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Host genetic factors may predict the outcome and treatment response in hepatitis C virus (HCV) infection. Very recently, three landmark genome-wide association studies identified single nucleotide polymorphisms near the interleukin 28B (IL28B) region which were more frequent in responders to treatment. IL28B encodes interferon (IFN)λ3, a type III IFN involved in host antiviral immunity. Favourable variants of the two most widely studied IL28B polymorphisms, rs12979860 and rs8099917, are strong pretreatment predictors of early viral clearance and sustained viral response in patients with genotype 1 HCV infection. Further investigations have implicated IL28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL28B may be a key factor involved in host immunity against HCV. This paper presents an overview about the biological activity and clinical applications of IL28B, summarizing the available data on its impact on HCV infection. Moreover, the potential usefulness of IFNλ in the treatment and natural history of this disease is also discussed.

Diabetic nephropathy affects a subset of about 30% of patients with type 1 Diabetes Mellitus (DM); it also develops in a less defined percentage (20–30%) of patients with type 2, after a period of 15–20 years. It is usually divided into stages. The aim of this study is to assess the usefulness of duplex sonography with Doppler wave form analysis in the evaluation of early diabetic nephropathy, in order to detect patients at risk for irreversible renal disease. 262 patients (61 males, 201 females; age range: 48–81 years) with type 2 diabetes mellitus were studied; 100 healthy volunteers with no evidence of diabetes mellitus (74 females, 26 males; age range: 50–80 years) composed the control group. All of them underwent duplex Doppler sonography of the kidneys; a scanner with a 3.5 MHz transducer (Toshiba 270 SSA) was used, Pulsatily Index (P.I.) and Resistive Index (R.I.) of Doppler waveform were obtained at the intrarenal arteries; the average value of 3 bilateral measurements was taken. Doppler sonography was done by the same authors without knowledge of the patient group (case or control). Both indexes (PI. and R.I.) resulted to be higher in patients with DM compared to controls in patients with microalbuminuria: PI. = 1.49 +/- 0.34 vs. 1.07 +/- 0.06, p< 0.05; R.I. = 0.79 +/- 0.15 vs 0.60 +/- 0.03, p

Background/objectives: We have previously described that low adherence to the Mediterranean diet (MD) in elderly patients admitted in internal medicine wards is linked to poorer clinical outcomes. This investigation was designed to explore whether adherence to the MD is related to circulating markers of redox balance and inflammation in this clinical scenario., Methods: A cross-sectional study was performed on 306 acute old patients hospitalized in internal medicine wards. Adherence to the MD was estimated by the Italian Mediterranean Index (IMI). The circulating markers of redox balance were assessed in serum and erythrocytes and correlated with inflammatory markers across different MD adherence groups., Results: Compared to the patients with high adherence, those with low adherence to the MD exhibited severely impaired redox balance, as evidenced by a higher GSSG/GSH ratio and increased serum hydroxynonenal/malondialdehyde-protein adducts. No modifications were described in the expression of antioxidant enzymes in peripheral blood mononuclear cells. Patients with low adherence to the MD exhibited a higher neutrophil-to-lymphocyte ratio and markers of systemic inflammation, as well as raised levels of interleukin-6 and tumor necrosis factor, compared to those with high MD adherence. A strong association was observed between the circulating markers of redox balance and inflammation/immune response, with the highest regression coefficients found in the low adherence group., Conclusions: Old patients admitted to internal medicine wards with low adherence to the MD display unfavorable profiles of the circulating markers of redox balance and inflammation. It is conceivable that such effects on redox balance can be linked to the high polyphenol content of MD. This study supports the rationale for intervention trials that attest to the effectiveness of MD as a nutritional strategy for disease prevention.

Background: Coronavirus Disease-19 (COVID-19) pandemic impacted the use of antibiotics in hospitalized patients. However, most data on antibiotic therapy (AT) were recorded in COVID-19 settings. This study analyzed the appropriateness of AT in the real-world scenario of a COVID-19-free internal medicine ward before, during, and after the pandemic., Methods: Clinical information of hospitalized patients was collected, and data related to AT prescription were analyzed. The appropriateness of AT was independently assessed by two specialists in internal medicine and infectious disease, combining evidence-based guidelines with a validated tool., Results: Records of 1249 patients were analyzed: AT was prescribed in 229 (55.2 %) patients before, 134 (53.2 %) patients during, and 315 (54.1 %) patients after COVID-19 pandemic. Compared to the pre-pandemic period, there was a decrease in monotherapy with 3rd and 4th generation cephalosporins and fluoroquinolones, and an increase in β-lactams + β-lactamase inhibitors and antibiotic combinations. Furthermore, AT was longer and more expensive during the pandemic, with duration and cost remaining higher after its end. The inappropriateness of AT increased during and after COVID-19 pandemic. Compared to the pre-pandemic period, inappropriate AT was longer and more expensive than appropriate AT. The COVID-19 pandemic had a significant impact on changes related to AT type and antibiotic classes., Conclusions: The COVID-19 pandemic increased the inappropriateness of AT in a COVID-19-free internal medicine ward. Most modifications persist despite the end of pandemic, potentially leading to negative effects on in-hospital antimicrobial resistance. There is an urgent need to re-establish antimicrobial stewardship policies to address the longer-term global threat of antimicrobial resistance., Competing Interests: Declaration of Competing Interest All Authors declare that there are no competing interests related to this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the interaction between dietary patterns and nutritional status in influencing health outcomes is crucial, especially in vulnerable populations. Our study investigates the impact of adherence to the Mediterranean diet (MD) and nutritional status on inflammatory markers (CRP) and the length of stay (LOS) in hospitalized frail elderly patients., Methods: We conducted two-way ANOVA and multiple regression analysis to evaluate the effects of nutritional status and MD adherence on the CRP levels and LOS in a cohort of 117 frail elderly patients aged 65 years or older. Patients with cancer or acute infection were excluded. Adherence to the MD was assessed using the 14-item PREDIMED questionnaire., Results: Significant interactions were found between nutritional status and MD adherence for both the CRP and LOS. The patients with low-level MD adherence and a poor nutritional status exhibited higher CRP levels and longer hospital stays compared to those with high MD adherence. Specifically, a statistically significant interaction was observed for the CRP ( F (1, 113) = 7.36, p = 0.008) and LOS ( F (1, 113) = 15.4, p < 0.001), indicating the protective effect of high-level MD adherence. Moderation analysis confirmed that high-level MD adherence mitigates the adverse effects of malnutrition on both the inflammatory response and LOS., Conclusions: These findings highlight the importance of promoting the MD, particularly in malnourished elderly patients, to improve health outcomes and reduce hospitalization duration. Further longitudinal studies are warranted to establish causality and explore the underlying mechanisms.

Skeletal muscle atrophy (SMA) is caused by a rise in muscle breakdown and a decline in protein synthesis, with a consequent loss of mass and function. This study characterized the effect of an amino acid mixture (AA) in models of SMA, focusing on mitochondria. C57/Bl6 mice underwent immobilization of one hindlimb (I) or cardiotoxin-induced muscle injury (C) and were compared with controls (CTRL). Mice were then administered AA in drinking water for 10 days and compared to a placebo group. With respect to CTRL, I and C reduced running time and distance, along with grip strength; however, the reduction was prevented by AA. Tibialis anterior (TA) muscles were used for histology and mitochondria isolation. I and C resulted in TA atrophy, characterized by a reduction in both wet weight and TA/body weight ratio and smaller myofibers than those of CTRL. Interestingly, these alterations were lightly observed in mice treated with AA. The mitochondrial yield from the TA of I and C mice was lower than that of CTRL but not in AA-treated mice. AA also preserved mitochondrial bioenergetics in TA muscle from I and C mice. To conclude, this study demonstrates that AA prevents loss of muscle mass and function in SMA by protecting mitochondria.

Background: Among elderly inpatients, malnutrition is one of the most important predictive factors affecting length of stay (LOS), mortality, and risk of re-hospitalization., Methods: We conducted an observational, retrospective study on a cohort of 2206 acutely inpatients. Serum albumin and lymphocytes were evaluated. Instant Nutritional Assessment (INA) and the Prognostic Nutritional Index (PNI) were calculated to predict in-hospital mortality, LOS, and risk of rehospitalization., Results: An inverse relationship between LOS, serum albumin, and PNI were found. Deceased patients had lower albumin levels, lower PNI values, and third- and fourth-degree INA scores. An accurate predictor of mortality was PNI (AUC = 0.785) after ROC curve analysis; both lower PNI values (HR = 3.56) and third- and fourth-degree INA scores (HR = 3.12) could be independent risk factors for mortality during hospitalization after Cox regression analysis. Moreover, among 309 subjects with a lower PNI value or third- and fourth-class INA, hospitalization was re-hospitalization., Conclusions: PNI and INA are two simple and quick-to-calculate tools that can help in classifying the condition of hospitalized elderly patients also based on their nutritional status, or in assessing their mortality risk. A poor nutritional status at the time of discharge may represent an important risk factor for rehospitalization in the following thirty days. This study confirms the importance of evaluating nutritional status at the time of hospitalization, especially in older patients. This study also confirms the importance for adequate training of doctors and nurses regarding the importance of maintaining a good nutritional status as an integral part of the therapeutic process of hospitalization in acute departments.

The Controlling Nutritional Status (CONUT) score has demonstrated its ability to identify patients with poor nutritional status and predict various clinical outcomes. Our objective was to assess the association between the CONUT score, inflammatory status, and body composition, as well as its ability to identify patients at risk of frailty in hospitalized elderly patients., Methods: a total of 361 patients were retrospectively recruited and divided into three groups based on the CONUT score., Results: patients with a score ≥5 exhibited significantly higher levels of inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Neutrophil/Lymphocytes ratio (NLR), main platelet volume (MPV), and ferritin, compared to those with a lower score. Furthermore, these patients showed unfavorable changes in body composition, including a lower percentage of skeletal muscle mass (MM) and fat-free mass (FFM) and a higher percentage of fatty mass (FM). A positive correlation was found between the CONUT score and inflammatory markers, Geriatric Depression Scale Short Form (GDS-SF), and FM. Conversely, the Mini Nutritional Assessment (MNA), Mini-Mental Status Examination, activity daily living (ADL), instrumental activity daily living (IADL), Barthel index, FFM, and MM showed a negative correlation. Frailty was highly prevalent among patients with a higher CONUT score. The receiver operating characteristic (ROC) curve demonstrated high accuracy in identifying frail patients (sensitivity)., Conclusions: a high CONUT score is associated with a pro-inflammatory status as well as with unfavorable body composition. Additionally, it is a good tool to identify frailty among hospitalized elderly patients.

Background: this study aimed to assess the complex relationship between EAT thickness, as measured with echocardiography, and the severity of coronary artery disease (CAD). We investigated whether individuals with higher EAT thickness underwent coronary revascularization. Subsequently, we conducted a three-year follow-up to explore any potential modifications in EAT depots post-angioplasty., Methods: we conducted a prospective and retrospective cross-sectional observational study involving 150 patients consecutively referred for acute coronary syndrome, including ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina. Upon admission (T0), all patients underwent coronary angiography to assess the number of pathologic coronary vessels. Percutaneous transluminal coronary angioplasty (PTCA) was performed based on angiogram results if indicated. The sample was categorized into two groups: non-revascularized (no-PTCA) and revascularized (PTCA). Transthoracic echocardiograms to measure epicardial fat thickness were conducted at admission (T0) and after a 3-year follow-up (T1)., Results and Conclusions: findings revealed a positive correlation between EAT thickness and the severity of coronary artery disease (CAD), with patients undergoing PTCA showing decreased EAT thickness after three years. Echocardiography demonstrated reliability in assessing EAT, offering potential for risk stratification. The study introduces a cut-off value of 0.65 cm as a diagnostic tool for cardiovascular risk. Incorporating EAT measurements into clinical practice may lead to more precise risk stratification and tailored treatment strategies, ultimately reducing the burden of cardiovascular disease.

Hepatic fibrosis is a complex process that develops in chronic liver diseases. Even though the initiation and progression of fibrosis rely on the underlying etiology, mutual mechanisms can be recognized and targeted for therapeutic purposes. Irrespective of the primary cause of liver disease, persistent damage to parenchymal cells triggers the overproduction of reactive species, with the consequent disruption of redox balance. Reactive species are important mediators for the homeostasis of both hepatocytes and non-parenchymal liver cells. Indeed, other than acting as cytotoxic agents, reactive species are able to modulate specific signaling pathways that may be relevant to hepatic fibrogenesis. After a brief introduction to redox biology and the mechanisms of fibrogenesis, this review aims to summarize the current evidence of the involvement of redox-dependent pathways in liver fibrosis and focuses on possible therapeutic targets.

(1) Background: The involvement of redox balance alterations and innate immunity is suggested to play a key role in the pathogenesis of sarcopenia. This investigation aimed to define and relate modifications in circulating markers of redox homeostasis and the innate immune response in human sarcopenia. (2) Methods: A total of 32 subjects aged >65 years old and affected by sarcopenia according to the second "European Working Group on sarcopenia in older people" guidelines were compared with 40 non-sarcopenic age-matched controls. To assess systemic redox homeostasis, reduced (GSH) and oxidized (GSSG) blood glutathione and plasma malondialdehyde (MDA)- and 4-hydroxy-2,3-nonenal (HNE)-protein adducts were measured. Immune cells and circulating interleukins were determined to compare the innate immune response between both groups. (3) Results: Impaired redox balance in sarcopenic patients, characterized by a high blood GSSG/GSH ratio and plasma MDA/HNE-protein adducts, was sustained by reduced antioxidants in peripheral blood mononuclear cells. Furthermore, sarcopenic patients showed higher neutrophil-to-lymphocyte ratios and interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor (TNF) with respect to non-sarcopenic patients. Linear regression analysis resulted in a strong association between redox balance and immune response markers in the sarcopenic group. (4) Conclusions: These results support the interplay between redox homeostasis alteration and disruption of the innate immune response in the pathogenesis of sarcopenia.

The Controlling Nutritional Status (CONUT) score is a simple screening tool able to assess poor nutritional status as well as to predict clinical adverse outcomes in different clinical settings. No data are available in older patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the CONUT score as a predictor of frequent exacerbations. We retrospectively enrolled 222 patients aged 65 years or older, classified in two groups according to the number of exacerbations (or hospitalizations because AECOPD) during the previous year. The two groups were further divided according to low (<5) or high (≥5) CONUT scores. A total of 67.2% of frequent exacerbators had a high CONUT score. These patients exhibited a significantly higher CAT score, lower FEV1 percentage value, and higher prevalence of severe GOLD stages compared to those with low CONUT. Multivariate analysis showed that a CONUT score ≥ 5 was the best independent predictor (OR 20.740, p < 0.001) of the occurrence of ≥2 exacerbations (or 1 hospitalization) during the previous year. The CONUT score seemed to have a high prognostic value for frequent exacerbations for COPD in older patients. The predictive role of different CONUT score cut-off values needs to be validated in larger COPD populations in future multi-center, prospective clinical studies.

The Controlling Nutritional Status (CONUT) score is a simple screening tool able to detect altered nutritional status as well as to predict clinical adverse outcomes in specific populations. No data are available in frail patients. This study aims to investigate the predictive role of the CONUT score on mortality and length of stay (LOS) in frail patients admitted to an Internal Medicine Department. We consecutively enrolled 246 patients aged 65 years or older, divided into two groups based on frailty status. The two groups were further divided according to low (<5) or high (≥5) CONUT score. Length of stay (LOS) was higher in frail patients than not-frail patients, as well as in the frail group with high CONUT scores compared to the frail group with low CONUT scores. Multiple linear regression showed an increase of 2.1 days for each additional point to the CONUT score. In-hospital mortality was higher in frail compared to not-frail patients, but it did not differ between frail patients with high CONUT scores and frail patients with low CONUT scores. An analysis of the survival curve for 30-day mortality showed a higher mortality rate for frail/high-CONUT-score patients as compared to the not-frail/low-CONUT-score group. The CONUT score shows high prognostic value for higher LOS-but not mortality-in the clinical setting of internal medicine departments for old frail patients.

Background: Mechanisms underpinning ARDS induced by COVID-19 are mostly immune-mediated, but need to be completely clarified. This study aimed to investigate redox balance in COVID-19 patients with ARDS, trying to recognize possible differences from typical ARDS related to the pathophysiology of severe disease., Methods: Patients affected by ARDS and positive for the SARS-CoV-2 virus (N = 40, COVID-19) were compared to ARDS patients negative to the molecular test (N = 42, No COVID-19). Circulating markers of redox balance were measured in serum and erythrocytes, and related to markers of inflammation and coagulability., Results: No differences in serum markers of oxidative damage were found between both groups, but a reduction in total antioxidant status and serum ceruloplasmin level was observed in COVID-19 rather than No COVID-19 patients. Redox balance alterations were described in erythrocytes from COVID-19 with respect to No COVID-19 group, characterized by increased lipofuscin and malondialdehyde concentration, and reduced glutathione S-transferase and glutathione reductase activity. These markers were associated with circulating indexes of respiratory disease severity (Horowitz index and alveolar-to-arterial oxygen gradient), inflammation (interleukin-6 and interleukin-10), and hypercoagulability (D-dimer) in COVID-19 patients with ARDS., Conclusions: ARDS caused by COVID-19 is sustained by impairment of redox balance, particularly in erythrocytes. This alteration is associated with the pro-inflammatory and pro-coagulant status which characterizes severe COVID-19., (© 2023. The Author(s).)

Background: The prevalence and mortality of sepsis in Internal Medicine Units (IMUs) is poorly understood as most of the data derive from studies conducted in Intensive Care Units. Aim of SEpsis Management in INternal medicine Apulia (SEMINA) study was to determine the prevalence of sepsis and the characteristics and outcomes of patients with Sepsis-3 criteria admitted in Apulia's Internal Medicine Units for over six months., Methods: The SEpsis Management in INternal medicine of Apulia study was a prospective, multicentre, observational study. Adult admissions to the 13 Apulia Region's Internal Medicine Units between November 15, 2018 and May 15, 2019 were screened for sepsis according to the Sepsis-3 criteria. Medical data were collected in electronic case report form., Results: Out of 7,885 adult patients of the Internal Medicine Units, 359 (4.55%) fulfilled the inclusion criteria, and 65 of them (18.1%) met the septic shock criteria. The patients enrolled were elderly, suffering from chronic poly-pathologies and from cognitive and functional impairment. The respiratory system was the most common site of infection and the most common pathogens isolated from blood cultures were Staphylococcus spp., E. coli, Klebsiella spp., Enterococcus spp. and Acinetobacter spp. The in-hospital fatality rate was 31.2% and was significantly higher for septic shock. Sequential Organ Failure Assessment score, dementia and infections from Acinetobacter spp. were independent risk factors for mortality., Conclusions: A high prevalence of sepsis and a high fatality rate were detected in Apulia Region's Internal Medicine Units. The high fatality rate observed in our study could be related to the underlying diseases and to the vulnerability of elderly patients admitted to our Internal Medicine Units.

The prevalence of metabolism-associated fatty liver disease (MAFLD) represents an urgent pandemic, complicated by a higher risk of morbidity and mortality as well as an increased socio-economic burden. There is growing evidence proving the impact of gut microbiota modifications on the development and progression of MAFLD through changes in metabolic pathways, modulation of the immune response, and activation of pro-inflammatory signals. Concurrently, metabolites produced by gut microbiota consisting of short chain fatty acids and bile acids contribute to the regulation of hepatic homeostasis by interacting with mitochondria. Evolving research indicates that innovative therapeutic targets for MAFLD may focus on gut microbiota-mitochondria interplay to regulate hepatic homeostasis. Recent investigations have explored the potential of new treatment strategies, such as prebiotics, probiotics, and metabolites, to change the composition of gut microbiota and simultaneously exert a positive impact on mitochondrial function to improve MAFLD. This review summarizes the significance of mitochondria and reports modifications in the composition of gut microbiota and its metabolites in MAFLD in order to illustrate the fascinating interplay between liver mitochondria and intestinal microbiota, discussing the potential effects of innovative treatments to modulate gut microbiota.

Redox homeostasis is determinant in the modulation of quiescence/self-renewal/differentiation of stem cell lines. The aim of this study consisted of defining the impact of redox modifications on cell fate in a human hepatic progenitor line. To achieve this, the HepaRG cell line, which shows oval ductular bipotent characteristics, was used. The impact of redox status on the balance between self-renewal and differentiation of HepaRG cells was investigated using different methodological approaches. A bioinformatic analysis initially proved that the trans-differentiation of HepaRG toward bipotent progenitors is associated with changes in redox metabolism. We then exposed confluent HepaRG (intermediate differentiation phase) to oxidized (H 2 O 2 ) or reduced (N-acetylcysteine) extracellular environments, observing that oxidation promotes the acquisition of a mature HepaRG phenotype, while a reduced culture medium stimulates de-differentiation. These results were finally confirmed through pharmacological modulation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2), a principal modulator of the antioxidant response, in confluent HepaRG. NRF2 inhibition led to intracellular pro-oxidative status and HepaRG differentiation, while its activation was associated with low levels of reactive species and de-differentiation. In conclusion, this study shows that both intra- and extracellular redox balance are crucial in the determination of HepaRG fate. The impact of redox status in the differentiation potential of HepaRG cells is significant on the utilization of this cell line in pre-clinical studies.

Oxidative stress is a key driver in the development and progression of several diseases, including metabolic associated fatty liver disease (MAFLD). This condition includes a wide spectrum of pathological injuries, extending from simple steatosis to inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Excessive buildup of lipids in the liver is strictly related to oxidative stress in MAFLD, progressing to liver fibrosis and cirrhosis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of redox homeostasis. NRF2 plays an important role for cellular protection by inducing the expression of genes related to antioxidant, anti-inflammatory, and cytoprotective response. Consistent evidence demonstrates that NRF2 is involved in every step of MAFLD deve-lopment, from simple steatosis to inflammation, advanced fibrosis, and ini-tiation/progression of hepatocellular carcinoma. NRF2 activators regulate lipid metabolism and oxidative stress alleviating the fatty liver disease by inducing the expression of cytoprotective genes. Thus, modulating NRF2 activation is crucial not only in understanding specific mechanisms underlying MAFLD progression but also to characterize effective therapeutic strategies. This review outlined the current knowledge on the effects of NRF2 pathway, modulators, and mechanisms involved in the therapeutic implications of liver steatosis, inflammation, and fibrosis in MAFLD., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interests for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

An impairment in mitochondrial homeostasis plays a crucial role in the process of aging and contributes to the incidence of age-related diseases, including sarcopenia, which is defined as an age-dependent loss of muscle mass and strength. Mitochondrial dysfunction exerts a negative impact on several cellular activities, including bioenergetics, metabolism, and apoptosis. In sarcopenia, mitochondria homeostasis is disrupted because of reduced oxidative phosphorylation and ATP generation, the enhanced production of reactive species, and impaired antioxidant defense. This review re-establishes the most recent evidence on mitochondrial defects that are thought to be relevant in the pathogenesis of sarcopenia and that may represent promising therapeutic targets for its prevention/treatment. Furthermore, we describe mechanisms of action and translational potential of promising mitochondria-targeted drug delivery systems, including molecules able to boost the metabolism and bioenergetics, counteract apoptosis, antioxidants to scavenge reactive species and decrease oxidative stress, and target mitophagy. Even though these mitochondria-delivered strategies demonstrate to be promising in preclinical models, their use needs to be promoted for clinical studies. Therefore, there is a compelling demand to further understand the mechanisms modulating mitochondrial homeostasis, to characterize powerful compounds that target muscle mitochondria to prevent sarcopenia in aged people.

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2-I) are the most recently approved drugs for type 2 diabetes (T2D). Recent clinical trials of these compounds reported beneficial cardiovascular (CV) and renal outcomes. A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress. Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress., Aim: To investigate the effects of SGLT2-I on markers of oxidative stress, inflammation, liver steatosis, and fibrosis in patients of T2D with non-alcoholic fatty liver disease (NAFLD)., Methods: We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre. We introduced the outpatients to an SGLT2-I (dapagliflozin, empagliflozin, or canagliflozin; n = 26) or a different hypoglycemic drug [other glucose-lowering drugs (OTHER), n = 26]. We evaluated circulating interleukins and serum hydroxynonenal (HNE)- or malondialdehyde (MDA)-protein adducts, fatty liver index (FLI), NAFLD fibrosis score, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST-to-platelet-ratio index (APRI), and fibrosis-4 on the day before (T0) and following treatment for six months (T1). We also performed transient elastography at T0 and T1., Results: Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups. Of note, following treatment for six months, a reduction of FLI and APRI, as well as of the FibroScan result, was reported in patients treated with SGLT2-I, but not in the OTHER group; furthermore, in the SGLT2-I group, we reported lower circulating levels of interleukin (IL)-1β, IL-6, tumor necrosis factor, vascular endothelial growth factor, and monocyte chemoattractant protein-1, and higher levels of IL-4 and IL-10. We did not observe any modification in circulating interleukins in the OTHER group. Finally, serum HNE- and MDA-protein adducts decreased significantly in SGLT2-I rather than OTHER patients and correlated with liver steatosis and fibrosis scores., Conclusion: The present data indicate that treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status, more than optimizing glycemic control., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The therapeutic potential of ultramicronized palmitoylethanolamide (um-PEA) was investigated in young (6-month-old) and adult (12-month-old) 3 × Tg-AD mice, which received um-PEA for 3 months via a subcutaneous delivery system. Mitochondrial bioenergetics, ATP homeostasis, and magnetic resonance imaging/magnetic resonance spectroscopy were evaluated in the frontal cortex (FC) and hippocampus (HIPP) at the end of um-PEA treatment. Glutamate release was investigated by in vivo microdialysis in the ventral HIPP (vHIPP). We demonstrated that chronic um-PEA treatment ameliorates the decrease in the complex-I respiration rate and the FoF1-ATPase (complex V) activity, as well as ATP content depletion in the cortical mitochondria. Otherwise, the impairment in mitochondrial bioenergetics and the release of glutamate after depolarization was not ameliorated by um-PEA treatment in the HIPP of both young and adult 3 × Tg-AD mice. Moreover, progressive age- and pathology-related changes were observed in the cortical and hippocampal metabolism that closely mimic the alterations observed in the human AD brain; these metabolic alterations were not affected by chronic um-PEA treatment. These findings confirm that the HIPP is the most affected area by AD-like pathology and demonstrate that um-PEA counteracts mitochondrial dysfunctions and helps rescue brain energy metabolism in the FC, but not in the HIPP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bellanti, Bukke, Moola, Villani, Scuderi, Steardo, Palombelli, Canese, Beggiato, Altamura, Vendemiale, Serviddio and Cassano.)

Malnutrition in hospitalized patients heavily affects several clinical outcomes. The prevalence of malnutrition increases with age, comorbidities, and intensity of care in up to 90% of old populations. However, malnutrition frequently remains underdiagnosed and undertreated in the hospital. Thus, an accurate screening to identify patients at risk of malnutrition or malnourishment is determinant to elaborate a personal nutritional intervention. Several definitions of malnutrition were proposed in the last years, affecting the real frequency of nutritional disorders and the timing of intervention. Diagnosis of malnutrition needs a complete nutritional assessment, which is often challenging to perform during a hospital stay. For this purpose, various screening tools were proposed, allowing patients to be stratified according to the risk of malnutrition. The present review aims to summarize the actual evidence in terms of diagnosis, association with clinical outcomes, and management of malnutrition in a hospital setting.

The global Coronavirus Disease 2019 (COVID-19) pandemic is characterized by a wide variety of clinical features, from no or moderate symptoms to severe illness. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that first affects the respiratory tract. Other than being limited to lungs, SARS-CoV-2 may lead to a multisystem disease that can even be durable (long COVID). The clinical spectrum of COVID-19 depends on variability in the immune regulation. Indeed, disease progression is consequent to failure in the immune regulation, characterized by an intensification of the pro-inflammatory response. Disturbance of systemic and organ-related redox balance may be a further mechanism underlying variability in COVID-19 severity. Other than being determinant for SARS-CoV-2 entry and fusion to the host cell, reactive species and redox signaling are deeply involved in the immune response. This review sums up the present knowledge on the role of redox balance in the regulation of susceptibility to SARS-CoV-2 infection and related immune response, debating the effectiveness of antioxidant compounds in the management of COVID-19.

Background: Senescence is characterized by a decline in hepatocyte function, with impairment of metabolism and regenerative capacity. Several models that duplicate liver functions in vitro are essential tools for studying drug metabolism, liver diseases, and organ regeneration. The human HepaRG cell line represents an effective model for the study of liver metabolism and hepatic progenitors. However, the impact of senescence on HepaRG cells is not yet known., Aim: To characterize the effects of senescence on the transdifferentiation capacity and mitochondrial metabolism of human HepaRG cells., Methods: We compared the transdifferentiation capacity of cells over 10 (passage 10 [P10]) vs P20. Aging was evaluated by senescence-associated (SA) beta-galactosidase activity and the comet assay. HepaRG transdifferentiation was analyzed by confocal microscopy and flow cytometry (expression of cluster of differentiation 49a [CD49a], CD49f, CD184, epithelial cell adhesion molecule [EpCAM], and cytokeratin 19 [CK19]), quantitative PCR analysis (expression of albumin, cytochrome P450 3A4 [CYP3A4], γ-glutamyl transpeptidase [γ-GT], and carcinoembryonic antigen [CEA]), and functional analyses (albumin secretion, CYP3A4, and γ-GT). Mitochondrial respiration and the ATP and nicotinamide adenine dinucleotide (NAD + )/NAD with hydrogen (NADH) content were also measured., Results: SA β-galactosidase staining was higher in P20 than P10 HepaRG cells; in parallel, the comet assay showed consistent DNA damage in P20 HepaRG cells. With respect to P10, P20 HepaRG cells exhibited a reduction of CD49a, CD49f, CD184, EpCAM, and CK19 after the induction of transdifferentiation. Furthermore, lower gene expression of albumin, CYP3A4, and γ-GT, as well as reduced albumin secretion capacity, CYP3A4, and γ-GT activity were reported in transdifferentiated P20 compared to P10 cells. By contrast, the gene expression level of CEA was not reduced by transdifferentiation in P20 cells. Of note, both cellular and mitochondrial oxygen consumption was lower in P20 than in P10 transdifferentiated cells. Finally, both ATP and NAD + /NADH were depleted in P20 cells with respect to P10 cells., Conclusion: SA mitochondrial dysfunction may limit the transdifferentiation potential of HepaRG cells, with consequent impairment of metabolic and regenerative properties, which may alter applications in basic studies., Competing Interests: Conflict-of-interest statement: All authors have nothing to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic may present with a broad range of clinical manifestations, from no or mild symptoms to severe disease. Patients with specific pre-existing comorbidities, such as obesity and type 2 diabetes, are at high risk of coming out with a critical form of COVID-19. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and, because of its frequent association with metabolic alterations including obesity and type 2 diabetes, it has recently been re-named as metabolic-associated fatty liver disease (MAFLD). Several studies and systematic reviews pointed out the increased risk of severe COVID-19 in NAFLD/MAFLD patients. Even though dedicated mechanistic studies are missing, this higher probability may be justified by systemic low-grade chronic inflammation associated with immune dysregulation in NAFLD/MAFLD, which could trigger cytokine storm and hypercoagulable state after severe acute respiratory syndrome coronavirus 2 infection. This review focuses on the predisposing role of NAFLD/MAFLD in favoring severe COVID-19, discussing the available information on specific risk factors, clinical features, outcomes, and pathogenetic mechanisms., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The stem cell ability to self-renew and lead regeneration relies on the balance of complex signals in their microenvironment. The identification of modulators of hepatic progenitor cell (HPC) activation is determinant for liver regeneration and may improve cell transplantation for end-stage liver disease. This investigation used different models to point out the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a key regulator of the HPC fate. We initially proved that in vivo models of biliary epithelial cells (BECs)/HPC activation show hepatic oxidative stress, which activates primary BECs/HPCs in vitro. NRF2 downregulation and silencing were associated with morphological, phenotypic, and functional modifications distinctive of differentiated cells. Furthermore, NRF2 activation in the biliary tract repressed the ductular reaction in injured liver. To definitely assess the importance of NRF2 in HPC biology, we applied a xenograft model by inhibiting NRF2 in the human derived HepaRG cell line and transplanting into SCID/beige mice administered with anti-Fas antibody to induce hepatocellular apoptosis; this resulted in effective human hepatocyte repopulation with reduced liver injury. To conclude, NRF2 inhibition leads to the activation and differentiation of liver progenitors. This redox-dependent transcription factor represents a potential target to regulate the commitment of undifferentiated hepatic progenitors into specific lineages.

Safety of healthcare workers in hospitals is a major concern during the COVID-19 pandemic. Being exposed for several working hours per day to infected patients, nurses dealing with COVID-19 face several issues that lead to physical/psychological breakdown. This study focused on burnout and its associated factors in nurses working in an Italian University Hospital during the first wave of COVID-19 pandemic. We designed a web-based cross-sectional study addressed to nurses working at the University Hospital in Foggia, Italy. The online questionnaire was organized in sections aimed at collecting demographic and occupational variables, including the Maslach Burnout Inventory (MBI) and the Oldenburg Burnout Inventory (OBI). Two hundred and ninety-three nurses agreed to participate. According to MBI, we reported moderate/high emotional exhaustion in 76.5%, depersonalization in 50.2%, and personal gratification in 54.6% of participants. COVID-19-related burnout measured by OBI resulted medium/high in 89.1% of participants. Among demographic and occupational factors, a multivariate regression analysis identified emotional support, consideration of leaving job, and workload as predictive of burnout in nurses. In conclusion, this study suggests that the improvement of employer and family support to nurses, as well as reduction of workload and job-related stress, would contribute to reducing burnout in nurses during COVID-19 pandemics.

Sarcopenia is defined by the age-related loss of skeletal muscle quality, which relies on mitochondrial homeostasis. During aging, several mitochondrial features such as bioenergetics, dynamics, biogenesis, and selective autophagy (mitophagy) are altered and impinge on protein homeostasis, resulting in loss of muscle mass and function. Thus, mitochondrial dysfunction contributes significantly to the complex pathogenesis of sarcopenia, and mitochondria are indicated as potential targets to prevent and treat this age-related condition. After a concise presentation of the age-related modifications in skeletal muscle quality and mitochondrial homeostasis, the present review summarizes the most relevant findings related to mitochondrial alterations in sarcopenia.

The integrated assessment of nutritional status and presence of sarcopenia would help improve clinical outcomes of in-hospital aged patients. We compared three common nutritional screening tools with the new Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria among hospitalized older patients. To this, 152 older patients were assessed consecutively at hospital admission by the Malnutrition Universal Screening Tool (MUST), the Subjective Global Assessment (SGA), and the Nutritional Risk Screening 2002 (NRS-2002). A 46% prevalence of malnutrition was reported according to GLIM. Sensitivity was 64%, 96% and 47%, and specificity was 82%, 15% and 76% with the MUST, SGA, and NRS-2002, respectively. The concordance with GLIM criteria was 89%, 53% and 62% for the MUST, SGA, and NRS-2002, respectively. All the screening tools had a moderate value to diagnose malnutrition. Moreover, patients at high nutritional risk by MUST were more likely to present with sarcopenia than those at low risk (OR 2.5, CI 1.3-3.6). To conclude, MUST is better than SGA and NRS-2002 at detecting malnutrition in hospitalized older patients diagnosed by the new GLIM criteria. Furthermore, hospitalized older patients at high risk of malnutrition according to MUST are at high risk of presenting with sarcopenia. Nutritional status should be determined by MUST in older patients at hospital admission, followed by both GLIM and the European Working Group on Sarcopenia in Older People (EWGSOP2) assessment.

Iron deficiency (ID) is the most frequent nutritional deficiency in the whole population worldwide, and the second most common cause of anemia in the elderly. The prevalence of anemia is expecting to rise shortly, because of an ageing population. Even though WHO criteria define anemia as a hemoglobin serum concentration <12 g/dL in women and <13 g/dL in men, several authors propose different and specific cut-off values for the elderly. Anemia in aged subjects impacts health and quality of life, and it is associated with several negative outcomes, such as longer time of hospitalization and a higher risk of disability. Furthermore, it is an independent risk factor of increased morbidity and mortality. Even though iron deficiency anemia is a common disorder in older adults, it should be not considered as a normal ageing consequence, but a sign of underlying dysfunction. Relating to the molecular mechanism in Iron Deficiency Anemia (IDA), hepcidin has a key role in iron homeostasis. It downregulates the iron exporter ferroportin, inhibiting both iron absorption and release. IDA is frequently dependent on blood loss, especially caused by gastrointestinal lesions. Thus, a diagnostic algorithm for IDA should include invasive investigation such as endoscopic procedures. The treatment choice is influenced by the severity of anemia, underlying conditions, comorbidities, and the clinical state of the patient. Correction of anemia and iron supplementation should be associated with the treatment of the causal disease., Competing Interests: the authors declare no conflict of interest.

Nutritional alterations are highly prevalent in older rather than adult hospitalized patients. In these subjects, a loss of physical performance is dependent on the impairment of muscle architecture. This study aimed to investigate the association between the nutritional status and muscle architecture in elderly patients hospitalized in internal medicine wards. 68 aged patients admitted in internal medicine wards were consecutively enrolled and stratified in three groups based on the Mini Nutritional Assessment (MNA) score: well-fed (WF), at risk of malnutrition (RM), and malnourished (M). Biochemical indices and anthropometric parameters were sampled at hospital admission. Furthermore, all patients were assessed at admission and after 7 days of hospitalization for muscle strength (hand-grip test), mass (bioimpedentiometry), and architecture (ultrasonography of vastus lateralis). At hospital admission, M patients showed lower percentage of fat free mass and muscle mass with respect to WF and RM. Furthermore, M group presented with lower muscle thickness and pennation angle, as compared to WF and RM. At admission, the MNA score was positively related to the pennation angle and muscle strength. Multivariate linear regression analysis showed that the nutritional status at admission was the only significant factor influencing pennation angle. Finally, during the first 7 days of hospitalization, a decrease of pennation angle occurred in all the groups studied. We conclude that malnutrition at admission is associated with impaired muscle architecture in elderly patients hospitalized in internal medicine wards. Moreover, muscle architecture is impacted by early hospitalization, irrespective of nutritional status., Competing Interests: The Authors declare that they have no conflict of interest.

The aging population is rapidly increasing all over the world. This results in significant implications for the planning and provision of health and social care. Aging is physiologically characterized by a decrease in lean mass, bone mineral density and, to a lesser extent, fat mass. The onset of sarcopenia leads to weakness and a further decrease in physical activity. An insufficient protein intake, which we often observe in patients of advanced age, certainly accelerates the progression of sarcopenia. In addition, many other factors (e.g., insulin resistance, impaired protein digestion and absorption of amino acids) reduce the stimulation of muscle protein synthesis in the elderly, even if the protein intake is adequate. Inadequate intake of foods can also cause micronutrient deficiencies that contribute to the development of frailty. We know that a healthy eating style in middle age predisposes to so-called "healthy and successful" aging, which is the condition of the absence of serious chronic diseases or of an important decline in cognitive or physical functions, or mental health. The Mediterranean diet is recognized to be a "healthy food" dietary pattern; high adherence to this dietary pattern is associated with a lower incidence of chronic diseases and lower physical impairment in old age. The aim of our review was to analyze observational studies (cohort and case-control studies) that investigated the effects of following a healthy diet, and especially the effect of adherence to a Mediterranean diet (MD), on the progression of aging and on onset of frailty., Competing Interests: The authors declare no conflict of interest.

Background: Insomnia seems to be related to disability, risk of injury, metabolic syndrome, risk for cardiovascular diseases, cognitive impairment, depression and impaired quality of life. Objectives: The goals in this paper was (1) to keep track of technological concepts and approaches to improve insomnia in elderly people, and (2) to define the effect that information and communication technologies (ICT) is having on patients' care. Design: A systematic review was conducted from existing literature. Our selection criteria included: (1) age ≥ 60 years; (2) diagnosis of insomnia with the International Classification of Sleep Disorders (ICSD-II), (3) CBTi (cognitive behavioural therapy insomnia), (4) use of technological tools, and (5) associations between insomnia-related variables and indices of disability, quality of life, and global clinical assessments. Data analysis: 11 articles were included. An inductive content analysis was used for data extraction. Results: Our review revealed any technological systems that could purportedly rehabilitate elderly patients with insomnia. Three categories of research were identified from the review: (1) Internet Deliver-CBTi, (2) virtual coaches, and (3) sleep technologies. Conclusions: The potential for ICT to support insomnia care at home can improve the quality of life for families and reduce health care costs and premature institutional care.

Objective: To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia., Patients and Methods: We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration., Results: Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; P <.001). Atorvastatin showed the highest odds (OR 2.66; 95% CI, 1.74-4.06; P <.001) followed by rosuvastatin (OR 1.35; 95% CI, 1.06-1.70; P =.01) and lovastatin (OR 1.53; 95% CI, 1.03-2.28; P =.04). Pravastatin, fluvastatin, and simvastatin yielded no statistically different odds compared with placebo., Conclusions: A dose-dependent risk of developing hypertransaminasemia occurs in patients taking atorvastatin, rosuvastatin, and lovastatin.

Aim: Aging is associated with increased inflammation, particularly in frailty. Indeed, such patient presents increased serum inflammatory markers, such as C-reactive protein and interleukin-6. Interleukin-6 is an important stimulating factor for the production of procalcitonin. The aim of this study is to evaluate the diagnostic reliability of serum PCT in the diagnosis of sepsis in frail elderly patients., Methods: Using Fried's criteria for frailty, 140 older patients hospitalized for any cause were consecutively enrolled and divided in two groups: no-frail (60 patients) and frail (80 patients). Patients were further categorized on the basis of the presence/absence of sepsis. Interleukin-6, procalcitonin and inflammatory indices were sampled at hospital admission., Results: Septic patients from frail and no-frail groups showed higher values of interleukin-6 and procalcitonin. However, focusing on groups without sepsis, a statistically significant difference of interleukin-6 and procalcitonin values among frail and no-frail groups was seen at the post-hoc analysis. In frail group, procalcitonin cut-off of 0.5 ng/ml had a sensibility and specificity, respectively, of 100 and 22%. Through receiver operating characteristic curve (ROC) analysis, we found that procalcitonin serum value of 1.4 ng/ml had better sensibility and specificity (respectively, 93.8 and 84.4%, AUC 0.965)., Conclusions: In our study, we confirm the diagnostic reliability of procalcitonin in frail elderly patients for the diagnosis of sepsis. We found that 1.4 ng/ml was the best cut-off in this population.

: This investigation aimed to explore the adherence to a Mediterranean Diet and its relationship with length of stay and in-hospital mortality, circulating interleukins, body composition, and frailty, in elderly patients hospitalized in internal medicine wards. Thus, a cross-sectional study in 194 acute hospitalized, community-dwelling elderly patients was performed. Adherence to a Mediterranean Diet was evaluated by the Italian Mediterranean Index (IMI). Length of stay, but not in-hospital mortality rate, was higher in patients with a low IMI score, as compared to subjects with high IMI score. Markers of systemic inflammation, as well as circulating interleukin-6 and tumor necrosis factor alpha, were higher in patients with a low IMI score, with respect to patients with high IMI score. Furthermore, patients with low IMI score had increased fat mass and reduced lean mass, together with a higher prevalence of frailty, as compared to those presenting with high IMI score. In a multivariate logistic regression model, an IMI score < 3 resulted as an independent predictor of longer length of stay. In conclusion, low adherence to a Mediterranean Diet in elderly patients hospitalized in internal medicine wards is associated with higher length of stay and related to unfavorable changes in circulating pro-inflammatory markers and body composition., Competing Interests: The authors declare no conflict of interest.

Chronic hepatitis C is associated with a high risk of developing hepatocellular carcinoma (HCC) because of a direct effect of the Hepatitis C Virus (HCV) proteins and an indirect oncogenic effect of chronic inflammation and impaired immune response. The treatment of chronic hepatitis C markedly reduces all-cause mortality; in fact, interferon-based treatment has shown a reduction of HCC incidence of more than 70%. The recent introduction of the highly effective direct-acting antivirals (DAAs) has completely changed the scenario of chronic hepatitis C (CHC) with rates of HCV cure over 90%. However, an unexpectedly high incidence of HCC recurrence was observed in patients after DAA treatment (27% versus 0.4⁻2% in patients who received interferon treatment). The mechanism that underlies the high rate of tumor relapse is currently unknown and is one of the main issues in hepatology. We reviewed the possible mechanisms involved in HCC recurrence after DAA treatment.

Obesity is a psychosomatic condition characterized by a complex interaction of biological and psychological factors and a large body of research has aimed to identify variables limiting efficacy and determining high attrition rates in weight loss programs. In this study, we used the Diagnostic Criteria for Psychosomatic Research (DCPR), designed to broaden the clinician's perspective on patients' problems by providing additional clinical information not found in the more traditional psychiatric classification, to predict psychosomatic variables that may limit efficacy and determine attrition in clinical interventions with people with obesity. We evaluated 82 consecutive participants with obesity at baseline for psychopathology, psychosomatic correlates, psychological distress, and eating-related symptoms before entering a weight loss program. Regression models were used to assess attrition and outcome at a 6-month follow-up and per-protocol and intention-to-treat analyses were performed. DPCR alexithymia significantly predicted attrition (OR = 6.9), and unsuccessful weight-loss (OR = 11.3). These findings suggest that the identification of psychosomatic factors, in addition to psychological and psychopathological factors, may predict adherence to weight-loss programs.

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury., (Copyright © 2017. Published by Elsevier B.V.)

Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case-control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD) on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil, could exert a protective role by the development and progression of prostate cancer.

Background: Although transarterial chemoembolization is considered the standard of care for intermediate hepatocellular carcinoma patients, robust data in favor of a clear superiority of chemoembolization (with chemotherapy injection) over bland embolization are lacking., Objective: The objective of this article is to systematically analyze the results provided by randomized controlled trials comparing these two treatments in hepatocarcinoma patients., Methods: A computerized bibliographic search on the main databases was performed. Survival rates assessed at one, two, and three years, objective response, one-year progression-free survival, and severe adverse event rate were analyzed. Comparisons were performed by using the Mantel-Haenszel test in cases of low heterogeneity or DerSimonian and Laird test in cases of high heterogeneity., Results: Six trials with 676 patients were included. No difference in one-year (risk ratio: 0.93, 0.85-1.03, p  = 0.16), two-year (risk ratio: 0.88, 0.74-1.06, p  = 0.18) and three-year survival (risk ratio: 0.97, 0.74-1.27, p  = 0.81) was observed. Objective response and one-year progression-free survival showed no significant difference between the two treatments ( p  = 0.36 and p  = 0.40, respectively). A statistically significant increase in severe toxicity after chemoembolization was found (risk ratio: 1.44, 1.08-1.92, p  = 0.01), although this result could be affected by the heterogeneity of techniques adopted., Conclusions: Our meta-analysis demonstrates a non-superiority of transarterial chemoembolization with respect to bland embolization in hepatocarcinoma patients.