Inflammatory processes are an integral part of the stress response and are likely to result from a programmed adaptation that is vital to the organism's survival and well-being.The whole inflammatory response is medi...Inflammatory processes are an integral part of the stress response and are likely to result from a programmed adaptation that is vital to the organism's survival and well-being.The whole inflammatory response is mediated by largely overlapping circuits in the limbic forebrain,hypothalamus and brainstem,but is also under the control of the neuroendocrine and autonomic nervous systems.Genetically predisposed individuals who fail to tune the respective contributions of the two systems in accordance with stressor modality and intensity after adverse experiences can be at risk for stress-related psychiatric disorders and cardiovascular diseases.Altered glucocorticoid(GC) homeostasis due to GC resistance leads to the failure of neural and negative feedback regulation of the hypothalamic-pituitary-adrenal axis during chronic inflammation,and this might be the mechanism underlying the ensuing brain and heart diseases and the high prevalence of co-morbidity between the two systems.By the combined use of light and genetically-encoded lightsensitive proteins,optogenetics allows cell-type-specific,fast(millisecond-scale) control of precisely defined events in biological systems.This method is an important breakthrough to explore the causality between neural activity patterns and behavioral profiles relevant to anxiety,depression,autism and schizophrenia.Optogenetics also helps to understand the "inflammatory dialogue",the inflammatory processes in psychiatric disorders and cardiovascular diseases,shared by heart and brain in the context of stress.展开更多
Buerger disease,also known as thromboangiitis obliterans(TAO),is a challenging vascular condition that primarily affects young male smokers.The pathogenesis involves a combination of inflammatory and thrombotic proces...Buerger disease,also known as thromboangiitis obliterans(TAO),is a challenging vascular condition that primarily affects young male smokers.The pathogenesis involves a combination of inflammatory and thrombotic processes leading to segmental occlusion of small-and medium-sized arteries and veins,primarily in the extremities.Despite advances in medical management,many patients with Buerger disease continue to experience debilitating symptoms,including rest pain,ischemic ulcers,and the threat of limb loss.This underscores the need for alternative therapeutic strategies when conventional treatments fail.展开更多
Ascites formation in solid tumor patients is associatedwith an increased risk of death[1,2].The lack of patho-physiological insight limited the development of targetedtreatment so far.With advances in immune modulatin...Ascites formation in solid tumor patients is associatedwith an increased risk of death[1,2].The lack of patho-physiological insight limited the development of targetedtreatment so far.With advances in immune modulatingtherapies,the inflammatory component of ascites movedinto focus.Experimental approaches targeting immuno-logic dysregulation have shown only limited success[3,4].Therefore,we investigated inflammatory processes ofascites,taking the presence of tumor cells into account,while focusing on gastrointestinal tract malignancies dueto their underrepresentation in literature.展开更多
AIM To evaluate the relation between 12 polymorphisms and the development of gastric cancer(GC) and colorectal cancer(CRC).METHODS In this study,we included 125 individuals with GC diagnosis,66 individuals with CRC di...AIM To evaluate the relation between 12 polymorphisms and the development of gastric cancer(GC) and colorectal cancer(CRC).METHODS In this study,we included 125 individuals with GC diagnosis,66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms(in CASP8,CYP2 E1,CYP19 A1,IL1 A,IL4,MDM2,NFKB1,PAR1,TP53,TYMS,UGT1 A1 and XRCC1 genes) were genotyped in a single PCR for each individual,followed by fragment analysis. To avoid misinterpretation due to population substructure,we applied a previously developed set of 61 ancestryinformative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2.3.4,R environment and SPSS v.20.RESULTS After statistical analyses with the control of confounding factors,such as genetic ancestry,three markers(rs79071878 in IL4,rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers(rs28362491) and the marker in the UGT1 A1 gene(rs8175347) were positively associated with the development of CRC. Therefore,we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL(rs79071878 and rs28361491,respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly,carriers of the combination of DEL + RARE(rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations.CONCLUSION These findings are important for the comprehension of gastric and CRC development,particularly in highly admixed populations,such as the Brazilian population.展开更多
Detecting multiple analytes simultaneously,crucial in disease diagnosis and treatment prognosis,remains challenging.While planar sensing platforms demonstrate this capability,optical fiber sensors still lag behind.An ...Detecting multiple analytes simultaneously,crucial in disease diagnosis and treatment prognosis,remains challenging.While planar sensing platforms demonstrate this capability,optical fiber sensors still lag behind.An operando dual lossy mode resonance(LMR)biosensor fabricated on a D-shaped single-mode fiber(SMF)is proposed for quantification of clinical indicators of inflammatory process,like in COVID-19 infection.Dual LMRs,created via two-step deposition process,yield a nanostructure with distinct SnO_(2) thicknesses on the flat surface of the fiber.Theoretical and experimental analyses confirm its feasibility,showing a sensitivity around 4500 nm/RIU for both LMRs.A novel insight in spatially-separated biofunctionalization of the sensitive fiber regions is validated through fluorescence assays,showcasing selectivity for different immunoglobulins.Real-time and label-free detection of two inflammatory markers,C-reactive protein and Ddimer,empowers the platform capability with a minimum detectable concentration below 1μg/mL for both biomolecules,which is of clinical interest.This proof-of-concept work provides an important leap in fiber-based biosensing for effective and reliable multi-analyte detection,presenting a novel,compact and multi-functional analytical tool.展开更多
The most cited articles in the Journal of Neurorestoratology(JNRT)for the year 2023 highlight significant advancements in the field of neurorestoratology.These include a deeper understanding of the pathogenesis of neu...The most cited articles in the Journal of Neurorestoratology(JNRT)for the year 2023 highlight significant advancements in the field of neurorestoratology.These include a deeper understanding of the pathogenesis of neurological diseases such as Alzheimer’s disease(AD)and Parkinson’s disease,as well as progress in neurorestorative mechanisms like anti-inflammatory processes,immune regulation,neuromodulation,neovascularization/neural repair,and neuroprotection.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by progressive synovial inflammation.It is characterized by dysregulation of inflammatory processes in the synovium of the joints,leading to the ...Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by progressive synovial inflammation.It is characterized by dysregulation of inflammatory processes in the synovium of the joints,leading to the destruction of articular cartilage and bone erosion,which in turn causes pain and swelling.In severe cases,joint deformity may even occur.展开更多
Existing gastrointestinal(GI)diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus.In the GI tract,local inflammatory processes induce alterations in tight...Existing gastrointestinal(GI)diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus.In the GI tract,local inflammatory processes induce alterations in tight junction proteins,enhancing paracellular ion permeability.Although transepithelial electrical resistance(TEER)may be used in the laboratory to assess mucosal barrier integrity,there are no existing methodologies for characterizing tight junction dilation in vivo.Addressing this technology gap,intraluminal bioimpedance sensing may be employed as a localized,non-invasive surrogate to TEER electrodes used in cell cultures.Thus far,bioimpedance has only been implemented in esophagogastroduodenoscopy(EGD)due to the need for external electronics connections.In this work,we develop a novel,noise-resilient Bluetooth-enabled ingestible device for the continuous,non-invasive measurement of intestinal mucosal“leakiness.”As a proof-of-concept,we validate wireless impedance readout on excised porcine tissues in motion.Through an animal study,we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure.Device measurements are validated using standard benchtop methods for assessing mucosal permeability.展开更多
基金supported by the National Natural Science Foundation of China(30970942,91132306)the National Basic Research Development Program(973 program) of China (2010CB529605,2011CB504405)+1 种基金the "Hundred Talents Program" of the Chinese Academy of Sciences,the Guangdong Innovation Research Team Fund for Low-cost Healthcare Technologiesa Shenzhen Governmental Basic Research Grant
文摘Inflammatory processes are an integral part of the stress response and are likely to result from a programmed adaptation that is vital to the organism's survival and well-being.The whole inflammatory response is mediated by largely overlapping circuits in the limbic forebrain,hypothalamus and brainstem,but is also under the control of the neuroendocrine and autonomic nervous systems.Genetically predisposed individuals who fail to tune the respective contributions of the two systems in accordance with stressor modality and intensity after adverse experiences can be at risk for stress-related psychiatric disorders and cardiovascular diseases.Altered glucocorticoid(GC) homeostasis due to GC resistance leads to the failure of neural and negative feedback regulation of the hypothalamic-pituitary-adrenal axis during chronic inflammation,and this might be the mechanism underlying the ensuing brain and heart diseases and the high prevalence of co-morbidity between the two systems.By the combined use of light and genetically-encoded lightsensitive proteins,optogenetics allows cell-type-specific,fast(millisecond-scale) control of precisely defined events in biological systems.This method is an important breakthrough to explore the causality between neural activity patterns and behavioral profiles relevant to anxiety,depression,autism and schizophrenia.Optogenetics also helps to understand the "inflammatory dialogue",the inflammatory processes in psychiatric disorders and cardiovascular diseases,shared by heart and brain in the context of stress.
文摘Buerger disease,also known as thromboangiitis obliterans(TAO),is a challenging vascular condition that primarily affects young male smokers.The pathogenesis involves a combination of inflammatory and thrombotic processes leading to segmental occlusion of small-and medium-sized arteries and veins,primarily in the extremities.Despite advances in medical management,many patients with Buerger disease continue to experience debilitating symptoms,including rest pain,ischemic ulcers,and the threat of limb loss.This underscores the need for alternative therapeutic strategies when conventional treatments fail.
文摘Ascites formation in solid tumor patients is associatedwith an increased risk of death[1,2].The lack of patho-physiological insight limited the development of targetedtreatment so far.With advances in immune modulatingtherapies,the inflammatory component of ascites movedinto focus.Experimental approaches targeting immuno-logic dysregulation have shown only limited success[3,4].Therefore,we investigated inflammatory processes ofascites,taking the presence of tumor cells into account,while focusing on gastrointestinal tract malignancies dueto their underrepresentation in literature.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES)Pró-Reitoria de Pesquisa e Pós-Graduacao da Universidade Federal do Pará/Fundacao Amparo e Desenvolvimento da Pesquisa(PROPESP-UFPA/FADESP)
文摘AIM To evaluate the relation between 12 polymorphisms and the development of gastric cancer(GC) and colorectal cancer(CRC).METHODS In this study,we included 125 individuals with GC diagnosis,66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms(in CASP8,CYP2 E1,CYP19 A1,IL1 A,IL4,MDM2,NFKB1,PAR1,TP53,TYMS,UGT1 A1 and XRCC1 genes) were genotyped in a single PCR for each individual,followed by fragment analysis. To avoid misinterpretation due to population substructure,we applied a previously developed set of 61 ancestryinformative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2.3.4,R environment and SPSS v.20.RESULTS After statistical analyses with the control of confounding factors,such as genetic ancestry,three markers(rs79071878 in IL4,rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers(rs28362491) and the marker in the UGT1 A1 gene(rs8175347) were positively associated with the development of CRC. Therefore,we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL(rs79071878 and rs28361491,respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly,carriers of the combination of DEL + RARE(rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations.CONCLUSION These findings are important for the comprehension of gastric and CRC development,particularly in highly admixed populations,such as the Brazilian population.
基金financial support from the Spanish Agencia Estatal de Investigación (AEI) through project PID2023-149895OB-I00a predoctoral research grant from the Public University of Navarrafinancial support under the National Recovery and Resilience Plan (NRRP),Mission 4,Component 2,Investment 1.1,Call for tender No.1409 published on 14.9.2022 by the Italian Ministry of University and Research (MUR),funded by the European Union–NextGenerationEU–Project Title‘‘Fiber optics sensors as a platform for cancer diagnosis and in vitro model testing”–CUP B53D23024170001-Grant Assignment Decree No.1383 adopted on 01/09/2023 by the Italian MUR.
文摘Detecting multiple analytes simultaneously,crucial in disease diagnosis and treatment prognosis,remains challenging.While planar sensing platforms demonstrate this capability,optical fiber sensors still lag behind.An operando dual lossy mode resonance(LMR)biosensor fabricated on a D-shaped single-mode fiber(SMF)is proposed for quantification of clinical indicators of inflammatory process,like in COVID-19 infection.Dual LMRs,created via two-step deposition process,yield a nanostructure with distinct SnO_(2) thicknesses on the flat surface of the fiber.Theoretical and experimental analyses confirm its feasibility,showing a sensitivity around 4500 nm/RIU for both LMRs.A novel insight in spatially-separated biofunctionalization of the sensitive fiber regions is validated through fluorescence assays,showcasing selectivity for different immunoglobulins.Real-time and label-free detection of two inflammatory markers,C-reactive protein and Ddimer,empowers the platform capability with a minimum detectable concentration below 1μg/mL for both biomolecules,which is of clinical interest.This proof-of-concept work provides an important leap in fiber-based biosensing for effective and reliable multi-analyte detection,presenting a novel,compact and multi-functional analytical tool.
文摘The most cited articles in the Journal of Neurorestoratology(JNRT)for the year 2023 highlight significant advancements in the field of neurorestoratology.These include a deeper understanding of the pathogenesis of neurological diseases such as Alzheimer’s disease(AD)and Parkinson’s disease,as well as progress in neurorestorative mechanisms like anti-inflammatory processes,immune regulation,neuromodulation,neovascularization/neural repair,and neuroprotection.
基金Supported by the Department of Science and Technology of State Administration of Traditional Chinese Medicine-Joint Science and Technology Plan of Zhejiang Provincial Administration of Traditional Chinese Medicine(No.GZY-ZJ-KJ-23044)the Zhejiang Provincial Natural Science Foundation(No.Y21H270014)the National Key R&D Program(No.2022YFC3501204)。
文摘Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by progressive synovial inflammation.It is characterized by dysregulation of inflammatory processes in the synovium of the joints,leading to the destruction of articular cartilage and bone erosion,which in turn causes pain and swelling.In severe cases,joint deformity may even occur.
基金supported by the National Science Foundation ECCS program,award#1939236NCS program,award#1926793。
文摘Existing gastrointestinal(GI)diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus.In the GI tract,local inflammatory processes induce alterations in tight junction proteins,enhancing paracellular ion permeability.Although transepithelial electrical resistance(TEER)may be used in the laboratory to assess mucosal barrier integrity,there are no existing methodologies for characterizing tight junction dilation in vivo.Addressing this technology gap,intraluminal bioimpedance sensing may be employed as a localized,non-invasive surrogate to TEER electrodes used in cell cultures.Thus far,bioimpedance has only been implemented in esophagogastroduodenoscopy(EGD)due to the need for external electronics connections.In this work,we develop a novel,noise-resilient Bluetooth-enabled ingestible device for the continuous,non-invasive measurement of intestinal mucosal“leakiness.”As a proof-of-concept,we validate wireless impedance readout on excised porcine tissues in motion.Through an animal study,we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure.Device measurements are validated using standard benchtop methods for assessing mucosal permeability.