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Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.
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Receptores de Orexina , Orexinas , Polimorfismo de Nucleótido Simple , Humanos , Orexinas/metabolismo , Orexinas/genética , Masculino , Femenino , Persona de Mediana Edad , Receptores de Orexina/metabolismo , Receptores de Orexina/genética , Adulto , Canales Catiónicos TRPP/genética , Canales Catiónicos TRPP/metabolismo , Riñón Poliquístico Autosómico Dominante/metabolismo , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/sangre , Estudios de Casos y Controles , Anciano , Presión Sanguínea , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/metabolismo , Enfermedades Renales Poliquísticas/sangreRESUMEN
Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in biological processes, both physiological and pathological, including cancer, cardiovascular diseases, multiple sclerosis, autoimmune hepatitis and types I and II diabetes. LncRNAs are also known to have a critical role in the physiology of skin, and in the pathology of cutaneous diseases. LncRNAs are involved in a wide range of biological activities, including transcriptional posttranscriptional processes, epigenetics, RNA splicing, gene activation and or silencing, modifications and/or editing; therefore, lncRNAs may be useful as potential targets for disease treatment. Hidradenitis suppurativa (HS), also termed acne inversa, is a major skin disease, being an inflammatory disorder that affects ~1% of global population in a chronic manner. Its pathogenesis, however, is only partly understood, although immune dysregulation is known to have an important role. To investigate the biological relevance of lncRNAs with HS, the most differentially expressed lncRNAs and mRNAs were first compared. Furthermore, the lncRNAmicroRNA regulatory network was also defined via reverse transcriptionquantitative PCR analysis, whereby a trio of lncRNA expression signatures, lncRNATINCR, lncRNARBM5ASI1 and lncRNAMRPL23AS1, were found to be significantly overexpressed in patients with HS compared with healthy controls. In conclusion, the three lncRNAs isolated in the present study may be useful for improving the prognostic prediction of HS, as well as contributing towards an improved understanding of the underlying pathogenic mechanisms, thereby potentially providing new therapeutic targets.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Hidradenitis Supurativa , ARN Largo no Codificante , Humanos , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/sangre , ARN Largo no Codificante/genética , ARN Largo no Codificante/sangre , Masculino , Adulto , Femenino , MicroARNs/genética , MicroARNs/sangre , ARN Mensajero/genética , ARN Mensajero/metabolismo , Persona de Mediana Edad , Regulación de la Expresión GénicaRESUMEN
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common monogenic disorder characterized by renal cysts and progressive renal failure. In kidney diseases, adipose tissue undergoes functional changes that have been associated with increased inflammation and insulin resistance mediated by release of adipokines. Adiponectin is involved in various cellular processes, such as energy and inflammatory and oxidative processes. However, it remains to be determined whether adiponectin is involved in the concomitant metabolic dysfunctions present in PKD. In this scenario, we aimed to analyze: (a) PPARγ, ADIPOQ, ADIPOR1 and ADIPOR2 gene variations in 92 ADPKD patients through PCR-Sanger sequencing; and (b) adiponectin levels and its oligomerization state by ELISA and Western Blot. Our results indicated that: (a) 14 patients carried the PPARγ SNP, 29 patients carried the ADIPOQ SNP rs1501299, and 25 patients carried the analyzed ADIPOR1 SNPs. Finally, 82 patients carried ADIPOR2 SNPs; and (b) Adiponectin is statistically lower in ADPKD patients compared to controls, and further statistically lower in ESRD than in non-ESRD patients. An inverse relationship between adiponectin and albumin and between adiponectin and creatinine and a direct relationship between adiponectin and eGFR were found. Interestingly, significantly lower levels of adiponectin were found in patients bearing the ADIPOQ rs1501299 SNP and associated with low levels of eGFR. In conclusion, adiponectin levels and the presence of ADIPOQ rs1501299 genotype are significantly associated with a worse ADPKD phenotype, indicating that both could potentially provide important insights into the disease. Further studies are warranted to understand the pathophysiological role of adiponectin in ADPKD patients.
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Adiponectina , Riñón Poliquístico Autosómico Dominante , Polimorfismo de Nucleótido Simple , Receptores de Adiponectina , Humanos , Adiponectina/genética , Adiponectina/metabolismo , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/patología , Riñón Poliquístico Autosómico Dominante/metabolismo , Femenino , Masculino , Receptores de Adiponectina/genética , Persona de Mediana Edad , Adulto , PPAR gamma/genética , PPAR gamma/metabolismoRESUMEN
Lifestyle factors, particularly physical inactivity, are closely linked to the onset of numerous metabolic diseases. Adipose tissue (AT) has been extensively studied for various metabolic diseases such as obesity, type 2 diabetes, and immune system dysregulation due to its role in energy metabolism and regulation of inflammation. Physical activity is increasingly recognized as a powerful non-pharmacological tool for the treatment of various disorders, as it helps to improve metabolic, immune, and inflammatory functions. However, chronic excessive training has been associated with increased inflammatory markers and oxidative stress, so much so that excessive training overload, combined with inadequate recovery, can lead to the development of overtraining syndrome (OTS). OTS negatively impacts an athlete's performance capabilities and significantly affects both physical health and mental well-being. However, diagnosing OTS remains challenging as the contributing factors, signs/symptoms, and underlying maladaptive mechanisms are individualized, sport-specific, and unclear. Therefore, identifying potential biomarkers that could assist in preventing and/or diagnosing OTS is an important objective. In this review, we focus on the possibility that the endocrine functions of AT may have significant implications in the etiopathogenesis of OTS. During physical exercise, AT responds dynamically, undergoing remodeling of endocrine functions that influence the production of adipokines involved in regulating major energy and inflammatory processes. In this scenario, we will discuss exercise about its effects on AT activity and metabolism and its relevance to the prevention and/or development of OTS. Furthermore, we will highlight adipokines as potential markers for diagnosing OTS.
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Diabetes Mellitus Tipo 2 , Deportes , Humanos , Adipoquinas , Ejercicio Físico , Tejido AdiposoRESUMEN
Introduction: Dimethyl sulfoxide (DMSO) is widely used as a diluent and/or solvent for pharmacological compounds. Furthermore, DMSO crosses the blood-brain barrier acting on the nervous system. The natural compounds phenylamides and lignanamides (LnHS) have protective effects on neuronal health, being promising neuroprotective candidates. In this scenario, we evaluated the impact of DMSO and/or LnHS on SH-SY5Y and U-87 cells, taken as in vitro model of neurons and glia. Methods: Cells were treated with DMSO and/or LnHS at different doses and proliferation (MTT and trypan blue counting, colony forming ability, autophagy, oxidative stress (NO, ROS determination) and inflammatory (IL8, IL6, TNFα mRNA expression) response was evaluated. Results: We found that DMSO reduces both neuronal and glial cell viability, while LnHS does not affect viability of SH-SY5Y cells but reduces that of U-87 cells. Therefore, we focused on SHSY5Y cells and investigated whether LnHS could counteract DMSO toxicity. LnHS partially attenuates the inhibitory effects of DMSO on cell viability and restores the colony-forming ability of SH-SY5Y cells exposed to DMSO. Furthermore, we found that co-administration of LnHS modulates the expression of SIRT3 and SOD2 enzymes, reduces nitrite release and ROS generation increasing IL-8 levels. Interestingly, co-administration of LnHS counteracts the DMSO-induced production of IL-6, while no modification in TNF-α was found. Discussion: Our study indicates LnHS as a potential feasible compound to support neuronal health as it counteracts DMSO induced cytotoxic effects by improving SH-SY5Y cells survival. Further studies are needed to clarify the molecular mechanisms underlying the LnHS biological activities.
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Background: Non-Hodgkin's lymphoma (NHL), the most frequent hematological neoplasm worldwide, represents a heterogeneous group of malignancies. The etiology of NHL remains to be fully elucidated, but the role of adipose tissue (AT) in immune function via the secretion of adipokines was recently recognized. Among adipokines, adiponectin has garnered attention for its beneficial properties. This study aimed to explore the in vitro effects of AdipoRon, an adiponectin agonist, on JVM-2, a lymphoblast cell line used as a representative disease model. Methods: JVM-2 cells were treated with different concentrations of AdipoRon to evaluate its effects on viability (via an MTT test), cell cycle distribution (via an FACS analysis), invasiveness (via a Matrigel assay) and colony-forming ability; protein expression was assessed via a real-time PCR (qPCR) and/or Western blotting (WB). Results: We found that the prolonged exposure of JVM-2 cells to AdipoRon led to a reduction in their viability due to a cytostatic effect. Additionally, AdipoRon stimulated both the formation of cell colonies and the expression of E-cadherin. Interestingly, the administration of AdipoRon increased the invasive potential of JVM-2 cells. Conclusions: Our findings indicate that adiponectin is involved in the regulation of different cellular processes of JVM-2 cells, supporting its potential association with a pro-tumorigenic phenotype and indicating that it might contribute to the increased aggressiveness and metastatic potential of B lymphoma cells. However, additional studies are required to fully understand the molecular mechanisms of adiponectin's actions on lymphoblasts and whether it may represent a marker of disease.
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Adipose tissue is actually regarded as an endocrine organ, rather than as an organ that merely stores energy. During the COVID-19 pandemic, obesity has undoubtedly emerged as one of the most important risk factors for disease severity and poor outcomes related to SARS-CoV-2 infection. The aberrant production of cytokine-like hormones, called adipokines, may contribute to alterations in metabolism, dysfunction in vascular endothelium and the creation of a state of general chronic inflammation. Moreover, chronic, low-grade inflammation linked to obesity predisposes the host to immunosuppression and excessive cytokine activation. In this respect, understanding the mechanisms that link obesity with the severity of SARS-CoV-2 infection could represent a real game changer in the development of new therapeutic strategies. Our review therefore examines the pathogenic mechanisms of SARS-CoV-2, the implications with visceral adipose tissue and the influences of the adipose tissue and its adipokines on the clinical behavior of COVID-19.
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COVID-19 , Humanos , Adipoquinas , SARS-CoV-2 , Pandemias , Citocinas , Inflamación , Obesidad/complicacionesRESUMEN
Multiple sclerosis (MS) is the most common disabling neurological disease characterized by chronic inflammation and neuronal cell viability impairment. Based on previous studies reporting that adiponectin exhibits neuroprotective effects in some models of neurodegenerative diseases, we analyzed the effects of AdipoRon treatment, alone or in combination with the cerebrospinal fluid of patients with MS (MS-CSF), to verify whether this adipokine acts on the basal neuronal cellular processes. To this aim, SH-SY5Y and U-87 cells (models of neuronal and glial cells, respectively) were exposed to MS-CSF alone or in co-treatment with AdipoRon. The cell viability was determined via MTT assay, and the possible underlying mechanisms were investigated via the alterations of oxidative stress and inflammation. MTT assay confirmed that AdipoRon alone did not affect the viability of both cell lines; whereas, when used in combination with MS-CSF, it reduces MS-CSF inhibitory effects on the viability of both SH-SY5Y and U-87 cell lines. In addition, MS-CSF treatment causes an increase in pro-inflammatory cytokines, whereas it determines the reduction in anti-inflammatory IL-10. Interestingly, the co-administration of AdipoRon counteracts the MS-CSF-induced production of pro-inflammatory cytokines, whereas it determines an enhancement of IL-10. In conclusion, our data suggest that AdipoRon counteracts the cytotoxic effects induced by MS-CSF on SH-SY5Y and U-87 cell lines and that one of the potential molecular underlying mechanisms might occur via reduction in oxidative stress and inflammation. Further in vivo and in vitro studies are essential to confirm whether adiponectin could be a neuro-protectant candidate against neuronal cell injury.
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Polycystic Kidney Diseases (PKDs) consist of a genetically and phenotypically heterogeneous group of inherited disorders characterized by numerous renal cysts. PKDs include autosomal dominant ADPKD, autosomal recessive ARPKD and atypical forms. Here, we analyzed 255 Italian patients using an NGS panel of 63 genes, plus Sanger sequencing of exon 1 of the PKD1 gene and MPLA (PKD1, PKD2 and PKHD1) analysis. Overall, 167 patients bore pathogenic/likely pathogenic variants in dominant genes, and 5 patients in recessive genes. Four patients were carriers of one pathogenic/likely pathogenic recessive variant. A total of 24 patients had a VUS variant in dominant genes, 8 patients in recessive genes and 15 patients were carriers of one VUS variant in recessive genes. Finally, in 32 patients we could not reveal any variant. Regarding the global diagnostic status, 69% of total patients bore pathogenic/likely pathogenic variants, 18.4% VUS variants and in 12.6% of patients we could not find any. PKD1 and PKD2 resulted to be the most mutated genes; additional genes were UMOD and GANAB. Among recessive genes, PKHD1 was the most mutated gene. An analysis of eGFR values showed that patients with truncating variants had a more severe phenotype. In conclusion, our study confirmed the high degree of genetic complexity at the basis of PKDs and highlighted the crucial role of molecular characterization in patients with suspicious clinical diagnosis. An accurate and early molecular diagnosis is essential to adopt the appropriate therapeutic protocol and represents a predictive factor for family members.
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Riñón Poliquístico Autosómico Dominante , Riñón Poliquístico Autosómico Recesivo , Humanos , Canales Catiónicos TRPP/genética , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Recesivo/diagnóstico , Riñón Poliquístico Autosómico Recesivo/genética , Exones , Genes Reguladores , Factores de Transcripción/genéticaRESUMEN
Obesity and related metabolic diseases represent a worldwide health problem. The main factor predisposing to obesity is an unhealthy lifestyle including the lack of physical activity. A pivotal role in the etio-pathogenesis of obesity is carried out by adipose tissue, an endocrine organ secreting several adipokines involved in numerous metabolic and inflammatory processes. Among these, of particular importance is adiponectin, an adipokine involved in the regulation of insulin sensibility and in anti-inflammatory processes. The aim of the study was to determine the effects of 24 weeks of two different training programs polarized (POL) and threshold training (THR) on body composition, physical capacities and adiponectin expression. Thirteen male obese subjects (BMI: 32.0 ± 3.0 kg m-2) followed 24 weeks of two different training programs, POL and THR, consisting of walking or running (or a combination of the two methods) in their normal living conditions. Before (T0) and after the end of the program (T1), the assessment of body composition was assessed by bioelectrical impedance and the concentration of salivary and serum adiponectin was analyzed by enzyme-linked immunosorbent assay and western blotting. Although the results obtained did not show significant differences between the two training programs, body mass and body mass index decreased by a mean of -4.46 ± 2.90 kg and 1.43 ± 0.92 kg m-2 (P < 0.05). Fat mass decreased by -4.47 ± 2.78 kg (P < 0.05). V'O2max increased by a mean of 0.20 ± 0.26 L min-1 (P < 0.05) Also, we observed an increase in saliva and in serum of adiponectin concentrations at T1 compared to T0 by 4.72 ± 3.52 µg mL-1 and 5.22 ± 4.74 ng mL-1 (P < 0.05) respectively. Finally, we found significant correlations between Δ serum adiponectin and Δ Hip (R = -0.686, P = 0.001) and between Δ salivary adiponectin and ΔWaist (R = -0.678, P = 0.011). Our results suggest that a 24 weeks training program, independently from intensity and volume, induces an amelioration of body composition and fitness performance. These improvements are associated with an increase in total and HMW adiponectin expression in both saliva and in serum.
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Chronic obstructive pulmonary disease (COPD) is characterized by respiratory symptoms and non-reversible airflow limitation with recurrent episodes of acute exacerbations. The concurrent presence of bronchiectasis in patients with COPD is associated with reduced respiratory function as well as increased exacerbation risk. Adiponectin is a promising biomarker in COPD, as greater high molecular weight (HMW) oligomer levels have been observed among COPD patients. Here, we investigate adiponectin levels in two groups of COPD patients characterized by the presence or absence of bronchiectasis (BCO), comparing both groups to healthy controls. We evaluated serum adiponectin levels in COPD patients, those with BCO, and healthy subjects and characterized the pattern of circulating adiponectin oligomers. We found that forced volume capacity % (FVC%) and forced expiratory volume % (FEV1%) were lower for BCO patients than for COPD patients. COPD patients had higher levels of adiponectin and its HMW oligomers than healthy controls. Interestingly, BCO patients had higher levels of adiponectin than COPD patients. We showed that expression levels of IL-2, -4, and -8, IFN-γ, and GM-CSF were significantly higher in BCO patients than in healthy controls. Conversely, IL-10 expression levels were lower in BCO patients. Our data suggest that the increased levels of adiponectin detected in the cohort of BCO patients compared to those in COPD patients without bronchiectasis might be determined by their worse airway inflammatory state. This hypothesis suggests that adiponectin could be considered as a biomarker to recognize advanced COPD patients with bronchiectasis.
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Obesity, through adipose tissue (AT) inflammation and dysregulation, represents a critical factor for COVID-19; here, we investigated whether serum levels of adiponectin, HMW oligomers, leptin, and resistin are modulated and/or correlated with clinical and biochemical parameters of severe COVID-19 patients. This study included 62 severe COVID-19 patients; 62 age and sex-matched healthy subjects were recruited as a control group. Anthropometric and biochemical parameters were obtained and compared. Adiponectin, HMW oligomers, leptin, and resistin were analyzed by ELISA. The adiponectin oligomerization state was visualized by Western blotting. When compared to healthy subjects, total adiponectin levels were statistically lower in severe COVID-19 while, in contrast, the levels of leptin and resistin were statistically higher. Interestingly, HMW adiponectin oligomers negatively correlated with leptin and were positively associated with LUS scores. Resistin showed a positive association with IL-6, IL-2R, and KL-6. Our data strongly support that adipose tissue might play a functional role in COVID-19. Although it needs to be confirmed in larger cohorts, adiponectin HMW oligomers might represent a laboratory resource to predict patient seriousness. Whether adipokines can be integrated as a potential additional tool in the evolving landscape of biomarkers for the COVID-19 disease is still a matter of debate. Other studies are needed to understand the molecular mechanisms behind adipokine's involvement in COVID-19.
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Adiponectina , COVID-19 , Humanos , Leptina , Resistina , SARS-CoV-2RESUMEN
Introduction: Hidradenitis suppurativa (HS) is a severe chronic skin disease. Although the pathogenesis remains unclear, at the basis of HS there is an enhancement of the immune and inflammatory response together with a susceptibility to environmental factors. Cytokine dysregulation is crucial in HS severity and progression. Objectives: The aim of this study was to analyze serum levels of different cytokines focusing on adiponectin concentration and its oligomers in HS patients compared to both obese and healthy subjects. Methods: The concentrations of adiponectin and cytokines were measured using enzyme-linked immunosorbent assay (ELISA); the oligomeric distribution of adiponectin (low molecular weight (LMW), medium molecular weight (MMW) and high molecular weight (HMW) oligomers)was evaluated through Western Blotting analysis. Results: Total adiponectin is statistically higher in HS patients compared to matched controls and obese subjects. Interestingly, Adiponectin oligomerization state is altered in HS, with an increase of HMW oligomers. Serum levels of PDGF-BB, IL-1ß, IL-5, Il-6, IL12, IL13, IL15, IL-17, GMCSF, INFγ, VEGF and MCP-1 are statistically higher while IL-1ra and RANTES levels are statistically lower in HS patients compared to healthy controls. Interestingly, adiponectin positively correlates with PDGF-BB, and IL-13. Conclusions: Our data confirmed that the complex network that links metabolism to immune homeostasis is dysregulated in HS and that adiponectin and its HMW oligomers are actively involved in this disease. In addition, the correlation between adiponectin and PDGF-BB, and IL-13 extends the role of this adipokine in modulation of the immune response, in particular regulating the innate immune system rather that the adaptive one. Further researches are needed to clarify the complex inflammatory milieu that characterizes HS syndrome.
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The airway epithelium is a protective barrier that is maintained by the self-renewal and differentiation of basal stem cells. Increasing age is a principle risk factor for chronic lung diseases, but few studies have explored age-related molecular or functional changes in the airway epithelium. We retrieved epithelial biopsies from histologically normal tracheobronchial sites from pediatric and adult donors and compared their cellular composition and gene expression profile (in laser capture-microdissected whole epithelium, fluorescence-activated cell-sorted basal cells, and basal cells in cell culture). Histologically, pediatric and adult tracheobronchial epithelium was similar in composition. We observed age-associated changes in RNA sequencing studies, including higher interferon-associated gene expression in pediatric epithelium. In cell culture, pediatric cells had higher colony formation ability, sustained in vitro growth, and outcompeted adult cells in a direct competitive proliferation assay. Our results demonstrate cell-intrinsic differences between airway epithelial cells from children and adults in both homeostatic and proliferative states.
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SARS-CoV-2 infection can induce a broad range of clinical symptoms, and the most severe cases are characterized by an uncontrolled inflammatory response with the overproduction of proinflammatory cytokines. Elevated levels of C-reactive protein, interleukin-1B, and interleukin-6 have become key signatures of severe COVID-19. For this reason, the use of 6 mg of dexamethasone has become a standard of care, although this regime may not be optimal. Even though various glucocorticoid doses have been proposed, it is still unclear which dose should be used to prevent adverse effects while at the same time reducing the inflammatory response. Here, we compared two different doses of corticosteroids in 52 elderly hospitalized patients with severe to critical COVID-19 to assess efficacy and safety. We showed that in patients receiving a higher dose of prednisone, the time to negative swab was significantly longer. Furthermore, although neither dose was correlated with the risk of death, patients receiving the high dose were more likely to have adverse events such as hyperglycemia, leukocytosis, an increase in systemic blood pressure, and others. Finally, the BMI, WBC number, and NLR value were directly related to death. In conclusion, although the optimal glucocorticoid dose is still undefined, our retrospective study supports the absence of beneficial effects in the utilization of higher doses of corticosteroids in elderly patients with severe to critical COVID-19.
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Hidradenitis suppurativa (HS) is a pathology characterized by chronic inflammation and skin lesions. The molecular basis of the inflammatory network remains unclear; however, since microRNAs (miRNAs) are involved in the modulation of inflammation, the composition of a micro-transcriptome RNA library using the blood of HS patients was analysed here. The total miRNA expression profiles of miRNAs from HS patients was assayed by real-time qPCR. Here, compared to healthy controls, miR-24-1-5p, miR-146a-5p, miR26a-5p, miR-206, miR338-3p, and miR-338-5p expression was found significantly different in HS. Knowing the significance of the miRNA mechanism in inflammatory and immune progression, we suggest that miRNA profiles found in HS patients can be significant in understanding the pathogenesis modality and establishing efficient biomarkers for HS early diagnosis. In particular, miR-338-5p was closely related to HS invasiveness and production of cytokines and was atypically overexpressed. miR-338-5p may represent a good promise as a non-invasive clinical biomarker for HS.
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MicroARN Circulante , Hidradenitis Supurativa , MicroARNs , Biomarcadores , MicroARN Circulante/genética , Citocinas , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/genética , Hidradenitis Supurativa/patología , Humanos , Inflamación , MicroARNs/metabolismoRESUMEN
Cannabidiolic acid (CBDA) is the main precannabinoid in industrial hemp. It represents a common constituent of hemp seed oil, but mainly abundant in the aerial parts of the plant (including their processing waste). Thus, the optimization of fast and low-cost purification strategies is mandatory, as well as a deep investigation on its nutraceutical and cosmeceutical properties. To this purpose, CBDA content in hemp seed oil is evaluated, and its recovery from wasted leaves is favorably achieved. The cytotoxicity screening towards HaCaT cells, by means of MTT, SRB and LDH release assays, suggested it was not able to decrease cell viability or perturb cell integrity up to 10 µM concentration. Thus, the ability of CBDA to differentially modulate the release of proinflammatory cytokines and chemokines mediators has been evaluated, finding that CBDA decreased IFN-γ, CXCL8, CXCL10, CCL2, CCL4 and CCL5, mostly in a dose-dependent manner, with 10 µM tested concentration exerting the highest activity. These data, together with those from assessing antimicrobial activity against Gram(+) and Gram(-) bacteria and the antibiofilm formation, suggest that CBDA is able to counteract the inflammatory response, also preventing bacteria colonization.
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Cannabinoides , Cannabis , Cannabinoides/farmacología , Extractos VegetalesRESUMEN
Mental alterations were described during the COVID-19 pandemic and sleep deprivation has been reported as a consequence of social isolation. In Italy, the COVID-19 pandemic spread out at the beginning of 2020 determining severe lockdown periods. The aim of our study was to observe the effects of lockdown on sleep and anxiety in trained non-professional subjects and professional athletes who continued to train during the lockdown period. Forty-six subjects (21 trained non-professional subjects and 25 professional athletes) were recruited from a variety of team and individual sports to complete a battery of previously validated and widely used questionnaires assessing psychometric and anthropometric parameters, physical activity levels, lifestyle habits, and sleep quality. Subjects were aged 27.0 ± 5.14. All items were evaluated as percentages and chi-square and Fisher's exact tests were performed, as appropriate. Our data showed that the prevalence of the difficulty of falling asleep (over 30%), the tendency of nocturnal awakenings (over 30%), and moderate anxiety (over 38%) were at the same extent in the two groups. Of the professional athletes, 72.73% declared snoring during sleep vs 42.86% of non-professional subjects. No other significant differences were found between the two groups except for the perception of being constant in daily activity, significantly more reported by trained subjects (p < 0.005). Our data show a similar scenario of anxiety and sleep disturbances for the two groups, suggesting that lockdown by the COVID-19 pandemic has partially mitigated the known beneficial effects due to physical activity on mental health and sleep quality. Further analyses are necessary to define the associated risk factors.
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Background: Childhood obesity (CO) is a serious medical condition affecting approximately 120 million children and adolescents worldwide. It is characterized by a persistent inflammatory state with inflammatory markers overexpressed, which in turn leads to a higher cardiovascular risk. It is well known that physical exercise reduces the inflammatory state in obese children. In the present study, we evaluated various biochemical parameters in obese children performing physical exercise compared to a group of obese sedentary children. Hence, the objective is to identify a panel of biomarkers to prevent numerous obesity-related complications. Methods: We examined two populations: 44 sedentary obese children (OSe), recruited on 5 November 2018 from Santobono−Pausilipon Children's Hospital, Naples (Italy) of age = 11 ± 3.3 and 30 obese children who practice sport (OSp) of age = 10 ± 2.5. We observed a significant variation in some biochemical parameters such as white blood cells, C-reactive protein (CRP), glycemia and insulinemia. Moreover, we determined the levels of interleukins, chemokines and defensins by ELISA assay. Results: Our results showed a reduction in serum level of glycemia (p-value < 0.001), neutrophils (p-value < 0.05) and CRP (p-value < 0.05), whereas no relevant variations have been reported in insulin levels. Moreover, we found a decrease in serum levels of PDGF-ß (p-value < 0.05), IL-9 (p-value < 0.01), IL-6 (p-value < 0.0001), IL-8 (p-value < 0.0001), IP-10 (p-value < 0.01), Eotaxin (p-value < 0.0001) and GM-CSF (p-value < 0.01) in OSp population in comparison to OSe. At the same time, we did not observe any significant variation in serum levels of IL-1ra and IL-17 between the two populations. On the other hand, we found an increase in HNP-1 (p-value < 0.0001) and HBD1 (p-value < 0.01) in OSp if compared to OSe. Conclusions: This study shed light on the role of physical exercise on CO, demonstrating in our population that an early evaluation of some biochemical parameters could be an assumption to prescribe physical exercise in order to monitor and prevent childhood obesity and related disorders.
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Enfermedades Cardiovasculares , Obesidad Infantil , Adolescente , Humanos , Niño , Obesidad Infantil/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Ejercicio Físico , Biomarcadores , Proteína C-Reactiva , Factores de Riesgo de Enfermedad Cardiaca , Italia/epidemiología , Sistema Inmunológico , Índice de Masa CorporalRESUMEN
Antibiotic resistance is becoming a severe obstacle in the fight against acute and chronic infectious diseases that accompany most degenerative illnesses from neoplasia to osteo-arthritis and obesity. Currently, the race is on to identify pharmaceutical molecules or combinations of molecules able to prevent or reduce the insurgence and/or progression of infectivity. Attempts to substitute antibiotics with antimicrobial peptides have, thus far, met with little success against multidrug-resistant (MDR) bacterial strains. During the last decade, we designed and studied the activity and features of human ß-defensin analogs, which are salt-resistant, and hence active also under high salt concentrations as, for instance, in cystic fibrosis. Herein, we describe the design, synthesis, and major features of a new 21 aa long molecule, peptide γ2. The latter derives from the γ-core of the ß-defensin natural molecules, a small fragment of these molecules still bearing high antibacterial activity. We found that peptide γ2, which contains only one disulphide bond, recapitulates most of the biological properties of natural human ß-defensins and can also counteract both Gram-positive and Gram-negative MDR bacterial strains and biofilm formation. Moreover, it has great stability in human serum thereby enhancing its antibacterial presence and activity without cytotoxicity in human cells. In conclusion, peptide γ2 is a promising new weapon also in the battle against intractable infectious diseases.