Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts.

Osteoarthritis (OA) stands as a prevalent and progressively debilitating clinical condition globally, impacting joint structures and leading to their gradual deterioration through inflammatory mechanisms. While both non-modifiable and modifiable factors contribute to its onset, numerous aspects of OA pathophysiology remain elusive despite considerable research strides. Presently, diagnosis heavily relies on clinician expertise and meticulous differential diagnosis to exclude other joint-affecting conditions. Therapeutic approaches for OA predominantly focus on patient education for self-management alongside tailored exercise regimens, often complemented by various pharmacological interventions primarily targeting pain alleviation. However, pharmacological treatments typically exhibit short-term efficacy and local and/or systemic side effects, with prosthetic surgery being the ultimate resolution in severe cases. Thus, exploring the potential integration or substitution of conventional drug therapies with natural compounds and extracts emerges as a promising frontier in enhancing OA management. These alternatives offer improved safety profiles and possess the potential to target specific dysregulated pathways implicated in OA pathogenesis, thereby presenting a holistic approach to address the condition's complexities.

Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson's Disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, primarily associated with dopaminergic neuron depletion in the Substantia Nigra. Current treatment focuses on compensating for dopamine (DA) deficiency, but the blood-brain barrier (BBB) poses challenges for effective drug delivery. Using differentiated SH-SY5Y cells, we investigated the co-administration of DA and the antioxidant Grape Seed Extract (GSE) to study the cytobiocompability, the cytoprotection against the neurotoxin Rotenone, and their antioxidant effects. For this purpose, two solid lipid nanoparticle (SLN) formulations, DA-co-GSE-SLNs and GSE-ads-DA-SLNs, were synthesized. Such SLNs showed mean particle sizes in the range of 187-297 nm, zeta potential values in the range of -4.1--9.7 mV, and DA association efficiencies ranging from 35 to 82%, according to the formulation examined. The results showed that DA/GSE-SLNs did not alter cell viability and had a cytoprotective effect against Rotenone-induced toxicity and oxidative stress. In addition, this study also focused on the evaluation of Alpha-synuclein (aS) levels; SLNs showed the potential to modulate the Rotenone-mediated increase in aS levels. In conclusion, our study investigated the potential of SLNs as a delivery system for addressing PD, also representing a promising approach for enhanced delivery of pharmaceutical and antioxidant molecules across the BBB.

Role of triglyceride-glucose index in metabolic assessment of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ. It leads to an increased risk of metabolic syndrome and insulin resistance, due to biochemical pathways involved in low-grade inflammation in both diseases. The aim of our retrospective case-control study was to evaluate the utility of triglyceride-glucose (TyG) index, a surrogate of insulin resistance, for metabolic assessment of sarcoidosis patients. A cohort of 90 sarcoidosis patients and a cohort of 90 control subjects were enrolled. Clinical, anamnestic, and biochemical data were collected. Results showed that TyG index values were higher in the sarcoidosis cohort than in the control group (p < 0.001), even after excluding the influence of diabetes and metabolic syndrome (p = 0.018). In the sarcoidosis cohort, TyG index was not correlated with clinical phenotyping (p = 0.358), gender (p = 0.139), radiological stage (p = 0.656), glucocorticoids cumulative dose (p = 0.682) or treatment regimen (p = 0.093), while significant positive correlations with waist circumference (p < 0.001), systolic and diastolic pressure (p = 0.041 and p = 0.029, respectively), Framingham score (p = 0.007) were found. Receiving operating characteristics curve analysis identified a TyG index optimal cut-off value of 8.64 (66.7% sensitivity, 77.8% specificity, area under the curve -AUC- 75%, 95% confidence interval -CI- 65-85, p < 0.001) to detect metabolic syndrome and a cut-off value of 8.69 (64.1% sensitivity, 70.6% specificity; AUC 67%, 95% CI 55-78, p = 0.007) to detect an intermediate cardiovascular risk according to Framingham risk score. Concluding, TyG index can be considered a useful tool for the metabolic assessment of sarcoidosis patients, given its capacity to predict metabolic syndrome and cardiovascular risk.

Serological Evidence for Circulation of Influenza D Virus in the Ovine Population in Italy.

Influenza D virus (IDV) is a novel orthomyxovirus initially isolated from pigs exhibiting influenza-like disease in the USA. Since then, IDV has been detected worldwide in several host species, including livestock animals, whilst specific antibodies have been identified in humans, raising concerns about interspecies transmission and zoonotic risks. Few data regarding the seroprevalence of IDV in small ruminants have been available to date. In this study, we assessed the prevalence of antibodies against IDV in ovine serum samples in Sicily, Southern Italy. Six hundred serum samples, collected from dairy sheep herds located in Sicily in 2022, were tested by haemagglutination inhibition (HI) and virus neutralization (VN) assays using reference strains, D/660 and D/OK, representative of two distinct IDV lineages circulating in Italy. Out of 600 tested samples, 168 (28.0%) tested positive to either IDV strain D/660 or D/OK or to both by HI whilst 378 (63.0%) tested positive to either IDV strain D/660 or D/OK or to both by VN. Overall, our findings demonstrate that IDV circulates in ovine dairy herds in Sicily. Since IDV seems to have a broad host range and it has zoonotic potential, it is important to collect epidemiological information on susceptible species.

Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease.

Parkinson's disease (PD) is a predominantly idiopathic pathological condition characterized by protein aggregation phenomena, whose main component is alpha-synuclein. Although the main risk factor is ageing, numerous evidence points to the role of type 2 diabetes mellitus (T2DM) as an etiological factor. Systemic alterations classically associated with T2DM like insulin resistance and hyperglycemia modify biological processes such as autophagy and mitochondrial homeostasis. High glucose levels also compromise protein stability through the formation of advanced glycation end products, promoting protein aggregation processes. The ability of antidiabetic drugs to act on pathways impaired in both T2DM and PD suggests that they may represent a useful tool to counteract the neurodegeneration process. Several clinical studies now in advanced stages are looking for confirmation in this regard.

Evaluation of immune response to SARS-CoV-2 Omicron sublineages six months after different vaccination regimens in Italy.

The Omicron variant is the most divergent, displaying more mutations than previous SARS-CoV-2 variants, particularly in the gene that encodes the spike protein. This study aimed to assess the persistence of neutralizing antibodies towards the SARS-CoV-2 Omicron sublineages (BA.2, BA.5, BQ.1, XBB and XBB1.5) six months after the third dose in different vaccination regimens. Subjects who received 3 doses of mRNA vaccine retained their neutralization activity against BA.2 and BA.5, even though 56.3% and 66.7% showed a ≥ 2-fold reduction in the neutralizing antibody titre, respectively. Subjects who had received the adenovirus-based vaccine plus a booster dose of mRNA vaccine retained their neutralization activity especially against BA.2. With regard to BQ.1, XBB and XBB.1.5, the majority of the subjects showed a ≥ 2-fold reduction in neutralizing antibody titre, with the greatest evasion being observed in the case of XBB. Overall, our results provide further evidence that triple homologous/heterologous vaccination and hybrid immunity result in detectable neutralizing antibodies against the ancestral virus; however, emerging Omicron sublineages, such as XBB and XBB.1.5, show a great evasive capacity, which compromises the effectiveness of current COVID-19 vaccines.

Cardiovascular risk in rare diseases: a prognostic stratification model in a cohort of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ; as other chronic diseases, it leads to increased risk of atherosclerosis and cardiovascular (CV) disease. The aim of our observational study was to define a prognostic stratification model of sarcoidosis patients based on the evaluation of CV risk through common carotid Doppler ultrasound and cardiovascular risk scores assessment; for this reason, a clinical phenotyping of sarcoidosis patients in four subgroups was done, based on the different organ involvement. A cohort of 53 sarcoidosis patients and a cohort of 48 healthy volunteers were enrolled. Results showed that CV risk was higher in sarcoidosis cohort than in the control group when evaluated through CV risk scores and Doppler parameters: peak-systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly lower in sarcoidosis cohort (p = 0.045 and p = 0.017, respectively), whereas intima media thickness (IMT) showed higher values in sarcoidosis group than in controls (p = 0.016). The analysis of sarcoidosis phenotypes showed no significative differences of CV risk among them when CV risk scores were considered, while partial differences emerged by evaluating subclinical atherosclerosis. Results also highlighted a relationship between CV risk score and carotid Doppler ultrasound parameters: EDV showed an inverse correlation with Framingham score (R = - 0.275, p = 0.004), whereas IMT showed a direct one (R = 0.429; p = 0.001); furthermore, an inverse correlation between PSV and EDV and illness duration (R = - 0.298, p = 0.030 and R = - 0.406, p = 0.002, respectively) was found, so suggesting a higher CV risk in patients with a longer story of disease.

SARS-CoV-2 epidemiological trend before vaccination era: a seroprevalence study in Apulia, Southern Italy, in 2020.

Aim: The present study aimed at assessing the prevalence of antibodies against SARS-CoV-2 in the general population in the province of Bari (Apulia region, Southern Italy) during the year 2020. Subject and methods: In this study, 1325 serum samples collected from January to December 2020 were tested for the presence of IgM and IgG antibodies against whole-virus SARS-CoV-2 antigen by commercial ELISA. Positive samples were further tested by in-house ELISA for the detection of anti-receptor binding domain (RBD) IgM and IgG antibodies and by micro-neutralization (MN) assay for the detection of neutralizing antibody. Results: One hundred (7.55%) samples had the presence of at least one antibody class against SARS-CoV-2 by commercial ELISA, of which 88 (6.6%) showed IgG and 19 (1.4%) showed IgM antibodies. The proportion of samples with IgG antibodies increased from 1.9% in January-February to 9.6% in November-December, while no significant increase was observed for IgM. When tested by in-house ELISA and MN assay, 17.0% and 31.6% were found positive to RBD IgG and RBD IgM, respectively, while 12.0% showed neutralizing antibody. Conclusion: The proportion of samples with SARS-CoV-2 IgG antibodies increased during 2020, especially in the second half of the year, consistent with data reported by the routine epidemiological surveillance of SARS-CoV-2 cases. Despite the high number of reported cases, the seroprevalence values are relatively low, and only a small proportion of samples had neutralizing antibodies. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-023-01834-3.

Direct Comparison of the Lowest Effect Concentrations of Mutagenic Reference Substances in Two Ames Test Formats.

The Ames assay is the standard assay for identifying DNA-reactive genotoxic substances. Multiple formats are available and the correct choice of an assay protocol is essential for achieving optimal performance, including fit for purpose detection limits and required screening capacity. In the present study, a comparison of those parameters between two commonly used formats, the standard pre-incubation Ames test and the liquid-based Ames MPF™, was performed. For that purpose, twenty-one substances with various modes of action were chosen and tested for their lowest effect concentrations (LEC) with both tests. In addition, two sources of rat liver homogenate S9 fraction, Aroclor 1254-induced and phenobarbital/ß-naphthoflavone induced, were compared in the Ames MPF™. Overall, the standard pre-incubation Ames and the Ames MPF™ assay showed high concordance (>90%) for mutagenic vs. non-mutagenic compound classification. The LEC values of the Ames MPF™ format were lower for 17 of the 21 of the selected test substances. The S9 source had no impact on the test results. This leads to the conclusion that the liquid-based Ames MPF™ assay format provides screening advantages when low concentrations are relevant, such as in the testing of complex mixtures.

Comparison of Chemical Composition and Safety Issues in Fish Roe Products: Application of Chemometrics to Chemical Data.

Processed fish roes are acquiring considerable importance in the modern food market, entering more and more often as an ingredient in food preparation and as caviar substitutes. In this study, we defined quality, traceability and safety issues related to processed fish roe products from different species. The results obtained allowed to distinguish eggs originated from different fish species and to discriminate between fish roes and caviar samples obtained from four different sturgeons species. We observed that roes showed a trend of grouping according to ecological and reproductive habits of fish species. We highlighted the differences between eggs originated by farmed and freshwater fish, enriched in n6 polyunsaturated fatty acids (PUFAs), and all the others, in which n3 PUFAs were prevalent. In addition, we evaluated processed fish roes under a food safety point of view, combining microbiological analysis with the determination of organic acids, used in some products as authorized preservatives. Microbiological characterization has proved a general good hygienic level for these products. Organic acids determination showed values in compliance with European Union (EU) regulations in almost of samples; in some cases, we found a mismatch between the organic acids detected and what was reported in labels. Processed fish roes could be considered a safe product that can provide to human nutrition a valuable content of essential fatty acids.