Encorafenib and binimetinib followed by radiotherapy for patients with BRAFV600-mutant melanoma and brain metastases (E-BRAIN/GEM1802 phase II study).

BACKGROUND: Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. METHODS: E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression.Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. RESULTS: The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). CONCLUSION: Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.

Corrigendum to "Towards generalization for Caenorhabditis elegans detection" [Comput Struct Biotechnol J 21 (2023) 4914-4922].

[This corrects the article DOI: 10.1016/j.csbj.2023.09.039.].

Changes in alcohol consumption during the COVID-19 among First-Year University Students in Spain, considering the risk of problematic use - UniHcos Project.

The aim of this study was to evaluate the possible impact of the COVID-19 pandemic on prevalence rates and self-reported changes in patterns of alcohol use among first-year university students in Spain, considering the risk of problematic alcohol use. A serial cross-sectional study based on the uniHcos project was carried out. Data from 10,518 first-year university students (73.3% female, mean age 19 (SD=1.6)) collected between 2012 and 2022 were analysed. The evolution of the pooled prevalence rates during the time series was analysed and the risk of problematic alcohol consumption was assessed using the AUDIT. Also, self-reported changes in alcohol use patterns during the pandemic were assessed. According to the results, during the COVID-19 pandemic, the prevalence of alcohol use in the past 30-days was reduced (76.3% in 2019 vs. 63.7% in COVID-19) and increased again in the New Normal period. Thus, a similar pattern in the practice of binge drinking was observed. Regarding the AUDIT score, 21.7% (95%CI 20.9, 22.6) of the students had harmful alcohol consumption, with a higher proportion among males. In the multivariable logistic models, a higher AUDIT score was significantly associated (p-value<0.001) with being male and living with roommates. According to self-reported changes in consumption patterns during the COVID-19 pandemic, a higher proportion of participants with harmful use reported an increase in alcohol consumption compared to those at low-risk (43% vs 19%). Finally, despite the overall reduction in drinking prevalence during COVID-19, changes were not equal for all students and depended on their previous level of problematic drinking, highlighting that this should be considered in the development of strategies against alcohol use in this population.

Water availability and extreme events under climate change scenarios in an experimental watershed of the Brazilian Atlantic Forest.

Climate change has diversified negative implications on environmental sustainability and water availability. Assessing the impacts of climate change is crucial to enhance resilience and future preparedness particularly at a watershed scale. Therefore, the goal of this study is to evaluate the impact of climate change on the water balance components and extreme events in Piabanha watershed in the Brazilian Atlantic Forest. In this study, extreme climate change scenarios were developed using a wide array of global climate models acquired from the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Reports (AR6). Two extreme climate change scenarios, DryHot and WetCool, were integrated into the Soil and Water Assessment Tools (SWAT) hydrological model to evaluate their impacts on the hydrological dynamics in the watershed. The baseline SWAT model was first developed and evaluated using different model performance evaluation metrics such as coefficient of determination (R2), Nash-Sutcliffe (NSC), and Kling-Gupta efficiency coefficient (KGE). The model results illustrated an excellent model performance with metric values reaching 0.89 and 0.64 for monthly and daily time steps respectively in the calibration (2008 to 2017) and validation (2018 to 2023) periods. The findings of future climate change impacts assessment underscored an increase in temperature and shifts in precipitation patterns. In terms of streamflow, high-flow events may experience a 47.3 % increase, while low-flows could see an 76.6 % reduction. In the DryHot scenario, annual precipitation declines from 1657 to 1420 mm, with evapotranspiration reaching 54 % of precipitation, marking a 9 % rise compared to the baseline. Such changes could induce water stress in plants and lead to modifications on structural attributes of the ecosystem recognized as the Atlantic rainforest. This study established boundaries concerning the effects of climate change and highlighted the need for proactive adaptation strategies and mitigation measures to minimize the potential adverse impacts in the study watershed.

Validity and reproducibility of the CALERA Research Sensor to estimate core temperature at different intensities of a cycling exercise in the heat.

Recent heatwaves have highlighted the importance of accurate and continuous core temperature (TCORE) monitoring in sports settings. For example, accentuated rises in TCORE caused by physical exercises under environmental heat stress increase the risk of heat illnesses. Thus, using valid and reproducible devices is essential to ensure safe sports practice. In this study, we assessed the validity and reproducibility of the Calera Research Sensor (CRS) in estimating the TCORE of male and female participants during cycling exercise in a hot environment. Seven male (age: 36.2 ± 10.1 years) and eight female cyclists (age: 30.1 ± 5.0 years) underwent two identical cycling trials in a dry-bulb temperature of 32 °C and relative humidity of 60%. The protocol consisted of an initial 10-min rest followed by a 60-min exercise comprising 10 min at 20%, 25 min at 55%, and 25 min at 75% of maximal aerobic power, and an additional 25 min of post-exercise recovery. TCORE was recorded simultaneously every minute using a gastrointestinal capsule (TGi) and the CRS (TSENSOR). Bland-Altman analysis was performed to calculate bias, upper (LCS) and lower (LCI) concordance limits, and the 95% confidence interval (95%CI). The maximum acceptable difference between the two devices was predetermined at ±0.4 °C. A mixed linear model was used to assess the paired differences between the two measurement systems, considering the participants, trials, and environmental conditions as random effects and the cycling stages as fixed effects. An intra-class correlation coefficient (ICC) of 0.98 was recorded when analyzing data from the entire experiment. A non-significant bias value of 0.01 °C, LCS of 0.38 °C, LCI of -0.35 °C, and CI95% of ±0.36 °C were found. When analyzing data according to the participants' sex, CRS reproducibility was high in both sexes: ICC values of 0.98 and 0.99 were reported for males and females, respectively. CI95% was 0.35 °C in experiments with males and 0.37 °C with females, thereby falling within the acceptable margin of difference. Therefore, CRS was considered valid (compared to TGi) and reproducible in estimating TCORE in both sexes at various intensities of cycling exercise in the heat.

Natural Products Have Increased Rates of Clinical Trial Success throughout the Drug Development Process.

Natural products (NPs) or their derivatives represent a large proportion of drugs that successfully progress through clinical trials to approval. This study explores the presence of NPs in both early- and late-stage drug discovery to determine their success rate, and the factors or features of natural products that contribute to such success. As a proxy for early drug development stages, we analyzed patent applications over several decades, finding a consistent proportion of NP, NP-derived, and synthetic-compound-based patent documents, with the latter group outnumbering NP and NP-derived ones (approximately 77% vs 23%). We next assessed clinical trial data, where we observed a steady increase in NP and NP-derived compounds from clinical trial phases I to III (from approximately 35% in phase I to 45% in phase III), with an inverse trend observed in synthetics (from approximately 65% in phase I to 55% in phase III). Finally, in vitro and in silico toxicity studies revealed that NPs and their derivatives were less toxic alternatives to their synthetic counterparts. These discoveries offer valuable insights for successful NP-based drug development, highlighting the potential benefits of prioritizing NPs and their derivatives as starting points.

Intraperitoneal drug delivery systems for peritoneal carcinomatosis: Bridging the gap between research and clinical implementation.

Several abdominal-located cancers develop metastasis within the peritoneum, what is called peritoneal carcinomatosis (PC), constituting a clinical challenge in their therapeutical management, often leading to poor prognoses. Current multidisciplinary strategies, including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC), demonstrate efficacy but have limitations. In response, alternative strategies are explored in the drug delivery field for intraperitoneal chemotherapy. Controlled drug delivery offers a promising avenue, maintaining localized drug concentrations for optimal PC management. Drug delivery systems (DDS), including hydrogels, implants, nanoparticles, and hybrid systems, show potential for sustained and region-specific drug release. The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration, focusing on their composition, main characteristics, and principal experimental outcomes, highlighting the importance of biomaterial rationale design and in vitro/vivo models for their testing. Moreover, since clinical data for human subjects are scarce, we offer a critical discussion of the gap between bench and bedside in DDS translation, emphasizing the need for further research.

Immunogenicity, reactogenicity and safety of a second booster with BNT162b2 or full-dose mRNA-1273: a randomised VACCELERATE trial in adults ≥75 years (EU-COVAT-1-AGED Part B).

OBJECTIVES: To assess safety and immunogenicity of a 4th vaccination (2nd booster) in individuals ≥75 years METHODS: Participants were randomised to BNT162b2 (Comirnaty®, 30µg) or mRNA-1273 (Spikevax®, 100µg). The primary endpoint was the rate of 2-fold antibody titre increase 14 days post-vaccination targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. Secondary endpoints included changes in neutralising activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AE) for seven days. RESULTS: 269 participants (mean age 81 years, mRNA-1273 n=135/BNT162b2 n=134) were included. 2-fold anti-RBD IgG titre increase was achieved by 101/129 (78%) and 116/133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (p=0.054). A 2nd booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titre: 21.326 IU/mL (95%-CI: 18.235; 24.940) vs. BNT162b2: 15.181 IU/mL (95%-CI: 13.172; 17.497). Higher neutralising activity was noted for the mRNA-1273 group. The most frequent AE was pain at injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs. 39%). CONCLUSIONS: A 2nd booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IGG levels and neutralising capacity against SARS-CoV-2 with similar safety profile for subjects of advanced age.

Position statement of the Spanish Society of Paediatric Infectious diseases on the diagnosis and treatment of Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae (M. pneumoniae) is a bacterium with particular characteristics that give rise to a broad clinical spectrum, being respiratory infection the most frequent presentation. Infection by M. pneumoniae occurs in cyclical epidemics, and paediatricians in Spain have noticed an increase in cases since January 2024, establishing hospital registers to collect surveillance data (as it is not a notifiable disease in Spain). The diagnosis of infection by M. pneumoniae is made through serological testing and/or the detection of genetic material by means of polymerase chain reaction (PCR). Neither methods can differentiate between colonization and active infection, so a precise diagnosis is not possible and testing should only be requested in the case of high clinical suspicion. The role of antibiotherapy in infection by M. pneumoniae in its different clinical variants is not well defined. Most infections are self-limiting and mild, and there is insufficient evidence to support the use of antibiotherapy in these cases. Antibiotic treatment is justified in patients with risk factors for the development of severe disease (Down syndrome, anatomical or functional asplenia, immunosuppression), in hospitalized patients with respiratory infection and in patients with moderate or severe extrapulmonary forms. Taking into account aspects concerning the rational use of antimicrobials, the treatment of choice would be clarithromycin, with azithromycin as an alternative, reserving the use of doxycycline and levofloxacin for cases of antimicrobial resistance and/or infections of the central nervous system.

Lysine grafted poly(lactic acid): An intrinsically antimicrobial polymer.

Nosocomial infections or healthcare-associated infections, normally develops after the healthcare treatment in the hospital. Most of them are caused by infected medical devices. Plastics are the most common materials for manufacturing these devices because of their good processability, sterilization efficacy, ease of handling and harmlessness, however, it usually do not display antimicrobial properties. Here, in order to infer antimicrobial activity to poly(lactic acid), it was modified by maleation, followed by l-lysine grafting to its structure. The chemical modifications were confirmed by FTIR and 1H NMR analysis, indicating the success of the reactions. The antimicrobial activity was tested using Escherichia coli and Staphylococcus aureus and the results showed that the sample was capable of inhibiting about 99 % of the S. aureus growth by contact. The samples cytotoxicity was also tested using the L929 mouse cells and the results indicated no cytotoxic effect. These results indicated the sample antimicrobial potential, without affect the normal eukaryotic cells. In addition, the processability of the modified PLA (PLA-g-Lys) was improved without compromising its mechanical properties, as shown by thermal analysis and tensile tests. Thus, this novel PLA derivative can be seen as a promising material for future applications in the manufacturing of biomedical devices.

International society of sports nutrition position stand: ketogenic diets.

POSITION STATEMENT: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus on exercise performance and body composition. However, this review does not address the use of exogenous ketone supplements. The following points summarize the position of the ISSN.1. A ketogenic diet induces a state of nutritional ketosis, which is generally defined as serum ketone levels above 0.5 mM. While many factors can impact what amount of daily carbohydrate intake will result in these levels, a broad guideline is a daily dietary carbohydrate intake of less than 50 grams per day.2. Nutritional ketosis achieved through carbohydrate restriction and a high dietary fat intake is not intrinsically harmful and should not be confused with ketoacidosis, a life-threatening condition most commonly seen in clinical populations and metabolic dysregulation.3. A ketogenic diet has largely neutral or detrimental effects on athletic performance compared to a diet higher in carbohydrates and lower in fat, despite achieving significantly elevated levels of fat oxidation during exercise (~1.5 g/min).4. The endurance effects of a ketogenic diet may be influenced by both training status and duration of the dietary intervention, but further research is necessary to elucidate these possibilities. All studies involving elite athletes showed a performance decrement from a ketogenic diet, all lasting six weeks or less. Of the two studies lasting more than six weeks, only one reported a statistically significant benefit of a ketogenic diet.5. A ketogenic diet tends to have similar effects on maximal strength or strength gains from a resistance training program compared to a diet higher in carbohydrates. However, a minority of studies show superior effects of non-ketogenic comparators.6. When compared to a diet higher in carbohydrates and lower in fat, a ketogenic diet may cause greater losses in body weight, fat mass, and fat-free mass, but may also heighten losses of lean tissue. However, this is likely due to differences in calorie and protein intake, as well as shifts in fluid balance.7. There is insufficient evidence to determine if a ketogenic diet affects males and females differently. However, there is a strong mechanistic basis for sex differences to exist in response to a ketogenic diet.

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection.

The spleen plays a pivotal role in the pathogenesis of visceral leishmaniasis. In severe forms of the disease, the spleen undergoes changes that can compromise its function in surveilling blood-circulating pathogens. In this study, we present an integrated analysis of the structural and gene expression alterations in the spleens of three patients with relapsing visceral leishmaniasis, two of whom were coinfected with HIV. Our findings reveal that the IL6 signaling pathway plays a significant role in the disorganization of the white pulp, while BCL10 and ICOSLG are associated with spleen organization. Patients coinfected with HIV and visceral leishmaniasis exhibited lower splenic CD4+ cell density and reduced expression of genes such as IL15. These effects may contribute to a compromised immune response against L. infantum in coinfected individuals, further impacting the structural organization of the spleen.

Biomarkers and prediction of anthracyclic cardiotoxicity in breast cancer.

BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

Goldfit Soccer: A Multidimensional Model for Talent Identification of Young Soccer Players.

Studies have provided empirical evidence on the prognostic relevance of test batteries and the "coach's eye" for talent identification. The aims were 1) to compare objective and subjective assessments as well as a combined soccer-specific potential index between future selected and non-selected players and 2) to evaluate the prognostic validity of a multidimensional model as a tool for talent identification in soccer. The sample was composed by 132 male players (14,5 ± 1,4 years; regional competitive level) from U13 to U17 age groups of a Brazilian soccer talent development program. Athletes completed a multidimensional test battery and were subjectively rated by their coaches for sporting potential. Players' success was evaluated five years later and was operationalized by achieving under-20 category of the Brazilian Championship or adult professional level (success rate, 15.9%). Confirming univariate prognostic validity, future selected outperformed non-selected players regarding 20-m sprint (p = .009), agility (p = .04), countermovement jump (p = .04), sit-and-reach (p = .001), Yo-Yo IR1 (p = .001), dribbling (p < .001), perceived competence (p = .007), peaking under pressure (p = .01), confidence/motivation (p = .03), coping skills (p = .03), intangibles (p < .001) and player potential (p < .001). A combined index (objective tests, athlete's assessments and coach's eye) named Gold Score Soccer (GSS) showed high prognostic validity (p < .001). A binary logistic regression estimated the probability of success (yes/not) with GSS, ambidextrous and predicted age at peak height velocity as predictors. This multidimensional model named GoldFit Soccer showed high prognostic validity (sensitivity = 85.7%; specificity = 83.8%; accuracy = 84.1%; area under the ROC curve = .93 [.87-.98]). Thus, GoldFit Soccer is a valid multidimensional scientific model for talent identification in soccer.

Aesthetic outcomes of different materials for delayed, single-tooth restorations for immediately placed implants. A randomized controlled clinical trial.

OBJECTIVES: The aim of this study is to compare the aesthetic outcomes of metal porcelain (C), lithium disilicate (T1) and porcelain-layered zirconium (T2) immediate implant-supported single crowns in the anterior maxilla. MATERIALS AND METHODS: Forty-five immediate dental implants were provided for 45 patients that required the extraction of a single tooth in the anterior maxilla. A temporary prosthesis was provided at 8 weeks after placement followed by the final prosthesis at 24 weeks post-implantation. The patients were randomly allocated into 3 groups: 15 patients in the control group (C) received a metal-porcelain restoration, 15 patients (T1) received a lithium disilicate (LD) restoration and 15 patients (T2) received a porcelain-layered, zirconium (Z) restoration. Pink (PES) and White (WES) esthetic scores, radiographic bone levels, periodontal parameters and patient's esthetic satisfaction using a visual analogue scale (VAS) were evaluated at the time of final restoration placement (t0) and at 12-months post-loading (t12). RESULTS: No implants were lost during the duration of this study. Statistically significant higher WES and VAS scores (p < 0.05) were recorded in T1 vs C and T1 vs T2 groups respectively. Similar radiographic bone levels and periodontal parameters were recorded in all groups. CONCLUSION: Within the limitations of this study, it was concluded that T1 restorations provided better WES outcomes when compared to C restorations and better VAS scores when compared to T2 restorations at 12 months post-loading. Besides, different material interphases did not have an impact in PES, bone levels or periodontal parameters. CLINICAL RELEVANCE: There is limited data comparing aesthetic outcomes of implant supported single crowns made of different ceramic materials based on accepted and comparable indexes and the evaluation of the patient's perspective regarding these aesthetic outcomes.

Cause-Specific Excess Mortality During the COVID-19 Pandemic (2020-2021) in 12 Countries of the C-MOR Consortium.

BACKGROUND: This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. METHODS: We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015-2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. RESULTS: Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortality in 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). CONCLUSIONS: This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021.

Residual energy use and energy efficiency improvement of European supermarket facilities during the post-COVID and energy crisis period.

Supermarkets are significant consumers of electricity and contribute to the generation of associated pollutant emissions. This will help to mitigate the impact of increased energy costs on the prices of products sold in supermarkets. Therefore, it is essential to reduce energy consumption, starting with the equipment that consumes the most electricity, such as refrigeration, and using the residual thermal energy generated in supermarkets. This paper discusses the impact of rising energy costs in the post-Covid era and during the energy crisis. It evaluates the environmental and energy benefits of implementing energy improvements and utilizing residual energy in real supermarkets. The analysis takes into account the socio-economic characteristics of the EU-27 countries, which affect the economic feasibility of these measures. This would prevent the release of 122 tons of CO2 per year for each supermarket, resulting in energy savings of around 70 % or 305 kWh/m2. The required investments would have a payback period of 4 years.

Impact of Cuminaldehyde and Indomethacin Co-Administration on Inflammatory Responses in MIA-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) remains a chronic incurable condition, presenting substantial challenges in treatment. This study explores a novel strategy by investigating the concurrent use of cuminaldehyde, a natural compound, with indomethacin in animal models of MIA-induced OA. Our results demonstrate that the co-administration of cuminaldehyde and indomethacin does indeed produce a superior effect when compared to these compounds individually, significantly enhancing therapeutic outcomes. This effect is evidenced by a marked reduction in pro-inflammatory cytokines IL-6 and IFN-γ, alongside a significant increase in the anti-inflammatory cytokine IL-10, compared to treatments with each compound alone. Radiographic analyses further confirm the preservation of joint integrity and a reduction in osteoarthritic damage, highlighting the association's efficacy in cartilage-reducing damage. These findings suggests that the association of cuminaldehyde and indomethacin not only slows OA progression but also offers enhanced cartilage-reducing damage and fosters the production of protective cytokines. This study underscores the potential benefits of integrating natural products with pharmaceuticals in OA management and stresses the importance of further research to fully understand the mechanisms underlying the observed potentiated effects.