[Second Report on Italian Sea Workers: Activities and risk factors]. / Secondo rapporto sui lavoratori marittimi: attività e fattori di rischio.

This is a summary of the results of a research work, born from a collaboration between multiple Italian bodies and published by the Italian Workers' Compensation Authority (Inail) in March 2024: Second report on maritime workers. Activities and risk factors of sea workers.To disseminate the contents, the work offers a global overview of safety and health in the sector: with an analysis of accidents in the sector (which also involves some remarks on the event reporting form), workers' risk perception is examined and occupational diseases monitored through the MalProf system, managed by the Inail Research Sector and the local health authorities. Finally, an in-depth study is dedicated to exposure to asbestos on ships.

Management Approaches to Health and Safety at Work during Prevention Intervention Planning.

This work deals with a systematic review of the literature data concerning the theme of integrated approaches to occupational health and safety management, with particular reference to the programming of assistance plans, which guide companies' organizational choices by also addressing the principles of Total Worker Health. In the current regulatory framework on this issue, the UNI ISO 45001: 2018 standard "Occupational health and safety management systems-Requirements and guidance for use" (published on 12 March 2018)" assumes relevance, defining dynamic approaches to occupational health and safety management systems-paying particular attention to external contextual factors that may influence corporate organizational decisions. The adoption of these systems is not mandatory but allows companies to fulfill their duties in terms of health and safety at work through an organizational approach aimed at the awareness, involvement, and participation of all subjects of the company prevention system, progressing past the phase of mere technological and prescriptive approaches towards a holistic vision of prevention that places the person at the center of preventive actions. In this context, the role of institutional networks and socio-economic partnerships assumes particular importance via the activation of territorial assistance interventions to support companies aimed at improving risk management levels. To this end, the importance of verifying the effectiveness of assistance interventions emerges from the scientific debate using indicators such as quantitative indicators aimed at measuring the performance of all phases of an intervention, with particular attention to their effects in terms of the improved solutions developed.

Endocan Promotes Pro-Tumorigenic Signaling in Lung Cancer Cells: Modulation of Cell Proliferation, Migration and lncRNAs H19 and HULC Expression.

Endocan is a circulating proteoglycan secreted by several cell lines and identified as a potential biomarker of inflammation and angiogenesis. Endocan-increased expression has been found in a broad spectrum of human tumors, including lung cancer, and is associated with a poor prognosis. To elucidate the possible mechanism, this study aimed to investigate the role of endocan in non-small-cell lung carcinoma (NSCLC) using an in vitro model of cultured cells. Endocan expression was knocked down by using a specific small interfering RNA. The effects of endocan knockdown have been evaluated on VEGF-A, VEGFR-2, HIF-1α, the long non-coding RNAs H19 and HULC expression, and AKT and ERK 1/2 degree of activation. Cell migration and proliferation have been studied as well. VEGF-A, VEGFR-2, HIF-1α, and the long non-coding RNAs H19 and HULC expression were significantly affected by endocan knockdown. These effects correlated with a reduction of cell migration and proliferation and of AKT and ERK 1/2 activation. Our findings suggest that endocan promotes a more aggressive cancer cell phenotype in NSCLC.

Endocan Knockdown Down-Regulates the Expression of Angiogenesis-Associated Genes in Il-1ß Activated Chondrocytes.

Endocan is a small soluble proteoglycan (PG) known to be involved in inflammation and angiogenesis. Increased endocan expression was found in the synovia of arthritic patients and chondrocytes stimulated with IL-1ß. Considering these findings, we aimed to investigate the effects of endocan knockdown on the modulation of pro-angiogenic molecules expression in a model of IL-1ß-induced inflammation in human articular chondrocytes. Endocan, VEGF-A, MMP-9, MMP-13, and VEGFR-2 expression was measured in both normal and endocan knockdown chondrocytes stimulated with IL-1ß. VEGFR-2 and NF-kB activation were also measured. Results have shown that endocan, VEGF-A, VEGFR-2, MMP-9, and MMP-13 were significantly up-regulated during IL-1ß-induced inflammation; interestingly, the expression of such pro-angiogenic molecules and NF-kB activation were significantly reduced by endocan knockdown. These data support the hypothesis that endocan released by activated chondrocytes may be involved in the mechanisms that stimulate cell migration and invasion, as well as angiogenesis, in the pannus of arthritic joints.

Drinking Water Supply in the Region of Antofagasta (Chile): A Challenge between Past, Present and Future.

Since the mid-nineteen century, when the first mining companies were established in the region of Antofagasta to extract saltpeter, mining managers and civil authorities have always had to face a number of problems to secure a water supply sufficient for the development of industrial activities and society. The unique features of the region, namely the scarcity of rainfall, the high concentration of arsenic in freshwaters and the increasing pressure of the mining sector, have made the supply of drinking water for local communities a challenge. In the 1950s, the town of Antofagasta experienced a serious drinking water crisis. The 300 km long aqueduct starting from the Toconce catchment, opened in 1958, temporarily ended this shortage of drinking water but created an even more dramatic problem. The concentration of arsenic in the water consumed by the population had grown by approx. ten times, reaching the value of 0.860 mg/L and seriously affecting people's health. The water treatment plants (WTPs) which were installed starting from the 1970s in the region (namely the Old and New Salar del Carmen in Antofagasta and Cerro Topater in Calama, plus the two recent desalination plants in Antofagasta and Tocopilla), have ensured, since 2014, that the drinking water coverage in the urban areas was practically universal (>99.9%). However, the rural areas have continued to experience significant shortcomings regarding their capacity to ensure the quality and continuity of the water supply service in the long run. Presently, approx. 42% of the rural population of the region of Antofagasta does not have a formal supply of drinking water. The recent amendments to the Chilean Water Code (March 2022) and the interventions carried out in the framework of the Agua Potable Rural (APR) program were intended to reduce the socio-ecological inequalities due to the lack of drinking water in the semi-concentrated and isolated rural population.

Corrigendum: Exploiting curcumin synergy with natural products using quantitative analysis of dose-effect relationships in an experimental in vitro model of osteoarthritis.

[This corrects the article DOI: 10.3389/fphar.2019.01347.].

Drug-Induced Photosensitivity: Clinical Types of Phototoxicity and Photoallergy and Pathogenetic Mechanisms.

Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, mostly ultraviolet A, with drugs. DIP includes phototoxicity and photoallergy. A phototoxic reaction is obtained when topical and systemic drugs or their metabolites absorb light inducing a direct cellular damage, while a photoallergic reaction takes place when the interaction between drugs and ultraviolet radiations causes an immune cutaneous response. Clinically, phototoxicity is immediate and appears as an exaggerated sunburn, whereas photoallergy is a delayed eczematous reaction. DIP may show several clinical subtypes. In this mini-review we report the pathogenetic mechanisms and causative drugs of DIP. We offer a detailed description of DIP clinical features in its classical and unusual subtypes, such as hyperpigmentation/dyschromia, pseudoporphyria, photo-onycolysis, eruptive teleangiectasia, pellagra-like reaction, lichenoid reaction, photodistributed erythema multiforme and subacute/chronic cutaneous lupus erythematosus. We described how physicians may early recognize and manage DIP, including diagnostic tests to rule out similar conditions. We made suggestions on how to improve sun exposure behaviors of patients at risk of DIP by means of an aware use of sunscreens, protective clothing and recent technologic tools. We highlighted the lack of sun safety programs addressed to patients at risk of DIP, who need a formal education about their condition.

Prevention from Sharp Injuries in the Hospital Sector: An Italian National Observatory on the Implementation of the Council Directive 2010/32/EU before and during the COVID-19 Pandemic.

Sharp injuries, determining the risk of bloodborne infections and psychological distress in healthcare workers, may be prevented by a set of strategies, legally enforced in Europe through the Directive 2010/32/EU. To assess its level of implementation in Italy, a national survey was conducted in 2017 and again in 2021, evaluating the progress and possible drawbacks of the COVID-19 pandemic. Altogether, 285 safety managers and 330 nurses from a representative sample of 97 and 117 public hospitals were interviewed using a standardized questionnaire. Knowledge of the Directive requirements decreased significantly, with <60% of participants answering correctly in 2021, and nurses' attendance in specific courses dropped to 25% in 2021 compared to 54% in 2017. Over 75% of hospitals introduced multiple safety-engineered devices (SED), though total replacement occurred in <50% of cases; routine SED availability increased for blood collection (89%) and venous access devices (83%). Incorrect behaviors in handling sharps decreased significantly over time. Nurses' HBV vaccination coverage was high (89% in both surveys); in the last year, 97% were vaccinated against COVID, and 47% against influenza. Average annual injuries per hospital did not increase significantly (32 in 2021 vs. 26 in 2017). In 2017, nurses' perceived safety barriers were working in emergency situations (49%) and lack of resources (40%); in 2021, understaffing (73%), physical fatigue (62%), and handling difficulties while wearing full protective equipment (59%). Safety measures were implemented in Italian hospitals, and although the average injuries per hospital did not show a decrease, these measures could have helped protect healthcare workers during the pandemic, mitigating its potential impact on the increase in situations at risk of injury.

miR9 inhibits 6-mer HA-induced cytokine production and apoptosis in human chondrocytes by reducing NF-kB activation.

The present study aimed to investigate the expression of miR9 and its correlation with cytokines, proteolytic enzymes and apoptosis in an experimental model of 6-mer HA induced inflammation in human chondrocytes. Human articular chondrocytes, transfected with a miR-9 mimic and miR-9 inhibitor, were stimulated with 6-mer HA in presence/absence of a specific NF-kB inhibitor. 6-mer HA induced a significant increase of TLR-4, CD44, IL-8, IL-18, MMP-9, ADAMTS-5, BAX and BCL-2 mRNAs expression and the related proteins, as well as NF-kB activation, associated with a significant up regulation of miR-9. In chondrocytes transfected with the miR-9 mimic before 6-mer HA treatment we found a decrease of such inflammatory cytokines, metalloproteases and pro-apoptotic molecules, while we found them increased in chondrocytes transfected with the miR9 inhibitor before 6-mer HA stimulation. The activities of TLR-4 and CD44, up regulated by 6-mer HA, were not modified by miR9 mimic/inhibitor, while the NF-kB activation was significantly affected. We suggested that the up regulation of miR9, induced by 6-mer HA, could be a cellular attempt to limit cell damage during inflammation.

Expression and Change of miRs 145, 221 and 222 in Hypertensive Subjects Treated with Enalapril, Losartan or Olmesartan.

miR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeutic approach. We aimed to evaluate if anti-hypertensive drugs enalapril, losartan or olmesartan have effects on monocyte miR profile in essential hypertensives without target organ involvement. For this purpose, 82 hypertensives and 49 controls were included; we evaluated SBP/DBP, lipid profile, glucose, CRP, fibrinogen, arterial stiffness indices (PWV; AIx), and cIMT at baseline (T0) and after 24 weeks of treatment (T1). Subjects with LDL-C ≥ 160 mg/dL, TG ≥ 200 mg/dL, BMI ≥ 30, and other additional CV risk factors were excluded. Patients who were prescribed to receive once-a-day enalapril 20 mg, losartan 100 mg or olmesartan 20 mg were eligible for the study. At T1, we found a significant improvement of SBP (-18.5%), DBP (-18%), HDL-C and LDL-C (+3% and -5.42%), glucose (-2.15%), BMI (-3.23%), fibrinogen (-11%), CRP (-17.5%,), AIx (-49.1%) PWV (-32.2%), and monocyte miR expression (miR-221: -28.4%; miR-222: -36%; miR-145: +41.7%) with respect to baseline. miR profile was compared to control subjects at baseline and at T1. We found some little difference in the behaviour of the three treatments on some variables: olmesartan was the most effective in reducing fibrinogen, DBP, CRP, and AIx (-13.1%, -19.3%, -21.4%, and -56.8%, respectively). Enalapril was the drug more significantly increasing the expression of miR-145. In conclusion, enalapril, losartan and olmesartan are effective in improving mechanical and humoral factors associated to AS and atherogenesis. These drugs appear to be able to modify miRs 221/222 and miR-145 expression in drug-naïve hypertensives, making it closer to that of control subjects; additionally, this provides a good blood pressure compensation, contributing to slow the progression of vascular damage.

Production and Destination of Sewage Sludge in the Piemonte Region (Italy): The Results of a Survey for a Future Sustainable Management.

The management of sewage sludge originated from municipal wastewater treatment plants (WWTPs) is an urgent issue. In 2019, the local authority of the Piemonte region started a survey with the aim of collecting recent data concerning wastewater and sludge management in the WWTPs located in its own territory. The survey's results revealed that 60% of the sludge (51,000 t, as dry substance, d.s.) produced by the local WWTPs was recovered or disposed of outside of the region, and a similar amount of sludge was recovered in agriculture directly or after composting. The increase in the costs to accommodate sewage sludge in recovery or disposal plants, followed to a recent Italian Sentence (27958/2017), and the more and more stringent requirements fixed by lots of European countries for the application of sludge in agriculture, are pushing the Piemonte region authority to re-organize its own network for sludge management, with solutions based onto proximity and diversification. Whether the provisions of the current German legislation are applied in the future also in Italy, approx. 90% of sewage sludge produced into the Piemonte region should be incinerated, with a subsequent step of phosphorous recovery. The new regional plan, according to the Regional Address Deed, should consider a diversification of sludge treatment and recovery practices. On this basis, a need for new plants for around 40,000 t d.s./y could be planned.

Endocan, a novel inflammatory marker, is upregulated in human chondrocytes stimulated with IL-1 beta.

Endocan is a circulating proteoglycan, involved in immunity, inflammation, and endothelial function. It has been recently suggested as a biomarker of inflammation, increased angiogenesis, and cancer. In vitro studies have shown that endocan expression could be upregulated by inflammatory cytokines and proangiogenic molecules. High endocan levels were also shown in arthritic joint tissues and particularly in sites characterized by severe inflammation. This study was performed to evaluate endocan expression in chondrocytes stimulated with IL-ß. mRNA and related protein production were measured for endocan, TNF-α, and IL-6. NF-kB activity was also evaluated. IL-1ß treatment induced a significant upregulation of both endocan and the inflammatory parameters as well as NF-kB activity. The treatment of chondrocytes with the specific NF-kB inhibitor before IL-1ß stimulation was able to reduce endocan and the inflammatory markers over-expression. The results of our study indicated that endocan is also expressed in human chondrocytes; furthermore, consistent with previous results in other cell types and tissues, IL-1ß-induced inflammatory response involves the expression of endocan through NF-kB activation. In this context, endocan seems to be an important inflammatory marker associated with the activation of NF-kB pathway.

miR146a up-regulation is involved in small HA oligosaccharides-induced pro-inflammatory response in human chondrocytes.

BACKGROUND: Small HA fragments are produced during cartilage degradation and their role seems to be preponderant during pathologies in which cartilage injury contribute to trigger and perpetuate the inflammatory mechanism. Several reports have increasingly shown that MicroRNAs (miRs), a small non-coding mRNAs are involved in the regulation of multiple biological processes, including cell proliferation and inflammation response in different pathologies, among them miR146a seems to be involved in inflammatory processes. METHODS: Starting by these evidences we investigated the levels of miR146a and its correlation with inflammatory mediators in an experimental model of 6-mer HA-induced inflammatory response in human cultured chondrocytes. RESULTS: Treatment of chondrocytes with 6-mer HA showed up-regulation in inflammation parameters such as TLR-4, and CD44 receptors activation, IL-6, IL-1ß and MMP-13 mRNA expression and proteins production, as well as NF-kB activation. We also revealed an up-regulation of miR146a. Transfection with a miR146a mimic or miR146a inhibitor produced the following effects: chondrocytes receiving miR146a mimic and then 6-mer HA significantly reduced inflammatory cytokines and MMP-13, while exposition of chondrocytes with miR146a inhibitor and then the 6-mer HA incremented the activity of damaging cytokines and MMP13. Expression of CD44 receptor was not affected by miR-146a treatments, while TLR-4 expression and NF-kB activation were modified. CONCLUSIONS: We concluded that up-regulation of miR146a occurred in 6-mer HA-induced inflammation response may reduce the inflammatory cascade by modulating TLR-4 and NF-kB activation. GENERAL SIGNIFICANCE: These results could be useful in develop new therapeutic strategies with the aim to reduce OA and RA incidence.

The Italian National Surveillance System for Occupational Injuries: Conceptual Framework and Fatal Outcomes, 2002-2016.

Background: A national database of work-related injuries has been established in Italy since 2002, collecting information on the injured person, his/her work tasks, the workplace and the risk factors contributing to incident dynamics, according to a model called Infor.Mo. Methods: A descriptive study of occupational fatal injuries, excluding work-related fatal traffic injuries, that occurred in Italy from 2002 to 2016 (15 years) was performed. Results: Among 4874 victims involved, all were males, mainly >51 years of age (43.2%), predominantly self-employed (27.8%) or workers with non-standard contracts (25%). About 18.4% and 17.3% of fatal events occurred in micro-enterprises belonging to, respectively, construction and agriculture. A wide range of nationalities (59 countries in addition to Italy) was identified. Overall, 18.9% of work-related fatal injuries were due to some form of hazardous energy-mechanical, thermal, electrical or chemical-that was normally present in the workplace. Workers' falls from height (33.5%), heavy loads falling on workers from height (16.7%) and vehicles exiting their route and overturning (15.9%) were the events causing the greatest proportion of occupational fatal injuries in the present study (from 2002 to 2016) and in the initial pilot phase, focused on years 2002-2004, with a similar distribution of fatal events between the two time periods. The activity of the injured person made up 43.3% of 9386 risk factors identified in 4874 fatalities. Less common risk factors were related to work equipment (20.2%), work environment (14.9%), third-party activity (9.8%), personal protective equipment/clothing (8.0%) and materials (3.7%). The activity of the injured person remained the most relevant contributing factor even when the incident was caused by two or more risk factors. Discussion: Occupational fatal injuries occurred mainly in small size firms (up to nine employees) in hazardous workplaces. Small companies, which account for 68% (2888/4249) of all firms in the present study, generally have fewer resources to remain current with the continuously evolving health and safety at work regulations; moreover, these firms tend to be less compliant with health and safety at work regulations since they are less likely to be inspected by occupational vigilance services. Perspectives: An approach being introduced in Italy relies on the use of economic incentives to promote safe and healthy workplaces. The comparison of pre-intervention and post-intervention rates of work-related injuries by means of interrupted time series analyses could detect whether the intervention will have an effect significantly greater than the underlying secular trend.

Hyaluronan oligosaccharides modulate inflammatory response, NIS and thyreoglobulin expression in human thyrocytes.

Autoimmune thyroid diseases, such as Hashimoto's thyroiditis, are characterized by lymphocytic infiltration and altered function of the thyroid. During inflammation, it has been reported a decreased expression in Tg and NIS, accompanied by an increase in HA production that accumulates in the gland. HA fragments produced in different pathological states can modulate gene expression in a variety of cell types and may prime inflammatory response by interacting with the TLR-2, TLR-4 and CD44 that, in turn, induce NF-kB activation finally responsible of inflammatory mediator transcription, such as IL-1ß, TNF-α and IL-6. The aim of this study was to investigate the potential inflammatory effect and the biochemical pathways activated by 6-mer HA oligosaccharides in cultured human thyrocytes. 6-mer HA treatment induced up-regulation of TLR-2, TLR-4, CD44 mRNA and related protein levels, increased HA production and NF-kB activation, that in turn increased IL-1ß and IL-6 concentrations. Instead, we found evidence of an opposite effect on thyroid specific-gene Tg and NIS, that were decreased after 6-mer HA addition. Thyrocytes exposition to specific blocking antibodies for TLR-2, TLR-4 and CD44 abolished up-regulation of NF-κB activation and the consequent pro-inflammatory cytokine production, while restored Tg and NIS levels. A further goal of this study was demonstrate that also other LMW HA have pro inflammatory proprieties. These data suggest that HA fragments, through the involvement of TLR-2, TLR-4 and CD44 signaling cascade, contribute to prime the inflammatory response in thyrocytes and, by reducing the expression of thyroid-specific genes, could promote the loss of function of gland such as in Hashimoto's thyroiditis.

Evaluation of Green Coffee-Roasting Biogas with Modeling Valorization of Possible Solutions.

According to the European Union Directive 2009/28/EC, the goals of obtaining 20% of all energy requirements from renewable sources and a 20% reduction in primary energy use must be fulfilled by 2020. In this work, an evaluation was performed, from the environmental and energy point of view, of anaerobic digestion as a valid solution for the treatment of the byproducts obtained from the coffee-roasting process. In particular, thermophilic anaerobic digestion tests were carried out. Output values from the laboratory were used as input for the MCBioCH4 model to evaluate the produced flow of biogas and biomethane and two different biogas valorization alternatives, namely, the traditional exploitation of biogas for heat/energy production and biomethane conversion. The results of the preliminary simulation showed that a full-scale implementation of the coffee waste biogas production process is technically feasible and environmentally sustainable. Furthermore, the performed analysis validates a general methodology for energy production compatibility planning.

Hyaluronan Fragmentation During Inflammatory Pathologies: A Signal that Empowers Tissue Damage.

The mechanisms that modulate the response to tissue injury are not fully understood. Abnormalities in the repair response are associated with a variety of chronic disease states characterized by inflammation, followed subsequently by excessive ECM deposition. As cell-matrix interactions are able to regulate cellular homeostasis, modification of ECM integrity appears to be an unspecific factor in promoting the onset and progression of inflammatory diseases. Evidence is emerging to show that endogenous ECM molecules supply signals to damage tissues and cells in order to promote further ECM degradation and inflammation progression. Several investigations have been confirmed that HA fragments of different molecular sizes exhibit different biological effects and responses. In fact, the increased deposition of HA into the ECM is a strong hallmark of inflammation processes. In the context of inflammatory pathologies, highly polymerized HA is broken down into small components, which are able to exacerbate the inflammatory response by inducing the release of various detrimental mediators such as reactive oxygen species, cytokines, chemokines and destructive enzymes and by facilitating the recruitment of leukocytes. However, strategies involving the modulation of the HA fragment with specific receptors on cell surface could represent different promising effects for therapeutic scope. This review will focus on the inflammation action of small HA fragments in recent years obtained by in vivo reports.

Biglycan and atherosclerosis: Lessons from high cardiovascular risk conditions.

Atherosclerosis (ATH) is a chronic, dynamic, evolutive process involving morphological and structural subversion of artery walls, leading to the formation of atherosclerotic plaques. ATH generally initiates during the childhood, occurring as a result of a number of changes in the intima tunica and in the media of arteries. A key event occurring during the pathobiology of ATH is the accumulation of lipoproteins in the sub-intimal spaces mediated by extracellular matrix (ECM) molecules, especially by the chondroitin sulfate/dermatan sulfate (CS/DS) -containing proteoglycans (CS/DSPGs). Among them, the proteoglycan biglycan (BGN) is critically involved in the onset and progression of ATH and evidences show that BGN represents the missing link between the pro-atherogenic status induced by both traditional and non-traditional cardiovascular risk factors and the development and progression of vascular damage. In the light of these findings, the role of BGN in dyslipidemia, hypertension, cigarette smoking, diabetes, chronic kidney disease and inflammatory status is briefly analyzed and discussed in order to shed new light on the underlying mechanisms governing the association between BGN and ATH.

Exploiting Curcumin Synergy With Natural Products Using Quantitative Analysis of Dose-Effect Relationships in an Experimental In Vitro Model of Osteoarthritis.

Introduction: Drug combination is widely used to treat chronic inflammatory diseases. A similar strategy might be worth of interest to design plant-derived natural products to treat inflammatory conditions. Curcumin is a natural phenolic compound which shares anti-inflammatory activity with both flavocoxid, a flavonoid mixture of baicalin and catechin, and ß-caryophyllene, a bicyclic sesquiterpene. The aim of this study was to investigate the synergy potential of curcumin with both flavocoxid and ß-caryophyllene in human articular chondrocytes triggered with lipopolysaccharide (LPS), in an experimental in vitro model of osteoarthritis. Materials and Methods: Human articular chondrocytes were stimulated with LPS alone or in combination with different treatments. Total RNA was extracted 4 h after treatment to study interleukin 1ß (IL-1ß), NF-κB, and STAT3 mRNA expression. A drug combination study was designed choosing 5 doses to demonstrate a synergistic effect of compounds, according to Chou and Talalay method. A median-effect equation was applied and finally, the combination index (CI) was used to clarify the nature of the compounds interaction (synergistic versus additive versus antagonistic inhibitory effects); CI < 1, CI = 1, and CI > 1 indicated synergistic, additive, and antagonistic effects, respectively. Results: LPS prompted IL-1ß expression. Curcumin, flavocoxid and ß-caryophyllene suppressed IL-1ß expression with different IC50. A synergistic action for the reduction of the inflammatory phenotype in human chondrocytes was observed for the combination curcumin-flavocoxid with a percentage from 10% to 90%, and for the combination curcumin-ß-caryophyllene from 50% to 90%. IC50 doses of either flavocoxid, ß-caryophyllene and curcumin alone or in combination were safe and did not affect cell vitality. Moreover, the same IC50 doses reduced the transcription factors NF-κB and STAT3 mRNA expression and interestingly the effects of the combinations were greater than the natural products alone, thus suggesting that the site where the synergy takes place could be at the signal transduction level. Discussion: The results suggest that curcumin synergizes with either flavocoxid or ß-caryophyllene, exerting an anti-inflammatory activity and thus strongly suggesting the potential of a dual combination of these compounds for the management of osteoarthritis and unmasking a new feature of these natural products.