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Grigore T. Popa University of Medicine and Pharmacy

UniversityIasi, Romania

Research output, citation impact, and the most-cited recent papers from Grigore T. Popa University of Medicine and Pharmacy (Romania). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
15.0K
Citations
434.0K
h-index
183
i10-index
10.8K
Also known as
Grigore T. Popa University of Medicine and PharmacyInstitute of Medicine and PharmacyUniversitatea de Medicină și Farmacie "Grigore T. Popa"Universitatea de Medicină și Farmacie Grigore T. Popa

Top-cited papers from Grigore T. Popa University of Medicine and Pharmacy

An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases
Daniel Mihai Teleanu, Adelina-Gabriela Niculescu, Iulia Ioana Lungu, Crina Ioana Radu +4 more
2022· International Journal of Molecular Sciences967doi:10.3390/ijms23115938

Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress of several neurodegenerative disorders. This review intends to summarize some of the findings that correlate the overproduction of reactive oxygen species with the pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Oxidative stress was also noted to modify the inflammatory response. Even though oxidative stress and neuroinflammation are two totally different pathological events, they are linked and affect one another. Nonetheless, there are still several mechanisms that need to be understood regarding the onset and the progress of neurodegenerative diseases in order to develop efficient therapies. As antioxidants are a means to alter oxidative stress and slow down the symptoms of these neurodegenerative diseases, the most common antioxidants, enzymatic as well as non-enzymatic, have been mentioned in this paper as therapeutic options for the discussed disorders.

Rising rural body-mass index is the main driver of the global obesity epidemic in adults
Honor Bixby, James Bentham, Bin Zhou, Mariachiara Di Cesare +4 more
2019· Nature742doi:10.1038/s41586-019-1171-x

Abstract Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3–6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition
Rolf Rossaint, Arash Afshari, Bertil Bouillon, Vladimír Černý +4 more
2023· Critical Care698doi:10.1186/s13054-023-04327-7

BACKGROUND: Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. METHODS: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. RESULTS: This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. CONCLUSION: A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Further improvement in outcomes will be achieved by optimising and standardising trauma care in line with the available evidence across Europe and beyond.

Bioactivity of dietary polyphenols: The role of metabolites
Simon Vlad Luca, Irina Macovei, Alexandra Bujor, Anca Miron +3 more
2019· Critical Reviews in Food Science and Nutrition691doi:10.1080/10408398.2018.1546669

A polyphenol-rich diet protects against chronic pathologies by modulating numerous physiological processes, such as cellular redox potential, enzymatic activity, cell proliferation and signaling transduction pathways. However, polyphenols have a low oral bioavailability mainly due to an extensive biotransformation mediated by phase I and phase II reactions in enterocytes and liver but also by gut microbiota. Despite low oral bioavailability, most polyphenols proved significant biological effects which brought into attention the low bioavailability/high bioactivity paradox. In recent years, polyphenol metabolites have attracted great interest as many of them showed similar or higher intrinsic biological effects in comparison to the parent compounds. There is a huge body of literature reporting on the biological functions of polyphenol metabolites generated by phase I and phase II metabolic reactions and gut microbiota-mediated biotransformation. In this respect, the review highlights the pharmacokinetic fate of the major dietary polyphenols (resveratrol, curcumin, quercetin, rutin, genistein, daidzein, ellagitannins, proanthocyanidins) in order to further address the efficacy of biometabolites as compared to parent molecules. The present work strongly supports the contribution of metabolites to the health benefits of polyphenols, thus offering a better perspective in understanding the role played by dietary polyphenols in human health.

The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD)
Daniela Maria Tănase, Evelina Maria Gosav, Claudia Florida Costea, Manuela Ciocoiu +4 more
2020· Journal of Diabetes Research610doi:10.1155/2020/3920196

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) remain as one of the most global problematic metabolic diseases with rapidly increasing prevalence and incidence. Epidemiological studies noted that T2DM patients have by two-fold increase to develop NAFLD, and vice versa. This complex and intricate association is supported and mediated by insulin resistance (IR). In this review, we discuss the NAFLD immunopathogenesis, connection with IR and T2DM, the role of screening and noninvasive tools, and mostly the impact of the current antidiabetic drugs on steatosis liver and new potential therapeutic targets.

Entrepreneurship Education through Successful Entrepreneurial Models in Higher Education Institutions
Gabriela Boldureanu, Alina Măriuca Ionescu, Ana‐Maria Bercu, Maria Viorica Bedrule-Grigoruță +1 more
2020· Sustainability605doi:10.3390/su12031267

In higher education institutions, entrepreneurship learning based on successful entrepreneurial role models may promote education for sustainable development. Several theoretical perspectives, such as the human capital theory, the entrepreneurial self-efficacy and self-determination theory, argue that entrepreneurship education is positively correlated with entrepreneurial intentions of students, as it provides adequate know-how and skills and motivates them to develop their entrepreneurial careers. In entrepreneurship education programmes, exposure to successful entrepreneurial models could be a significant factor for stimulating students’ confidence in their ability to start a business and for improving their attitudes towards entrepreneurship. This study aims (i) to identify characteristics viewed by students as being specific to a successful entrepreneur, (ii) to establish the influence of exposure to successful entrepreneurial role models (chosen by students) during entrepreneurship education classes on student entrepreneurial intentions, and (iii) to assess how such exposure influences the attitudes of students towards entrepreneurship. For this purpose, the authors ran a pilot experiment with 30 graduate students enrolled in a Business Creation course using a research methodology that combined qualitative techniques with quantitative measures. Content and statistical analyses were utilised to examine differences in student entrepreneurial intentions and attitudes towards entrepreneurship after being exposed to successful entrepreneurial models. Our study provides evidence that entrepreneurship education based on successful entrepreneurial role models may positively influence the entrepreneurial attitudes and intentions of students and could lead to higher orientation of student perception towards social benefits of entrepreneurship (new jobs) compared to financial ones (high income). However, our findings stress that if educators want to improve the efficiency of education focused on developing entrepreneurial skills, graduate programmes should be designed differently for business and non-business students, since studying successful entrepreneurial stories impacts these two groups differently.

A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury: Part 1: definitions, conservative management and contrast-induced nephropathy
The ad-hoc working group of ERBP:, Danilo Fliser, Maurice Laville, Adrian Covic +4 more
2012· Nephrology Dialysis Transplantation569doi:10.1093/ndt/gfs375

The broad clinical syndrome of acute kidney injury (AKI) encompasses various aetiologies, including specific kidney diseases (e.g. acute interstitial nephritis), non-specific conditions (e.g. renal ischaemia) as well as extrarenal pathology (e.g. post-renal obstruction). AKI is a serious condition that affects kidney structure and function acutely, but also in the long term. Recent epidemiological evidence supports the notion that even mild, reversible AKI conveys the risk of persistent tissue damage, and severe AKI can be accompanied by an irreversible decline of kidney function and progression to end-stage kidney failure [1–3]. The Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for AKI [4] were designed to systematically compile information on this topic by experts in the field. These guidelines are based on the systematic review of relevant trials published before February 2011. Nevertheless, for many sections of the guidelines, appropriate supporting evidence is lacking in the literature. As a consequence, variations in practice will inevitably occur when clinicians take into account the needs of individual patients, available resources and limitations unique to a region, an institution or type of practice. Therefore, in line with its philosophy [5], the European Renal Best Practice (ERBP) wanted to issue a position statement on these guidelines. A working group was established to produce guidance from the European nephrology perspective, based on the compiled evidence as presented, with an update of the literature up to March 2012, following the methodology as explained in the ERBP instructions to authors [6]. The present document will deal with the diagnosis and prevention of AKI, and contrast-induced nephropathy (CIN) (Sections 1–4 of the KDIGO document), and other chapters will be discussed in a separate position statement. As a general rule, we will only mention those guideline statements of the KDIGO document that we have amended, even when the change is small. If a KDIGO recommendation is not repeated, it can be considered as endorsed by ERBP as is, unless specifically stated otherwise.

Flavor Chemistry of Cocoa and Cocoa Products—An Overview
Ana Clara Aprotosoaie, Simon Vlad Luca, Anca Miron
2015· Comprehensive Reviews in Food Science and Food Safety479doi:10.1111/1541-4337.12180

Cocoa originates from beans of the cocoa tree (Theobroma cacao L.) and it is an important commodity in the world and the main ingredient in chocolate manufacture. Its value and quality are related to unique and complex flavors. Bulk cocoas (Forastero type) exhibit strong basic cocoa notes, whereas fine varieties (Criollo, Nacional) show aromatic, floral, or smoother flavor characteristics. About 600 various compounds (alcohols, carboxylic acids, aldehydes, ketones, esters, and pyrazines) have been identified as odor-active components. The specific cocoa aroma arises from complex biochemical and chemical reactions during the postharvest processing of raw beans, and from many influences of the cocoa genotype, chemical make-up of raw seeds, environmental conditions, farming practices, processing, and manufacturing stages. There has been much research on cocoa flavor components. However, the relationships between all chemical components that are likely to play a role in cocoa flavor, their sensory properties, and the sources and mechanisms of flavor formation are not fully understood. This paper provides an overview on cocoa flavor from a compositional and a sensory perspective. The nonvolatile and volatile chemical components of cocoa and chocolate flavor, and their sensory properties correlated to the main influences involved in flavor formation, are reviewed.

Kidney Disease: Improving Global Outcomes guidelines on anaemia management in chronic kidney disease: a European Renal Best Practice position statement
Francesco Locatelli, Peter Bárány, Adrian Covic, Angel de Francisco +4 more
2013· Nephrology Dialysis Transplantation472doi:10.1093/ndt/gft033

Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anaemia in CKD patients. These guidelines addressed all of the important points related to anaemia management in CKD patients, including therapy with erythropoieis stimulating agents (ESA), iron therapy, ESA resistance and blood transfusion use. Because most guidelines were 'soft' rather than 'strong', and because global guidelines need to be adapted and implemented into the regional context where they are used, on behalf of the European Renal Best Practice Advisory Board some of its members, and other external experts in this field, who were not participants in the KDIGO guidelines group, were invited to participate in this anaemia working group to examine and comment on the KDIGO documents in this position paper. In this article, the group concentrated only on those guidelines which we considered worth amending or adapting. All guidelines not specifically mentioned are fully endorsed.

Advance on the Flavonoid<i>C</i>-glycosides and Health Benefits
Jianbo Xiao, Esra Çapanoğlu, Amir Reza Jassbi, Anca Miron
2015· Critical Reviews in Food Science and Nutrition452doi:10.1080/10408398.2015.1067595

The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. Almost all natural flavonoids exist as their O-glycoside or C-glycoside forms in plants. The dietary flavonoid C-glycosides have received less attention than their corresponding O-glycosides. This review summarizes current knowledge regarding flavonoid C-glycosides and their influence on human health. Among the flavonoid C-glycosides, flavone C-glycosides, especially vitexin, isoorientin, orientin, isovitexin and their multiglycosides are more frequently mentioned than others. Flavonoid C-monoglycosides are poorly absorbed in human beings with very few metabolites in urine and blood and are deglycosylated and degraded by human intestinal bacteria in colon. However, flavonoid C-multiglycosides are absorbed unchanged in the intestine and distributed to other tissues. Flavonoid C-glycosides showed significant antioxidant activity, anticancer and antitumor activity, hepatoprotective activity, anti-inflammatory activity, anti-diabetes activity, antiviral activity, antibacterial and antifungal activity, and other biological effects. It looks like that the C-glycosylflavonoids in most cases showed higher antioxidant and anti-diabetes potential than their corresponding O-glycosylflavonoids and aglycones. However, there is a lack of in vivo data on the biological benefits of flavonoid C-glycosides. It is necessary to investigate more on how flavonoid C-glycosides prevent and handle the diseases.

Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group
Suzana Jordan, Jörg H. W. Distler, Britta Maurer, Dörte Huscher +4 more
2014· Annals of the Rheumatic Diseases427doi:10.1136/annrheumdis-2013-204522

OBJECTIVES: To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design. METHODS: Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures. RESULTS: 63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs -7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs -7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases. CONCLUSIONS: The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.

COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration
Luuk B. Hilbrands, Raphaël Duivenvoorden, Priya Vart, Casper Franssen +4 more
2020· Nephrology Dialysis Transplantation411doi:10.1093/ndt/gfaa261

BACKGROUND: Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. METHODS: We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. RESULTS: Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3-30.2%] in kidney transplant and 25.0% (95% CI 20.2-30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59-1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07-0.56, P < 0.01). CONCLUSIONS: The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Gut Microbiota and Complications of Type-2 Diabetes
Camelia Oana Iațcu, Aimee Steen, Mihai Covașă
2021· Nutrients403doi:10.3390/nu14010166

The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset of type 2 diabetes through decreased glucose tolerance and insulin resistance. Uncontrolled diabetes can lead to serious health consequences such as impaired kidney function, blindness, stroke, myocardial infarction and lower limb amputation. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising new approach to diabetes focuses on modulating the gut microbiota with probiotics, prebiotics, synbiotics and fecal microbial transplantation. Differences in gut microbiota composition have been observed in preclinical animal models as well as patients with type 2 diabetes and complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, cerebrovascular disease, coronary heart disease and peripheral artery disease compared to healthy controls. Severity of gut microbiota dysbiosis was associated with disease severity and restoration with probiotic administration in animal models and human patients has been associated with improvement of symptoms and disease progression. Characterizing the gut microbiota dysbiosis in different diseases and determining a causal relationship between the gut microbiota and disease can be beneficial in formulating therapeutic interventions for type 2 diabetes and associated complications. In this review, we present the most important findings regarding the role of the gut microbiota in type 2 diabetes and chronic complications as well as their underlying mechanisms.

Medicinal Plants of the Family Lamiaceae in Pain Therapy: A Review
Cristina Mariana Urîtu, Cosmin Mihai, Gabriela Dumitriţa Stanciu, Gianina Dodi +4 more
2018· Pain Research and Management358doi:10.1155/2018/7801543

Recently, numerous side effects of synthetic drugs have lead to using medicinal plants as a reliable source of new therapy. Pain is a global public health problem with a high impact on life quality and a huge economic implication, becoming one of the most important enemies in modern medicine. The medicinal use of plants as analgesic or antinociceptive drugs in traditional therapy is estimated to be about 80% of the world population. The Lamiaceae family, one of the most important herbal families, incorporates a wide variety of plants with biological and medical applications. In this study, the analgesic activity, possible active compounds of Lamiaceae genus, and also the possible mechanism of actions of these plants are presented. The data highlighted in this review paper provide valuable scientific information for the specific implications of Lamiaceae plants in pain modulation that might be used for isolation of potentially active compounds from some of these medicinal plants in future and formulation of commercial therapeutic agents.

Vibrational Spectroscopy Fingerprinting in Medicine: from Molecular to Clinical Practice
Vera Bălan, Cosmin Mihai, Florina-Daniela Cojocaru, Cristina Mariana Urîtu +3 more
2019· Materials343doi:10.3390/ma12182884

In the last two decades, Fourier Transform Infrared (FTIR) and Raman spectroscopies turn out to be valuable tools, capable of providing fingerprint-type information on the composition and structural conformation of specific molecular species. Vibrational spectroscopy's multiple features, namely highly sensitive to changes at the molecular level, noninvasive, nondestructive, reagent-free, and waste-free analysis, illustrate the potential in biomedical field. In light of this, the current work features recent data and major trends in spectroscopic analyses going from in vivo measurements up to ex vivo extracted and processed materials. The ability to offer insights into the structural variations underpinning pathogenesis of diseases could provide a platform for disease diagnosis and therapy effectiveness evaluation as a future standard clinical tool.

The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes
Ionuț Luchian, Ancuța Goriuc, Darius Sandu, Mihai Covașă
2022· International Journal of Molecular Sciences342doi:10.3390/ijms23031806

Severe periodontitis, a destructive inflammatory disease of the supporting tissues of the teeth, ranks sixth in terms of global spread, affecting about 11% of the population. Metalloproteinases (MMPs) are extracellular matrix (ECM) macromolecules that are important in cellular development and morphogenesis, and they are capable of activating growth factors in their proximity, cell surface receptors, and adhesion molecules. MMPs are part of a major family of zinc-dependent endopeptidases, and their activity is modulated and regulated by certain inhibitors known as tissue metalloproteinase inhibitors (TIMPs). Because type I collagen is the major component of the periodontal extracellular matrix, special attention has been paid to the role of collagenases, especially MMP-8 and MMP-13 and gelatinases, MMP-2 and MMP-9, in periodontal diseases. In fact, MMP-8 (or collagenase 2) is currently one of the most promising biomarkers for periodontitis in oral fluids. Among them, salivary MMP-9 has been shown to be a more sensitive marker for periodontal inflammation during orthodontic treatment, which opens new perspectives in reducing periodontal hazards during such treatments. Both MMP-8 and MMP-9 are extremely valuable diagnostic tools in treating periodontitis, and future studies and healthcare policies should focus on implementing more accessible methods of chairside testing in order to reduce the prevalence of this disease.

Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry
Laura Izquierdo‐Sánchez, Ángela Lamarca, Adelaida La Casta, Stefan Buettner +4 more
2022· Journal of Hepatology340doi:10.1016/j.jhep.2021.12.010

•CCA subtypes present different risk factors and tumor features.•CA19-9 shows low sensitivity in early stages but increased sensitivity in advanced disease.•Under surgery, positive margins and lymph node invasion compromise survival.•ECOG-PS, disease status and CA19-9 are independent prognostic factors. Background & AimsCholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence and related mortality is increasing. This study investigates the clinical course of CCA and subtypes (intrahepatic [iCCA], perihilar [pCCA], and distal [dCCA]) in a pan-European cohort.MethodsThe ENSCCA Registry is a multicenter observational study. Patients were included if they had a histologically proven diagnosis of CCA between 2010-2019. Demographic, histomorphological, biochemical, and clinical studies were performed.ResultsOverall, 2,234 patients were enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity and chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA (n = 592) with primary sclerosing cholangitis; and dCCA (n = 399) with choledocholithiasis. At diagnosis, 42.2% of patients had local disease, 29.4% locally advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD (odds ratio 5.88; 95% CI 3.69-9.25). Patients undergoing resection (50.3%) had the best outcomes, particularly with negative-resection margin (R0) (median overall survival [mOS] = 45.1 months); however, margin involvement (R1) (hazard ratio 1.92; 95% CI 1.53-2.41; mOS = 24.7 months) and lymph node invasion (hazard ratio 2.13; 95% CI 1.55-2.94; mOS = 23.3 months) compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. ECOG performance status, MD and CA19-9 were independent prognostic factors.ConclusionCCA is frequently diagnosed at an advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis remains dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality.Lay summaryThis is, to date, the largest international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of cholangiocarcinoma has been investigated, comparing the 3 subtypes based on the latest International Classification of Diseases 11th Edition (ICD-11) (i.e., intrahepatic [2C12], perihilar [2C18], or distal [2C15] affected bile ducts), which come into effect in 2022. General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, are presented and compared, outlining the current clinical state of cholangiocarcinoma in Europe. Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence and related mortality is increasing. This study investigates the clinical course of CCA and subtypes (intrahepatic [iCCA], perihilar [pCCA], and distal [dCCA]) in a pan-European cohort. The ENSCCA Registry is a multicenter observational study. Patients were included if they had a histologically proven diagnosis of CCA between 2010-2019. Demographic, histomorphological, biochemical, and clinical studies were performed. Overall, 2,234 patients were enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity and chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA (n = 592) with primary sclerosing cholangitis; and dCCA (n = 399) with choledocholithiasis. At diagnosis, 42.2% of patients had local disease, 29.4% locally advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD (odds ratio 5.88; 95% CI 3.69-9.25). Patients undergoing resection (50.3%) had the best outcomes, particularly with negative-resection margin (R0) (median overall survival [mOS] = 45.1 months); however, margin involvement (R1) (hazard ratio 1.92; 95% CI 1.53-2.41; mOS = 24.7 months) and lymph node invasion (hazard ratio 2.13; 95% CI 1.55-2.94; mOS = 23.3 months) compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. ECOG performance status, MD and CA19-9 were independent prognostic factors. CCA is frequently diagnosed at an advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis remains dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality.

Contact inhibition controls cell survival and proliferation via YAP/TAZ-autophagy axis
Mariana Pavel-Tanasă, Maurizio Renna, So Jung Park, Fiona M. Menzies +4 more
2018· Nature Communications338doi:10.1038/s41467-018-05388-x

Contact inhibition enables noncancerous cells to cease proliferation and growth when they contact each other. This characteristic is lost when cells undergo malignant transformation, leading to uncontrolled proliferation and solid tumor formation. Here we report that autophagy is compromised in contact-inhibited cells in 2D or 3D-soft extracellular matrix cultures. In such cells, YAP/TAZ fail to co-transcriptionally regulate the expression of myosin-II genes, resulting in the loss of F-actin stress fibers, which impairs autophagosome formation. The decreased proliferation resulting from contact inhibition is partly autophagy-dependent, as is their increased sensitivity to hypoxia and glucose starvation. These findings define how mechanically repressed YAP/TAZ activity impacts autophagy to contribute to core phenotypes resulting from high cell confluence that are lost in various cancers.

Linalool: a review on a key odorant molecule with valuable biological properties
Ana Clara Aprotosoaie, Monica Hăncianu, Irina‐Iuliana Costache, Anca Miron
2014· Flavour and Fragrance Journal336doi:10.1002/ffj.3197

ABSTRACT This paper reports on the occurrence, biosynthesis, metabolism, biological and toxicological profile, and assessment of the authenticity of linalool. The main biological properties of linalool – sedative, anxiolytic, analgesic, anticonvulsant, anti‐inflammatory, local anaesthetic – are discussed in terms of the molecule's chirality influence, the mechanisms of activity and type of study ( in vitro , in vivo , clinical studies). Also, there is a discussion of the recent data on the skin sensitizing potential of linalool based on numerous scientific studies which have been performed in the last few years. Comments of the authenticity assessment of linalool are made considering the limitations imposed by the chemical structure, vegetal matrix or processing methods, but also from the perspective of the powerful and sophisticated analytical techniques available today (GC‐C‐IRMS, enantio‐MDGC coupled to GC‐C‐IRMS, SNIF‐NMR). Copyright © 2014 John Wiley &amp; Sons, Ltd.

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers
Cornelia Vasile, Daniela Pamfil, Elena Stoleru, Mihaela Baican
2020· Molecules322doi:10.3390/molecules25071539

New trends in biomedical applications of the hybrid polymeric hydrogels, obtained by combining natural polymers with synthetic ones, have been reviewed. Homopolysaccharides, heteropolysaccharides, as well as polypeptides, proteins and nucleic acids, are presented from the point of view of their ability to form hydrogels with synthetic polymers, the preparation procedures for polymeric organic hybrid hydrogels, general physico-chemical properties and main biomedical applications (i.e., tissue engineering, wound dressing, drug delivery, etc.).