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Background: The molecular crosstalk between periodontitis and diabetes is well established. The role of the NLRP3 inflammasome, a multicomponent inflammatory machinery, is an emerging field of research on the relationship between these two uncommunicable diseases. Recent advances are revealing further molecular details regarding the biological function and the mechanism behind the NLRP3 inflammasome dysregulation and highlighting an unexpected role for the caspase-1 in immune homeostasis. We aimed to understand which metabolic checkpoints are involved in contributing to and instigating the relationship between periodontitis and diabetes. We tried to explore the involvement of the NLRP3 in regulating the cytokine-chemokines profile and discussed the potential synergism in these mechanisms when these two diseases coexist in the same patient. Methods: A literature search was carried out in the electronic databases (MEDLINE, EMBASE, and Cochrane Library) for relevant studies from inception until January 2022 for trials and cohort studies that investigated the activation and regulation mechanism of the NLRP3 inflammasome in patients with periodontitis and type two diabetes. Two investigators independently extracted data. The data quality assessment was rated by the Joanna Briggs Institute (JBI). Results: from twenty-six references identified, three studies (two case-control and one cross-sectional) met the inclusion criteria. Analysis of periodontal tissue samples in diabetic individuals exhibited significant overexpression of the NLRP3 inflammasome when compared with healthy controls. Conclusions: there is insufficient evidence to sustain the involvement of the upregulation of genes and proteins involved in the activation of NLRP3 inflammasome components in patients with periodontitis and diabetes.

Background: Hemp seed oil and terpenes are emerging as a dietary supplement and complementary therapy for patients suffering from knee osteoarthritis (KOA). However, the mechanisms and effects induced by these molecules on inflammatory cytokines are not yet fully understood. The aim of this study was to evaluate the changes in the cytokine IL-1β, IL-1α, IL-2, IL-6, and TNF-α levels from two oral hemp seed oil-based dietary supplements, of which only one included the addition of terpenes, in a population of KOA patients. Methods: Sera from venous blood samples were collected from thirty-eight patients who were divided into two subgroups. The control group underwent a 45-day treatment with a dietary supplement containing only hemp seed oil, while the treatment group assumed a hemp seed oil and terpene-based dietary supplement for the same number of days. A Bio-Plex Human Cytokine assay was performed by a customized human cytokine five-plex panel for IL-1β, IL-1α, IL-2, IL-6, and TNF-α. Patients were evaluated before the beginning of the treatment (T0) and soon after it (T1). Results: No measurable levels of IL-2 and TNF-α were found in any of the subjects. Low levels of IL-1β were found, which were significantly decreased in the treatment group. No change in IL-1α levels was observed, while treated patients had a significant increase in IL-6 levels. Conclusions: Hemp seed oil and terpene treatment modified the IL-1β and IL-6 levels, counteracting KOA inflammation in this way. In this study, IL-6 revealed its new and alternative action, since it is traditionally known as a pro-inflammatory factor, but it recently has been found to have anti-inflammatory activity in the muscle-derived form, which is the one it assumes as a myokine when activated by terpenes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 patients admitted for COVID-19 from March to June 2021 to “F. Perinei” Murgia Hospital in Altamura, Italy, were divided into survivors (n = 100) and non-survivors groups (n = 50). Blood counts, inflammation-related biomarkers and lymphocyte subsets were analyzed into two groups in the first 24 h after admission and compared by Student’s t-test. A multivariable logistic analysis was performed to identify independent risk factors associated with in-hospital mortality. Total lymphocyte count and CD3+ and CD4+ CD8+ T lymphocyte subsets were significantly lower in non-survivors. Serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein (CRP) and procalcitonin (PCT) were significantly higher in non-survivors. Age > 65 years and presence of comorbidities were identified as independent risk factors associated with in-hospital mortality, while IL-6 and LDH showed a borderline significance. According to our results, markers of inflammation and lymphocytopenia predict in-hospital mortality in COVID-19.

Background and Objectives: Nutraceuticals are gaining more and more importance as a knee osteoarthritis (KOA) complementary treatment. Among nutraceuticals, hemp seed oil and terpenes are proving to be very useful as therapeutic support for many chronic diseases, but there are still few studies regarding their effectiveness for treating KOA, both in combination and separately. The aim of this study is thus to compare the effect of two dietary supplements, both containing hemp seed oil, but of which only one also contains terpenes, in relieving pain and improving joint function in patients suffering from KOA. Materials and Methods: Thirty-eight patients were recruited and divided into two groups. The control group underwent a 45 day treatment with a hemp seed oil-based dietary supplement, while the treatment group assumed a hemp seed oil and terpenes dietary supplement for the same period. Patients were evaluated at the enrollment (T0) and at the end of treatment (T1). Outcome measures were: Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), Short-Form-12 (SF-12), Knee Injury Osteoarthritis Outcome Score (KOOS), and Oxford Knee Score (OKS). Results: All outcome measures improved at T1 in both groups, but NRS, KOOS and OKS had a greater significant improvement in the treatment group only. Conclusions: Hemp seed oil and terpenes resulted a more effective integrative treatment option in KOA, improving joint pain and function and representing a good complementary option for patients suffering from osteoarthritis.

Synovial fluid (SF) is a viscous and mucinous substance produced by the synovium, a specialized connective tissue that lines diarthrodial joints. SF represents a source of disease-related proteins that could be used as potential biomarkers in several articular diseases. Based on these findings the study of SF has been gaining increasing importance, in recent years. This review aims to summarize the usefulness of synovial fluid in orthopaedics research and clinical practice, mainly focusing on osteoarthritis (OA) and periprosthetic joint infections (PJIs). Proteomics of the SF has shown the up-regulation of several components of the classic complement pathway in OA samples, including C1, C2, C3, C4A, C4B, C5, and C4 C4BPA, thus depicting that complement is involved in the pathogenesis of OA. Moreover, proteomics has demonstrated that some pro-inflammatory cytokines, namely IL-6, IL-8, and IL-18, have a role in OA. Several SF proteins have been studied to improve the diagnosis of PJIs, including alpha-defensin (Alpha-D), leukocyte esterase (LE), c-reactive protein (CRP), interleukin-6 (IL-6), calprotectin and presepsin. The limits and potentials of these SF biomarkers will be discussed.

l-Carnitine is an amino acid derivative widely known for its involvement in the transport of long-chain fatty acids into the mitochondrial matrix, where fatty acid oxidation occurs. Moreover, l-Carnitine protects the cell from acyl-CoA accretion through the generation of acylcarnitines. Circulating carnitine is mainly supplied by animal-based food products and to a lesser extent by endogenous biosynthesis in the liver and kidney. Human muscle contains high amounts of carnitine but it depends on the uptake of this compound from the bloodstream, due to muscle inability to synthesize carnitine. Mitochondrial fatty acid oxidation represents an important energy source for muscle metabolism particularly during physical exercise. However, especially during high-intensity exercise, this process seems to be limited by the mitochondrial availability of free l-carnitine. Hence, fatty acid oxidation rapidly declines, increasing exercise intensity from moderate to high. Considering the important role of fatty acids in muscle bioenergetics, and the limiting effect of free carnitine in fatty acid oxidation during endurance exercise, l-carnitine supplementation has been hypothesized to improve exercise performance. So far, the question of the role of l-carnitine supplementation on muscle performance has not definitively been clarified. Differences in exercise intensity, training or conditioning of the subjects, amount of l-carnitine administered, route and timing of administration relative to the exercise led to different experimental results. In this review, we will describe the role of l-carnitine in muscle energetics and the main causes that led to conflicting data on the use of l-carnitine as a supplement.

Background: Malnutrition-inflammation complex syndrome (MICS) is a common and usually concurrent condition occurring in patients undergoing hemodialysis (HD), with a pathogenesis linked to biological and in situ environmental traditional risk factors. Periodontitis, one of the major types of infection-driven inflammation, often co-occurs in the in the hemodialysis population and correlates with markers of malnutrition and inflammation, such as albumin, creatinine, and C-reactive protein. Aim: The present study aimed to determine whether the periodontal inflammatory status parameters correlate with the albumin, creatinine, and C-reactive protein serum concentrations in HD patients, and investigate whether periodontal treatment improves these markers of nutritional and systemic inflammation. Materials and Methods: The serum creatinine, albumin, and C-reactive Protein (CRP) levels were measured at baseline and after non-surgical periodontal treatment, at 3 months and 6 months. Results: At 3 months, a significant correlation between plaque index and C-reactive protein (p = 0.012), bleeding on probing and C-reactive protein (p < 0.0019), and clinical attachment level and C-reactive protein (p = 0.022) was found. No significant correlation was found between clinical periodontal parameters and nutrition markers at each time. Conclusions: Our results confirmed the association between C-reactive protein serum concentration and periodontal inflammatory status, but further research is necessary to identify the contributing role of periodontitis on the onset and progression of MICS.

The few therapeutic strategies for advance hepatocellular carcinoma (HCC) on poor knowledge of its biology. For several years, sorafenib, a tyrosine kinase inhibitors (TKI) inhibitor, has been the approved treatment option, to date, for advanced HCC patients. Its activity is the inhibition of the retrovirus-associated DNA sequences protein (RAS)/Rapidly Accelerated Fibrosarcoma protein (RAF)/mitogen-activated and extracellular-signal regulated kinase (MEK)/extracellular-signal regulated kinases (ERK) signaling pathway. However, the efficacy of sorafenib is limited by the development of drug resistance, and the major neuronal isoform of RAF, BRAF and MEK pathways play a critical and central role in HCC escape from TKIs activity. Advanced HCC patients with a BRAF mutation display a multifocal and/or more aggressive behavior with resistance to TKI. Moreover, also long non-coding RNA (lnc-RNA) have been studied in epigenetic studies for BRAF aggressiveness in HCC. So far, lnc-RNA of BRAF could be another mechanism of cancer proliferation and TKI escape in HCC and the inhibition could become a possible strategy treatment for HCC. Moreover, recent preclinical studies and clinical trials evidence that combined treatments, involving alternative pathways, have an important role of therapy for HCC and they could bypass resistance to the following TKIs: MEK, ERKs/ribosomal protein S6 kinase 2 (RSK2), and phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR). These initial data must be confirmed in clinical studies, which are currently ongoing. Translational research discoveries could create new strategies of targeted therapy combinations, including BRAF pathway, and they could eventually bring light in new treatment of HCC.

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70−80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standard care for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results in an alternative first-line treatment for the Chinese clinical oncology guidelines. Moreover, nivolumab and pembrolizumab, two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approved for subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessment of new ICIs-based combinatory approaches.

Immune suppressed renal transplant patients are more prone to developing oral tissue alterations due to medications associated with a pleiotropic set of side effects involving the oral cavity. Drug-induced gingival overgrowth (DIGO) is the most commonly encountered side effect resulting from administration of calcineurin inhibitors such as cyclosporine-A (CsA), the standard first-line treatment for graft rejection prevention in transplant patients. Pathogenesis of gingival overgrowth (GO) is determined by the interrelation between medications and a pre-existing inflammatory periodontal condition, the main modifiable risk factor. Severity of gingival hyperplasia clinical manifestation is also related to calcium channel blocker association, frequently provided in addition to pharmacological therapy of transplant recipients. Specifically, nifedipine-induced enlargements have a higher prevalence rate compared to amlodipine-induced enlargements; 47.8% and 3.3% respectively. Available epidemiological data show a gender difference in prevalence, whereby males are generally more frequently affected than females. The impact of GO on the well-being of an individual is significant, often leading to complications related to masticatory function and phonation, a side effect that may necessitate switching to the tacrolimus drug that, under a similar regimen, is associated with a low incidence of gingival lesion. Early detection and management of GO is imperative to allow patients to continue life-prolonging therapy with minimal morbidity. The purpose of this study was threefold: firstly, to determine the prevalence and incidence of GO under the administration of CsA and Tacrolimus; secondly, to assess the correlation between periodontal status before and after periodontal therapy and medications on progression or recurrence of DIGO; and finally, to analyse the effect of immunosuppressant in association to the channel blocker agents on the onset and progression of gingival enlargement. We compared seventy-two renal transplant patients, including 33 patients who were receiving CsA, of which 25% were also receiving nifedipine and 9.72% also receiving amlodipine, and 39 patients who were receiving tacrolimus, of which 37.5% were also receiving nifedipine and 5.55% also receiving amlodipine, aged between 35 and 60 years. Medical and pharmacological data were recorded for all patients. Clinical periodontal examination, in order to establish the inflammatory status and degree of gingival enlargement, was performed at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3). All patients were subjected to periodontal treatment. Statistically significant correlation between the reduction of the mean value of periodontal indices and degree of gingival hyperplasia at the three times was revealed. The prevalence of GO in patients taking cyclosporine was higher (33.3%) in comparison with those taking tacrolimus (14.7%). In accordance with previous studies, this trial highlighted the clinical significance of the pathological substrate on stimulating drug-induced gingival lesion, confirming the key role of periodontal inflammation in pathogenesis of gingival enlargement, but did not confirm the additional effect of calcium-channel blocker drugs in inducing gingival enlargement.

This study aimed to evaluate the combined use of the Concentrated Growth Factor (CGF) and the liquid phase of CGF (LPCGF) on dental implant surfaces, using a medical device to determine the migration of growth factors, from the implant surface to the recipient. The implants were permeated by autologous growth factors, using a specific centrifuge device. CGF adhesion on the implant surface was evaluated through a scanning electron microscope analysis. To assess the release of the vascular endothelial growth factor (VEGF) from CGF, LPCGF, and CGF- or LPCGF-permeated implant, an ELISA assay was carried out. The results showed that the concentration of the growth factor VEGF was greater in CGF than in LPCGF. Our innovative technique allowed the incorporation of autologous growth factors on the surface of the dental implants. Moreover, we reported the release of VEGF, over time, by CGF- or LPCGF-permeated implant. On this basis, it was possible to obtain a biologically active implant surface, essential to create intercellular communication and neo-angiogenesis, to facilitate wound healing and tissue regeneration.