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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

Metabolomic fingerprinting of porcine lung tissue during pre-clinical prolonged ex vivo lung perfusion using in vivo SPME coupled with LC-HRMS

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Journal of Pharmaceutical Analysis 2022年第4期12卷 590-600页

作者： Nikita Looby Anna Roszkowska Aadil Ali barbara Bojko Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooN2L 3G1Canada Department of Pharmaceutical Chemistry Medical University of Gdansk80-416GdanskPoland Division of Thoracic Surgery University Health NetworkTorontoM5G 2C4Canada Department of Pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089BydgoszczPoland

Normothermic ex vivo lung perfusion(NEVLP)has emerged as a modernized organ preservation technique that allows for detailed assessment of donor lung function prior to *** main goal of this study was to identify potential biomarkers of lung function and/or injury during a prolonged(19 h)NEVLP procedure using in vivo solid-phase microextraction(SPME)technology followed by liquid chromatography-high resolution mass spectrometry(LC-HRMS).The use of minimally invasive in vivo SPME fibers for repeated sampling of biological tissue permits the monitoring and evaluation of biochemical changes and alterations in the metabolomic profile of the *** in vivo SPME fibers were directly introduced into the lung and were also used to extract metabolites(on-site SPME)from fresh perfusate samples collected alongside lung samplings.A subsequent goal of the study was to assess the feasibility of SPME as an in vivo method in metabolomics studies,in comparison to the traditional inlab metabolomics *** upregulated biochemical pathways involved in pro-and antiinflammatory responses,as well as lipid metabolism,were observed during extended lung perfusion,especially between the 11th and 12th hours of the procedure,in both lung and perfusate ***,several unstable and/or short-lived metabolites,such as neuroprostanes,have been extracted from lung tissue in vivo using SPME ***-site monitoring of the metabolomic profiles of both lung tissues through in vivo SPME and perfusate samples on site throughout the prolonged NEVLP procedure can be effectively performed using in vivo SPME technology.

关键词： Normothermic ex vivo lung perfusion Solid phase microextraction Lung metabolomics

Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury

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Neural Regeneration Research 2017年第11期12卷 1786-1790页

作者： barbara Vigani Silvia Rossi Giuseppina Sandri Maria Cristina Bonferoni Franca Ferrari Department of Drug Sciences University of PaviaViale TaramelliPaviaItaly

The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the poly- mers more investigated in the production of neural fibrous scaffolds is also provided.

关键词： spinal cord injury biomaterials electrospun fibers conductive scaffolds morphological properties biodegradability

CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and balneological treatment

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第5期16卷 404-411页

作者： Danuta RO Przemyslaw ADAMCZYK Joanna BOINSKA Robert SZAFKOWSKI Irena PONIKOWSKA Katarzyna STANKOWSKA barbara GóRALCZYK barbara RUSZKOWSKA-CIASTEK Department of Pathophysiology Faculty of Pharmacy Nicolaus Copernicus University in ToruńCollegium Medicum in Bydgoszcz Clinic of Balneology and Physical Medicine Faculty of Health Science Nicolaus Copernicus University in ToruńCollegium Medicum in Bydgoszcz

Objective：The aim of this study was to evaluate the concentrations of C-reactive protein （CRP）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6）, and the degree of homeostasis model assessment-insulin resistance （HOMA-IR） in patients with morbid obesity exposed to a three-week low-calorie diet and balneotherapy. Methods：The study included 33 patients （25 females and 8 males; mean age 46 years） with body mass index （BMI） values of〉40 kg/m2. Evaluations of CRP, IL-6, TNF-α, lipid profile, HOMA-IR, and fasting glucose were carried out before （baseline data） and three weeks after the treatment. The control group consisted of 20 healthy volunteers （15 females and 5 males） with a mean age of 39 years and BMI values of≤24.9 kg/m2. Results：In the blood of patients with morbid obesity we found significantly elevated levels of CRP, TNF-α, triglycerides, HOMA-IR and fasting glucose, but a de-creased level of high density lipoprotein （HDL）-cholesterol, compared with the healthy individuals. The treatment resulted in about a 9.4%reduction in body weight from 122.5 to 111.0 kg and a significant decrease in the concen-tration of CRP, but no change in TNF-αor IL-6. HOMA-IR was significantly reduced. Conclusions：The decrease in CRP level without changes in TNF-α or IL-6 concentrations after the low-calorie diet and balneological treatment, suggests that an essential amount of adipose tissue must be removed before proper adipocyte function is restored. The decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is beneficial in obese patients.

关键词： pro-inflammatory cytokines Tumor necrosis factor-α (TNF-α) Interleukin-6 (IL-6) Morbid obesity

production of the Cancer-Preventive Glucoraphanin in Tobacco

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Molecular Plant 2010年第4期3卷 751-759页

作者： Michael Dalgaard Mikkelsen Carl Erik Olsen barbara Ann Halkier University of Copenhagen Faculty of Life Sciences Department of Plant Biology Plant Biochemistry Laboratory VKR Research Centre for Pro-Active Plants 40 Thorvaldsensvej DK-1871 Frederiksberg C Copenhagen Denmark University of Copenhagen Faculty of Life Sciences Department of Basic Sciences and Environment/Bioorganic Chemistry 40 Thorvaldsensvej DK-1871 Frederiksberg C Copenhagen Denmark

Epidemiological studies have demonstrated reduced risk of developing cancer upon consumption of diets rich in cruciferous vegetables. This chemoprevention has been largely attributed to the presence of the natural products glu- cosinolates, particularly the methionine-derived glucoraphanin from broccoli. Improved nutrition by functional foods or health-promoting dietary supplements is an attractive means for prevention of lifestyle-based diseases. Towards this goal, we have engineered the glucoraphanin pathway into tobacco. First, we engineered elongation of the side chain of methionine to produce the key intermediate dihomo-methionine. This process is catalyzed through two cycles in a chain-elongation pathway that takes place partly in the cytosol and partly in the chloroplast. Second, by coupling the five enzymes of the chain-elongation pathway to eight enzymes of the glucosinolate pathway, we show production of glucoraphanin together with other glucosinolates derived from chain-elongated isoleucine and/or leucine. The conver- sion of methionine to glucoraphanin is obtained via 14 intermediates. Demonstrating the production of the high-value glucoraphanin in a heterologous host has great potential in the food and medicinal industry as a means to generate a stable, rich source of glucoraphanin for the benefit of human health.

关键词： Compartmentation secondary metabolism/natural products Agrobacterium Arabidopsis tobacco glucosinolates metabolic engineering.

Bortezomib effect on E2F and cyclin family members in human hepatocellular carcinoma cell lines

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World Journal of Gastroenterology 2014年第3期20卷 795-803页

作者： Daniele Baiz barbara Dapas Rossella Farra Bruna Scaggiante Gabriele Pozzato Fabrizio Zanconati Nicola Fiotti Lara Consoloni Sara Chiaretti Gabriele Grassi Department of Life Sciences University of Trieste Wake Forest School of Medicine Department of Cancer Biology and Comprehensive Cancer CenterMedical Center BoulevardWinston SalemNC 27157United States Department of Industrial Engineering and Information Technology University of Trieste Department of ‘‘Scienze Mediche Chirurgiche e della Salute''University of TriesteCattinara Hospital

AIM: To evaluate the effects of the proteasome inhibitor bortezomib (BZB) on E2Fs and related genes in hepatocellular carcinoma (HCC) cells.

关键词： Bortezomib Cyclins E2F family Hepatocellular carcinoma Liver Microarray 26S proteasome

Influence of mental stress on platelet bioactivity

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World Journal of Psychiatry 2012年第6期2卷 134-147页

作者： Pia Koudouovoh-Tripp barbara Sperner-Unterweger Clinic for Biological Psychiatry Department of Psychiatry and PsychotherapyInnsbruck Medical UniversityAnichstrasse 356020 InnsbruckAustria Clinic for General Psychiatry Department of Psychiatry and PsychotherapyInnsbruck Medical UniversityAnichstrasse 356020 InnsbruckAustria

It is well established that various mental stress conditions contribute, or at least influence, underlying pathophysiological mechanisms in somatic, as well as in psychiatric disorders; blood platelets are supposed to represent a possible link in this respect. The anculeated platelets are the smallest corpuscular elements circulating in the human blood. They display different serotonergic markers which seem to reflect the central nervous serotonin metabolism. They are known as main effectors in haematological processes but recent research highlights their role in the innate and adaptive immune system. Platelets are containing a multitude of pro-inflammatory and immune-modulatory bioactive compounds in their granules and are expressing immune-competent surface markers. Research gives hint that platelets activation and reactivity is increased by mental stress. This leads to enhanced cross talk with the immune system via paracrine secretion, receptor interaction and formation of platelet leucocyteaggregates. Recently it has been demonstrated that the immune system can have a remarkable impact in the development of psychiatric disorders. Thereforeplatelets represent an interesting research area in psychiatry and their role as a possible biomarker has been investigated. We review the influence of mental stress on what is termed platelet bioactivity in this article, which subsumes the mainly immune-modulatory activity of platelets in healthy volunteers, elderly persons with chronic care-giving strain, patients with cardiovascular diseases who are prone to psychosocial stress, as well as in patients with posttraumatic stress disorder. Research data suggest that stress enhances platelet activity, reactivity and immune-modulatory capacities.

关键词： Mental stress Caregiving strain Posttraumatic stress disorder Cardiovascular disease Serotonin Platelet activation Platelet bioactivity

Alcohol,nutrition and liver cancer:Role of Toll-like receptor signaling

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World Journal of Gastroenterology 2010年第11期16卷 1344-1348页

作者： Samuel W French Joan Oliva barbara A French Fawzia Bardag-Gorce Department of Pathology Harbor-UCLA Medical Center

This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (TLR) signaling as the mechanism of liver stem cell/progenitor transformation to HCC. Two exemplary models of this phenomenon are reviewed in detail. One model applies chronic ethanol/lipopolysaccharide feeding to the activated TLR4 signaling pathway. The other applies chronic feeding of a carcinogenic drug, in which TLR2 and 4 signaling pathways are activated. In the drug-induced model, two major methyl donors, S-adenosylmethionine and betaine, prevent the upregulation of the TLR signaling pathways and abrogate the stem cell/progenitor proliferation response when fed with the carcinogenic drug. This observation supports a nutritional approach to liver cancer prevention and treatment. The observation that upregulation of the TLR signaling pathways leads to liver tumor formation gives evidence to the popular concept that the chronic pro-inflammatory response is an important mechanism of liver oncogenesis. It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases.

关键词： Toll-like receptor Hepatocellular carcinoma Methyl donors, Epigenetic processes Inflammation Alcohol Drug toxicity Lipopolysaccharides

Local renin angiotensin system and sperm DNA fragmentation

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Asian Journal of Andrology 2022年第2期24卷 139-146页

作者： María Victoria Aparicio Prieto María Victoria Rodríguez Gallego Asier Valdivia Palacín Yosu Franco Iriarte Gotzone Hervás barbara Enrique Echevarría Orella Luis Casis Saenz Human Reproduction Unit Cruces University HospitalBarakaldo 48903Spain Human Reproduction Unit San Pedro HospitalLogroño 26006Spain Department of Physiology Faculty of Medicine and NursingUniversity of the Basque Country(UPV/EHU)Leioa 48940Spain Human Reproduction Unit Ruber International HospitalMadrid 28034Spain

The renin angiotensin system(RAS)appears to influence male fertility at multiple *** this work,we analyzed the relationship between the RAS and DNA *** male volunteers were divided into two groups(25 each):control(DNA fragmentation≤20%)and pathological(DNA fragmentation>20%)*** of five peptidases controlling RAS were measured fluorometrically:prolyl endopeptidase(which converts angiotensin[A]I and A II to A 1–7),neutral endopeptidase(NEP/CD10:A I to A 1–7),aminopeptidase N(APN/CD13:A III to A IV),aminopeptidase A(A II to A III)and aminopeptidase B(A III to A IV).Angiotensin-converting enzyme(A I to A II),APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays,as were the receptors of all RAS components:A II receptor type 1(AT1R),A II receptor type 2(AT2R),A IV receptor(AT4R or insulin-regulated aminopeptidase[IRAP]),(pro)renin receptor(PRR)and A 1–7 receptor or Mas receptor(MasR)None of the enzymes that regulate levels of RAS components,except for APN/CD13(decrease in fragmented cells),showed significant differences between both *** of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented *** of AT1R(94.3%normozoospermic vs 84.1%fragmented),AT4R(96.2%vs 95.3%)and MasR(97.4%vs 87.2%)was similar between the ***2R(87.4%normozoospermic vs 63.1%fragmented)and PRR(96.4%vs 48.2%)were higher in non-fragmented *** findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.

关键词： DNA fragmentation local renin angiotensin system sperm fertility