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Small heat shock protein B8:from cell functions to its involvement in diseases and potential therapeutic applications

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Neural Regeneration Research 2025年第10期20卷 2872-2886页

作者： marta Chierichetti Riccardo Cristofani Valeria Crippa Veronica Ferrari marta Cozzi Elena Casarotto paola Pramaggiore Laura Cornaggia Guglielmo Patelli Ali mohamed margherita Piccolella mariarita Galbiati paola Rusmini Barbara Tedesco Angelo Poletti Laboratory of Experimental Biology Dipartimento di Scienze Farmacologiche e Biomolecolari“Rodolfo Paoletti”(DiSFeB)Universitàdegli Studi di MilanoMilanItaly

Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock ***8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and ***8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective *** line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and *** cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under ***,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar *** note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other *** is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial *** review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its ***-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.

关键词： aggregation autophagy cancer chaperone chaperone-assisted selective autophagy cognitive impairment HSPB8 neuroinflammation neuromuscular diseases therapy

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L-2 and IL-15 dependent thymic development of Foxp3-expressing regulatory T lymphocytes

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Protein & Cell 2018年第4期9卷 322-332页

作者： Cecile Apert paola Romagnoli Joost P, m. van meerwijk CPTP Universite de Toulouse CNRS Inserm UPS Toulouse France

Immunosuppressive regulatory T lymphocytes （Treg） expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 （IL-2） and IL-15. The more recently appreciated involvement of TGF-β in thymic Treg development is also briefly discussed. Finally, we discuss how cytokine-dependence of Treg development allows for temporal, quantitative, and potentially qualitative modulation of this process.

关键词： regulatory T cells thymus differentiation,IL-2 IL-15

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Xanthophyll β-cryptoxanthin treatment inhibits hepatic steatosis without altering vitamin A status inβ-carotene 9',10'-oxygenase knockout mice

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Hepatobiliary Surgery and Nutrition 2022年第2期11卷 188-198页

作者： Chun Liu Bruna paola m.Rafacho Xiang-Dong Wang Nutrition and Cancer Biology Laboratory JM USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonMAUSA

Background:β-cryptoxanthin(BCX),one of the major carotenoids detected in human circulation,can protect against the development of fatty liver *** can be metabolized throughβ-carotene-15,15'-oxygenase(BCO1)andβ-carotene-9',10'-oxygenase(BCO2)cleavage pathways to produce both vitamin A and apo-carotenoids,respectively,which are considered important signaling molecules in a variety of biological ***,we have demonstrated that BCX treatment reduced hepatic steatosis severity and hepatic total cholesterol levels in both wide type and BCO1^(-/-)/BCO2^(-/-)double knock out(KO)*** the protective effect of BCX is seen in single BCO2^(-/-)KO mice is ***:In the present study,male BCO2^(-/-)KO mice at 1 and 5 months of age were assigned to two groups by age and weight-matching as follows:(I)-BCX control diet alone(AIN-93 purified diets);(II)+BCX 10 mg(supplemented with 10 mg of BCX/kg of diet)for 3 *** 4 and 8 months of age,hepatic steatosis and inflammatory foci were evaluated by *** and BCX concentrations in liver tissue were analyzed by high-performance liquid chromatography(HPLC).Hepatic protein expressions of SIRT1,acetylated and total FoxO1,PGC1α,and PPARαwere determined by the Western blot ***-time PCR for gene expressions(mCAD,SCD1,FAS,TNFα,and IL-1βgene expression relative toβ-actin)was conducted in the ***:Steatosis was detected at 8 months but not at 4 months of ***,BCX supplementation significantly reduced the severity of steatosis in the livers of BCO2KO mice,which was associated with changes in hepatic SIRT1 acetylation of FOXO1,PGC1αprotein expression and PPARαprotein expression in BCO2^(-/-)KO *** analysis showed that hepatic BCX was detected in BCX supplemented groups,but there were no differences in the hepatic levels of retinol and retinyl palmitate(RP)among all ***:The present study provided experimental evidence that BCX intervention can r

关键词： β-cryptoxanthin(BCX) oxygenases fatty liver

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Hepatocellular carcinoma in nonalcoholic fatty liver: Role of environmental and genetic factors

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World Journal of Gastroenterology 2014年第36期20卷 12945-12955页

作者： paola Dongiovanni Stefano Romeo Luca Valenti Internal medicine 1B Fondazione IRCCS Ca’ Granda Ospedale Policlinico 20122 Milano Italy Department of Pathophysiology and Transplantation Università degli Studi di Milano 20122 Milano Italy Wallenberg Laboratory Department of Molecular and Clinical Medicine University of Gothenburg 40530 Gothenburg Sweden Clinical Nutrition Unit Department of Medical and Surgical Sciences University Magna Graecia 88100 Catan-zaro Italy

Hepatocellular carcinoma(HCC) is the fourth cause of cancer related mortality, and its incidence is rapidly increasing. Viral hepatitis, alcohol abuse, and exposure to hepatotoxins are major risk factors, but nonalcoholic fatty liver disease(NAFLD) associated with obesity, insulin resistance, and type 2 diabetes, is an increasingly recognized trigger, especially in developed countries. Older age, severity of insulin resistance and diabetes, and iron overload have been reported to predispose to HCC in this context. Remarkably, HCCs have been reported in non-cirrhotic livers in a higher proportion of cases in NAFLD patients than in other etiologies. Inherited factors have also been implicated to explain the different individual susceptibility to develop HCC, and their role seems magnified in fatty liver, where only a minority of affected subjects progresses to cancer. In particular, the common I148 m variant of the PNPLA3 gene influencing hepatic lipid metabolism influences HCC risk independently of its effect on the progression of liver fibrosis. Recently, rare loss-of-function mutations in Apolipoprotein B resulting in very low density lipoproteins hepatic retention and in Telomerase reverse transcriptase influencing cellular senescence have also been linked to HCC in NAFLD. Indeed, hepatic stellate cells senescence has been suggested to bridge tissue aging with alterations of the intestinal microbiota in the pathogenesis of obesity-related HCC. A deeper understanding of the mechanisms mediating hepatic carcinogenesis during insulin resistance, and the identification of its genetic determinants will hopefully provide new diagnostic and therapeutic tools.

关键词： Nonalcoholic fatty liver disease Steatosis Hepatocellular carcinoma Cirrhosis Fibrogenesis Liver disease Genetics Single nucleotide polymorphism Patatin-like phospholipase domain-containing 3

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Bedrock geology interacts with altitude in affecting leaf growth and foliar nutrient status of mountain vascular plants

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Journal of Plant Ecology 2017年第5期10卷 839-850页

作者： Renato Gerdol Roberta marchesini paola Iacumin Department of Life Sciences and Biotechnology University of FerraraCorso Ercole I d’Este 32I-44121 FerraraItaly Department of Physics and Earth Sciences University of ParmaViale delle Scienze 158/AI-43124 ParmaItaly

Aims Altitude is often used as a proxy for ascertaining how warming affects plant growth and leaf level ***,we have a poor understanding of how the effects of altitude-related warming varies across ***,this study examined the independ-ent and interactive effects of altitude and geology and species on plant growth and foliar nutrient *** We determined leaf growth rates and concentrations of major nutrients(nitrogen,N and phosphorus,P)in leaves of five spe-cies across two altitudinal gradients(1200-2200 m)in the Dolomites(south-eastern Alps,Italy).the two transects were located on carbonate bedrock and silicate bedrock,*** also determined concentrations of inorganic and organic N and P forms in soils,andδ15N signature in leaves and *** Findings Foliar N concentrations were unrelated to bedrock *** negative foliarδ^(15)N signature suggested that organic N was the primary source of N supply across the *** P concentrations were strongly affected by bedrock geology and their altitudinal patterns depended on the concentrations of organic and inorganic P forms in the *** and organic P appeared to be the main sources of P *** growth rates increased with higher altitude on silicate bedrock and decreased with higher altitude on carbonate bedrock and presented a significant positive correlation with foliar N:*** conclusion,bedrock geology inter-acted with altitude in controlling the foliar nutrient status mainly owing to availability of soil P and its effect on foliar nutrient stoichiometry.

关键词： altitude mycorrhiza plant functional type soil chemistry ^(15)N

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Overcast sky condition prevails on and influences the biometeorology of the tropical Andean Páramos

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Journal of mountain Science 2023年第1期20卷 78-86页

作者： paola mONTENEGRO-DÍAZ Rolando CELLERIALVEAR Galo CARRILLO-ROJAS Departamento de Recursos Hídricos y Ciencias Ambientales Universidad de CuencaCuenca010207Ecuador Facultad de Ingeniería Universidad de CuencaCuenca010207Ecuador Facultad de Ciencias Químicas Universidad de CuencaCuenca010207Ecuador

Clouds play a major role in modulating the biometeorological processes. We studied the influence of cloudiness on four biometeorological variables:daily air temperature(Tair), relative humidity(RH),reference evapotranspiration(ETr),and photosynthetic active radiation(PAR), recorded at four sites of Andean Páramos in southern Ecuador during 2.5 to 5.5 years. First, we quantified both the cloud cover percentage(Cloud%) creating cloud masks over the visible bands of Landsat 7 images and the sky condition(K_(T)) using the records of solar and extraterrestrial radiation. Second, we estimated KTfrom Cloud%. Finally, we quantified T_(air), RH, ET_(r), and PAR under clear, cloudy, and overcast K_(T) and their dependence on KT. The average Cloud% ranged between 65%–76%, and KTcorroborated the prevailing overcast sky(between 55% and 72.5% of the days) over the páramos. The proposed model performed well in the sites of calibration(R^(2)= 0.80;mBE = 0.00;RmSE = 0.05) and validation(R^(2)= 0.74;mBE =-0.07;RmSE = 0.11). The overcast sky diminished T_(air)(≤ 10℃), ET_(r)(≤ 1.6 mm day-1), and PAR(4 mJ m^(-2)day^(-1)) and increased RH(≥ 88%),while the variables showed the opposite behavior during the uncommon clear sky(≤ 5.5% of the days).Thus, mostly the dynamic of RH(R^(2)≥ 0.62), ETr(R^(2)≥ 0.85), and PAR(R2≥ 0.77) depended on K_(T). Hence,the prevailing overcast sky influenced the biometeorology of the páramos.

关键词： Cloudiness indicator Clearness index Satellite imagery Tropical Andes

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Current review of Excimer laser Trabeculostomy

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Eye and Vision 2020年第1期7卷 232-240页

作者： Georges m.Durr marc Töteberg-Harms Richard Lewis Antonio Fea paola marolo Iqbal Ike K.Ahmed Department of Ophthalmology Universitéde MontréalMontrealQuebecCanada Department of Ophthalmology Centre Hospitalier Universitaire de Montréal(CHUM)1051 Rue SanguinetMontreal H2X 3E4QuebecCanada Department of Ophthalmology University Hospital ZurichZurichSwitzerland Sacramento Eye Consultants SacramentoCaliforniaUSA Struttura Complessa Oculistica Cittàdella Salute e della Scienza di TorinoDipartimento di Scienze ChirurgicheUniversitàdegli Studi di TorinoTorinoItaly Department of Ophthalmology&Vision Sciences University of TorontoTorontoOntarioCanada

Background:Excimer laser trabeculostomy(ELT)is a microinvasive glaucoma surgery(mIGS)that creates multiple laser channels through the trabecular meshwork using a cold laser system,which minimizes tissue fibrosis and aids in bypassing the main area of resistance to aqueous *** purpose of this review is to evaluate the current body of evidence surrounding ELT in terms of efficacy and review the safety profile of the *** text:Studies screened had to show clear inclusion and exclusion criteria as well as well-defined outcome ***,mEDLINE,EmBASE and the Cochrane Controlled Trial Database were *** Reporting Items of Systematic Reviews(PRISmA)guidelines were used to assess for study quality and for any ***-four articles were initially identified with 18 meeting preliminary screening ***,8 studies met inclusion criteria and 2 additional non-referenced publications were also included:1 randomized control trial,4 prospective case series and 5 retrospective *** studies showed moderate intraocular pressure(IOP)lowering of between 20%and 40%from baseline without medication washout and mostly a decrease in glaucoma medications with few ***:Current literature shows a significant IOP-lowering effect of ELT with a favorable safety-profile in standalone cases or combined with cataract *** to these studies are the lack of controls and washout ***,ELT is an attractive mIGS option that does not require any residual device remaining in the angle.

关键词： Excimer laser trabeculostomy Trabeculotomy ELT Intraocular pressure Glaucoma mIGS Cataract

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Long-noncoding RNAs as epigenetic regulators in neurodegenerative diseases

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Neural Regeneration Research 2023年第6期18卷 1243-1248页

作者： paola Ruffo Francesca De Amicis Emiliano Giardina Francesca Luisa Conforti medical Genetics Laboratory Department of PharmacyHealth and Nutritional SciencesUniversity of CalabriaRendeItaly Department of Pharmacy Health and Nutritional SciencesUniversity of CalabriaRendeItaly Genomic medicine Laboratory UILDm IRCCS Fondazione Santa LuciaRomeItaly Department of Biomedicine&Prevention Tor Vergata University of RomeRomeItaly

The growing and rapid development of high-throughput sequencing technologies have allowed a greater understanding of the mechanisms underlying gene expression *** the epigenome and epitranscriptome directs the fate of the transcript influencing the functional outcome of each *** this context,non-coding RNAs play a decisive role in addressing the expression regulation at the gene and chromosomal ***-noncoding RNAs,consisting of more than 200 nucleotides,have been shown to act as epigenetic regulators in several key molecular processes involving neurodegenerative disorders,such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis and Huntington’s ***-noncoding RNAs are abundantly expressed in the central nervous system,suggesting that their deregulation could trigger neuronal degeneration through RNA *** evaluation of their diagnostic significance and therapeutic potential could lead to new treatments for these diseases for which there is no cure.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis epigenetic mechanism Huntington’s disease long-noncoding RNAs neurodegenerative disease non-coding RNAs Parkinson’s disease

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Efficacy of medium-chain fatty acid salts distilled from coconut oil against two enteric pathogen challenges in weanling piglets

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Journal of Animal Science and Biotechnology 2020年第1期11卷 251-267页

作者： paola López-Colom Lorena Castillejos Agustina Rodríguez-Sorrento mónica Puyalto Juan Josémallo Susana maría martín-Orúe Animal Nutrition and Welfare Service Animal and Food Science DepartmentFacultat de VeterinàriaUniversitat Autònoma de BarcelonaBellaterraSpain Norel S.A MadridSpain.

Background:The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties,such as medium-chain fatty acids(mCFA)as in-feed *** study evaluated the potential of a novel blend of mCFA salts(DIC)from distilled coconut oil with a lauric acid content to reduce enteropathogens and control intestinal diseases around *** experimental disease models were implemented in early-weaned piglets,consisting of two oral challenges:Salmonella Typhimurium(1.2×10~8 CFU)or enterotoxigenic Escherichia coli(ETEC)F4(1.5×10~9 CFU).The parameters assessed were:animal performance,clinical signs,pathogen excretion,intestinal fermentation,immune-inflammatory response,and intestinal ***:The Salmonella challenge promoted an acute course of diarrhea,with most of the parameters responding to the challenge,whereas the ETEC F4 challenge promoted a mild clinical course.A consistent antipathogenic effect of DIC was observed in both trials in the hindgut,with reductions in Salmonella *** counts in the cecum(P=0.03)on d 8 post-inoculation(PI)(Salmonella trial),and of enterobacteria and total coliform counts in the ileum and colon(Pmicrobiota(16 S rRNA gene sequencing),this additive tended(P=0.13)to reduce the Firmicutes/Bacteroidetes ratio and enriched Fibrobacteres after the Salmonella *** the ETEC F4 challenge,DIC prompted structural changes in the ecosystem with increases in Dialister,and a trend(P=0.14)to increase the Veillonellaceae *** parameters such as the intestinal fermentation products or serum pro-inflammatory mediators were not modified by DIC supplementation,nor were the histological *** the intraepithelial lymphocyte(IEL)counts were lowered by DIC in animals challenged with Salmonella(P=0.07).With ETEC F4,the IEL counts were higher with DIC on d 8 PI(P=0.08).Conclusions:This study c

关键词： Enteric pathogen Gut microbiota Intestinal immunity medium-chain fatty acids Weaning pig

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A QTL associated with leaf trichome traits has a major influence on the abundance of the predatory mite Typhlodromus pyri in a hybrid grapevine population

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Horticulture Research 2019年第1期6卷 639-650页

作者： paola Barba Rebecca Loughner Karen Wentworth Jan Peter Nyrop Gregory m.Loeb Bruce I.Reisch Plant Breeding and Genetics Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853USA Department of Entomology Cornell AgriTechGenevaNY 14456USA Horticulture Section School of Integrative Plant ScienceCornell AgriTechGenevaNY 14456USA Instituto de Investigaciones Agropecuarias INIA La PlatinaSantiago 8831314Chile

The abundance of predatory phytoseiid mites,Typhlodromus pyri,important biological control agents of spider mite pests in numerous crops,is positively influenced by the density of leaf trichomes and tuft-form domatia in vein *** of the genetic regions controlling both trophic levels could facilitate the improvement of predatory mite habitat in breeding *** abundance of *** and non-glandular trichomes was measured in a segregating F1 family derived from the cross of the complex Vitis hybrid,‘Horizon’,with Illinois 547-1(*** B38×*** B9),finding positive correlation among *** density genetic maps were used to localize one major quantitative trait locus(QTL)on chromosome 1 of Illinois 547-1 associated with both predatory mite abundance and leaf *** QTL explained 23%of the variation in phytoseiid abundance and similar amounts of variance in domatia rating(21%),domatia size(16%),leaf bristle density(37%in veins and 33%in blades),and leaf hair density(20%in veins and 15%in blades).Another nine QTL distributed among chromosomes 1,2,5,8,and 15 were associated solely with trichome density,and explained 7–17%of the phenotypic ***,our results provide evidence of the genetic architecture of non-glandular trichomes in Vitis,with a major locus influencing trichome densities,domatia size and predatory mite *** information is relevant for breeding grapevines with a more favorable habitat for biological control agents.

关键词： breeding crops predator

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