Flavonoids are a diverse group of plant-derived compounds that have been shown to have various health benefits, including anti-inflammatory effects. However, their use in the treatment of inflammatory diseases has been limited due to their low bioavailability. The nanoparticle-mediated delivery of flavonoids has been proposed as a potential solution to this issue, as it allows the sustained release of the flavonoids over time. There are several different nanoparticle systems that have been developed for flavonoid delivery, including polymeric nanoparticles, liposomes, and inorganic nanoparticles. This systematic review aims to evaluate the impact of nanoparticle-mediated delivery of flavonoids on pro-inflammatory cytokine production in various diseases. We analyzed the performance of flavonoid-encapsulated nanoparticles in regulating cytokine production in different in vitro and in vivo studies. To this end, we followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to conduct a comprehensive search of the literature and to assess the quality of the included studies. The results showed that flavonoid-encapsulated nanoparticles significantly downregulated pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-18. In some cases, this effect was significantly greater than that observed with non-encapsulated flavonoids These findings suggest that nanoparticle-mediated delivery of flavonoids may have potential as a therapeutic approach for the treatment of inflammatory diseases.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks estrogen and progesterone receptors and does not overexpress the human epidermal growth factor receptor 2 (HER2). Previous treatment options for TNBC were limited to chemotherapy alone, resulting in a poor patient prognosis. In 2018, an estimated 2.1 million new cases of breast cancer were diagnosed globally, with the incidence increasing by 0.5% annually from 2014 to 2018. The exact prevalence of TNBC is difficult to determine because it is based on the absence of certain receptors and overexpression of HER2. Treatment options for TNBC include surgery, chemotherapy, radiation therapy, and targeted therapy. The available evidence suggests that combination immunotherapy using PD-1/PD-L1 inhibitors may be a promising treatment option for metastatic TNBC. In this review, we evaluated the efficacy and safety of different immunotherapies regimens for the treatment of TNBC. In many clinical trials, the overall response rate and survival were better in patients treated with these drug combinations than those treated with chemotherapy alone. Although definitive treatments are not within reach, efforts to gain a deeper understanding of combination immunotherapy have the potential to overcome the urge for safe and effective treatments.

Pancreatic cancer has one of the highest mortality rates among cancers, and a combination of nab-paclitaxel with gemcitabine remains the cornerstone of first-line therapy. However, major advances are required to achieve improvements in patient outcomes. For this reason, several research groups have proposed supplementing treatment with other therapeutic agents. Ongoing studies are being conducted to find the optimal treatment in a first-line setting. In this work, we used a search strategy to compare studies on the efficacy and safety of nab-paclitaxel with gemcitabine in combination with other therapeutic agents based on the criteria of the Preferred Reporting Items for Systematic Reviews. We found seven studies in different clinical phases that met the inclusion criteria. The seven therapeutic agents were ibrutinib, necuparanib, tarextumab, apatorsen, cisplatin, enzalutamide, and momelotinib. Although these therapeutic agents have different mechanisms of action, and molecular biology studies are still needed, the present review was aimed to answer the following question: which formulations of the nab-paclitaxel/gemcitabine regimen in combination with other therapeutic agents are safest for patients with previously untreated metastatic pancreas ductal adenocarcinoma? The triple regimen is emerging as the first-line option for patients with pancreatic cancer, albeit with some limitations. Thus, further studies of this regimen are recommended.

Tree nuts are rich in polar (phenolic compounds) and non-polar (tocols) antioxidants, with recognized effects in the prevention of diseases such as cancer. These biomolecules possess antiproliferative activity on cancer cells; however, the combined effect of both types of compounds has been scarcely studied, and this approach could give valuable information on the real anticancer potential of tree nuts. In the present study, the antiproliferative activity of pure tocols and phenolic compounds, tocol- and phenolic-rich extracts (TRE and PRE, respectively) from tree nuts and the extracts combinations, was evaluated in four cancer (HeLa, MCF7, PC3, A549) and one control (ARPE) cell lines. The most sensible cell lines were HeLa and MCF7. TRE and PRE from nuts were chemically characterized; γ and δ tocopherols, total tocols, total tocopherols and total phenolic compounds were negatively correlated with cell viability in MCF7 cells. In HeLa cells, only δ and total tocopherols were negatively correlated with cell viability. TRE and PRE had a low effect in reducing cell viability of the cancer cell lines, the most effective extracts were those of emory oak acorn (EOA), pecan nut (PEC) and walnut (WAL), and these were further studied for their pharmacological interactions, using the combination index and the isobologram methods. Combinations of both extracts showed a synergistic and strongly synergistic behavior in the three nuts (EOA, PEC and WAL), with combination indexes between 0.12 and 0.55. These results highlight the need to understand the interactions among components found in complex natural extracts or food products in order to fully understand their bioactivities.

Background: Food rich in tocopherols (T) and tocotrienols (T3) are considered functional due to their ability to reduce oxidative stress and modulate anti-viability and pro-apoptotic pathways with anticancer potential; however, their efficacy differs between T and T3 and among isoforms (α and γ) likely due to differences in intracellular uptake and, consequently, in the activation of anticancer signaling pathways. To address these isoform-dependent differences, HeLa and MCF7 cancer cell lines were used to assess the antiproliferative activity of α-tocopherol (αT), γ-tocopherol (γT) and tocotrienols (Tocomin) as well as their pharmacological interactions according to Loewe and Chou–Talalay models. Methods: The tocol profile of the commercial mixture of T3 (Tocomin) was quantified by normal-phase HPLC. HeLa, MCF7, and ARPE-19 cells were cultured in DMEM supplemented with 10% FBS and exposed to αT, γT, or Tocomin (50–800 µg/mL; DMSO vehicle) for 48 h; viability was measured by the MTT assay and EC50 values were obtained from log(dose)–response fits (n = 3). Fixed-ratio (1:1) combinations were evaluated in HeLa and MCF7, and interactions were quantified using Loewe additivity and Chou–Talalay combination indices, supported by isobologram analysis. Results: Tocomin showed greater potency with αT and γT, and synergy with αT/γT; however, the combination of αT + γT showed antagonism in both cell lines. Conclusions: The higher potency of Tocomin and its synergistic interactions with αT or γT suggest that tocotrienol-rich mixtures may enhance the antiproliferative response, whereas combining αT and γT together may reduce efficacy under the tested conditions.