Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understandi...Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.展开更多
The presence of illicit drugs and their metabolites in surface waters has to be considered a new type of hazard, still unknown, for both the human health and the aquatic ecosystem, due to the potent pharmacological ac...The presence of illicit drugs and their metabolites in surface waters has to be considered a new type of hazard, still unknown, for both the human health and the aquatic ecosystem, due to the potent pharmacological activities of all the illicit drugs. Our research was aimed at evaluating the presence of illicit drugs in the Sarno River (Campania region, Italy), crossing a densely populated area, the basin of the Sarno River, one of the largest and most important economic areas in Campania region, famous for the presence of zones with high landscape-environmental value. The drugs selected for this study were the most used in Campania region. The presence of illicit drugs in surface water was analyzed by a selective multi-residue assay based on liquid chromatographytandem mass spectrometry. The analysis showed the presence of all the illicit drugs investigated: cocaine and its main metabolites (benzoylecgonine, nor-benzoylecgonine), morphine, THC-COOH and codeine;cocaine was the most abundant illicit drug. The presence of illicit drugs and their metabolites in the Sarno River suggests new potential risk for the basin’s inhabitants, using water in the food chain, via field irrigation and animal feed, and for the health of the aquatic fauna.展开更多
Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing ...Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%;95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.展开更多
"China has the opportunity to lead the world not only in research quantity, but also in quality" Lancet has affirmed[1].There is no reason to exclude the possibility that the above authoritative prediction c..."China has the opportunity to lead the world not only in research quantity, but also in quality" Lancet has affirmed[1].There is no reason to exclude the possibility that the above authoritative prediction could be applied to the research in Nephrology.However, how to comply with this goal? Methodologically rigorous randomized controlled trials have the ability to address relevant research questions on safety and efficacy of new interventions.Indispensable conditions for successful conduct of clinical trials rely on the two major principles on which Good Clinical Practice is based[2]: One is strict ethical rules to safeguard the rights and safety of patients and another is high level of validity and credibility of trial data.However, absence of formal training in research ethics and methodology for investigators, reduced time for research activities, lack of adequate infrastructures, bureaucratic limitations and poor financial resources still represent major barriers to the successful performance of high quality randomized controlled trials[3].展开更多
In cancer,myeloid cells have tumor-supporting roles.We reported that the protein GPNMB(glycoprotein nonmetastatic B)was profoundly upregulated in macrophages interacting with tumor cells.Here,using mouse tumor models,...In cancer,myeloid cells have tumor-supporting roles.We reported that the protein GPNMB(glycoprotein nonmetastatic B)was profoundly upregulated in macrophages interacting with tumor cells.Here,using mouse tumor models,we show that macrophage-derived soluble GPNMB increases tumor growth and metastasis in Gpnmb-mutant mice(DBA/2J).GPNMB triggers in the cancer cells the formation of self-renewing spheroids,which are characterized by the expression of cancer stem cell markers,prolonged cell survival and increased tumor-forming ability.Through the CD44 receptor,GPNMB mechanistically activates tumor cells to express the cytokine IL-33 and its receptor UR1L. We also determined that recombinant IL-33 binding to IL-1R1L is sufficient to induce tumor spheroid formation with features of cancer stem cells.Overall,our results reveal a new paracrine axis,GPNMB and IL-33,which is activated during the cross talk of macrophages with tumor cells and eventually promotes cancer cell survival,the expansion of cancer stem cells and the acquisition of a metastatic phenotype.展开更多
基金supported by fellowship to a grant from CRT Foundation,No.1393-2017(to LT)grants from the Fondazione Cariplo,Nos.2013-0795(to AAG),2014-1094(to DL)grants from The Universitàdel Piemonte Orientale,Nos.FAR-2016(to DL),FAR-2019(to DL)。
文摘Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.
文摘The presence of illicit drugs and their metabolites in surface waters has to be considered a new type of hazard, still unknown, for both the human health and the aquatic ecosystem, due to the potent pharmacological activities of all the illicit drugs. Our research was aimed at evaluating the presence of illicit drugs in the Sarno River (Campania region, Italy), crossing a densely populated area, the basin of the Sarno River, one of the largest and most important economic areas in Campania region, famous for the presence of zones with high landscape-environmental value. The drugs selected for this study were the most used in Campania region. The presence of illicit drugs in surface water was analyzed by a selective multi-residue assay based on liquid chromatographytandem mass spectrometry. The analysis showed the presence of all the illicit drugs investigated: cocaine and its main metabolites (benzoylecgonine, nor-benzoylecgonine), morphine, THC-COOH and codeine;cocaine was the most abundant illicit drug. The presence of illicit drugs and their metabolites in the Sarno River suggests new potential risk for the basin’s inhabitants, using water in the food chain, via field irrigation and animal feed, and for the health of the aquatic fauna.
文摘Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%;95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.
文摘"China has the opportunity to lead the world not only in research quantity, but also in quality" Lancet has affirmed[1].There is no reason to exclude the possibility that the above authoritative prediction could be applied to the research in Nephrology.However, how to comply with this goal? Methodologically rigorous randomized controlled trials have the ability to address relevant research questions on safety and efficacy of new interventions.Indispensable conditions for successful conduct of clinical trials rely on the two major principles on which Good Clinical Practice is based[2]: One is strict ethical rules to safeguard the rights and safety of patients and another is high level of validity and credibility of trial data.However, absence of formal training in research ethics and methodology for investigators, reduced time for research activities, lack of adequate infrastructures, bureaucratic limitations and poor financial resources still represent major barriers to the successful performance of high quality randomized controlled trials[3].
基金supported by IG grants from the Italian Association for Cancer Research(AIRC)to P.A.grants from the Italian Ministry of Health(GR-2013-02356521)to E.M.B.
文摘In cancer,myeloid cells have tumor-supporting roles.We reported that the protein GPNMB(glycoprotein nonmetastatic B)was profoundly upregulated in macrophages interacting with tumor cells.Here,using mouse tumor models,we show that macrophage-derived soluble GPNMB increases tumor growth and metastasis in Gpnmb-mutant mice(DBA/2J).GPNMB triggers in the cancer cells the formation of self-renewing spheroids,which are characterized by the expression of cancer stem cell markers,prolonged cell survival and increased tumor-forming ability.Through the CD44 receptor,GPNMB mechanistically activates tumor cells to express the cytokine IL-33 and its receptor UR1L. We also determined that recombinant IL-33 binding to IL-1R1L is sufficient to induce tumor spheroid formation with features of cancer stem cells.Overall,our results reveal a new paracrine axis,GPNMB and IL-33,which is activated during the cross talk of macrophages with tumor cells and eventually promotes cancer cell survival,the expansion of cancer stem cells and the acquisition of a metastatic phenotype.
