Innate immune response induces positive inflammatory transducers and regulators in order to attack pathogens, while simultaneously negative signaling regulators are transcribed to maintain innate immune homeostasis and to avoid persistent inflammatory immune responses. The gene expression of many of these regulators is controlled by different epigenetic modifications. The remarkable impact of epigenetic changes in inducing or suppressing inflammatory signaling is being increasingly recognized. Several studies have highlighted the interplay of histone modification, DNA methylation, and post-transcriptional miRNA-mediated modifications in inflammatory diseases, and inflammation-mediated tumorigenesis. Targeting these epigenetic alterations affords the opportunity of attenuating different inflammatory dysregulations. In this regard, many studies have identified the significant anti-inflammatory properties of distinct naturally-derived phytochemicals, and revealed their regulatory capacity. In the current review, we demonstrate the signaling cascade during the immune response and the epigenetic modifications that take place during inflammation. Moreover, we also provide an updated overview of phytochemicals that target these mechanisms in macrophages and other experimental models, and go on to illustrate the effects of these phytochemicals in regulating epigenetic mechanisms and attenuating aberrant inflammation.

This work aims to develop and optimize blended polylactide-co-glycolide (PLGA) and poly(ε-caprolactone, PCL) loaded with Boswellia sacra oil (BO) to improve BO’s physicochemical properties and anti-breast cancer effects via enhancing apoptosis. In this context, BO was extracted from B. sacra oleo gum resins (BO) via hydrodistillation and chemically characterized by evaluating its essential oil’s composition using gas chromatography–mass spectrometry. Then, BO/PLGA–PCL NPs were formulated using the emulsion (O/W) solvent evaporation technique using a PLGA–PCL mixture at five different ratios (1:1, 2:1, 3:1, 1:2, and 1:3, respectively). The optimized NPs had a spherical morphology with no agglomerations and the lowest hydrodynamic size (230.3 ± 3.7 nm) and polydispersity index (0.13 ± 0.03) and the highest ζ potential (−20.36 ± 4.89 mV), as compared to the rest of the formulas. PLGA–PCL NPs could entrap 80.59 ± 3.37% of the BO and exhibited a controlled, sustained release of BO (83.74 ± 3.34%) over 72 h. Encapsulating BO in the form of BO/PLGA–PCL NPs resulted in a lower IC50 value as assessed by the MTT assay. Furthermore and upon assessing the apoptotic effect of both BO and BO/PLGA–PCL NPs, there was an increase in the percentage of apoptotic and necrotic cell percentages compared to the control and free BO. Encapsulation of BO in PLGA–PCL NPs doubled the percentage of apoptotic and necrotic cells exerted by free BO. These findings support the potential use of BO/PLGA–PCL NPs in treating breast cancer.

This study aims to design a pH-responsive dual-loaded nanosystem based on PEGylated chitosan nanoparticles loaded with ascorbic acid (AA) and oxaliplatin (OX) for the effective treatment of breast cancer. In this regard, non-PEGylated and PEGylated chitosan nanoparticles (CS NPs) loaded with either ascorbic acid (AA), oxaliplatin (OX), or dual-loaded with AA-OX were fabricated using the ionotropic gelation method. The hydrodynamic diameters of the fabricated AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs were 157.20 ± 2.40, 188.10 ± 9.70, and 261.10 ± 9.19 nm, respectively. While the hydrodynamic diameters of the designed AA/PEG-CS NPs, OX/PEG-CS NPs, and AA-OX/PEG-CS NPs were 152.20 ± 2.40, 156.60 ± 4.82, and 176.00 ± 4.21 nm, respectively. The ζ-potential of the prepared nanoparticles demonstrated high positive surface charges of +22.02 ± 1.50, +22.58 ± 1.85 and +40.4 ± 2.71 mV for AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs, respectively. The ζ-potential of the PEGylated CS NPs was reduced owing to the shielding of the positive charges by the PEG chains. Additionally, all the prepared nanoparticles exhibited high entrapment efficiencies (EE%) and spherical-shaped morphology. The chemical features of the prepared nanoparticles were investigated using Fourier transform infrared (FTIR) spectroscopy. Release studies showed the capability of the prepared non-PEGylated and PEGylated chitosan NPs to release their cargo in the acidic environment of cancer tissue (pH 5.5). Furthermore, the AA/CS NPs, AA/PEG-CS NPs, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs and AA-OX/PEG-CS NPs exhibited remarkable cytotoxic activities against breast adenocarcinoma (MCF-7) cells with IC50 values of 44.87 ± 11.49, 23.3 ± 3.73, 23.88 ± 6.29, 17.98 ± 3.99, 18.69 ± 2.22, and 7.5 ± 0.69 µg/mL, respectively; as compared to free AA and OX (IC50 of 150.80 ± 26.50 and 147.70 ± 63.91 µg/mL, respectively). Additionally, treatment of MCF-7 cells with IC50 concentrations of AA, AA/CS NPs, AA/PEG-CS NPs, OX, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs or AA-OX/PEG-CS NPs increased the percentages of early apoptotic cells to 5.28%, 9.53%, 11.20%, 5.27%, 13.80%, 8.43%, 2.32%, and 10.10%, respectively, and increased the percentages of late apoptotic cells to 0.98%, 0.37%, 2.41%, 2.06%, 0.97%, 9.66%, 56%, and 81.50%, respectively. These results clearly indicate that PEGylation enhances the apoptotic effect of AA and OX alone, in addition to potentiating the apoptotic effect of AA and OX when combined on MCF-7 cells. In conclusion, PEGylated chitosan nanoparticles encapsulating AA, OX, or AA and OX represent an effective formula for induction of apoptosis in MCF-7 cells.

Graphical abstract Sets of 3-alkenyl-2-oxindoles were synthesized of potential antiproliferative (against PaCa-2 and MCF7cancer cell lines) and promising properties against SARS-CoV-2.

The Covid-19 pandemic is with no doubt the biggest health crisis of the 21 st century. The disease is caused by a virus of the Coronaviridae family and is closely related to the virus responsible for the severe acute respiratory Syndrome (SARS). Since December 2019, the virus has continued to spread way beyond the location of the first recorded cases (Wuhan, China). As of now, over 5 million cases have been diagnosed with the disease worldwide and over 300 thousand have died. COVID-19 patients suffer from respiratory symptoms that can rapidly turn into potentially fatal acute respiratory distress syndrome (ARDS) in a portion of patients. Although many drugs and vaccines are currently under clinical trials, there is no currently approved treatment or vaccine. It is therefore critical to correctly identify risk factors that lead to the exacerbation of symptoms in highly susceptible groups. Groups that are at high risk include those aged 55 or older especially those with underlying conditions such as cardiovascular diseases. Certain ethnicities such as African-Americans have been found to be at a higher risk and males seem to be higher both in numbers as well as severity of cases. It is hypothesized that these groups are at risk as their molecular landscape is more permissive of viral infection and growth. Different occupations, especially those related to health-care as well as populations that do not cultivate a mask-wearing culture are at higher risk due to environmental exposure. In this article, we examine the evidence regarding different groups that are more sensitive to the disease and review hypotheses pertaining to COVID-19 infection and prognosis. Risk factors that can be related to the molecular landscape of COVID-19 infection as well as those related to environmental and occupational conditions are discussed.