarize the roles of inflammation factors(such as chemokines and cytokines) in PC and CRPC. Taken together, this review gives an insight into therapy for PC and CRPC through anti-inflammation.展开更多
Periarthritis humeroscapularis is alsoknown as adhesive capsulitis of theshoulder,or commonly called frozen shoul-der;evidently it is related to seniledegenerative changes.It is usually due torupture of the rotator cu...Periarthritis humeroscapularis is alsoknown as adhesive capsulitis of theshoulder,or commonly called frozen shoul-der;evidently it is related to seniledegenerative changes.It is usually due torupture of the rotator cuff,chronic inflam-mation of the periarticular muscles,the ten-dons,the synovial bursa or articular展开更多
Temporomandibular joint dysfunctionsyndrome(TJDS)is non-bacterial inflam-mation of the tissues around the joint due toinjury of neuromuscular structures causedby lengthy dysfunctioning of mastication,such as unilatera...Temporomandibular joint dysfunctionsyndrome(TJDS)is non-bacterial inflam-mation of the tissues around the joint due toinjury of neuromuscular structures causedby lengthy dysfunctioning of mastication,such as unilateral mastication,or to trauma.The author has treated 22 cases of this kindwith acupuncture combined展开更多
This article presents the joint use of electricacupuncture and moxibustion in the treatment of95 cases of chronic PID.Clinical cure in 42 cases,marked improvement in 22 cases,some improve-ment in 17 cases,and no effec...This article presents the joint use of electricacupuncture and moxibustion in the treatment of95 cases of chronic PID.Clinical cure in 42 cases,marked improvement in 22 cases,some improve-ment in 17 cases,and no effect in 12 cases.Theoverall effective rate was 88.4%,which was superiorto that of the control group (P【0.05) using an-tibiotics.展开更多
Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the...Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.展开更多
OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS...OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.展开更多
According to formula we can simulate their driven force and acceleration.The mechanical formula is used to obtain dynamics is used to simulate.The driven force increases when torque increases and tire diameter decreas...According to formula we can simulate their driven force and acceleration.The mechanical formula is used to obtain dynamics is used to simulate.The driven force increases when torque increases and tire diameter decreases.We need torque to increase so this is our plan.Acceleration raises when torque raises and it reduces when its weight raises.With the decreasing of radius of road the centripetal acceleration is increasing in the condition of light vehicle.It is that it decreases sluggishly before 0.35m/s2 then it maintains a steep decline to 0.62m/s2 and at last becomes sluggish again.It is valued that the economical efficiency about consumed fuel under different power.In the time of 0.2hr the fuel inflamer inclines sharply first then turns stable.It is the smallest value.Beyond it the fuel maintains a high value all the time.The discharged pollution gas decreases with the decreasing initial temperature.The low initial temperature is good to fuel gas.Meantime the smallest incline range is 300~350K which explains that it is the most save one.展开更多
Dear Editor,In treating autoimmune diseases like rheumatoid arthritis(RA),the ultimate goals are resolving inflammation and establishing peripheral tolerance.These processes are closely associated with efferocytosis,t...Dear Editor,In treating autoimmune diseases like rheumatoid arthritis(RA),the ultimate goals are resolving inflammation and establishing peripheral tolerance.These processes are closely associated with efferocytosis,the clearance of apoptotic cells and debris by phagocytes in inflamed tissue,which fosters the reprogramming of efferocytic cells to an anti-inflammatory and repair-oriented phenotype while silencing inflammatory signaling cues and antigen presentation.Thus,efferocytosis-modulatory molecules have emerged as therapeutic targets to boost immune resolution.Salt-inducible kinases(SIKs)regulate intracellular signaling and transcriptional machinery.However,the roles of SIKs in efferocytosis and RA immune responses have not been investigated.展开更多
The ubiquitin-editing enzyme A20 is known to regulate inflammation and maintain homeostasis,but its role in self-DNA-mediated inflammation in acute kidney injury(AKI)is not well understood.Here,our study demonstrated ...The ubiquitin-editing enzyme A20 is known to regulate inflammation and maintain homeostasis,but its role in self-DNA-mediated inflammation in acute kidney injury(AKI)is not well understood.Here,our study demonstrated that oxidized self-DNA accumulates in the serum of AKI mice and patients.This oxidized self-DNA exacerbates the progression of AKI by activating the cGAS-STING pathway and NLRP3 inflammasome.While inhibition of the STING pathway only slightly attenuates AKI progression,suppression of NLRP3 inflammasome-mediated pyroptosis significantly alleviates AKI progression and improves the survival of AKI mice.Subsequently,we found that Tnfaip3(encoding A20)is significantly upregulated following oxidized self-DNA treatment.A20 significantly alleviates AKI development by dampening STING signaling pathway and NLRP3-mediated pyroptosis.Moreover,A20-derived peptide(P-II)also significantly alleviates ox-dsDNA-induced pyroptosis and improves the survival and renal injury of AKI mice.Mechanistically,A20 competitively binds with NEK7 and thus inhibiting NLRP3 inflammasome.A20 and P-II interfere with the interaction between NEK7 and NLRP3 through Lys140 of NEK7.Mutation of Lys140 effects on the interaction of NEK7 with A20 and/or NLRP3 complex.Conditional knockout of NEK7 in macrophages or pharmacological inhibition of NEK7 both significantly rescue AKI mouse models.This study reveals a new mechanism by which A20 attenuates oxidized self-DNA-mediated inflammation and provides a new therapeutic strategy for AKI.展开更多
文摘BACKGROUND The bidirectional link between periodontitis and diabetes mellitus(DM)has been established.Periodontitis causes systemic inflammatory burden through inflammatory mediators.The currently utilized tools[clinical attachment loss(CAL)and probing pocket depth(PPD)]are linear measurements,that do not exactly quantify the inflammatory burden of periodontitis.Periodontal inflamed surface area(PISA)quantifies the surface area of bleeding pocket epithelium and estimates the inflammatory burden.Studies relating to the periodontal status of diabetic patients with and without microvascular complications are scarce.This study assessed the proportion of periodontitis and correlation of PISA with glycemic status in controlled,uncontrolled type 2 DM(T2DM)with and without microvascular complications.AIM To assess the proportion of periodontitis and correlation of PISA with glycemic status in controlled,and uncontrolled T2DM with and without microvascular complications.METHODS This study comprised 180 T2DM patients.Based on glycated hemoglobin(HbA1c)levels,they were grouped into:(1)Controlled T2DMgroup:(HbA1c≤7%);(2)Uncontrolled T2DM group:(HbA1c>7%)without microvascular complications;and(3)Uncontrolled T2DM group:(HbA1c>7%)with microvascular complications.Each group comprised 60 patients.All patients were assessed for periodontal parameters(Bleeding on Probing,PPD,CAL,Oral hygiene index simplified and PISA),and systemic parameters(HbA1c,fasting plasma glucose and post prandial plasma glucose).RESULTS The proportion of periodontitis among controlled T2DM group,uncontrolled T2DM group without microvascular complications,uncontrolled T2DM group with micro-vascular complications was 75%,93.4%and 96.6%respectively.Extent and severity of periodontitis were high in the uncontrolled T2DM group.A significant positive correlation was found between PISA and HbA1c among all patients(r=0.393,P<0.001).The dose–response relationship between PISA and HbA1c was observed.An increase of PISA with 168 mm^(2) was associated with a 1.0%increase of HbA1c.CONCLUSION High proportion and severity of periodontitis,and increased inflamed surface area in uncontrolled T2DM may have contributed to the poor glycemic control and microvascular complications.
基金the Japan Society for the Promotion of Science(JSPS)through a Grant-in-aid for Young Scientist B(No.24700481)
文摘In recent years, it has been shown that inflammatory biomarkers can be used as an effective signal for disease diagnoses. The early detection of these signals provides useful information that could prevent the occurrence of severe diseases. Here, we employed surface-enhanced Raman scattering(SERS) probe gold nanorods(GNRs) as a tool for the early detection of inflammatory molecules in inflamed cells. A murine macrophage cell line(Raw264.7) stimulated with lipopolysaccharide(LPS) was used as a model in this study. The prepared SERS probe GNRs containing 4-mercaptobenzoic acid as a Raman reporter to generate SERS signals were used for detection of intracellular adhesion molecule-1(ICAM-1) in macrophages after treatment with LPS for varying lengths of time. Our results show that SERS probe GNRs could detect significant differences in the expression of ICAM-1 molecules in LPS-treated macrophages compared to those in untreated macrophages after only 1 h of LPS treatment. In contrast, when using fluorescent labeling or enzyme-linked immunosorbent assays(ELISA) to detect ICAM-1, significant differences between inflamed and un-inflamed macrophages were not seen until the cells had been treated with LPS for 5 h. These results indicate that our SERS probe GNRs provide a higher sensitivity for detecting biomarker molecules in inflamed macrophages than the conventional fluorescence and ELISA techniques, and could therefore be useful as a potential diagnostic tool for managing disease risk.
文摘BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus(T2DM)is well established.Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentuating diabetic complications.An inflammatory link exists between diabetic retinopathy(DR)and periodontitis,but the studies regarding this association and the role of lipoprotein(a)[Lp(a)]and interleukin-6(IL-6)in these conditions are scarce in the literature.AIM To determine the correlation of periodontal inflamed surface area(PISA)with glycated Hb(HbA1c),serum IL-6 and Lp(a)in T2DM subjects with retinopathy.METHODS This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR.All subjects were assessed for periodontal parameters[bleeding on probing(BOP),probing pocket depth,clinical attachment loss(CAL),oral hygiene index-simplified,plaque index(PI)and PISA],and systemic parameters[HbA1c,fasting plasma glucose and postprandial plasma glucose,fasting lipid profile,serum IL-6 and serum Lp(a)].RESULTS The proportion of periodontitis in T2DM with and without DR was 47.5%and 27.5%respectively.Severity of periodontitis,CAL,PISA,IL-6 and Lp(a)were higher in T2DM with DR group compared to T2DM without DR group.Significant difference was observed in the mean percentage of sites with BOP between T2DM with DR(69%)and T2DM without DR(41%),but there was no significant difference in PI(P>0.05).HbA1c was positively correlated with CAL(r=0.351,P=0.001),and PISA(r=0.393,P≤0.001)in study subjects.A positive correlation was found between PISA and IL-6(r=0.651,P<0.0001);PISA and Lp(a)(r=0.59,P<0.001);CAL and IL-6(r=0.527,P<0.0001)and CAL and Lp(a)(r=0.631,P<0.001)among study subjects.CONCLUSION Despite both groups having poor glycemic control and comparable plaque scores,the periodontal parameters were higher in DR as compared to T2DM without DR.Since a bidirectional link exists between periodontitis and DM,the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.
文摘Egypt is a river of tension in the wake of the anti-President Morsi demonstrators demanding his removal for abuse of power,leading to the army ousting the country＇s first democratically elected president in a July 3 military coup.The preceding violent days in early August saw Islamist President Morsi＇s supporters clashing with the country＇s police force in ongoing clashes that have already seen more than 1.000 lives lost,most of them Islamists and their supporters.The court decision to release former President Hosni Mubarak from prison may also inflame public anger.
基金supported by the National Natural Science Foundation of China Nos.82370983,81671015(X.W.),82230030(Y.L.),82101043(S.C.)and 82370922(Y.F.)Beijing International Science and Technology Cooperation Project No.Z221100002722003(Y.L.)+4 种基金Beijing Natural Science Foundation Nos.L234017,JL23002(Y.L.),No.7242282(S.C.)and 7232217(Y.G.)Clinical Medicine Plus X-Young Scholars Project of Peking University No.PKU2024LCXQ039(Y.L.)National Program for Multidisciplinary Cooperative Treatment on Major Diseases No.PKUSSNMP-202013(X.W.)Hygiene and Health Development Scientific Research Fostering Plan of Haidian District Beijing No.HP2023-12-509001(J.Z.)Young Clinical Research Fund of the Chinese Stomatological Association No.CSA-02022-03(J.Z.).
文摘Temporomandibular joint(TMJ)disc displacement is one of the most significant subtypes of temporomandibular joint disorders,but its etiology and mechanism are poorly understood.In this study,we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc.By constructing a rat model of TMJ arthritis,we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund’s complete adjuvant.By mimicking inflammatory conditions with interleukin-1 beta in vitro,we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment.In contrast,three-dimensional(3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils,inappropriate arrangement,and decreased Young’s modulus.Mechanistically,inflammation-related activation of the nuclear factor kappa-B(NF-κB)pathway occurs during the progression of TMJ arthritis.NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro,and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo.Therefore,the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs,offering a potential therapeutic target for disc displacement.
基金supported by grants from the Natural Science Foundation of Guangdong Province (Grant no: 2017A030313670)the National Natural Science Foundation of China (81572175 and 81772386)。
文摘The inflammatory response is induced by the overexpression of inflammatory cytokines, mainly interleukin(IL)-1β, and is one of the main causes of intervertebral disc degeneration(IVDD). NLR pyrin domain containing 3(NLRP3) inflammasome activation is an important source of IL-1β. As an anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its roles in IVDD are still not well understood and require more examination. First, we demonstrated that melatonin delayed the progression of IVDD and relieved IVDD-related low back pain in a rat needle puncture IVDD model;moreover, NLRP3 inflammasome activation(NLRP3, p20, and IL-1β levels) was significantly upregulated in severely degenerated human discs and a rat IVDD model. Subsequently, an IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop was found in nucleus pulposus(NP) cells that were treated with IL-1β. In these cells, expression of NLRP3 and p20 was significantly increased, NF-κB signaling was involved in this regulation, and mitochondrial reactive oxygen species(mt ROS)production increased. Furthermore, we found that melatonin disrupted the IL-1β/NF-κB-NLRP3 inflammasome activation positive feedback loop in vitro and in vivo. Melatonin treatment decreased NLRP3, p20, and IL-1β levels by inhibiting NF-κB signaling and downregulating mt ROS production. Finally, we showed that melatonin mediated the disruption of the positive feedback loop of IL-1β in vivo. In this study, we showed for the first time that IL-1β promotes its own expression by upregulating NLRP3 inflammasome activation. Furthermore, melatonin disrupts the IL-1β positive feedback loop and may be a potential therapeutic agent for IVDD.
基金Supported by The Children’s Memorial Health Institute Internal Grant S129/2013(in part)
文摘AIM: To verify the impact of induction therapy with infliximab(IFX) on mucosal healing in children with ulcerative colitis(UC).METHODS: The study included all UC pediatric patients treated with IFX at our center over the last10 years. The data were collected from patients' medical charts and analyzed retrospectively. A total of 16 patients with UC underwent colonoscopy with sample collection before and after three IFX injections.Pediatric Ulcerative Colitis Activity Index(PUCAI)was used to assess the clinical condition; endoscopic features were classified according to the Baron scale;and histological changes were evaluated according to the protocol of The British Society of Gastroenterology and Geboes Index. Clinical response was defined as a ≥ 20-point reduction in PUCAI index, and clinical remission as PUCAI index < 10 points. Endoscopic mucosal remission was defined as completely normal(score 0) on the Baron scale. Histological remission was defined as grade 0 in the Geboes Index. To assess correlation between variables, Spearman's rank correlation coefficient was used.RESULTS: Clinical remission(PUCAI < 10) at week 8 was achieved in 68.75% of investigated subjects. Endoscopic mucosal remission at week 8(Baron 0) was observed in 12.5% of patients. Histological remission(Geboes 0)after induction therapy with IFX was noticed in 18.75%cases. A general histological improvement, expressedby normal surface and crypt architecture, number of crypts, and lamina propria cellularity, was observed in six(37.5%) patients; there was no improvement in nine(56.25%) individuals, and worsening was observed in one(3.75%) case. Changes were not related to UC location. A reduction of inflammatory process was observed in 10(62.5%) patients; there were no changes in four(25%) individuals, and the inflammation became more severe in two(12.5 %) cases. Simultaneous clinical, endoscopic and histological improvement of parameters assessing disease activity at week 8 was noticed in six(37.5%) patients. 55.5% of investigated patients with normal mucosa seen on endoscopy showed no inflammation on histology. A Baron score of 2 and 3showed a good correlation with histology results(78.2%of patients with a Geboes Index ≥ 3).CONCLUSION: IFX has a positive histological effect in more than one-third of UC patients. IFX reduces intestinal inflammation and improves clinical condition.
文摘300 cases of chronic atrophic gastritis were classified into 3 types of qi-dificiency of spleen and stomach, yang-deficiency of spleen and stomach, and yin-deficiency of spleen and stomach according to syndrom differentiation of traditional Chinese medicine. The biopsy specimens of gastric mucosa were examined histopathologically and for the presence of pyloric spirobaeteria. The results showed that the type of yin-deficiency was the most seri-ous in the degree of pathologic changes, or the glandular atrophy and the interstitial inflam-matory cellular infiltration, while the rate of pyloric spirobacteria presence was comparable in all types.
基金supported by a Neurological Foundation First Postdoctoral Research Fellowship(2001 FFE)an Auckland Medical Research Foundation Grant (1121013)(to OOM)。
文摘Key points:With aging,there is increased nucleotide-binding oligomerization domain-(NOD-)like receptor(NLR) protein-3(NLRP3) activation in neural and ocular tissues.Activation of the NLRP3 inflammasome appears to be a common denominator in the pathogenesis of age-related diseases of the eye and brain.Pharmacological inhibition of the NLRP3 inflammasome may be a potent therapy for preventing the development and progression of age-related eye and brain diseases.
文摘Recent studies showed that inflammation is a critical cause for initiation and/or development of many cancers. In prostate cancer(PC), the inflammatory cells usually populate an immune-competent organ. This inflammatory organ can be involved in the initiation and progression of PC. Here, we mainly focus on the role of inflammation in the PC and progression of castration-resistant PC(CRPC). Moreover, we summarize the roles of inflammation factors(such as chemokines and cytokines) in PC and CRPC. Taken together, this review gives an insight into therapy for PC and CRPC through anti-inflammation.
文摘Periarthritis humeroscapularis is alsoknown as adhesive capsulitis of theshoulder,or commonly called frozen shoul-der;evidently it is related to seniledegenerative changes.It is usually due torupture of the rotator cuff,chronic inflam-mation of the periarticular muscles,the ten-dons,the synovial bursa or articular
文摘Temporomandibular joint dysfunctionsyndrome(TJDS)is non-bacterial inflam-mation of the tissues around the joint due toinjury of neuromuscular structures causedby lengthy dysfunctioning of mastication,such as unilateral mastication,or to trauma.The author has treated 22 cases of this kindwith acupuncture combined
文摘This article presents the joint use of electricacupuncture and moxibustion in the treatment of95 cases of chronic PID.Clinical cure in 42 cases,marked improvement in 22 cases,some improve-ment in 17 cases,and no effect in 12 cases.Theoverall effective rate was 88.4%,which was superiorto that of the control group (P【0.05) using an-tibiotics.
基金supported by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science(15H04730,16H05186,16K08772,17K12004,19H03467,21J00572)a contract research fund from the Japan Program for Infectious Diseases Research and Infrastructure for research on emerging and re-emerging infectious diseases provided by the Japan Agency for Medical Research and Development(AMED)the Project for Promoting Leading-edge Research in Oral Science at Tokyo Medical and Dental University。
文摘Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.
文摘OBJECTIVE To investigate the effects of imperatorin on the spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease(AD)induced by intracerebroventricular injection of Aβ1-42.METHODS Mouse model of AD was established by injection of Aβ1-42 into the lateral ventricles.Im⁃peratorin(2.5 and 5.0 mg·kg-1,daily)was inject⁃ed by intraperitoneally 1 h after intracerebroven⁃tricular injection for 13 d.The effect of imperato⁃rin on the spatial learning and memory impair⁃ment was assessed by eight arm maze tests.The levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in mouse cortex and hip⁃pocampus were detected by ELISA.The protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK were detected by Western blotting.RESULTS As compared with the AD model group,imperatorin treatment significantly attenuated Aβ1-42-induced spatial learning and memory impairment assessed by eight arm maze tests.In addition,imperatorin significantly reduced the levels of cytokines TNF-α,IL-1β,IL-6,IL-18 and chemokines MCP-1 in the cerebral cortex and hippocampus.Meanwhile,Western blotting results showed that imperatorin treat⁃ment significantly down-regulated the protein expression of NF-κB P65,TLR4,MyD88,p-P38,p-ERK,and p-JNK.CONCLUSION Imperatorin has neuroprotective effects in the Aβ1-42 induced AD model mice and its mechanism may be partially associated with the inhibition of inflam⁃matory response in the cortex and hippocampus.
文摘According to formula we can simulate their driven force and acceleration.The mechanical formula is used to obtain dynamics is used to simulate.The driven force increases when torque increases and tire diameter decreases.We need torque to increase so this is our plan.Acceleration raises when torque raises and it reduces when its weight raises.With the decreasing of radius of road the centripetal acceleration is increasing in the condition of light vehicle.It is that it decreases sluggishly before 0.35m/s2 then it maintains a steep decline to 0.62m/s2 and at last becomes sluggish again.It is valued that the economical efficiency about consumed fuel under different power.In the time of 0.2hr the fuel inflamer inclines sharply first then turns stable.It is the smallest value.Beyond it the fuel maintains a high value all the time.The discharged pollution gas decreases with the decreasing initial temperature.The low initial temperature is good to fuel gas.Meantime the smallest incline range is 300~350K which explains that it is the most save one.
基金supported by the Basic Science Research Program Planning(NRF-2018R1A5A2024418,RS-2020-NR046219,NRF-2021R1I1A1A01053114,RS-2024-00456194)through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT,and Future Planningby the Research Grant(860-20240137)funded by School of Dentistry,Seoul National University.
文摘Dear Editor,In treating autoimmune diseases like rheumatoid arthritis(RA),the ultimate goals are resolving inflammation and establishing peripheral tolerance.These processes are closely associated with efferocytosis,the clearance of apoptotic cells and debris by phagocytes in inflamed tissue,which fosters the reprogramming of efferocytic cells to an anti-inflammatory and repair-oriented phenotype while silencing inflammatory signaling cues and antigen presentation.Thus,efferocytosis-modulatory molecules have emerged as therapeutic targets to boost immune resolution.Salt-inducible kinases(SIKs)regulate intracellular signaling and transcriptional machinery.However,the roles of SIKs in efferocytosis and RA immune responses have not been investigated.
基金funded by the National Natural Science Foundation of China(Nos.8197219382171003).
文摘The ubiquitin-editing enzyme A20 is known to regulate inflammation and maintain homeostasis,but its role in self-DNA-mediated inflammation in acute kidney injury(AKI)is not well understood.Here,our study demonstrated that oxidized self-DNA accumulates in the serum of AKI mice and patients.This oxidized self-DNA exacerbates the progression of AKI by activating the cGAS-STING pathway and NLRP3 inflammasome.While inhibition of the STING pathway only slightly attenuates AKI progression,suppression of NLRP3 inflammasome-mediated pyroptosis significantly alleviates AKI progression and improves the survival of AKI mice.Subsequently,we found that Tnfaip3(encoding A20)is significantly upregulated following oxidized self-DNA treatment.A20 significantly alleviates AKI development by dampening STING signaling pathway and NLRP3-mediated pyroptosis.Moreover,A20-derived peptide(P-II)also significantly alleviates ox-dsDNA-induced pyroptosis and improves the survival and renal injury of AKI mice.Mechanistically,A20 competitively binds with NEK7 and thus inhibiting NLRP3 inflammasome.A20 and P-II interfere with the interaction between NEK7 and NLRP3 through Lys140 of NEK7.Mutation of Lys140 effects on the interaction of NEK7 with A20 and/or NLRP3 complex.Conditional knockout of NEK7 in macrophages or pharmacological inhibition of NEK7 both significantly rescue AKI mouse models.This study reveals a new mechanism by which A20 attenuates oxidized self-DNA-mediated inflammation and provides a new therapeutic strategy for AKI.
