Abstract Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse ...effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy.
Aims
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low‐density lipoprotein cholesterol (LDL‐C)‐lowering agents. In spite of their known effects on lipids, ...the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high‐sensitivity C‐reactive protein (hs‐CRP) levels through a meta‐analysis of randomized controlled trials (RCTs).
Methods
A systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs‐CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random‐effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics.
Results
Sixteen treatment arms, with a total of 2546 participants, were included. Random‐effects meta‐analysis did not show any significant effect of PCSK9 inhibitors on hs‐CRP levels (WMD: 0.002 mg l–1, CI: –0.017, 0.021; P = 0.807; I2 = 37.26%). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l–1, CI: –0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l–1, CI: –0.11, 0.40; P = 0.259; I2 = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l–1, CI: –0.20, 0.46; P = 0.433; I2 = 55.19%; monthly: WMD: 0.003 mg l–1, CI: –0.01, 0.01; P = 0.59; I2 = 0%). Random‐effects meta‐regression did not suggest any association of changes in hs‐CRP levels with changes in plasma LDL‐C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980).
Conclusions
This meta‐analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs‐CRP concentrations.
Abstract
Background
A universal definition of sarcopenia is still lacking. Since the European criteria have been recently revised, we aimed at studying prevalence of low muscle strength (LMS) and low ...muscle mass (LMM), as defined according to the European Working Group of Sarcopenia in Older People (EWGSOP) 2 and 1 definitions, and their individual contribution toward mortality and incident mobility disability in a cohort of community-dwelling older people.
Methods
Longitudinal analysis of 535 participants of the InCHIANTI study. LMS and LMM were defined according to the criteria indicated in the EWGSOP2 and 1. Cox and log-binomial regressions were used to examine association with mortality and 3-year mobility disability (inability to walk 400 m).
Results
We observed a lower prevalence of the combination LMM/LMS according to EWGSOP2 compared to EWGSOP1 (3.2% vs 6.2%). Using the new criteria, all sarcopenia components were associated with mortality, although the hazard ratio HR for the group LMM/LMS was no longer significant after adjustment for confounders (LMM: HR 2.69, 95% confidence interval CI 1.04–6.94; LMS: HR 3.18, 95% CI 1.44–7.01; LMM/LMS: HR 2.95, 95% CI 0.86–10.16). Using EWGSOP1, LMS alone was independently associated with mortality (HR 4.43, 95% CI 1.85–10.57). None of the sarcopenia components conferred a higher risk of mobility disability.
Conclusions
The EWGSOP2 algorithm leads to a reduction in the estimated prevalence of sarcopenia defined as combination of LMM/LMS. The finding that, independent of the adopted criteria, people with LMS and normal mass have a higher mortality risk compared to robust individuals, confirms that evaluation of muscle strength has a central role for prognosis evaluation.
Abstract
Context
Irisin is a hormonelike molecule that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5). It ameliorates bone status and ...muscle atrophy and influences energy homeostasis. PTH exerts several metabolic effects that may interact with the effects of irisin.
Objectives
To test the hypothesis that irisin and PTH mutually affect their biological action, we evaluated FNDC5 mRNA and protein expression in myotubes treated with PTH (1–34) and parathyroid hormone receptor (PTH-r) mRNA expression in osteoblasts treated with r-irisin. To confirm the in vivo impact of PTH on irisin, we compared irisin serum concentrations in postmenopausal women with primary hyperparathyroidism (PHPT) and control subjects.
Design and Intervention
C2C12 myotubes were treated with short-term and continuous 10−10 M teriparatide and MC3T3-E1 osteoblasts with 100 ng/mL r-irisin for 8 hours. In a cross-sectional open-label trial, we enrolled 26 postmenopausal women with PHPT and 31 age-/body mass index (BMI)‒matched control subjects without impairment of calcium/phosphate metabolism.
Results
Teriparatide treatment on myotubes significantly downregulated FNDC5 expression by acting through its own receptor, which in turn activated Erk11/2 phosphorylation. r-Irisin led to a 50% downregulation of PTH-r mRNA expression compared with untreated cells (P < 0.001). Irisin was significantly lower in the PHPT group than in age-/BMI-matched controls (4.5 ± 1.1 vs 12 ± 5.2 µg/mL; P < 0.001). No significant correlation between irisin and bone mineral density or PTH was recorded in the PHPT group.
Conclusion
Preclinical findings suggest the existence of an interplay between PTH and irisin metabolism that seems to be confirmed by the significant reduction of irisin concentration in postmenopausal women with PHPT.
In vitro findings suggest the existence of interplay between PTH and irisin metabolism that seems to be confirmed by a significant reduction in irisin concentration in postmenopausal women with PHPT.
When kidneys and lungs suffer together Sorino, Claudio; Scichilone, Nicola; Pedone, Claudio ...
JN. Journal of Nephrology,
10/2019, Letnik:
32, Številka:
5
Journal Article
Recenzirano
Odprti dostop
A significant interaction between kidneys and lungs has been shown in physiological and pathological conditions. The two organs can both be targets of the same systemic disease (eg., some ...vasculitides). Moreover, loss of normal function of either of them can induce direct and indirect dysregulation of the other one. Subjects suffering from COPD may have systemic inflammation, hypoxemia, endothelial dysfunction, increased sympathetic activation and increased aortic stiffness. As well as the exposure to nicotine, all the foresaid factors can induce a microvascular damage, albuminuria, and a worsening of renal function. Renal failure in COPD can be unrecognized since elderly and frail patients may have normal serum creatinine concentration. Lungs and kidneys participate in maintaining the acid-base balance. Compensatory role of the lungs rapidly expresses through an increase or reduction of ventilation. Renal compensation usually requires a few days as it is achieved through changes in bicarbonate reabsorption. Chronic kidney disease and end-stage renal diseases increase the risk of pneumonia. Vaccination against Streptococcus pneumonia and seasonal influenza is recommended for these patients. Vaccines against the last very virulent H1N1 influenza A strain are also available and effective. Acute lung injury and acute kidney injury are frequent complications in critical illnesses, associated with high morbidity and mortality. The concomitant failure of kidneys and lungs implies a multidisciplinary approach, both in terms of diagnostic processes and therapeutic management.
Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment. Nutritional supplements have been ...extensively investigated, and citicoline seems to be a promising agent; its role in clinical practice, however, has not been established. We systematically reviewed studies on the effect of citicoline on cognitive performance.
We searched the PubMed and Cochrane Library databases for articles published between 2010 and 2022. Relevant information was extracted and presented following the PRISMA recommendations. Data were pooled using the inverse-variance method with random effects models.
We selected seven studies including patients with mild cognitive impairment, Alzheimer's disease or post-stroke dementia. All the studies showed a positive effect of citicoline on cognitive functions. Six studies could be included in the meta-analysis. Overall, citicoline improved cognitive status, with pooled standardized mean differences ranging from 0.56 (95% CI: 0.37-0.75) to 1.57 (95% CI: 0.77-2.37) in different sensitivity analyses. The overall quality of the studies was poor.
Available data indicate that citicoline has positive effects on cognitive function. The general quality of the studies, however, is poor with significant risk of bias in favor of the intervention. Other: PubMed and the Cochrane Library.
Daily parathyroid hormone (PTH) (1-34) administrations can reduce the required total daily dose of calcium and calcitriol and restore normocalcemia in refractory hypoparathyroidism. However, most ...PTH(1-34) trials have been conducted on small cohorts including subjects with hypoparathyroidism of various etiologies, and quality of life (QOL) was not investigated.
To investigate the effects of 24-month PTH(1-34) treatment in a homogeneous cohort of adult subjects with postoperative hypoparathyroidism and to evaluate QOL changes.
Prospective open-label study.
Italian multicenter study.
42 subjects.
Twice-daily PTH(1-34) 20 μg subcutaneous injection.
Calcium and vitamin D supplementation requirements, serum calcium, phosphate, and urinary calcium excretion (3, 6, 12, 18, 24 months). At baseline and at 6 and 24 months, QOL was evaluated by the RAND 36-Item Short Form (SF-36) Health Survey, covering eight domains of physical and mental health.
Mean serum calcium concentration significantly increased from baseline to 3 months (7.6 ± 0.6 vs 8.9 ± 1.1 mg/dL, P < 0.001) and remained stable until the end of the study, despite reductions in calcium and vitamin D supplementation. Phosphate levels gradually decreased from baseline to 6 months (4.3 ± 1.1 vs 3.9 ± 0.6 mg/dL, P < 0.019), remaining stable until 24 months. Serum alkaline phosphatase and calcium excretion gradually increased from baseline to 24 months. Data from SF-36 showed a significant improvement in the mean scores of all eight domains (P < 0.001).
This study demonstrates the efficacy and safety of PTH(1-34) to treat adult patients with postsurgical hypoparathyroidism. PTH(1-34) may improve their mental and physical health.
Hospitalized patients with respiratory failure due to SARS-CoV-2 pneumonia are at increased risk of malnutrition and related mortality. The predictive value of the Mini-Nutritional Assessment short ...form (MNA-sf
), hand-grip strength (HGS), and bioelectrical impedance analysis (BIA) was determined with respect to in-hospital mortality or endotracheal intubation. The study included 101 patients admitted to a sub-intensive care unit from November 2021 to April 2022. The discriminative capacity of MNA-sf, HGS, and body composition parameters (skeletal mass index and phase angle) was assessed computing the area under the receiver operating characteristic curves (AUC). Analyses were stratified by age groups (<70/70+ years). The MNA-sf alone or in combination with HGS or BIA was not able to reliably predict our outcome. In younger participants, HGS showed a sensitivity of 0.87 and a specificity of 0.54 (AUC: 0.77). In older participants, phase angle (AUC: 0.72) was the best predictor and MNA-sf in combination with HGS had an AUC of 0.66. In our sample, MNA- sf alone, or in combination with HGS and BIA was not useful to predict our outcome in patients with COVID-19 pneumonia. Phase angle and HGS may be useful tools to predict worse outcomes in older and younger patients, respectively.
The present study aims to evaluate whether influenza and pneumococcal vaccinations are associated with positive nasopharyngeal swab (NPS) testing to detect SARS-CoV-2. Data from the Italian ...cross-sectional web-based survey (EPICOVID19), based on a self-selection sample of individuals aged ≥18, were considered. The probability of a positive SARS-CoV-2 NPS test result as a function of influenza or anti-pneumococcal vaccination was evaluated using multivariable logistic regression, stratifying analysis by age (<65 years, ≥65 years). From April 2020, 170,731 individuals aged <65 years and 28,097 ≥65 years filled out the EPICOVID19 questionnaire. Influenza and anti-pneumococcal vaccinations were received, respectively, by 16% and 2% of those <65 years, and by 53% and 13% of those ≥65 years. SARS-CoV-2 NPS testing was reported by 6680 participants. Anti-pneumococcal and influenza vaccinations were associated with a decreased probability of a SARS-CoV-2 NPS positive test in the younger participants (OR = 0.61, 95% CI 0.41–0.91; OR = 0.85, 95%CI 0.74–0.98; respectively). A significantly lower probability of a positive test result was detected in the individuals ≥65 years who received anti-pneumococcal vaccination (OR = 0.56, 95%CI 0.33–0.95). These results need to be confirmed by further investigations, but they are relevant given the probable coexistence of influenza, bacterial infections, and COVID-19 over the coming autumn–winter season.
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