The recent pandemic crisis has highlighted the importance of the availability and management of health data to respond quickly and effectively to health emergencies, while respecting the fundamental rights of every in...The recent pandemic crisis has highlighted the importance of the availability and management of health data to respond quickly and effectively to health emergencies, while respecting the fundamental rights of every individual. In this context, it is essential to find a balance between the protection of privacy and the safeguarding of public health, using tools that guarantee transparency and consent to the processing of data by the population. This work, starting from a pilot investigation conducted in the Polyclinic of Bari as part of the Horizon Europe Seeds project entitled “Multidisciplinary analysis of technological tracing models of contagion: the protection of rights in the management of health data”, has the objective of promoting greater patient awareness regarding the processing of their health data and the protection of privacy. The methodology used the PHICAT (Personal Health Information Competence Assessment Tool) as a tool and, through the administration of a questionnaire, the aim was to evaluate the patients’ ability to express their consent to the release and processing of health data. The results that emerged were analyzed in relation to the 4 domains in which the process is divided which allows evaluating the patients’ ability to express a conscious choice and, also, in relation to the socio-demographic and clinical characteristics of the patients themselves. This study can contribute to understanding patients’ ability to give their consent and improve information regarding the management of health data by increasing confidence in granting the use of their data for research and clinical management.展开更多
The scientific community is continuously working to translate the novel biomedical techniques into effective medical treatments.CRISPR-Cas9 system(Clustered Regularly Interspaced Short Palindromic Repeats-9),commonly ...The scientific community is continuously working to translate the novel biomedical techniques into effective medical treatments.CRISPR-Cas9 system(Clustered Regularly Interspaced Short Palindromic Repeats-9),commonly known as the“molecular scissor”,represents a recently developed biotechnology able to improve the quality and the efficacy of traditional treatments,related to several human diseases,such as chronic diseases,neurodegenerative pathologies and,interestingly,oral diseases.Of course,dental medicine has notably increased the use of biotechnologies to ensure modern and conservative approaches:in this landscape,the use of CRISPR-Cas9 system may speed and personalize the traditional therapies,ensuring a good predictability of clinical results.The aim of this critical overview is to provide evidence on CRISPR efficacy,taking into specific account its applications in oral medicine.展开更多
AIM To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide(HO/CO) pathway in the constipating effects of granisetron. METHODS For in vivo studies, gastrointestinal mo...AIM To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide(HO/CO) pathway in the constipating effects of granisetron. METHODS For in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous(sc)], zinc protoporphyrin IX [Zn PPIX, 50 μg/kg/intraperitoneal(ip)] and hemin(50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation(EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine(ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron(3 μmol/L, 15 min), Zn PPIX(10 μmol/L, 60 min) or CO-releasing molecule-3(CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment withor without atropine(3 μmol/L, a muscarinic receptor antagonist) or NG-nitro-L-Arginine(L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor).RESULTS Administration of granisetron(50, 75 μg/kg) in vivo significantly increased the time to first defecation(P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of Zn PPIX or hemin alone had no effect on this gastrointestinal motility parameter, Zn PPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro, granisetron alone(3 μmol/L) did not significantly modify the colon's contractile response to either EFS or ACh. Incubation with Zn PPIX alone(10 μmol/L) significantly reduced the colon's contractile response to EFS(P = 0.016) but had no effect on contractile response to ACh. Co-administration of Zn PPIX and atropine(3 μmol/L) abolished the Zn PPIX-mediated decrease in contractile response to EFS. Conversely, incubation with CORM-3(400 μmol/L) alone increased both the contractile response to EFS at 10 Hz(10 Hz: 71.02 ± 19.16 vs 116.25 ± 53.70, P = 0.01) and the contractile response to ACh(100 μmol/L)(P = 0.012). Co-administration of atropine abolished the CORM-3-mediated effects on the EFS-mediated response. When granisetron was co-incubated in vitro with ZnP PIX, the ZnP PIX-mediated decrease in colon contractile response to EFS was lost. On the other hand, co-incubation of granisetron and CORM-3(400 μmol/L) further increased the colon's contractile response to EFS(at 5 Hz: P = 0.007; at 10 Hz: P = 0.001) and to ACh(ACh 10 μmol/L: P = 0.001; ACh 100 μmol/L: P = 0.001) elicited by CORM-3 alone. L-NNA co-administered with granisetron and CORM-3 abolished the potentiating effect of CORM-3 on granisetron on both the EFSinduced and ACh-induced contractile response.CONCLUSION Taken together, findings from in vivo and in vitro studies suggest that the HO/CO pathway is involved in the constipating effects of granisetron.展开更多
The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cl...The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan,China in December 2019.Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines,based on scientific evidence and experts’opinions with clinical experience,are constantly being updated.On January 30,2020,the World Health Organization declared the SARS-CoV-2 outbreak as a"Public Health Emergency of International Concern".The total lack of immune protection brought about a severe spread of the contagion all over the world.For this reason,diagnostic tools,patient management and therapeutic approaches have been tested along the way,in the desperate race to break free from the widespread infection and its fatal respiratory complications.Current medical knowledge and research on severe and critical patients’management and experimental treatments are still evolving,but several protocols on minimizing risk of infection among the general population,patients and healthcare workers have been approved and diffused by International Health Authorities.展开更多
Background: Endometrial cell implantation after abdominal surgery, mainly after caesarean section, may result in formation of endometrioma, which is usually described to be of various sizes, and adjacent to the surgic...Background: Endometrial cell implantation after abdominal surgery, mainly after caesarean section, may result in formation of endometrioma, which is usually described to be of various sizes, and adjacent to the surgical scar. Case: A 36-year old woman complaining of a mass of the abdominal wall with pain during the menstrual period, with a caesarean section 5 years earlier, presented a rounded tumour not contiguous to the Pfannenstiel’s laparotomy scar, of hard consistence, fixed and adherent to the deep abdominal wall structures, located on the left paramedian epigastric region. Magnetic Resonance imaging showed the nodule, involving the deep layers of the abdominal wall and the distance from the laparotomic scar. Surgical removal was performed with wide excision of the lesion, causing a large wall defect. After histological confirmation (endometriosis) by frozen section, reconstruction of the abdominal wall required prolene mesh grafting. After twelve months the patient is healthy. Conclusion: When abdominal wall endometrioma is located distant from the scar, perhaps more frequently after Pfannenstiel’s laparotomic incision, the differential diagnosis may be more difficult and MRI can help differentiating many of these lesions, and histological confirmation should be obtained intraoperatively, by frozen section, to allow an oncological resection if required.展开更多
AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Re...AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constantly increased.MDA-TBA levels were five-fold increased from 9.1 ± 1.2 nmol/g to 75.6 ± 5.4 nmol/g on day 30,P < 0.001(CD) and doubled with HFD on day 60.Realsil administration significantly lowered the extent of fat infiltration,maintained liver glutathione levels during the first half period,and halved its decrease during the second half.Also,Realsil modulated thioredoxin changes and the production of NO derivatives and significantly lowered MDA-TBA levels both in liver(from 73.6 ± 5.4 to 57.2 ± 6.3 nmol/g day 30 CD,P < 0.01 and from 27.3 ± 2.1 nmol/g to 20.5 ± 2.2 nmol/g day 60 HFD,P < 0.01) and in plasma.Changes in mitochondrial respiratory complexes were also attenuated by Realsil in HFD rats with a major protective effect on Complex Ⅱ subunit CII-30.CONCLUSION:Realsil administration effectively contrasts hepatocyte fat deposition,NO derivatives formation,and mitochondrial alterations,allowing the liver to maintain a better glutathione and thioredoxin antioxidant activity.展开更多
Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into ...Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells.As stem cells age,their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired.From a molecular perspective,these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration(i.e epigenomic profile)as well as changes in the tissue microenviroment,both into the niche and by systemic circulating factors.Strikingly,it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders.Therefore,understanding how resident stem cell age and affects near and distant tissues is fundamental.Here,we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number,function and phenotype that determine the loss of tissue renewal properties.Furthermore,we examine the possible cell rejuvenation strategies.Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.展开更多
BACKGROUND Congenital analbuminemia(CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old wom...BACKGROUND Congenital analbuminemia(CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old woman presenting with hypercholesterolemia. Our findings contribute to shed light on the molecular genetics of the disorder and confirm that safe and well tolerated hypocholesterolemic treatment with atorvastatin may be administered in dislipidemic patient with CAA in order to reduce their cardiovascular risk.CASE SUMMARY Our patient presented with a history of hypercholesterolemia and referred asthenia and heaviness in both legs. She was born from healthy and nonconsanguineous parents and her development was normal. She had not familiarity for early cardiovascular disease, and did not report personal history of hypertension, chronic kidney or liver diseases. Clinical laboratories results showed critically reduced value of albumin whereas other serum proteins were elevated. Main causes of hypoalbuminemia(proteinuria, inflammatory state and insufficient hepatic synthesis) were ruled out by normal procedures and laboratory tests. So the hypothesis of a CAA was tested through mutation analysis of the albumin gene that revealed a homozygous CA deletion in exon 12,at nucleotide positions c1614-1615. This finding brought to the diagnosis of CAA.Currently the patient receives Atorvastatin 20 mg od and undergoes clinical and laboratory follow-up every six months. She never needed albumin infusions.CONCLUSION Our experience shows how treatment with atorvastatin may be safely administered and well tolerated in patients affected by CAA.展开更多
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worl...Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.展开更多
Aim:For many years,systemic treatment of metastatic Renal Cell Carcinoma(mRCC)was based on sequential targeted agent monotherapies.In this real-life case series,we evaluated easily accessible clinical factors useful f...Aim:For many years,systemic treatment of metastatic Renal Cell Carcinoma(mRCC)was based on sequential targeted agent monotherapies.In this real-life case series,we evaluated easily accessible clinical factors useful for disease course prediction.Methods:We exploited patients'clinical pathological characteristics and systemic treatment outcomes in a real-world population of 365 mRCC patients who received sequential monotherapies in the targeted therapy era,and we identified an early progressors subpopulation,resistant to first-line VEGFR-TKI monotherapy in less than 6 months.Results:Early progressors(n=124)show a far worse OS compared with patients progressing beyond the sixth month of therapy(13.5 vs.44.8 months,P-value<0.0001,HR=0.41,95%CI:0.29-0.53).However,these patients did not show far worse performance in second and third-line settings compared to first-line responders.In the univariate analysis,IMDC risk class,sarcomatoid features,and Systemic Inflammation Index(SII)were correlated with first-line therapy Progression-Free Survival(PFS1).In multivariate analysis,variables correlated with first-line outcome were IMDC risk class,histotype,and number of metastatic sites at the diagnosis.Conclusion:Real-world data can contribute to developing easy-to-use prognostic factors associated with refractory disease that could support clinicians in identifying the most appropriate treatment strategy for each patient.展开更多
文摘The recent pandemic crisis has highlighted the importance of the availability and management of health data to respond quickly and effectively to health emergencies, while respecting the fundamental rights of every individual. In this context, it is essential to find a balance between the protection of privacy and the safeguarding of public health, using tools that guarantee transparency and consent to the processing of data by the population. This work, starting from a pilot investigation conducted in the Polyclinic of Bari as part of the Horizon Europe Seeds project entitled “Multidisciplinary analysis of technological tracing models of contagion: the protection of rights in the management of health data”, has the objective of promoting greater patient awareness regarding the processing of their health data and the protection of privacy. The methodology used the PHICAT (Personal Health Information Competence Assessment Tool) as a tool and, through the administration of a questionnaire, the aim was to evaluate the patients’ ability to express their consent to the release and processing of health data. The results that emerged were analyzed in relation to the 4 domains in which the process is divided which allows evaluating the patients’ ability to express a conscious choice and, also, in relation to the socio-demographic and clinical characteristics of the patients themselves. This study can contribute to understanding patients’ ability to give their consent and improve information regarding the management of health data by increasing confidence in granting the use of their data for research and clinical management.
文摘The scientific community is continuously working to translate the novel biomedical techniques into effective medical treatments.CRISPR-Cas9 system(Clustered Regularly Interspaced Short Palindromic Repeats-9),commonly known as the“molecular scissor”,represents a recently developed biotechnology able to improve the quality and the efficacy of traditional treatments,related to several human diseases,such as chronic diseases,neurodegenerative pathologies and,interestingly,oral diseases.Of course,dental medicine has notably increased the use of biotechnologies to ensure modern and conservative approaches:in this landscape,the use of CRISPR-Cas9 system may speed and personalize the traditional therapies,ensuring a good predictability of clinical results.The aim of this critical overview is to provide evidence on CRISPR efficacy,taking into specific account its applications in oral medicine.
基金Supported by Universitàdegli Studi di Bari,protocol No.10110 tit-VIII/2
文摘AIM To investigate the mechanisms underlying the potential contribution of the heme oxygenase/carbon monoxide(HO/CO) pathway in the constipating effects of granisetron. METHODS For in vivo studies, gastrointestinal motility was evaluated in male rats acutely treated with granisetron [25, 50, 75 μg/kg/subcutaneous(sc)], zinc protoporphyrin IX [Zn PPIX, 50 μg/kg/intraperitoneal(ip)] and hemin(50 μmol/L/kg/ip), alone or in combination. For in vitro studies, the contractile neurogenic response to electrical field stimulation(EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting 10 s), as well as the contractile myogenic response to acetylcholine(ACh, 0.1-100 μmol/L) were evaluated on colon specimens incubated with granisetron(3 μmol/L, 15 min), Zn PPIX(10 μmol/L, 60 min) or CO-releasing molecule-3(CORM-3, 100, 200, 400 μmol/L) alone or in combination. These experiments were performed under co-treatment withor without atropine(3 μmol/L, a muscarinic receptor antagonist) or NG-nitro-L-Arginine(L-NNA, 100 μmol/L, a nitric oxide synthase inhibitor).RESULTS Administration of granisetron(50, 75 μg/kg) in vivo significantly increased the time to first defecation(P = 0.045 vs vehicle-treated rats), clearly suggesting a constipating effect of this drug. Although administration of Zn PPIX or hemin alone had no effect on this gastrointestinal motility parameter, Zn PPIX co-administered with granisetron abolished the granisetron-induced constipation. On the other hand, co-administration of hemin and granisetron did not modify the increased constipation observed under granisetron alone. When administered in vitro, granisetron alone(3 μmol/L) did not significantly modify the colon's contractile response to either EFS or ACh. Incubation with Zn PPIX alone(10 μmol/L) significantly reduced the colon's contractile response to EFS(P = 0.016) but had no effect on contractile response to ACh. Co-administration of Zn PPIX and atropine(3 μmol/L) abolished the Zn PPIX-mediated decrease in contractile response to EFS. Conversely, incubation with CORM-3(400 μmol/L) alone increased both the contractile response to EFS at 10 Hz(10 Hz: 71.02 ± 19.16 vs 116.25 ± 53.70, P = 0.01) and the contractile response to ACh(100 μmol/L)(P = 0.012). Co-administration of atropine abolished the CORM-3-mediated effects on the EFS-mediated response. When granisetron was co-incubated in vitro with ZnP PIX, the ZnP PIX-mediated decrease in colon contractile response to EFS was lost. On the other hand, co-incubation of granisetron and CORM-3(400 μmol/L) further increased the colon's contractile response to EFS(at 5 Hz: P = 0.007; at 10 Hz: P = 0.001) and to ACh(ACh 10 μmol/L: P = 0.001; ACh 100 μmol/L: P = 0.001) elicited by CORM-3 alone. L-NNA co-administered with granisetron and CORM-3 abolished the potentiating effect of CORM-3 on granisetron on both the EFSinduced and ACh-induced contractile response.CONCLUSION Taken together, findings from in vivo and in vitro studies suggest that the HO/CO pathway is involved in the constipating effects of granisetron.
文摘The severe acute respiratory syndrome-coronavirus-2(commonly known as SARS-CoV-2)is a novel coronavirus(designated as 2019-nCoV),which was isolated for the first time after the Chinese health authorities reported a cluster of pneumonia cases in Wuhan,China in December 2019.Optimal management of the Coronavirus Disease-2019 disease is evolving quickly and treatment guidelines,based on scientific evidence and experts’opinions with clinical experience,are constantly being updated.On January 30,2020,the World Health Organization declared the SARS-CoV-2 outbreak as a"Public Health Emergency of International Concern".The total lack of immune protection brought about a severe spread of the contagion all over the world.For this reason,diagnostic tools,patient management and therapeutic approaches have been tested along the way,in the desperate race to break free from the widespread infection and its fatal respiratory complications.Current medical knowledge and research on severe and critical patients’management and experimental treatments are still evolving,but several protocols on minimizing risk of infection among the general population,patients and healthcare workers have been approved and diffused by International Health Authorities.
文摘Background: Endometrial cell implantation after abdominal surgery, mainly after caesarean section, may result in formation of endometrioma, which is usually described to be of various sizes, and adjacent to the surgical scar. Case: A 36-year old woman complaining of a mass of the abdominal wall with pain during the menstrual period, with a caesarean section 5 years earlier, presented a rounded tumour not contiguous to the Pfannenstiel’s laparotomy scar, of hard consistence, fixed and adherent to the deep abdominal wall structures, located on the left paramedian epigastric region. Magnetic Resonance imaging showed the nodule, involving the deep layers of the abdominal wall and the distance from the laparotomic scar. Surgical removal was performed with wide excision of the lesion, causing a large wall defect. After histological confirmation (endometriosis) by frozen section, reconstruction of the abdominal wall required prolene mesh grafting. After twelve months the patient is healthy. Conclusion: When abdominal wall endometrioma is located distant from the scar, perhaps more frequently after Pfannenstiel’s laparotomic incision, the differential diagnosis may be more difficult and MRI can help differentiating many of these lesions, and histological confirmation should be obtained intraoperatively, by frozen section, to allow an oncological resection if required.
基金Supported by Grants from MIUR(Ministero Università e Ricerca Scientifica COFIN2006)"Fondi Ateneo Ricerca Scientifica 2005/2006" from the University of Bari,Italy
文摘AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constantly increased.MDA-TBA levels were five-fold increased from 9.1 ± 1.2 nmol/g to 75.6 ± 5.4 nmol/g on day 30,P < 0.001(CD) and doubled with HFD on day 60.Realsil administration significantly lowered the extent of fat infiltration,maintained liver glutathione levels during the first half period,and halved its decrease during the second half.Also,Realsil modulated thioredoxin changes and the production of NO derivatives and significantly lowered MDA-TBA levels both in liver(from 73.6 ± 5.4 to 57.2 ± 6.3 nmol/g day 30 CD,P < 0.01 and from 27.3 ± 2.1 nmol/g to 20.5 ± 2.2 nmol/g day 60 HFD,P < 0.01) and in plasma.Changes in mitochondrial respiratory complexes were also attenuated by Realsil in HFD rats with a major protective effect on Complex Ⅱ subunit CII-30.CONCLUSION:Realsil administration effectively contrasts hepatocyte fat deposition,NO derivatives formation,and mitochondrial alterations,allowing the liver to maintain a better glutathione and thioredoxin antioxidant activity.
文摘Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells.As stem cells age,their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired.From a molecular perspective,these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration(i.e epigenomic profile)as well as changes in the tissue microenviroment,both into the niche and by systemic circulating factors.Strikingly,it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders.Therefore,understanding how resident stem cell age and affects near and distant tissues is fundamental.Here,we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number,function and phenotype that determine the loss of tissue renewal properties.Furthermore,we examine the possible cell rejuvenation strategies.Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.
基金a Grant of the Italian Ministry of Education,University and Research to the Department of Molecular Medicine of the University of Pavia under the initiative "Dipartimenti di Eccellenza(2018-2022)",and Compagnia di S.Paolo,No.ROL9849
文摘BACKGROUND Congenital analbuminemia(CAA) is a very rare disorder. Our data describes the clinical features and laboratory results of a new case established by mutation analysis of the albumin gene in a 39-year-old woman presenting with hypercholesterolemia. Our findings contribute to shed light on the molecular genetics of the disorder and confirm that safe and well tolerated hypocholesterolemic treatment with atorvastatin may be administered in dislipidemic patient with CAA in order to reduce their cardiovascular risk.CASE SUMMARY Our patient presented with a history of hypercholesterolemia and referred asthenia and heaviness in both legs. She was born from healthy and nonconsanguineous parents and her development was normal. She had not familiarity for early cardiovascular disease, and did not report personal history of hypertension, chronic kidney or liver diseases. Clinical laboratories results showed critically reduced value of albumin whereas other serum proteins were elevated. Main causes of hypoalbuminemia(proteinuria, inflammatory state and insufficient hepatic synthesis) were ruled out by normal procedures and laboratory tests. So the hypothesis of a CAA was tested through mutation analysis of the albumin gene that revealed a homozygous CA deletion in exon 12,at nucleotide positions c1614-1615. This finding brought to the diagnosis of CAA.Currently the patient receives Atorvastatin 20 mg od and undergoes clinical and laboratory follow-up every six months. She never needed albumin infusions.CONCLUSION Our experience shows how treatment with atorvastatin may be safely administered and well tolerated in patients affected by CAA.
文摘Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.
文摘Aim:For many years,systemic treatment of metastatic Renal Cell Carcinoma(mRCC)was based on sequential targeted agent monotherapies.In this real-life case series,we evaluated easily accessible clinical factors useful for disease course prediction.Methods:We exploited patients'clinical pathological characteristics and systemic treatment outcomes in a real-world population of 365 mRCC patients who received sequential monotherapies in the targeted therapy era,and we identified an early progressors subpopulation,resistant to first-line VEGFR-TKI monotherapy in less than 6 months.Results:Early progressors(n=124)show a far worse OS compared with patients progressing beyond the sixth month of therapy(13.5 vs.44.8 months,P-value<0.0001,HR=0.41,95%CI:0.29-0.53).However,these patients did not show far worse performance in second and third-line settings compared to first-line responders.In the univariate analysis,IMDC risk class,sarcomatoid features,and Systemic Inflammation Index(SII)were correlated with first-line therapy Progression-Free Survival(PFS1).In multivariate analysis,variables correlated with first-line outcome were IMDC risk class,histotype,and number of metastatic sites at the diagnosis.Conclusion:Real-world data can contribute to developing easy-to-use prognostic factors associated with refractory disease that could support clinicians in identifying the most appropriate treatment strategy for each patient.