Chemotherapy is the treatment of cancerous cells through the use of cytotoxic drugs. Whilst the use of systemic (intravenous) chemotherapy in equine practice is generally limited to the management of lymphoma, cytotoxic drugs are commonly used in the treatment of accessible skin tumors, either by topical application in the form of ointments or injected intralesionally. These drugs should be employed with caution due to the risk of serious adverse effects. In addition, extreme caution should be followed when preparing, handling, administering, and disposing them, due to their carcinogenic, mutagenic, and teratogenic properties.

One new compound, methyl 3-((1-((2-carbamoylphenyl)amino)-1-oxopropan-2-yl)amino)-3-oxopropanoate (1), along with nine known secondary metabolites (2-10) were isolated and elucidated chemical structures from the methanol extract of the marine-derived fungus Penicillium chrysogenum VH17. Subsequent bioassays showed the antimicrobial and cytotoxic potential of the isolated compounds. All compounds 1-10 displayed antimicrobial effects against at least one tested reference microorganism with MIC values ranging from 32 to 256 μg mL-1. Furthermore, compound 4 exhibited significant cytotoxicity against all tested cell lines HepG2, A549, and MCF7 with IC50 values of 29.43 ± 1.37, 33.02 ± 1.53, and 36.72 ± 1.88 µM, respectively, whereas compound 3 exhibited weak cytotoxicity against MCF7 and HepG2 cell lines with IC50 values of 87.17 ± 6.31 and 97.32 ± 5.66 µM, respectively.

The objective of this study was to analyze the chemical composition and evaluate the biological capabilities of the essential oils (EOs) extracted from leaves and stems of wild Aeschynomene indica L. plants by the hydrodistillation method. By using GC-FID/MS, fifty-six and fifty-five compounds, representing 95.1 and 97.6% of the essential oils in the leaves and stems, respectively, were characterized. The predominant constituents of A. indica EOs were (E)-caryophyllene, linalool, viridiflorol, phytol, hexadecanoic acid, trans-verbenol, and α-guaiene. The antibacterial and synergistic activities of the EOs were assessed by microdilution and checkerboard assays. The results revealed a potent inhibition and bactericidal activity against Staphylococcus aureus and Bacillus subtilis with MICs of 0.312-0.625 mg/mL. When combined with traditional antibiotics, the essential oils of A. indica possessed excellent synergistic effects against all tested bacteria. Additionally, the EOs of A. indica leaves showed higher antioxidant activity (IC50 = 0.11 ± 0.01 µg/mL) compared to the stem oil (IC50 = 0.19 ± 0.01 µg/mL) using the ABTS radical scavenging assay. The in vitro cytotoxicity of EOs against human cancer cell lines HepG2, MCF-7, A-549, and HCT-116 was examined, and MTT assays showed that the EOs possessed a significant cytotoxic potential against MCF-7 breast cancer cells, with IC50 values of 10.04 ± 1.82 and 15.89 ± 1.66 μg/mL, and a moderate cytotoxic activity against other tested cells. In conclusion, the A. indica EOs could be considered a potential source of pharmacologically active compounds.

This study investigates the phytochemical composition and biological activities of hemp (Cannabis sativa L.) leaves, flowers\' methanolic extracts from the Sofia variety, and its sprouts cultivated under different light conditions (natural light, darkness, blue, and white LED light for 5, 7, and 9 days). Phytochemical analysis using HPLC identified four key polyphenolic compounds in sprouts\' extracts: chlorogenic, caffeic, and gallic acids, and myricetin, with a predomination of the chlorogenic acid. In contrast, leaves and flowers\' extracts contained cannflavins A and B and chlorogenic, p-coumaric, and ferulic acids, with a significant presence of isochlorogenic acid. Antioxidant capacity, assessed by FRAP method, revealed higher antioxidant potential in leaves compared to flowers and sprouts, with sprouts grown under blue and white LED lights exhibiting the highest activity. Cytotoxic activity was evaluated on human colon cancer cell lines (HT29, HCT116, DLD-1) and normal colon epithelial cells (CCD 841 CoN). Results demonstrated significant and selective cytotoxicity against cancer cell lines, with leaves showing more pronounced effects than flowers, and sprouts only moderate activity. All samples revealed an anti-inflammatory effect in vitro. To conclude, sprouts, leaves, and flowers of the Sofia hemp may be considered promising products for chemoprevention in the future.

The study evaluated the preservative potential of Lafoensia replicata Pohl. leaf extracts in cosmetics, highlighting their antioxidant, antimicrobial, and in vitro cytotoxic activities for ethanolic extract prepared by the maceration and tincture method. Total phenol content showed a higher phenol concentration in ethanolic extract and tinctures, and by LC-MS/MS-ESI-QTOF analysis, flavonoids, hydrolyzed tannins, and phenolic acids were identified. The ethanolic extract and tincture showed high antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans (MIC < 50 µg mL-1), high antioxidant activity (EC50 < 50 µg mL-1 in the DPPH method, and results > 450 µmol trolox equivalent in the ABTS and FRAP method), and low cytotoxicity in human keratinocytes (IC50 > 350 µg mL-1). The results suggest these extracts could be an alternative to synthetic preservatives in the cosmetic industry.

Autophagy is a normal physiological process that aids the recycling of cellular nutrients, assisting the cells to cope with stressed conditions. However, autophagy\'s effect on cancer, including glioma, is uncertain and involves complicated molecular mechanisms. Several contradictory reports indicate that autophagy may promote or suppress glioma growth and progression. Autophagy inhibitors potentiate the efficacy of chemotherapy or radiation therapy in glioma. Numerous compounds stimulate autophagy to cause glioma cell death. Autophagy is also involved in the therapeutic resistance of glioma. This review article aims to detangle the complicated molecular mechanism of autophagy to provide a better perception of the two-sided role of autophagy in glioma and its therapeutic implications. The protein and epigenetic modulators of the cytoprotective and cytotoxic role of autophagy are described in this article. Moreover, several signaling pathways are associated with autophagy and its effects on glioma. We have reviewed the molecular pathways and highlighted the signaling axis involved in cytoprotective and cytotoxic autophagy. Additionally, this article discusses the role of autophagy in therapeutic resistance, including glioma stem cell maintenance and tumor microenvironment regulation. It also summarizes several investigations on the anti-glioma effects of autophagy modulators to understand the associated mechanisms and provide insights regarding its therapeutic implications.

Four new homoisoflavonoids, 7-hydroxy-3-[hydroxy(4\'-methoxyphenyl)methyl]-benzopyran-4-one (1), (3R)-7, 8-dihydroxy-3-(4\'-methoxybenzyl)-chroman-4-one (2), 7-hydroxy-3-(2\'-hydroxy-4\'-methoxybenzyl)-chroman-4-one (3), and 7-hydroxy-3-(2\'-hydroxy-4\'-methoxybenzyl)-benzopyran-4-one (4), were isolated from the seeds of Caesalpinia pulcherrima. The structures of new compounds were elucidated by MS and NMR spectra. Their absolute configurations were assigned using electronic circular dichroism spectrum. Compounds 2 and 4 exhibited cytotoxic effects on MCF-7/TAM cells with the IC50 values of 101.4 ± 0.03 and 93.02 ± 0.03 μM, respectively.

During chronic infection, virus-specific CD8+ cytotoxic T lymphocytes (CTLs) progressively lose their ability to mount effective antiviral responses. This \"exhaustion\" is coupled to persistent upregulation of inhibitory receptor programmed death-1 (PD-1) (Pdcd1)-key in suppressing antiviral CTL responses. Here, we investigate allelic Pdcd1 subnuclear localization and transcription during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Pdcd1 alleles dissociate from transcriptionally repressive chromatin domains (lamin B) in virus-specific exhausted CTLs but not in naive or effector CTLs. Relative to naive CTLs, nuclear positioning and Pdcd1-lamina dissociation in exhausted CTLs reflect loss of Pdcd1 promoter methylation and greater PD-1 upregulation, although a direct correlation is not observed in effector cells, 8 days post-infection. Genetic deletion of B lymphocyte-induced maturation protein 1 (Blimp-1) enhances Pdcd1-lamina dissociation in effector CTLs, suggesting that Blimp-1 contributes to maintaining Pdcd1 localization to repressive lamina. Our results identify mechanisms governing Pdcd1 subnuclear localization and the broader role of chromatin dynamics in T cell exhaustion.

Development of resistance to cisplatin, oxaliplatin and carboplatin remains a challenge for their use as chemotherapies, particularly in breast and colorectal cancer. Here, we compare the anticancer effect of novel complexes [Pt(1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO3)2 (PtIIPHENSS), [Pt(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO3)2 (PtII5MESS) and [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO3)2 (PtII56MESS) and their platinum(IV)-dihydroxy derivatives with cisplatin. Complexes are greater than 11-fold more potent than cisplatin in both 2D and 3D cell line cultures with increased selectivity for cancer cells over genetically stable cells. ICP-MS studies showed cellular uptake occurred through an active transport mechanism with considerably altered platinum concentrations found in the cytoskeleton across all complexes after 24 h. Significant reactive oxygen species generation was observed, with reduced mitochondrial membrane potential at 72 h of treatment. Late apoptosis/necrosis was shown by Annexin V-FITC/PI flow cytometry assay, accompanied by increased sub-G0/G1 cells compared with untreated cells. An increase in S and G2+M cells was seen with all complexes. Treatment resulted in significant changes in actin and tubulin staining. Intrinsic and extrinsic apoptosis markers, MAPK/ERK and PI3K/AKT activation markers, together with autophagy markers showed significant activation of these pathways by Western blot. The proteomic profile investigated post-72 h of treatment identified 1597 MDA-MB-231 and 1859 HT29 proteins quantified by mass spectroscopy, with several differentially expressed proteins relative to no treatment. GO enrichment analysis revealed a statistically significant enrichment of RNA/DNA-associated proteins in both the cell lines and specific additional processes for individual drugs. This study shows that these novel agents function as multi-mechanistic chemotherapeutics, offering promising anticancer potential, and thereby supporting further research into their application as cancer therapeutics.

Three new polyprenylated benzophenone derivatives named burlemarxione G-I (1-3) were isolated from C. burle-marxii trunks (compound 1) and leaves (compounds 2 and 3), along with the known compound burlemarxione F. Burlemarxione G (1) was isolated after methylation with diazomethane and it is the keto-enol tautomeric pair of burlemarxione F. Burlemarxione H (2) derives from burlemarxiones F and G, but it has additional rings due to cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. Burlemarxione I (3) has two additional cyclizations: the first encompasses the cyclization of the former isopentenyl group into an 11,11-dimethyl-six-membered ring, whereas the second produces additional rings due to the cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. All three compounds showed moderate anti-glioma activity. These results show that C. burle-marxii is an important source of sophisticated polyprenylated benzophenone derivatives.