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Axonal growth inhibitors and their receptors in spinal cord injury:from biology to clinical translation

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Neural Regeneration Research 2023年第12期18卷 2573-2581页

作者： s.lvia sousa Chambel Célia Duarte Cruz experimental Biology Unit Department of BiomedicineFaculty of Medicine of PortoUniversity of PortoPortoPortugal Translational NeuroUrology Instituto de Investigação e Inovação em Saúde-i3S and IBMCUniversidade do PortoPortoPortugal

Axonal growth inhibitors are released during traumatic injuries to the adult mammalian central nervous system, including after spinal cord injury. These molecules accumulate at the injury site and form a highly inhibitory environment for axonal regeneration. Among these inhibitory molecules, myelinassociated inhibitors, including neurite outgrowth inhibitor A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein, chondroitin sulfate proteoglycans and repulsive guidance molecule A are of particular importance. Due to their inhibitory nature, they represent exciting molecular targets to study axonal inhibition and regeneration after central injuries. These molecules are mainly produced by neurons, oligodendrocytes, and astrocytes within the scar and in its immediate vicinity. They exert their effects by binding to specific receptors, localized in the membranes of neurons. Receptors for these inhibitory cues include Nogo receptor 1, leucine-rich repeat, and Ig domain containing 1 and p75 neurotrophin receptor/tumor necrosis factor receptor superfamily member 19(that form a receptor complex that binds all myelin-associated inhibitors), and also paired immunoglobulin-like receptor B. Chondroitin sulfate proteoglycans and repulsive guidance molecule A bind to Nogo receptor 1, Nogo receptor 3, receptor protein tyrosine phosphatase σ and leucocyte common antigen related phosphatase, and neogenin, respectively. Once activated, these receptors initiate downstream signaling pathways, the most common amongst them being the Rho A/ROCK signaling pathway. These signaling cascades result in actin depolymerization, neurite outgrowth inhibition, and failure to regenerate after spinal cord injury. Currently, there are no approved pharmacological treatments to overcome spinal cord injuries other than physical rehabilitation and management of the array of symptoms brought on by spinal cord injuries. However, several novel therapies aiming to modulate these inhibitory prot

关键词： chondroitin sulphate proteoglycans collapsin response mediator protein 2 inhibitory molecules leucine-rich repeat and Ig domain containing 1 leucocyte common antigen related myelin-associated glycoprotein neurite outgrowth inhibitor A Nogo receptor 1 Nogo receptor 3 oligodendrocyte myelin glycoprotein p75 neurotrophin receptor Plexin A2 Ras homolog family member A/Rho-associated protein kinase receptor protein tyrosine phosphataseσ repulsive guidance molecule A spinal cord injury tumour necrosis factor receptor superfamily member 19

Dietary Green Tea extract and Antioxidants Improve Insulin secretory Functions of Pancreatic β-Cells in Mild and severe experimental Rodent Model of Chronic Pancreatitis

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Open Journal of endocrine and Metabolic Diseases 2024年第2期14卷 53-72页

作者： Galande sheethal Ranjeet K. Tokala pavan Pondugala Krishna Vemula Vijayalakshmi Venkatesan Pothani suresh surya satyanarayana singh Guduru Venkat Rao Duvvur Nageshwar Reddy Mitnala sasikala Basic science and Translational Research Division Asian Healthcare Foundation AIG Hospitals Hyderabad India Division of Cell and Molecular Biology National institute of Nutrition Hyderabad India National Animal Resource Facility for Biomedical Research Hyderabad India Department of Biochemistry Osmania University Hyderabad India Department of surgical Gastroenterology Asian Institute of Gastroenterology Hyderabad India Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (eGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&e and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% eGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with eGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (eGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

关键词： Dietary Intervention C57BL6/J Mice epigallocatechin-3-Gallate N-Acetyl Cysteine Curcumin Chronic Pancreatitis Islets Glucose stimulated Insulin secretion

Distal renal tubular acidosis:genetic causes and management

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World Journal of Pediatrics 2019年第5期15卷 422-431页

作者： s.lvia Bouissou Morais soares Luiz Alberto Wanderley de Menezes silva Flávia Cristina de Carvalho Mrad Ana Cristina simoes e silva Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineFederal University of Minas Gerais(UFMG)Av.Prof.Alfredo Balena190Room#281Belo HorizonteMG 30130-100Brazil Pediatric Nephrology Unit Faculty of MedicineUFMGBelo HorizonteBrazil

Background Distal renal tubular acidosis(dRTA)is a kidney tubulopathy that causes a state of normal anion gap metabolic acidosis due to impairment of urine *** review aims to summarize the etiology,pathophysiology,clinical findings,diagnosis and therapeutic approach of dRTA,with emphasis on genetic causes of *** sources Literature reviews and original research articles from databases,including PubMed and Google *** searching was performed to identify additional studies about *** dRTA is characterized as the dysfunction of the distal urinary acidification,leading to metabolic *** pediatric patients,the most frequent etiology of dRTA is the genetic alteration of genes responsible for the codification of distal tubule channels,whereas,in adult patients,dRTA is more commonly secondary to autoimmune diseases,use of medications and *** with dRTA exhibit failure to thrive and important laboratory alterations,which are used to define the *** oral alkali and potassium supplementation can correct the biochemical defects,improve clinical manifestations and avoid nephrolithiasis and *** dRTA is a multifactorial disease leading to several clinical *** and laboratory alterations can be corrected by alkali replacement therapy.

关键词： Renal tubular acidosis Distal tubule physiology Metabolic acidosis Gene mutations Proton pump

Odorants could elicit repair processes in melanized neuronal and skin cells

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Neural Regeneration Research 2017年第9期12卷 1401-1404页

作者： Barbara pavan Alessandro Dalpiaz Department of Life sciences and Biotechnology University of Ferrara Department of Chemistry and Pharmaceutical sciences University of Ferrara

The expression of ectopic olfactory receptors （ORs） in melanized cells, such as the human brain nigrostri- atal dopaminergic neurons and skin melanocytes, is here pointed out. ORs are recognized to regulate skin melanogenesis, whereas OR expression in the dopaminergic neurons, characterized by accumulation of pigment neuromelanin, is downregulated in Parkinson＇s disease. Furthermore, the correlation between the pigmentation process and the dopamine pathway through ct-synuclein expression is also highlighted. Purposely, these ORs are suggested as therapeutic target for neurodegenerative diseases related to the pig- mentation disorders. Based on this evidence, a possible way of turning odorants into drugs, acting on three specific olfactory receptors, OR51e2, OR2AT4 and VN1R1, is thus introduced. Various odorous molecules are shown to interact with these ORs and their therapeutic potential against melanogenic and neurodegen- erative dysfunctions, including melanoma and Parkinson＇s disease, is suggested. Finally, a direct functional link between olfactory and endocrine systems in human brain through VNIR1 is proposed, helping to counteract female susceptibility to Parkinson＇s disease in quiescent life.

关键词： OR51e2 OR2AT4 VN1R1 melanoma Parkinson's disease β-ionone sandalore hedione

Glycoprotein biomarkers for the detection of pancreatic ductal adenocarcinoma

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World Journal of Gastroenterology 2018年第24期24卷 2537-2554页

作者： esther Llop Pedro e Guerrero AdriàDuran s.lvia Barrabés Anna Massaguer María JoséFerri Maite Albiol-Quer Rafael de Llorens Rosa Peracaula Department of Biology Biochemistry and Molecular Biology UnitUniversity of GironaGirona 17003Spain Biomedical Research Institute of Girona(IdIBGi).Parc Hospitalari Martíi Julià-edifici M2 Salt 17190Spain Clinic Laboratory University Hospital Dr Josep TruetaGirona 17007Spain Department of surgery Hepato-biliary and Pancreatic Surgery UnitUniversity Hospital Dr Josep TruetaGirona 17007Spain

Pancreatic cancer(Pa C) shows a clear tendency to increase in the next years and therefore represents an important health and social challenge. Currently, there is an important need to find biomarkers for PaC early detection because the existing ones are not useful for that purpose. Recent studies have indicated that there is a large window of time for PaC early detection, which opens the possibility to find early biomarkers that could greatly improve the dismal prognosis of this tumor. The present manuscript reviews the state of the art of the existing PaC biomarkers. It focuses on the anomalous glycosylation process and its role in PaC. Glycan structures of glycoconjugates such as glycoproteins are modified in tumors and these modifications can be detected in biological fluids of the cancer patients. several studies have found serum glycoproteins with altered glycan chains in PaC patients, but they have not shown enough specificity for PaC. To find more specific cancer glycoproteins we propose to analyze the glycan moieties of a battery of glycoproteins that have been reported to increase in PaC tissues and that can also be found in serum. The combination of these new candidate glycoproteins with their aberrant glycosylation together with the existing biomarkers could result in a panel, which would expect to give better results as a new tool for early diagnosis of PaC and to monitor the disease.

关键词： Pancreatic cancer Aberrant glycosylation Glycoproteins Biomarkers Diagnosis

Bartter's syndrome:clinical findings,genetic causes and therapeutic approach

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World Journal of Pediatrics 2021年第1期17卷 31-39页

作者： Flavia Cristina Carvalho Mrad s.lvia Bouissou Morais soares Luiz Alberto Wanderley de Menezes silva Pedro Versiani dos Anjos Menezes Ana Cristina simoes-e-silva Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineFederal University of Minas Gerais(UFMG)Av.Alfredo Balena190Room#281Belo HorizonteMG 30130-100Brazil Pediatric Nephrology Unit Faculty of MedicineUFMGBelo HorizonteBrazil

Backgound Bartter's syndrome(Bs)is a rare group of salt losing tubulopathies due to the impairment of transport mecha-nisms at the thick ascending limb of the Henle's *** sources Literature reviews and original research articles were collected from database,including PubMed and *** According to the time of onset and symptoms,Bs can be classified into antenatal and classic *** studies have identified different subtypes of *** types Ⅰ,Ⅱ and Ⅲ are caused by mutations on genes encoding the luminal Na^(+)-K^(+)-2Cl^(-) co-transporter,the luminal K+ channel ROMK,and the basolateral chloride channel ClC-Kb(CLCNKB),***-of-function mutations of Barttin CLCNK type accessory beta subunit cause Bs type Ⅳ*** mutations of CLCNKB and CLCNKA cause Bs type Ⅳ*** type Ⅴ consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGe family member *** gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of *** clinical and biochemical alterations in Bs include polyuria,dehydration,hypokalemia,hypochloremic metabolic alka-losis,hyperreninemia,high levels of prostaglandins,normal or low blood pressure,hypercalciuria and failure to *** focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria,including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin e2 *** early diagnosis and treatment of Bs may prevent long-term consequences such as growth failure,nephrocal-cinosis and end-stage renal disease.

关键词： Bartter's syndrome Hypercalciuria Hypokalemia Metabolic alkalosis Nephrocalcinosis

Non-static plane symmetric inflationary Universe in scalar tensor theory

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Research in Astronomy and Astrophysics 2012年第6期12卷 636-642页

作者： Rangavajhala Venkateswarlu Janjeti satish Kakarlapati pavan Kumar GITAM school of International Business GITAM UniversityVisakhapatnam530045India Vignan's Institute of engineering for Women Visakhapatnam530046India Narasaraopet engineering College Narasaraopet522601India

Non-static plane symmetric cosmological solutions are presented in the presence of cosmic strings in the scalar-tensor theory of gravitation formulated by sen ＆ Dunn. It is shown that string cosmological models representing geometric strings （ρ = λ） and massive strings （ρ ＋λ = 0） do exist in this theory. Further, it is found that the Takabayasi string, i.e. ρ= （1 ＋ζ）λ, does not exist. some physical and geometrical features of these models are discussed.

关键词： string fields -- inflation -- plane symmetry -- acceleration of particles-- gravitation

Influence of a nucleotide oligomerization domain 1 (NOD1) polymorphism and NOD2 mutant alleles on Crohn's disease phenotype

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World Journal of Gastroenterology 2007年第41期13卷 5446-5453页

作者： elisabet Cantó elena Ricart David Busquets David Monfort esther García-Planella Dolors González Joaquim Balanzó José L Rodríguez-sánchez s.lvia Vidal Department of Immunology Sant Pau Hospital & Research Inst.Sant Pau HospitalBarcelona 08025Spain Department of Gastroenterology CIBER-EHD.Clinic HospitalBarcelona-08025Spain Department of Digestive Pathology Sant Pau HospitalBarcelona 08025Spain

AIM： To examine genetic variation of nucleotide oligomerization domain 1 （NOD/） and NOD2, their respective influences on Crohn＇s disease phenotype and gene-gene interactions. MeTHODs：（ND1＋32656＊1） NOD1 polymorphism and sNPs, sNP12 and sNP13 of NOD2 were analyzed in 97 patients and 50 controls. NOD2 variants were determined by reaction restriction fragment length polymorphism analysis. NOD1 genotyping and NOD2 variant confirmation were performed by specific amplification and sequencing. ResULTs： The distribution of NOD1 polymorphism in patients was different from controls （P = 0.045） and not altered by existence of NOD2 mutations. In this cohort, 30.92% patients and 6% controls carried at least one NOD2 variant （P 〈 0.001） with R702W being the most frequent variant. Presence of at least one NOD2 mutation was inversely associated with colon involvement （9.09% with colon vs 36.4% with ileal or ileocolonic involvement, P = 0.04） and indicative of risk of penetrating disease （52.63% with penetrating vs 25.64% with non-penetrating or stricturing behavior, P = 0.02）. L1007finsC and double NOD2 mutation conferred the highest risk for severity of disease （26.3% with penetrating disease vs 3.8% with non-penetrating or stricturing behavior presented L1007finsC, P = 0.01 and 21.0% with penetrating disease vs 2.5% with non-penentrating or stricturing behavior carried double NOD2 mutation, P = 0.007）. exclusion of patients with NOD2 mutations from phenotype/NODl-genotype analysis revealed higher prevalence of ＊1＊1 genotype in groups of younger age at onset and colonic location.CONCLUsION： This study suggests population differences in the inheritance of risk NOD1 polymorphism and NOD2 mutations. Although no interaction between NOD1-NOD2 was noticed, a relationship between disease location and Nod-like receptor molecules was established.

关键词： Crohn's disease Nucleotide oligomerization domain 1 Nucleotide oligomerization domain 2

Parameter estimation in Manneville–Pomeau processes

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Probability, Uncertainty and Quantitative Risk 2023年第2期8卷 213-234页

作者： Barbara P.Olbermann s.lvia R.C.Lopes Artur O.Lopes Faculdade de Matemática-PUCRs 90650-002 Porto AlegreRSBrazil Instituto de Matemática e estatística-UFRGs 91500-900 Porto AlegreRSBrazil

In this paper,we study a class of stochastic processes{X_(t)}t∈N,where X_(t)=φ■T_(s)^(t)(X_(0))is obtained from the iterations of the transformation T_(s),invariant for an ergodic probabilityμ_(s)on[0,1]and a certain constant by partial functionφ:[0,1]→*** consider here the family of transformations T_(s):[0,1]→[0,1]indexed by a parameters>0,known as the Manneville–Pomeau family of *** autocorrelation function of the resulting process decays hyperbolically(or polynomially)and we obtain efficient methods to estimate the parameter s from a finite time *** a consequence,we also estimate the rate of convergence of the autocorrelation decay of these *** compare different estimation methods based on the periodogram function,the smoothed periodogram function,the variance of the partial sum,and the wavelet *** obtain our results we analyzed the properties of the spectral density function and the associated Fourier series.

关键词： Manneville–Pomeau maps Long and not so long dependence estimation Autocorrelation decay spectral density function